Journal articles: 'Extra non-Cancer death risk'

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Botta, Laura, Gemma Gatta, Annalisa Trama, and Riccardo Capocaccia. "Excess risk of dying of other causes of cured cancer patients." Tumori Journal 105, no. 3 (March 25, 2019): 199–204. http://dx.doi.org/10.1177/0300891619837896.

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Background: The proportion of patients cured of cancer is usually estimated with cure models assuming they have the same death risk as the general population. These patients, even when cured, often maintain an extra death risk compared to the overall population. Our aims were to estimate this extra risk, and to take it into account in estimating cure proportions and relative survival (RS). Methods: We used RS mixture model with an additional parameter expressing the extra noncancer death risk of patients, assumed constant with age. We applied the model to the SEER registries survival data (1990–1994 diagnosed patients) with colorectal, breast, and lung cancers, and followed up to 2013. Results: The estimated relative risk of death for cured patients versus the general population was 1.11 for colorectal, 1.16 for breast, and 2.17 and 2.12, respectively, for female and male lung cancers. Taking this extra risk into account leads, for all cancers, to a higher estimated proportion of cured and a lower RS of uncured patients. In addition, it leads to a higher estimated RS for all patients aged >70 years, and for lung cancer patients aged >50 years, at diagnosis. Conclusions: Mortality of survivors not directly due to the diagnosed cancer was significantly higher than in the general population. It affected the estimates of cure proportions for all age classes and RS in the elderly.

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Kedves, Melinda, Fruzsina Kósa, Péter Kunovszki, Péter Takács, Melinda Zsuzsanna Szabó, Chetan Karyekar, Jennifer H. Lofland, and György Nagy. "Large-scale mortality gap between SLE and control population is associated with increased infection-related mortality in lupus." Rheumatology 59, no. 11 (May 1, 2020): 3443–51. http://dx.doi.org/10.1093/rheumatology/keaa188.

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Abstract Objective The aim of the present study was to analyse the incidence, prevalence, mortality and cause of death data of adult SLE patients and matched controls in a full-populational, nationwide, retrospective study. Methods This non-interventional study was based on database research of the National Health Insurance Fund of Hungary. A total of 7888 patients were included in the analyses, within which two subgroups of incident patients were created: the ‘All incident SLE patients’ group consisted of all incident SLE patients (4503 patients), while the ‘Treated SLE patients’ group contained those who received relevant therapy in the first 6 months after diagnosis (2582 patients). Results The median age of the SLE population was found to be 46.5 years (women 85%). The incidence rate was 4.86 and 2.78 per 100 000 inhabitants in the ‘All incident SLE patients’ and ‘Treated SLE patients’ groups, respectively. The standardized mortality ratio was 1.63 and 2.09 in the ‘All incident SLE patients’ and ‘Treated SLE patients’ groups, respectively. Overall survival was significantly lower (P < 0.001) in both groups than in the general population, with hazard ratio = 2.17 in the ‘All incident SLE patients’ group and hazard ratio = 2.75 in the ‘Treated SLE patients’ group. There was no significant difference between SLE and control deaths regarding cerebrovascular conditions as the cause of death. Generally, cancer-related deaths were less common, while haematological cancer and infection-related deaths were more common in SLE patients. Conclusion Infections, especially sepsis, had the largest positive effect on top of the extra mortality of SLE. This highlights that SLE patients are at increased risk of infection-related death.

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Agarwal, Shashi K. "Smoking and Its Relationship with Cancer." Journal of Cancer Research Reviews & Reports 3, no. 2 (June 30, 2021): 1–9. http://dx.doi.org/10.47363/jcrr/2021(3)136.

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Tobacco smoking is a popular pastime all over the world. It is the leading preventable cause of cancer. Tobacco smoke is loaded with carcinogens that harm literally every tissue in the human body. It is the main cause of cancers of the lung, esophagus, and urinary bladder. Besides its deleterious effect on the primary smokers, exhaled smoke and side-stream smoke from their cigarettes also increase the risk of cancer in non-smokers from passive inhalation. Almost one-half of the cancer sufferers continue to smoke after its diagnosis, and this interferes with treatment, increases the risk of recurrence, is associated with a poor quality of life, and markedly hikes mortality. Tobacco smoking is implicated in about a third of all cancer deaths. It also increases the risk of developing a second primary cancer. Smoking cessation not only reduces the risk of developing new cancer but also favorably alters the course of established cancer. It can also bestow an extra 20 years of life. This manuscript briefly reviews the noxious relationship between tobacco smoke and cancer.

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Henson, K., R. Brock, J. Charnock, B. Wickramasinghe, O. Will, L. Elliss-Brookes, and A. Pitman. "Risk of Suicide After a Cancer Diagnosis in England: A Population-Based Study." Journal of Global Oncology 4, Supplement 2 (October 1, 2018): 228s. http://dx.doi.org/10.1200/jgo.18.92200.

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Background: Previous research has identified an increased risk of suicide among cancer patients, however this has not been investigated at a population level in England. Those subgroups of patients most at risk need to be identified to ensure appropriate access to psychological support. Aim: To examine the variation in suicide risk among individuals diagnosed with cancer in England. Methods: We identified 4,453,547 individuals (21 million person-years at risk) aged 18 to 99 years at diagnosis of cancer during 1995 to 2015 from the national cancer registry, and followed them up until 31 August 2017. The outcomes of interest were both suicide and open verdicts (ICD-10 X60-X84, Y87.0, Y10-Y34 [excluding Y33.9, Y87.2]). Population-based expected deaths were as published by ONS [2]. We calculated standardized mortality ratios (SMRs) and absolute excess risks (AERs), and explored variation in suicide risk by cancer type, age at death, sex, deprivation, ethnicity, and years since cancer diagnosis. Results: 2352 cancer patients died by suicide. This was 0.08% of all deaths. The overall SMR for suicide was 1.19 (95% CI 1.14-1.24) and AER per 10,000 person-years was 0.18 (0.13-0.22). The risk was highest among individuals diagnosed with mesothelioma, with a 4.34-fold risk corresponding to 4.00 extra deaths per 10,000 person-years. This was followed by pancreatic (3.94-fold), esophageal (2.53-fold), lung (2.52-fold), and stomach (2.14-fold) cancer (all significantly elevated). Suicide risk was highest in the first 6 months following cancer diagnosis (SMR: 2.64 [2.42-2.89]), but a significantly increased risk persisted for 2 years (SMR: 1.21 [1.08-1.35]). Conclusion: Despite low numbers, the elevated risk of suicide in patients with certain cancers is a concern, representing potentially preventable deaths. The increased risk in the first 6 months after diagnosis, which is consistent with previous studies, highlights unmet needs for psychological support delivered alongside cancer diagnosis and treatment. Our findings suggest a need for improved risk stratification across cancer services, followed by targeted psychological support.

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Beemsterboer, P. M. M., P. G. Warmerdam, R. Boer, and H. J. de Koning. "Radiation risk of mammography related to benefit in screening programmes: a favourable balance?" Journal of Medical Screening 5, no. 2 (June 1, 1998): 81–87. http://dx.doi.org/10.1136/jms.5.2.81.

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Objectives To estimate the number of breast cancer deaths induced by low dose radiation in breast cancer screening programmes compared with numbers prevented. Methods A computer simulation model on the natural history of breast cancer was combined with a model from BEIR-V on induced breast cancer mortality from low levels of radiation. The improvement in prognosis resulting from screening was based on the results of the Swedish overview of the randomised screening trials for breast cancer and the performance of screening in the Netherlands. Different scenarios (ages and intervals) were used to explore the objectives. Sensitivity analyses were carried out for latency period, dose of mammography, sensitivity of the screening test, early detection by screening of induced breast tumours, and new 1996 risk estimates by Howe and McLaughlin. Results For a screening programme, age group 50–69, two year interval, 2 mGy per view, the balance between the number of deaths induced versus those prevented was favourable: 1:242. When screening is expanded to the age group 40–49 with a one or two year interval the results may be less favourable, that is, 1:66 and 1:97. According to these scenarios and with the Dutch scenario as reference, one breast cancer death from radiation may be expected to occur to save eight extra deaths from breast cancer. If screening was equally effective in young women as in women aged 50–69, the marginal value was 1:±30. Assuming detection of induced cancers by screening could influence the ratios by about 30%, but did not substantially change the conclusions. The new risk estimates by Howe and McLaughlin resulted in five times to eight times favourable ratios breast cancer deaths induced to prevented. Besides age group of screening, dose of mammography is the other determinant of risk. Conclusions For screening under the age of 50, the balance between the number of breast cancer deaths prevented by screening compared with the number induced by radiation seem less favourable. Credibility intervals were however wide, because of many uncertainties of radiation risk at very low doses.

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Daniels, Robert Douglas, and Stephen J. Bertke. "Exposure–response assessment of cancer mortality in styrene-exposed boatbuilders." Occupational and Environmental Medicine 77, no. 10 (May 29, 2020): 706–12. http://dx.doi.org/10.1136/oemed-2020-106445.

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ObjectivesTo improve exposure estimates and reexamine exposure–response relationships between cumulative styrene exposure and cancer mortality in a previously studied cohort of US boatbuilders exposed between 1959 and 1978 and followed through 2016.MethodsCumulative styrene exposure was estimated from work assignments and air-sampling data. Exposure–response relationships between styrene and select cancers were examined in Cox proportional hazards models matched on attained age, sex, race, birth cohort and employment duration. Models adjusted for socioeconomic status (SES). Exposures were lagged 10 years or by a period maximising the likelihood. HRs included 95% profile-likelihood CIs. Actuarial methods were used to estimate the styrene exposure corresponding to 10-4 extra lifetime risk.ResultsThe cohort (n= 5163) contributed 201 951 person-years. Exposures were right-skewed, with mean and median of 31 and 5.7 ppm-years, respectively. Positive, monotonic exposure–response associations were evident for leukaemia (HR at 50 ppm-years styrene = 1.46; 95% CI 1.04 to 1.97) and bladder cancer (HR at 50 ppm-years styrene =1.64; 95% CI 1.14 to 2.33). There was no evidence of confounding by SES. A working lifetime exposure to 0.05 ppm styrene corresponded to one extra leukaemia death per 10 000 workers.ConclusionsThe study contributes evidence of exposure–response associations between cumulative styrene exposure and cancer. Simple risk projections at current exposure levels indicate a need for formal risk assessment. Future recommendations on worker protection would benefit from additional research clarifying cancer risks from styrene exposure.

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Khatun, F., B. Rawat, A. Vaidya, S. Rajbhandari, and Y. Bhatta. "Percutaneous transluminal coronary angioplasty in Nepalese diabetic patients: Do they carry extra risk to revascularization process?" Journal of Kathmandu Medical College 1, no. 1 (December 18, 2012): 16–20. http://dx.doi.org/10.3126/jkmc.v1i1.7250.

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Background and Objectives: There is evidence that diabetes carries risk of various complications and adverse outcome with coronary revascularisation procedures. The aim of this study was to analyze the outcomes and complications of Percutaneous Transluminal Coronary Angioplasty in Nepalese diabetic patients compared to non-diabetic patients. Method: A hospital-based comparative cross-sectional study was conducted at Norvic International Hospital, Kathmandu, Nepal. A total of 702 consecutive Percutaneous Transluminal Coronary Angioplasty patients coming to the hospital from 2002 to 2010 were included. Angioplasty was performed using radial and femoral routes in a standard setting with standard techniques. Information on other background risk factors was recorded. Success of the procedures and presence of major and minor complications were observed. Results: Of the 702 patients participating in this study, 259 were diabetic and 443 were non-diabetic. Success rates were similar: 256 (98.8%) of diabetic and 438 (98.8%) of non-diabetic had a successful Percutaneous Transluminal Coronary Angioplasty. Complications of the procedure were however higher in the diabetic patients with higher in-hospital death (odds ratio 3.4, 95% confidence Interval: 0.6-19.1), compared to non-diabetic patients. Conclusion: The overall outcome of Percutaneous Transluminal Coronary Angioplasty was equally successful in diabetic and non-diabetic populations groups. But the complications were higher with the diabetic group which were because of presence of other co-morbidities in this group and were not procedure-related. DOI: http://dx.doi.org/10.3126/jkmc.v1i1.7250 Journal of Kathmandu Medical College, Vol. 1, No. 1, Issue 1, Jul.-Sep., 2012 pp.16-20

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Sobrero, Alberto, Sara Lonardi, Gerardo Rosati, Maria Di Bartolomeo, Monica Ronzoni, Nicoletta Pella, Mario Scartozzi, et al. "FOLFOX or CAPOX in Stage II to III Colon Cancer: Efficacy Results of the Italian Three or Six Colon Adjuvant Trial." Journal of Clinical Oncology 36, no. 15 (May 20, 2018): 1478–85. http://dx.doi.org/10.1200/jco.2017.76.2187.

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Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX and 36% CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95% CI, 0.99 to 1.32; P [for noninferiority] = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9% (95% CI, -0.7% to 4.4%). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95% CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95% CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95% CI, 1.05 to 1.89) and 1.23 (95% CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.

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Piper, Thomas B., Hans J. Nielsen, and Ib Jarle Christensen. "Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy." Tumor Biology 44, no. 1 (February 14, 2022): 1–16. http://dx.doi.org/10.3233/tub-211501.

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BACKGROUND: It was previously shown in three subpopulations that subjects not identified with colorectal cancer (CRC) at bowel endoscopy, but with increased serological cancer-associated protein biomarker levels had an increased risk of being diagnosed with subsequent malignant diseases. Objective: The aim of the present study was to perform a pooled analysis of subjects from the three subpopulations and subsequently validate the results in an independent study. The study population denoted the training set includes N = 4,076 subjects with symptoms attributable to CRC and the independent validation set N = 3,774 similar subjects. METHODS: Levels of CEA, CA19-9, TIMP-1 and YKL-40 were determined in blood samples collected prior to diagnostic bowel endoscopy. Follow-up of subjects not diagnosed with CRC at endoscopy, was ten years and identified subjects diagnosed with primary intra- or extra-colonic malignant diseases. The primary analysis was time to a newly diagnosed malignant disease and was analyzed with death as a competing risk in the training set. Subjects with HNPCC or FAP were excluded. The cumulated incidence was estimated for each biomarker and in a multivariate model. The resulting model was then validated on the second study population. RESULTS: In the training set primary malignancies were identified in 515 (12.6%) of the 4,076 subjects, who had a colorectal endoscopy with non-malignant findings. In detail, 33 subjects were subsequently diagnosed with CRC and 482 subjects with various extra-colonic cancers. Multivariate additive analysis of the dichotomized biomarkers demonstrated that CEA (HR = 1.50, 95% CI:1.21–1.86, p < 0.001), CA19-9 (HR = 1.41, 95% CI:1.10–1.81, p = 0.007) and TIMP-1 (HR = 1.25 95% CI: 1.01–1.54, p = 0.041) were significant predictors of subsequent malignancy. The cumulated incidence at 5 years landmark time was 17% for those subjects with elevated CEA, CA19-9 and TIMP-1 versus 6.7% for those with low levels of all. When the model was applied to the validation set the cumulated 5-year incidence was 10.5% for subjects with elevated CEA, CA19-9 and TIMP-1 and 5.6% for subjects with low levels of all biomarkers. Further analysis demonstrated a significant interaction between TIMP-1 and age in the training set. The age dependency of TIMP-1 indicated a greater risk of malignancy in younger subjects if the biomarker was elevated. This observation was validated in the second set. CONCLUSION: Elevated cancer-associated protein biomarker levels in subjects with non-malignant findings at large bowel endoscopy identifies subjects at increased risk of being diagnosed with subsequent primary malignancy. CEA, CA19-9 and TIMP-1 were significant predictors of malignant disease in this analysis. TIMP-1 was found dependent on age. The results were validated in an independent symptomatic population.

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Garcia-Guasch, Maite, Mireia Medrano, Irmgard Costa, Elena Vela, Marta Grau, Eduard Escrich, and Raquel Moral. "Extra-Virgin Olive Oil and Its Minor Compounds Influence Apoptosis in Experimental Mammary Tumors and Human Breast Cancer Cell Lines." Cancers 14, no. 4 (February 11, 2022): 905. http://dx.doi.org/10.3390/cancers14040905.

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Breast cancer is the most common malignancy among women worldwide. Modifiable factors such as nutrition have a role in its etiology. In experimental tumors, we have observed the differential influence of high-fat diets in metabolic pathways, suggesting a different balance in proliferation/apoptosis. In this work, we analyzed the effects of a diet high in n-6 polyunsaturated fatty acids (PUFA) and a diet high in extra-virgin olive oil (EVOO) on the histopathological features and different cell death pathways in the dimethylbenz(a)anthracene-induced breast cancer model. The diet high in n-6 PUFA had a stimulating effect on the morphological aggressiveness of tumors and their proliferation, while no significant differences were found in groups fed the EVOO-enriched diet in comparison to a low-fat control group. The high-EVOO diet induced modifications in proteins involved in several cell death pathways. In vitro analysis in different human breast cancer cell lines showed an effect of EVOO minor compounds (especially hydroxytyrosol), but not of fatty acids, decreasing viability while increasing apoptosis. The results suggest an effect of dietary lipids on tumor molecular contexts that result in the modulation of different pathways, highlighting the importance of apoptosis in the interplay of survival processes and how dietary habits may have an impact on breast cancer risk.

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Ng, Lawrence Cheng Kiat, Shin Yeu Ong, Xinxin Huang, Aditi Ghosh, Chandramouli Nagarajan, Yeow Tee Goh, Yunxin Chen, et al. "Outcome of Extra-Nodal Follicular Lymphoma Affected By Selection of Induction Chemoimmunotherapy and Maintenance Rituximab - Real-World Retrospective Study." Blood 144, Supplement 1 (November 5, 2024): 6277. https://doi.org/10.1182/blood-2024-193417.

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Background: Extra-nodal involvement is frequently observed in follicular lymphoma, yet there is limited evidence regarding its prognostic significance and optimal treatment strategies. We present our institutional experience treating follicular lymphoma, focusing on the impact of extra-nodal involvement. Methods: We conducted a retrospective analysis of demographic, treatment, and outcome data from patients with follicular lymphoma treated at two major cancer institutions in Singapore from 2010 to 2023, using registry data. Patients with grade 3B histology were excluded. Progression-free survival (PFS) was defined as the time from treatment initiation to disease progression or death. Overall survival (OS) was defined as the time from treatment initiation to death from any cause. Progression within 24 months (POD24) was defined as disease progression within 24 months from treatment initiation. Survival distributions were estimated using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, and multivariate analysis was conducted using Cox proportional hazards modelling. Results: A total of 190 patients were included in the study. The median age was 60 years, with 55% male and 45% female. Stage distribution included 7% stage 1, 14% stage 2, 19% stage 3, and 60% stage 4. According to FLIPI stratification, 22% were low (0-1), 22% intermediate (2), and 54% high (3-5). Histologically, 55% had grade 1/2 and 45% grade 3A disease. Extra-nodal involvement was present in 67% of patients, most commonly affecting bone marrow (43%), skeletal system (10%), liver (6%), and other sites (n=15, including skin, intestine, lung, renal, and breast). The median time from diagnosis to treatment initiation was 25 days (range: 0-1488 days). Treatment regimens included R-CHOP in 44%, BR in 31%, and other treatments in 25% (R-CVP/R-lenalidomide/Rituximab monotherapy). Maintenance Rituximab (MR) was administered to 28% of patients. With a median follow-up of 70.3 months, median PFS and OS were not reached, with estimated 5-year PFS of 62% and 5-year OS of 85%. POD24 occurred in 15% of patients. The leading causes of death were lymphoma (n=12), unknown (n=11), pneumonia (n=6), secondary malignancy (n=3), and other causes (n=1). Univariate analysis of patients treated with R-CHOP or BR showed significantly inferior PFS in those with extra-nodal involvement (5-year PFS 64% vs. 69%, p=0.041), but no differences in POD24 or OS. FLIPI score showed no prognostic value in PFS (p=0.53) or POD24 (p=0.65), although high FLIPI score correlated with inferior OS (p=0.03), likely due to age-factor within FLIPI. This is because age more than 60 years alone stand out with inferior OS (p=0.03). In multivariate analysis, extra-nodal involvement marginally lost statistical significance for PFS (p=0.057) whereas FLIPI score (p=0.15) and age (p=0.26) do not affect OS on multivariate analysis. Subgroup analysis of 95 patients with extra-nodal disease treated with R-CHOP or BR showed trends towards superior PFS and lower POD24 with rituximab maintenance (p=0.06 each). R-CHOP was associated with a non-statistically higher risk of POD24 compared to BR (p=0.057), with no impact on OS. No prognostic differences were found based on the number of extra-nodal sites or involvement of solid organs. Among patients with extra-nodal involvement treated with R-CHOP without MR, significantly shorter PFS (p=0.006) and higher POD24 risk (p=0.02) were observed compared to those receiving R-CHOP with MR, translating into inferior OS (p=0.014). This trend was not observed among BR-treated patients without maintenance rituximab. Conclusion: Extra-nodal involvement in follicular lymphoma appears to confer high-risk status. R-CHOP induction in these patients may result in poorer outcomes unless followed by maintenance rituximab.

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Lüdecke, Gerson, Florian Hasner, Herbert Hanitzsch, and Matthias Schmidt. "The German study group of intravesical hyperthermia-chemotherapy in non-muscle-invasive bladder cancer presents their long-term results in efficacy and tolerability for optimized adjuvant therapy and bladder preservation." Journal of Clinical Oncology 31, no. 6_suppl (February 20, 2013): 268. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.268.

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268 Background: In NMIBC recurrence and progression in high-risk BC are the dominant aspects for the clinical management. Intravesical chemotherapy and BCG treatment are the techniques to reduce both risks. HTC has a potentiating synergistic action in BC cell death induction. In consequence we proved HTC in the adjuvant indication and the ablativ indication in high-risk BC. Methods: We treated 138 patients in 1,443 treatment sessions in 3 institutions with intravesical hyperthermia-chemotherapy with Mitomycin C applied with the Synergo device. After an initial inductive weekly therapy for 6 to 8 weeks maintenance followed once every 6 weeks 6 times and cystoscopy every 3 month. Results: In the adjuvant indication 52 patients were treated. The over all recurrence free rate was 78.3% over 2.9 years in mean (3.6m – 6.9y). Only 10 patients recurred but none progressed or needed a cystectomy. In the ablative indication 86 patients were treated. For efficacy 69 could be evaluated. 17 patients must be excluded because of protocol violation or extra-vesical TCC or simultanious second malignancy. 85.5% of the patients (58) reached CR and this persited for 26.1 months in mean. 48 patients (69.6%) were tumor free over the hole investigation time. In total 8 patients (11.6%) needed a cystectomy. 3 patient (4.3%) progressed to metastatic disease and the other 5 demonstrated low-risk new tumors again treated transurethral. In total 53 patient (76.8%) achieved organ preservation in high-risk situation. Side effects included allergy, UTI, spasm, difficulties with catheterization and nocturia ascending from 1.4% to 5.6%. Conclusions: HTC is a safe and effective therapy in NMIBC to prevent intermediate risk BC patients for recurrence and to ensure organ preservation in high-risk BC patients in more than 75% with a long lasting efficacy.

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Malik, Ajaz A. "Role of Asprin in Healthy Elderly." JMS SKIMS 21, no. 1 (December 3, 2018): 68–69. http://dx.doi.org/10.33883/jms.v21i1.330.

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Cardiovascular disease are among the principal causes of disability and death in older persons and therefore preventive interventions for such diseases are a high priority.Secondary prevention trials have established the efficacy of low dose aspirin for the prevention of cardiovascular disease (fatal , non-fatal myocardial infarction fatal or non-fatal stroke , or hospitalisation for heart failure). The benefits of low dose ASPRIN outweigh the risk of majorhaemorrhage (hemorrhagic stroke, symptomatic intracranial bleeding are clinically significant extra-cranial bleeding) associated with it in the secondary prevention of cardiovascular events. However, the role of low dose aspirin in primary prevention in elderly healthy individuals is unclear. JMS 2018;21(1):68-69

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Dusi, Vidya Sagar, Suresh VS Attili, Anuradha Vutukuru, Soumya V. Peri, and Rakesh Sharma. "Correlation of breast arterial calcification with overall survival in patients with breast cancer." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e12501-e12501. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e12501.

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e12501 Background: Calcifications in breast tissue are common and indicate an array of conditions. Based on pattern of calcifications it indicate cancerous/ precancerous changes. Similarly vascular calcifications indicate a systemic vasculopathy. Aim of this study is to correlate Breast Arterial Calcification (BAC) with overall survival/all cause mortality in patients with breast cancer. Methods: It is a retrospective analysis of all breast cancer patients diagnosed across 3 specialty hospitals In the period of 2013-2017 with at least 5 years of follow up. All cause mortality, breast cancer specific mortality were measured. The comparison was made between the patients with no calcifications (Gr I), vascular calcifications (GrII) ductal calcifications (Gr III), and any breast calcification (Gr IV). Results: The baseline characters of all these groups and the treatment received were balanced. The median survival of the Groups were 43.6+22.6 mo vs 28.6+14.2 mo vs38.5+20.2 mo vs41.6+22.3 months (p=<0.02). Presence of vascular calcifications confers shorter overall survival and the main reason being death due to cardiovascular events. The risk is more in presence of co-morbid conditions (>2 have increased risk of 2.8 fold compared to less than 2), which were defined as diabetes, hypertension, dyslipidemia, history of cardiac illness in family, obesity. Those who received Adriamycin based therapy have 1.16 times higher risk than those who did not. Those who smoke are 3.2 times at higher risk than non smokers to have cardiovascular event in presence of breast arterial calcification. Alcohol did not have any impact. Conclusions: BAC is an important marker to predict underlying vasculopathy and risk of coronary cardiac diseases. It confers poor prognosis and reduced overall survival compared to those who do not have it. The challenges to assess CAD risk through CT/angio on community basis is high. Mammograms are being done annually across nations as a routine basis. Risk factors of breast cancer and CAD are common. The cancer detection rates of mammo as <0.2% compared to arterial calcifications, which is almost 12.8%. A simple extra attention towards BAC could help in preventing cardiac related mortality in women both with and without cancer. [Table: see text] [Table: see text]

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Di Paolo, M., and B. Guidi. "Medicolegal Reflections about a Case of Cardiac Death after Renal Transplantation." International Journal of Artificial Organs 30, no. 7 (July 2007): 649–55. http://dx.doi.org/10.1177/039139880703000713.

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Cardiovascular disease is the most common cause of death in patients with renal transplant. Acute coronary syndrome due to coronary artery disease, and left ventricular hypertrophy leading to chronic heart failure account for the majority of sudden arrhythmic deaths after transplantation. Furthermore death with functioning graft represents the main cause of graft loss, particularly after the first post-transplantation year. Although cardiovascular disease leads to morbidity and mortality in renal transplant recipients, its pathogenesis is poorly understood. The high incidence of cardiovascular disease in patients after renal transplant is chiefly due to high occurence and accumulation of traditional risk factors before and after transplantation. Hypertension, post-transplant diabetes mellitus and hyperlipidemia increase the risk for cardiovascular events. Also “non traditional” risk factors are associated with cardiovascular disease. Moreover several immunosuppressive drugs interfere with the cardiovascular system. The authors present a case of cardiac death following renal transplant in a patient with history of cardiovascular disease prior transplantation. Initially treated by hemodialysis, after 3 years he received a cadaveric renal transplant. The post-transplantation period was without surgery complications, immunological or infectious, except for a scarce control of blood pressure. A month after the operation, the patient developed thrombophlebitis, plus extra-peritoneal swelling. After ten days in hospital he suddenly died. The aim of the manuscript is to remark on the legal relevance of patient's consensus to transplant. It is necessary to well inform patients of an operation's risks and complications. Furthermore, the exceeding demand with respect to organ availability raises ethical issues about organ allocation. (Int J Artif Organs 2007; 30: 649–55)

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Pavithra GB, R. Prassanna Adithiyan, Charumathi B, and Timsi Jain. "Qualitative Assessment of Adherence to Anti-Tuberculosis Medication Among Active Tuberculosis Patients." National Journal of Community Medicine 13, no. 05 (May 31, 2022): 308–12. http://dx.doi.org/10.55489/njcm.1305202214.

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Background: Non- adherence is one of the major risk factors for the emergence of MDR and XDR TB. It is also one of the key factors responsible for treatment failure, disease relapse, prolonged infection and death. This study was conducted to explore the various factors contributing to non-adherence to the Anti-TB medication. Methods: A qualitative study was done on Adult Pulmonary and extra pulmonary TB patients who were in course of the treatment. A total of 20 patients were enrolled. Socio –demographic details and specific questions regarding TB were collected using a semi-structured questionnaire. In depth telephonic interviews were conducted among all participants. Results: The study participants comprised between 15 to 68 years of age with a mean age of 36 ±14.9years. Factors influencing non-adherence to medication were grouped under Patient, medication, Socio-economic and Health care related factors, Motive. Almost all patients reported more than one factor. Conclusion: Increasing the awareness of various TB services in the community may increase knowledge and improve attitude among the patients. Providing more information about the effects of medication may reduce the risk of being non adherent. TB anonymous groups can be organized for patients to discuss their challenges while on treatment.

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Fader, A. Nickles, P. G. Rose, H. Frasure, P. A. Gehrig, K. N. Moore, L. J. Havrilesky, W. K. Huh, A. E. Axtell, D. M. O'Malley, and K. M. Zanotti. "Can primary recurrences in surgical stage I-II uterine papillary serous carcinoma (UPSC) patients be salvaged?" Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e16503-e16503. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16503.

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e16503 Background: There is an absence of data in the literature on salvage rates for vaginal, pelvic, and extra-pelvic recurrences for early-stage UPSC patients (pts). The purpose of this study is to determine whether primary recurrences can be salvaged with chemotherapy or radiotherapy. Methods: A retrospective, multi-institution study of pts with stage I-II UPSC diagnosed from 1993–2006. All pts underwent comprehensive surgical staging. Postoperative treatment included either observation (OBS), radiotherapy (RT: brachytherapy, pelvic, abdominal or combo) or ≥ 3 cycles carboplatin/paclitaxel (CT) alone or with RT (CT+RT). Results: We identified 197 stage I-II pts; 44/197 (22.3%) experienced a primary recurrence during a median follow-up of 35 months. Patterns of recurrence analysis revealed that 17 (38.6%) were vaginal/pelvic (V/P) and 27 (61.4%) were extra-pelvic (EP). Multi-site relapses occurred in 13/44 (30%). Pts initially treated with adjuvant CT±RT (n = 108) had a significantly decreased risk of primary recurrence (9.9%) when compared to those patients treated with RT alone (n = 45; 37%) or OBS (n = 43; 35%; p < 0.001). There were no distinguishing risk factors for development of V/P versus EP recurrence. Median time to recurrence after diagnosis was 16 months. The majority of pts (86%) were not salvaged by second line therapy, with a median time from recurrence to death of 8.9 months. However, more pts with isolated vaginal recurrences (5/12 or 42%) were salvaged when compared to those with pelvic or EP recurrences (1/32 or 3.1%; p = 0.004). The 5 pts who are NED after vaginal relapse were treated with CT±RT (n = 3) or RT (n = 2); 80% had not received prior treatment and 20% had received prior CT. To date, more pts with EP recurrence are dead of disease (23/27) than with V/P recurrences (7/17; p = 0.003). Conclusions: Stage I-II USPC pts are more likely to experience an extra-pelvic than vaginal/pelvic primary recurrence, are unlikely to be salvaged and will have a short interval from recurrence to death. The exception is in those with isolated vaginal recurrence, who may be salvaged in select cases. The current best strategy to avoid primary recurrences in this setting is an initial staging surgery followed by adjuvant carboplatin/paclitaxel. No significant financial relationships to disclose.

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Soriano, Lucía, Héctor Bueno, Angel Lanas, and Luis Rodríguez. "Cardiovascular and upper gastrointestinal bleeding consequences of low-dose acetylsalicylic acid discontinuation." Thrombosis and Haemostasis 110, no. 12 (2013): 1298–304. http://dx.doi.org/10.1160/th13-04-0326.

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SummaryIt was the aim of this study to investigate whether low-dose acetylsalicylic acid (ASA) therapy for secondary cardiovascular prevention should continue, despite the risk of gastrointestinal bleeding. We aimed to make a clinically meaningful benefit–risk assessment regarding the cardiovascular and gastrointestinal consequences of ASA discontinuation. This case–control study used The Health Improvement Network UK primary care database to identify patients aged 50–84 years during 2000–2007 with a first ASA prescription for secondary cardiovascular prevention (N = 39,513). New cases of non-fatal myocardial infarction (MI)/coronary death (n = 1,222), ischaemic stroke (IS)/transient ischaemic attack (TIA) (n = 673) and upper gastrointestinal bleeding (UGIB) (n = 169) were identified after a mean follow-up of 3.2, 3.4 and 4.0 years, respectively. ASA discontinuers before the index date were identified. Attributable risks associated with ASA discontinuation were calculated and National Institute for Health and Clinical Excellence annual economic data were used to estimate healthcare costs. The cumulative incidences of non-fatal MI/coronary death, IS/TIA and UGIB among ASA discontinuers within the first year of follow-up were 17, 11 and 1.6 per 1,000 persons, respectively. This corresponds to eight extra cardiovascular events, and a reduction of 0.4 UGIB events per year compared with current ASA users. Extrapolating to the UK population aged over 50 years, avoiding discontinuation of ASA could prevent 12,786 coronary and 7,672 cerebrovascular events/year, at the expense of 1023 extra UGIB events, saving approximately £100 million/year. In conclusion, preventing patients with cardiovascular disease from discontinuing ASA could result in substantial clinical and economic gains.

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Kim, Whi-Young, and Jun-Hyoung Kim. "DESIGN OF PORTABLE EPLDALTERA MAX EPM719SQC160-7 AND DSPTMS320V5410PGE APPLICATION FOR NON-INVASIVE IN-EXTRA CRANIAL ARTERIES VASCULAR SYSTEM." Biomedical Engineering: Applications, Basis and Communications 27, no. 03 (May 28, 2015): 1550025. http://dx.doi.org/10.4015/s1016237215500258.

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The incidence of brain diseases, such as dementia, Parkinson's disease and motor nerve disorder, has increased since 1980s. According to a survey conducted on the incidence in England, US, Japan, Germany and Spain, the dementia death rate, including Alzheimer's disease, had increased by three times for men. The death rate from brain disease, such as Parkinson's disease and motor nerve disorder, has increased by 50% for both men and women. Although this increase can be assumed to be caused by changes in DNA when observing from a genetic perspective, it would take hundreds of years to confirm this. Therefore, environmental factors are regarded as the actual cause. In this situation of a rapidly increasing aging population, the prevention of senile and brain diseases is considered the most important measure because treatment is difficult and the after-effects are severe. A cerebrovascular ultrasonogram, which can frequently allow a self-inspection of the blood vessels for the early detection of the risk factors for disease, is actualized to model with a characteristic test and has shown performance. Supplementation of the system can facilitate an application in the measurement of brain disorder patients with other diseases in the future. This study examined the atypical characteristics through the production of a prototype.

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Ronsini, Carlo, Stefania Napolitano, Irene Iavarone, Pietro Fumiento, Maria Giovanna Vastarella, Antonella Reino, Rossella Molitierno, Lugi Cobellis, Pasquale De Franciscis, and Stefano Cianci. "The Role of Adjuvant Therapy for the Treatment of Micrometastases in Endometrial Cancer: A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 13, no. 5 (March 5, 2024): 1496. http://dx.doi.org/10.3390/jcm13051496.

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Endometrial cancer is the most incident gynecological cancer. Lymph node dissemination is one of the most important factors for the patient’s prognosis. Pelvic lymph nodes are the primary site of extra-uterine dissemination in endometrial cancer (EC), setting the 5-year survival to 44–52%. It is standard practice for radiation therapy (RT) and/or chemotherapy (CTX) to be given as adjuvant treatments to prevent the progression of micrometastases. Also, administration of EC patients with RT and/or CTX regimens before surgery may decrease micrometastases, hence the need for lymphadenectomy. The primary aim of the systematic review and meta-analysis is to assess whether adjuvant RT and/or CTX improve oncological outcomes through the management of micrometastases and nodal recurrence. We performed systematic research using the string “Endometrial Neoplasms” [Mesh] AND “Lymphatic Metastasis/therapy” [Mesh]. The methods for this study were specified a priori based on the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Outcomes were 5-year overall survival, progression-free survival, recurrence rate, and complications rate. We assessed the quality of studies using the Newcastle–Ottawa Scale (NOS). A total of 1682 patients with stage I-to-IV EC were included. Adjuvant treatment protocols involved external-beam RT, brachytherapy, and CTX either alone or in combination. The no-treatment group showed a non-statistically significant higher recurrence risk than any adjuvant treatment group (OR 1.39 [95% CI 0.68–2.85] p = 0.36). The no-treatment group documented a non-statistically significant higher risk of death than those who underwent any adjuvant treatment (RR 1.47 [95% CI 0.44–4.89] p = 0.53; I2 = 55% p = 0.000001). Despite the fact that early-stage EC may show micrometastases, adjuvant treatment is not significantly associated with better survival outcomes, and the combination of EBRT and CTX is the most valid option in the early stages.

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Noble, Victoria Vardell, Daniel A. Ermann, and Peter T. Silberstein. "Primary Thyroid Lymphoma: An Analysis of the National Cancer Database." Blood 132, Supplement 1 (November 29, 2018): 2988. http://dx.doi.org/10.1182/blood-2018-99-120145.

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Abstract Background Primary Thyroid Lymphoma (PTL) is a rare malignancy, representing only 1-5% of thyroid malignancies and 2.5-7% of all extra nodal lymphomas. Most cases of PTL are of B-cell origin, and 98% of all PTL is non-Hodgkin's lymphoma. Case series and case reports represent the majority of the available studies on PTL, with a paucity of large retrospective population studies available for this disease. Due to limited studies the optimal treatment of PTL has not yet been established. Using the National Cancer Database (NDCB) we aimed to evaluate patient characteristics, treatment modalities, and overall survival. This is the first NCDB study completed on PTL, and the only large retrospective study to examine the use of chemotherapy and immunotherapy in treatment of these patients. Methods The NCDB for Non-Hodgkin lymphoma was utilized to identify 3466 patients diagnosed with PTL between 2004-2015. The database was used to examine demographic information including age, race, gender, histology, stage, and treatment modality. Bivariate Kaplan-Meier analysis with log-rank tests was used to analyze overall survival. Multivariate analysis was performed with Cox proportional hazards regression models to obtain hazard ratios to assess the association of patient characteristics and treatment methods with survival. Results Median overall survival was 11.6 years (95% Confidence Interval (CI) 11.1 - 12.1 years), with a 59% 5-year overall survival and 49% 10-year overall survival. The majority of PTL patients were female (68%) and white (93%), with a mean age of 65.8 years. Histologically 59.5% of cases were diffuse large B-cell lymphoma, 18.3% marginal zone lymphoma, 8% follicular lymphoma, and 1.9% Burkitt lymphoma. Regarding treatment, 57.6% of patients received no radiation and 40.6% received beam radiation. 54% received some form of surgical treatment. Single agent chemotherapy was used in 3.5% of patients, 60.7% received multiagent chemotherapy and 29.9% of patients received no chemotherapy. Immunotherapy was used in 11.1% of patients. On multivariate analysis, increased risk of death was significantly associated with increasing age, race other than white, and higher disease stage. Hazard ratios for treatment modalities were found to be 0.684 with beam radiation (p<.001), 0.58 for surgical treatment (p<.001), 0.63 for chemotherapy (p<.001), and 1.082 for immunotherapy (p=.560). Other factors associated with decreased risk of death include treatment at academic centers (HR 0.846, p<.05) and integrated cancer centers (HR 0.76 p<.05) when compared to community centers. Conclusion This is the largest study to date to describe patient characteristics, treatment modalities, and overall survival in PTL and to compare treatment options with overall survival. Beam radiation, chemotherapy, and surgical resection all reveal significant survival benefit, where immunotherapy is not associated with a significantly reduced risk of death. Disclosures No relevant conflicts of interest to declare.

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Paggiaro, Pierluigi, Francesco Costa, Laura Malagrinò, and Barbara Vagaggini. "Chronic obstructive pulmonary disease and comorbidity: possible implications in the disease management." Reviews in Health Care 2, no. 1 (January 26, 2011): 41–52. http://dx.doi.org/10.7175/rhc.v2i1.21.

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Chronic obstructive pulmonary disease (COPD) is becoming the first cause of pulmonary disability and death. Because of the increase in the mean age of the population, COPD is frequently associated with important comorbidities that require medical attention. In the last 10 years many observational studies (large surveys of population or databases of the main health organisations or of General Practitioners in different Countries) have extensively documented that many diseases (cardiovascular diseases, metabolic syndrome, osteoporosis, diabetes, depression, and lung cancer) have a higher prevalence in COPD patients than in non-COPD ones (after correction for many confounding factors, such as smoking habit). There are two different views relating the association between COPD and comorbidities. These comorbidities may be just randomly associated with COPD (due to common risk factors including age), but many data support the hypothesis that chronic inflammation derived from airway wall and lung parenchima of COPD patients may “spill over” the systemic circulation and mediate, at least partially, negative effects on other organs or systems. Some comorbidities seem more commonly associated with the functional abnormalities of COPD (like skeletal muscle dysfunction and malnutrition, or osteoporosis, which are related to the inactivity due to dyspnoea), while for others the systemic effect of some cytokines (IL-6,TNFalfa, etc.) or mediators (CRP, serum amyloid A, etc.) may play a role.Since comorbidities represent major causes of death in COPD patients, and are responsible of poorer quality of life and hospitalisation during COPD exacerbations, their presence requires a new approach, including an interdisciplinary co-operation and the use of specific strategies able to affect the several pulmonary and extra-pulmonary components of the disease. New pharmacologic options (such as roflumilast) active on both pulmonary and extra-pulmonary inflammation might be useful in the future.

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Piperno-Neumann, Sophie, Manuel Jorge Rodrigues, Vincent Servois, Gaëlle Pierron, Lauris Gastaud, Sylvie Negrier, Christine Levy-Gabriel, et al. "A randomized multicenter phase 3 trial of adjuvant fotemustine versus surveillance in high risk uveal melanoma (UM) patients (FOTEADJ)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 9502. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9502.

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9502 Background: Up to 30% of UM patients will develop metastases, with a median survival of 12 months in the metastating setting. Prognostic factors combine clinical features of the primary tumor (diameter, thickness, retinal detachment, extra-scleral extension) and genetic factors (monosomy 3, 8 q gain and class 1 /2 gene expression profiling).The genomic analysis is feasible by fine needle aspiration biopsies before radiotherapy for small UM or on enucleated eyes. Methods: Multicenter randomized phase 3 trial with adjuvant fotemustine, 6 cycles, 100 mg/m2 versus surveillance for 3 years (liver tests/3 months, liver MRI or CT/6 months, whole body CT/12 months) in patients with high risk of recurrence, defined by clinical criteria (diameter > 15 mm with extra scleral extension and/or retinal detachment or diameter > 18 mm) or genomic high risk signature by array-CGH (monosomy 3 or deletion of 3p associated with gain of chromosome 8). The primary objective was 5-year Metastasis Free Survival (MFS). With an expected increase of 5-year MFS from 50 to 70%, 302 patients and 99 events were required to achieve an 95%-power with a 5% type I error rate. Secondary objectives were overall survival (OS), safety (NCI-CTC v3), quality of life (QLQ-C30). Interim analyses were planned for safety and after 50 events, disclosed to an independent safety monitoring board. Results: The trial was stopped for futility after 244 patients had been recruited between June 2009 and January 2016. No unexpected toxicity was found in the chemotherapy group. The study was amended to go on with intensive surveillance in new high risk patients. Ninety-one metastases and 43 deaths were reported, with no treatment-related death. With a median follow-up of 3 years, the 3-year MFS is 60.3% in the chemo group and 60.7% in the surveillance group (HR 0.97 [0.64-1.47]). The 3-year OS is 79.4% [73.2-85.7], with no difference between the 2 groups of patients. Conclusions: FOTEADJ is the first adjuvant randomized phase 3 trial based on genomic analysis in high risk UM patients. Despite negative results, it shows the feasibility of multicenter adjuvant studies in this rare cancer and provides genomic data in small tumors for future trials. Clinical trial information: NCT02843386.

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Zhang, Yuanyuan, Jonathan Schoenhals, Alana Christie, Chiachien Wang, Osama Mohamad, Nirmish Singla, Neil Desai, et al. "Outcomes of stereotactic ablative radiotherapy for extra-cranial oligo-metastatic renal cell cancer." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 599. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.599.

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599 Background: Stereotactic ablative radiotherapy (SAbR) is a standard of care for treating renal cell cancer (RCC) cranial metastasis. We describe the effect of SAbR on oligometastatic extra-cranial RCC disease course. Methods: We retrospectively reviewed 49 patients with oligometastatic RCC with 68 extra-cranial lesions. Patients were treated with SAbR with a curative intent from 2007 to 2017. We analyzed local control, systemic therapy free survival (mPFS), and overall survival. Results: With a median follow-up of 28 months (IQR: 16.0-40.3), the 1-year and 2-year overall survival after SAbR was 93.4% (95% CI: 81.0-97.8), and 83% (95% CI: 67.4-91.5) respectively. The median overall survival was not reached. The median time to systemic therapy was 13.4 months from the first SAbR(95% CI: 8.8-27.6). Median times from the first SabR course to second and third line systemic therapy (or death) were 31.8 months and 45 months, respectively. Patients in the favorable risk group by the Heng’s criteria (HR = 8.67, p = 0.04), with nometastatic disease at diagnosis (HR = 10.38, p < 0.01) and with clear cell histology (HR = 6.15, p < 0.01) exhibited better survival, as shown by univariate analysis. Patients with no metastatic disease at diagnosis (HR = 2.56, p = 0.02) and only one metastasis treated with SAbR (HR = 2.36, p = 0.03) also exhibited better systemic therapy-free survival. SAbR had an excellent local control rate of 94% at 2 years with no reported grade 3 or higher toxicity. Conclusions: SAbR is an effective and safe treatment for oligometastatic RCC, offering excellent local control with minimal toxicity. SAbR delayed the start of systemic therapy for this RCC cohort, offering quality of life benefits for patients without adversely affecting the progression on subsequent lines of systemic therapy. These findings call for prospective verification.

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Rama Rao, Tadikonda, B. Pratiksha, C. Navyasri, Dwip Jyoti Kalita, and Shahzad Alam. "Non-Alcoholic Fatty Liver Disease." Journal of Drug Delivery and Therapeutics 13, no. 10 (October 15, 2023): 149–53. http://dx.doi.org/10.22270/jddt.v13i10.6226.

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Non-alcoholic fatty liver disease (NAFLD) is characterized by the buildup of fat in the liver, and it is not caused by excessive alcohol consumption. NAFLD is highly prevalent, affecting approximately 30% of the population in developed countries and around 10% in developing nations. As a result, NAFLD has become the most prevalent liver condition worldwide. The development of NAFLD is closely linked to insulin resistance, making it common among individuals who have central obesity or diabetes. Insulin resistance and excess body fat contribute to a higher influx of lipids into the liver and an increased production of new fats within the liver, known as de novo hepatic lipogenesis. These processes ultimately lead to the accumulation of triglycerides in the liver, a characteristic feature of NAFLD. NAFLD is closely associated with components of the metabolic syndrome, and individuals with type 2 diabetes have an increased risk of developing cirrhosis and its related complications. While cardiovascular disease and extra hepatic malignancy are the leading causes of death in people with NAFLD, the presence of advanced liver fibrosis is a significant indicator of liver-related outcomes and overall mortality. Non-invasive tests that combine various methods can be used to assess the extent of liver fibrosis. Patients diagnosed with cirrhosis should undergo screenings for hepatocellular carcinoma (a type of liver cancer) and esophageal varices. Currently, there are no approved therapies for NAFLD; however, there are several drugs in advanced stages of development that show promise for future treatment options. Keywords: Non-alcoholic fatty liver disease, Weight management, Bariatric surgery, Metabolic surgery, Conservative therapy.

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Smith, Stephen D., Craig Okada, Andy I. Chen, Stephen E. Spurgeon, Guang Fan, Jennifer B. Dunlap, Nicky Leeborg, Rita M. Braziel, and Richard T. Maziarz. "Prognostic Features, Treatments, and Disease-Specific Mortality Among Patients with Diffuse Large B-Cell Lymphoma Over the Age of 75: A Single-Center Retrospective Analysis." Blood 120, no. 21 (November 16, 2012): 3673. http://dx.doi.org/10.1182/blood.v120.21.3673.3673.

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Abstract Abstract 3673 Background: Very elderly pts (age > 75) with diffuse large B-cell lymphoma will increasingly be considered for cancer treatment as the population of the United States ages. However, such pts are under-represented in clinical trials, and standardized therapeutic algorithms are lacking. The impact of proliferation index (Ki67) and cell-of-origin are not well-studied in this group. For these reasons, and to inform the development of clinical trials, we retrospectively studied very elderly DLBCL pts since 2002. Methods: The Oregon Health and Science University Tumor Registry was queried for all DLBCL cases treated since 2002. Those over 75 years of age were selected for in-depth study under IRB approval. Primary CNS lymphoma, unconfirmed diagnoses, and inadequate follow-up for survival were excluded. Baseline clinical and pathologic features (immunohistochemical, EBV [EBV-encoded RNA, EBER] staining, and translocations involving MYC and BCL2) were recorded. Outcomes including relapse/progression, treatment failure, and death (with cause of death), were analyzed using Kaplan-Meier modeling. Relapse-free survival (RFS) and disease-specific survival (DSS) were measured from diagnosis, censoring deaths not related to lymphoma or immediate therapy complications. Stage, LDH, performance status, disease bulk <10cm, renal failure at diagnosis, initial treatment (RCHOP vs. non-anthracycline), and IPI risk factors were assessed for an impact on outcome using JMP statistical software (SAS) and log-rank testing. Results: 109 pts over the age of 75 were identified, 76 of whom fit above criteria. Median follow-up is 27 months. Pt characteristics are summarized in Table 1. Extra-nodal involvement was present in 57% of pts; sinus/orbit/ENT disease was seen in 26%. IPI factors were available for a fraction of pts, but an age-adjusted IPI (AA-IPI) of High-Int (2) or High (3) was identified in 15/32. DSS/OS and RFS curves are shown in Figures 1 and 2. AA-IPI predicted DSS (p=.01). Neither Ki67 index (>80% vs. less) nor BCL6 positivity impacted DSS or RFS. Non-GCB cell-of-origin showed a trend toward poorer RFS (p=.09). > 1 extra-nodal site predicted poor DSS (p=.003) and RFS (p=.005); individually, stage, performance status, LDH, or renal failure at presentation were not prognostic. RCHOP-like therapy (RCHOP, or REPOCH in 2 pts) was given to 59% (45/76), achieving a 5 year RFS of 60% (censoring non-lymphoma deaths) and OS of 50%. 14 RCHOP pts required a change in regimen due to toxicity, and 4 of these pts died during therapy. Non-anthracycline systemic therapy was administered to 14 (18%) pts, and included RCVP, RCEOP, RCOPP, and single agent R; though not statistically different from RCHOP in DSS or RFS, no evident plateau on the RFS curve was observed with such therapies. Finally, 8% (6) pts were treated palliatively; all died of lymphoma complications at a median of 4 months. Salvage therapies included R+ chemo (4 pts), prednisone alone (1), rituximab alone (1), radiotherapy (4); median time from relapse to death was 8 months. Overall, 37 deaths have occurred, 27 due to lymphoma or immediate therapy complications. Conclusion: Despite 4/45 treatment-related deaths and frequent changes to therapy, RCHOP affords long-term disease control in a proportion of very elderly pts. This suggests a regimen alternating RCHOP with other active agents can be tolerated and may produce the ideal balance of efficacy and safety in this pt population. High AA-IPI pts should be targeted for novel approaches, as pathologic biomarkers (Ki67, cell-of-origin by IHC) do not predict relapse or disease-specific survival outcomes. Further trials in this under-studied population are warranted. Disclosures: Spurgeon: Gilead: Research Funding.

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Tanvetyanon, T., L. Robinson, E. Sommers, S. Altiok, E. Haura, J. Kim, and G. Bepler. "Survival predictors after surgical resection of synchronous bilateral non-small cell lung cancers (NSCLC)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 7517. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.7517.

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7517 Background: Non-small cell lung cancer (NSCLC) that presents with bilateral lung lesions, but without extra-thoracic metastasis, is uncommon. Prognosis is typically poor: No long-term survivor is expected with systemic chemotherapy. However, small reports have suggested the feasibility of bilateral resections. To date, the predictors of survival following this treatment approach remain unknown. Methods: Our institutional tumor registry was searched for patients who underwent bilateral resections of NSCLC during 1998–2006. Patients with metachronous presentations (second lesion found ≥ 2 years afterward) were excluded. Kaplan-Meier survival estimate and Cox proportional hazards model were used to identify survival predictors. Results: Of the 2582 patients operated for NSCLC, 50 patients were included in this analysis. Median age was 69.2 years. Median tumor sizes were 2.0 cms; Adenocarcinomas were the most common (51%). Of 103 thoracotomies, pneumonectomy was performed in 3 patients. Overall peri-operative mortality was 1.9%. Median progression-free survival was 46.0 months (95% CI, 33.1–66.6); overall survival was 77.5 months (95% CI, 43.1–111.1). Performance status, presence of comorbidity, and pathological vascular invasion were important prognostic factors (Table). Risk score based on the sum of these factors (present =1; absent =0) was a strong predictor of survival. Patients with score ≥ 2 (N=11) had a median survival of 17.2 months, compared with 83.5 months among those with score ≤ 1 (HR 5.52, 95% CI 2.27–13.46; p=0.0002). Conclusions: In this largest series of surgery for synchronous bilateral NSCLC to date, the overall survival rate at 5 years is approximately 50%. Performance status, comorbidity, and vascular invasion are strong predictors of survival. Patients with vascular invasion are at an increased risk of progression or death and adjuvant therapy should be considered. [Table: see text] No significant financial relationships to disclose.

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Uddin, SM Belal, Abu Noman Mohammad Mosleh Uddin, and Mohammad Abdul Malek. "Myocardial Infarction: An analysis of Socio-demographic and Modifiable Risk Factors among Armed Forced Personnel in Bangladesh." Anwer Khan Modern Medical College Journal 11, no. 2 (August 10, 2020): 97–101. http://dx.doi.org/10.3329/akmmcj.v11i2.62751.

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Introduction: Myocardial Infarction, major part of Coronary Artery Disease (CAD) is the leading cause of death for both men and women in the World. In 2008 among all death caused by non-communicable diseases CAD causes more than 27% of death in Bangladesh. Objective: To analyze the socio-demographic and modifiable risk factors of Myocardial Infarction among Armed Forces personnel attended at the Combined Military Hospital Dhaka Methods: This cross sectional study was conducted in July 2012 to Dec 2012 among 104 purposively selected armed forces personnel reported in Combined Military Hospital Dhaka. Data were collected through face-to-face interview using a pretested semi-structured questionnaire. Result: Majority of the respondents (66.3%)age group was 45-60 years and 93.3% were Muslim and most are (69.2%) retired. Smoking rate were 61.5% and almost all of them used to do physical exercise in terms of mild, moderate and strenuous forms (26.0%, 54.8% and 19.2%) respectively. About 62.5% had a history of taking extra salt with food. Almost all of them had several chronic diseases like hypertension, DM and Bronchial Asthma. Conclusion: The study found group of Socio-demographic and modifiable risk factors are responsible for Myocardial Infarction which could be minimized by preventive measures taken by competent authority. Study on larger sample size is necessary for more appropriate description. AKMMC J 2020; 11(2) : 97-101

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Pathak, Manish Raj, Mahesh Gautam, and Yagya Raj Pathak. "Evaluation of Extracranial Carotid Arteries in Ischemic Stroke Patients Using Color Doppler Sonography and Correlation with Various Risk Factors." Journal of Nobel Medical College 8, no. 2 (December 15, 2019): 10–14. http://dx.doi.org/10.3126/jonmc.v8i2.26716.

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Background: Cerebral ischemic stroke is the major cause of death after ischemic heart disease and malignancies, among which major cases of stroke results from atherosclerosis of intra and extra-cranial carotid vessels. The aim of this study is to evaluate the extracranial carotid arteries in patients with ischemic stroke and correlation with various risk factors. Materials and Methods: A cross sectional study of the patients with ischemic stroke presented in Radiology department of Nobel Medical College were evaluated for a period of one year from February 2017- January 2018 using color Doppler ultrasound and correlated with various risk factors. A total of 50 patients were included in the study. All age groups and sex were included. Results: Out of 50 patients, 29 patients (58%) were males and 21 patients (42%) were females. Stroke was present in 24 patients on right side and 26 patients on left side. A total of 36 patients had extra-cranial carotid stenosis. Among them, 18 patients had <50% stenosis, 17 patients had >50% stenosis and 1 patient had complete occlusion. The most common cause of obstruction was found to be atherosclerotic changes in the form of atheromatous plaque. Out of 50 patients 27 had history of hypertension and 19 had history of smoking. Out of 27 hypertensive patients, 23 had stenosis which is statistically significant (p value 0.024). Conclusion: The current study shows the importance of color Doppler ultrasound as an economic, safe and non-invasive method of demonstrating the cause of stroke in extra-cranial carotid artery system

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Upadhyay, Dakshadhwari, Rashmi Ahmed, and Manjit Boruah. "Dietary risk factors of non-communicable diseases among industrial common workers: a cross-sectional study." International Journal Of Community Medicine And Public Health 6, no. 8 (July 26, 2019): 3428. http://dx.doi.org/10.18203/2394-6040.ijcmph20193466.

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Background: Non-communicable diseases (NCDs) are the leading cause of death and morbidity throughout the world. Unhealthy diet is a risk factor for NCDs. There is a lack of studies on the prevalence of dietary risk factors among the industrial population in India particularly in North East India.Methods: A cross-sectional study was conducted among industrial workers of a major industry in Assam. The sample size was 330 considering a prevalence of 50% and 95% confidence interval, and a design effect of 1.5. Data was collected using methods described in WHO STEPS instrument v3.1.Results: A total of 318 subjects consented to participate in the study. Consumption of less than 5 servings of fruit and/or vegetables on average per day was observed in majority 98.4% of the study participants. In a typical week, fruits and vegetables were consumed on 2.99 and 6.89 days respectively. Mean number of servings of fruit consumed on average per day was 0.5 and for vegetables were 2.33.46 (14.5%) of the study participants added extra salt always or often to their food before eating or while eating. 132 (41.5%) of the study participants always or often ate processed foods high in salt.Conclusions: Inadequate consumption of fruits and vegetables was observed in 98.4% of industrial workers included in the study. Increasing awareness among this population about adequate consumption of fruits and vegetables to prevent NCDs is necessary.

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Valsecchi, Matias Emanuel, Nancy Shockley, Deborah Summers, Carol L. Shields, Jerry A. Shields, Michael J. Mastrangelo, and Takami Sato. "Adjuvant sunitinib in high-risk patients with uveal melanoma: A pilot study." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 8560. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.8560.

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8560 Background: Uveal melanoma is the most common primary intraocular cancer in adults. Despite the successful treatments for primary tumors, up to 50% of the patients later die of distant metastases. Currently no effective adjuvant treatment is available for these patients. Our group previously reported that sunitinib stabilized systemic metastases in 65% of uveal melanoma patients who failed prior treatments. In this pilot study, we tested sunitinib in an adjuvant setting in high-risk patients with primary uveal melanoma. Methods: Patients with estimated metastatic death rate ≥ 50% based on the following criteria were eligible: (1) monosomy 3 and 8q amplification; (2) large tumor (≥ 15 mm in diameter and ≥7 mm in thickness); (3) monosomy 3 and other risk factors (large tumor, epithelioid dominant cell type, local recurrence, or extra-scleral extension). Sunitinib was given at 25 mg PO daily for at least 6 months. Primary endpoint was disease-free survival (DFS) and overall survival (OS), estimated with Kaplan-Meier analysis (SPSS 17.0). Secondary endpoint was safety. Results: A total of 23 Caucasian patients (median, 54 years; range: 25 – 77) were enrolled. All patients received sunitinib for at least 6 months (range: 6 – 12). Eighteen patients had confirmed monosomy 3, from whom 13 (72%) also showed 8q amplification. The median follow-up was 24 months (range 12 – 54 months). Only one patient died of unknown cause (OS: 30.4 months). A total of seven patients (30%) developed systemic metastases, all of which were liver metastases. The DFS and OS rates at 2 years were 70% (95% CI: 47 – 86%) and 100%, respectively. The OS rate at 2 years was better than historical control with monosomy 3 patients (51%, 95% CI: 31 – 71%) (Invest Ophthalmol Vis Sci 2003; 44:1008). In those patients who relapsed, the median time to progression after finishing sunitinib was 2 months (range: 0 – 8). The most common adverse events were: diarrhea (47%), fatigue (39%), dermatitis (30%), stomatitis (13%), leucopenia (8%), and nausea (4%). Most were grade 1 or 2 (88%) and only one was considered grade 4 (diarrhea). Conclusions: In high-risk uveal melanoma patients with estimated metastatic death rate of ≥ 50%, adjuvant sunitinib showed promising results and deserves further investigation.

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Porta, Matteo G. Della, Andrea Kuendgen, Luca Malcovati, Esther Zipperer, Cristiana Pascutto, Erica Travaglino, Margherita Maffioli, et al. "Myelodysplastic Syndrome (MDS)-Specific Comorbidity Index for Predicting the Impact of Extra-Hematological Comorbidities on Survival of Patients with MDS." Blood 112, no. 11 (November 16, 2008): 2677. http://dx.doi.org/10.1182/blood.v112.11.2677.2677.

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Abstract Myelodysplastic syndromes (MDS) occur mainly in older persons, who are likely to be affected with extra-hematological comorbidities. Recent findings suggest that proper assessment of comorbidities is useful to predict the outcome of MDS patients receiving allogeneic transplantation. However, the results obtained in this highly selected subset of patients cannot be applied to the whole MDS population. In this study, we evaluated the impact of extra-hematological comorbidities on the natural history of MDS with the aim of developing a specific prognostic index. The patients comprised a “learning cohort”, in which we defined the set of variables to be included in the prognostic model and their weighted scores, and a “validation cohort”, in which we confirmed the prognostic value of the scoring system. The learning cohort included 840 MDS patients diagnosed at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, between 1992 and 2006, while the validation cohort consisted of 504 patients seen at the Heinrich-Heine-University Hospital, Duesseldorf, Germany, between 1982 and 2006. All cases were classified according to the WHO criteria. Patients who underwent allogeneic transplantation or intensive chemotherapy were censored at the time of the procedure. One or more comorbidities were present in 455 (54%) patients in the learning cohort at the time of diagnosis: the older the age, the higher the prevalence. Cardiac disease was the most frequent extra-hematological morbidity (25% of patients) and the main cause (63%) of non-leukemic death (NLD). In a Cox multivariable analysis with time-dependent covariates, the onset of a comorbidity significantly affected the risk of NLD (HR=2.29, P<.001) and worsened overall survival (OS, HR=1.51, P=.01). Patients who developed RBC transfusion-dependency had a significantly higher risk of NLD (HR=4.31 P=<.001), cardiac disease and death (HR 4.16 and HR 4.88, respectively; P=<.001). In this group, serum ferritin levels were significantly associated with the risk of cardiac disease and death (P=.001). The onset of cardiac, liver, renal, pulmonary disease and solid tumor were found to independently affect the risk of NLD in a multivariable Cox regression (HR from 3.57 to 1.97; P values from <0.001 to 0.04). Based on these results, we developed a dynamic prognostic model (MDS-specific comorbidity index, MDS-CI) for predicting the effect on NLD and OS of comorbidities either present at the time of diagnosis or occurring during the follow-up. Risk scores for each comorbidity were estimated from the regression coefficients (Table 1). Table 1. MDS-specific comorbidity index (MDS-CI) Comorbidity Score Cardiac disease 2 Moderate-to-severe hepatic disease 1 Severe pulmonary disease 1 Renal disease 1 Solid tumor 1 Risk groups: Low (score 0), Intermediate (score 1–2), High (score >2). MDS-CI allowed us to identify 3 groups of patients with different probability of NLD and OS (P<.001). The prognostic value of the MDS-CI was then evaluated in the validation cohort of patients, where the 3 MDS-CI risk groups showed significantly different probabilities of NLD (P<.001) and OS (P=.005), with a 2-year risk of NLD since diagnosis of 24%, 42% and 61% in the low, intermediate and high risk group, respectively. In summary, extra-hematological comorbidities significantly worsen the natural history of MDS patients, specifically increasing the risk of NLD. In particular, transfusion-dependency and secondary iron overload are associated with a higher risk of cardiac complications. The MDS-CI improves our ability to stratify the outcome of MDS patients and may be a useful tool for clinical decision-making. An accurate evaluation of extra-hematological comorbidity should be part of the prognostic assessment of patients with MDS.

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Belousova, L. N., O. Yu Chizhova, I. G. Bakulin, and A. G. Sushilova. "Gastroesophageal reflux disease and atrial fibrillation: comorbidity or overlap syndrome? View of gastroenterologist." Experimental and Clinical Gastroenterology 1, no. 10 (March 2, 2020): 26–32. http://dx.doi.org/10.31146/1682-8658-ecg-170-10-26-32.

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Аtrial fibrillation (AF) still occupies a special place in the structure of cardiovascular diseases, both due to its high prevalence, close association with socially significant diseases, and due to the high risks of death, stroke, and other thromboembolic complications. In turn, a patient with AF is always a comorbid patient, and among extracardiac pathology, the prevalence of diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), pay attention. Recently more and more data have appeared that indicate the non-randomness of this combination. Many authors consider GERD as another independent risk factor for AF, while others propose to consider AF as an extra-esophageal manifestation of GERD, of course, in the absence of other cardiac risk factors. This review discusses the main pathophysiological mechanisms that determine the pathogenetic relationship of AF and GERD, known to date.

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Lorente, David, Robert Diaz, Barbara Torres, Adela Cañete, Jorge Aparicio, Alejandra Gimenez, Encarni Reche, Esteban Rodrigo, Amparo Verdeguer, and Joaquin Montalar. "Multimodality treatment of pediatric and adult patients with Ewing sarcoma: A single-institution experience." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 10082. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.10082.

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10082 Background: Treatment of Ewing sarcoma pts. usually follows pediatric protocols, both in children and in adults. However, older patients fare poorly in most series. We analyze our experience with the 2001 protocol of the Spanish Society of Pediatric Oncology. Methods: Retrospective analysis. Schema: 6 cycles (cy) of VIDE chemotherapy (CT: vincristine, ifosfamide, etoposide, doxorrubicin). If no progression, local treatment (surgery or RT) and consolidation adjusted to risk: VACx8 (vincristine, dactinomycin, ciclophosphamyde) in standard-risk pts; if increased risk (axial, complete response in lung metastases or non-pulmonary metastases) VACx1, high-dose CT (busulphan-melphalan) and autologous transplant (ATSP). Analysis: induction CT toxicity, pathological response rates, consolidation treatment, disease-free (DFS) and overall survival (OS) (Kaplan- Meier). Log-rank and Cox regression analysis of prognostic factors in OS. Results: 35 patients (01.2003-05.2011). 60% male. Median age 16 y (r 7-57). Axial (43%), extremities (34%), extra-osseous (18%) and ribs (9%). Metastases: 54% (lung 58%, bone 26%, others 12%). > 1 location: 29%. Induction CT: 83% received 6 cy. 6% early progressions and 3% toxic deaths. 196 cycles of CT. Dose reduction (etoposide) in 60%. Grade 3-4 toxicity: neutropenia 13%, anemia 14%, neutropenic fever 13%, diarrhoea-stomatitis 7%.Local treatment: surgery (49%), radiotherapy (29%), none (22%). In 17 resections, > 90% necrosis in 53%. Consolidation: VACx8 29%; VACx1-ATSP in 34%; 37% other treatments (progression). No ATSP-related mortality. Median follow-up: 36 m ( 5-101 m). Median DFS 25 m (16-34 m). Median OS 28 m (15-41 m), 3-year OS 40%. Median time to progression 7 m (0.4-15 m). Median OS from progression 7 m (0.4-15 m). Age < 15 years, a non-axial primary and no extra-pulmonary metastases were favourable prognostic factors in the univariate analysis. Conclusions: Induction CT with the VIDE regimen is feasible in most patients, with a low risk of early progression. Hematological toxicity is substantial but manageable. Adults patients have a worse prognosis compared to pediatric patients. Unfortunately, survival after progression is dismal.

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Müller, Mandy D., and Leo H. Bonati. "Carotid artery stenosis – Current evidence and treatment recommendations." Clinical and Translational Neuroscience 5, no. 1 (January 1, 2021): 2514183X2110016. http://dx.doi.org/10.1177/2514183x211001654.

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Background: Carotid artery stenosis is an important cause for stroke. Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic carotid stenosis and to some extent in patients with asymptomatic carotid stenosis. More than 20 years ago, carotid artery stenting (CAS) emerged as an endovascular treatment alternative to CEA. Objective and Methods: This review summarises the available evidence from randomised clinical trials in patients with symptomatic as well as in patients with asymptomatic carotid stenosis. Results: CAS is associated with a higher risk of death or any stroke between randomisation and 30 days after treatment than CEA (odds ratio (OR) = 1.74, 95% CI 1.3 to 2.33, p < 0.0001). In a pre-defined subgroup analysis, the OR for stroke or death within 30 days after treatment was 1.11 (95% CI 0.74 to 1.64) in patients <70 years old and 2.23 (95% CI 1.61 to 3.08) in patients ≥70 years old, resulting in a significant interaction between patient age and treatment modality (interaction p = 0.007). The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up also favoured CEA (OR = 1.51, 95% CI 1.24 to 1.85, p < 0.0001). In asymptomatic patients, there is a non-significant increase in death or stroke occurring within 30 days of treatment with CAS compared to CEA (OR = 1.72, 95% CI 1.00 to 2.97, p = 0.05). The risk of peri-procedural death or stroke or ipsilateral stroke during follow-up did not differ significantly between treatments (OR = 1.27, 95% CI 0.87 to 1.84, p = 0.22). Discussion and Conclusion: In symptomatic patients, randomised evidence has consistently shown CAS to be associated with a higher risk of stroke or death within 30 days of treatment than CEA. This extra risk is mostly attributed to an increase in strokes occurring on the day of the procedure in patients ≥70 years. In asymptomatic patients, there may be a small increase in the risk of stroke or death within 30 days of treatment with CAS compared to CEA, but the currently available evidence is insufficient and further data from ongoing randomised trials are needed.

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Blann, Andrew D., and Simon Dunmore. "Arterial and Venous Thrombosis in Cancer Patients." Cardiology Research and Practice 2011 (2011): 1–11. http://dx.doi.org/10.4061/2011/394740.

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The most frequent ultimate cause of death is myocardial arrest. In many cases this is due to myocardial hypoxia, generally arising from failure of the coronary macro- and microcirculation to deliver enough oxygenated red cells to the cardiomyocytes. The principle reason for this is occlusive thrombosis, either by isolated circulating thrombi, or by rupture of upstream plaque. However, an additionally serious pathology causing potentially fatal stress to the heart is extra-cardiac disease, such as pulmonary hypertension. A primary cause of the latter is pulmonary embolus, considered to be a venous thromboembolism. Whilst the thrombotic scenario has for decades been the dominating paradigm in cardiovascular disease, these issues have, until recently, been infrequently considered in cancer. However, there is now a developing view that cancer is also a thrombotic disease, and notably a disease predominantly of the venous circulation, manifesting as deep vein thrombosis and pulmonary embolism. Indeed, for many, a venous thromboembolism is one of the first symptoms of a developing cancer. Furthermore, many of the standard chemotherapies in cancer are prothrombotic. Accordingly, thromboprophylaxis in cancer with heparins or oral anticoagulation (such as Warfarin), especially in high risk groups (such as those who are immobile and on high dose chemotherapy), may be an important therapy. The objective of this communication is to summarise current views on the epidemiology and pathophysiology of arterial and venous thrombosis in cancer.

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Dawe, EJC, E. Lindisfarne, T. Singh, I. McFadyen, and P. Stott. "Sernbo score predicts survival after intracapsular hip fracture in the elderly." Annals of The Royal College of Surgeons of England 95, no. 1 (January 2013): 29–33. http://dx.doi.org/10.1308/003588413x13511609954653.

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Introduction The Sernbo score uses four factors (age, social situation, mobility and mental state) to divide patients into a high-risk and a low-risk group. This study sought to assess the use of the Sernbo score in predicting mortality after an intracapsular hip fracture. Methods A total of 259 patients with displaced intracapsular hip fractures were included in the study. Data from prospectively generated databases provided 22 descriptive variables for each patient. These included operative management, blood tests and co-mobidities. Multivariate analysis was used to identify significant predictors of mortality. Results The mean patient age was 85 years and the mean follow-up duration was 1.5 years. The one-year survival rate was 92% (±0.03) in the low-risk group and 65% (±0.046) in the high-risk group. Four variables predicted mortality: Sernbo score >15 (p=0.0023), blood creatinine (p=0.0026), ASA (American Society of Anaesthesiologists) grade >3 (p=0.0038) and non-operative treatment (p=0.0377). Receiver operating characteristic curve analysis showed the Sernbo score as the only predictor of 30-day mortality (area under curve 0.71 [0.65–0.76]). The score had a sensitivity of 92% and a specificity of 51% for prediction of death at 30 days. Conclusions The Sernbo score identifies patients at high risk of death in the 30 days following injury. This very simple score could be used to direct extra early multidisciplinary input to high-risk patients on admission with an intracapsular hip fracture.

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Kotova, D. P., V. S. Shemenkova, and V. A. Demina. "Possibilities of therapy with beta‑blockers in the perioperative period in patients during cardiac and extra‑cardiac surgery." Clinician 14, no. 1-2 (May 8, 2020): 73–81. http://dx.doi.org/10.17650/1818-8338-2020-14-1-2-73-81.

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Сardiac complications are the most frequent non-surgical complications after surgical interventions, increasing the length of the patient’s stay in the hospital, the economic costs and the percentage of deaths. The frequency of patients with cardiovascular diseases who require surgery is also high. Optimization of drug therapy in the perioperative period is one of the factors of successful outcome of the surgical intervention.The pathophysiological basis for the development of many cardiac events in the postoperative period is an increase in the activity of the sympathetic nervous system, which leads to an increase in heart rate (HR) and myocardial oxygen demand. These changes may increase the risk of myocardial ischemia, arrhythmias, and other cardiovascular events in the early postoperative period. For example, the development of myocardial infarction (MI) in the perioperative period leads to an increase in hospital mortality by 15–25 %, and increase in the risk of developing cardiac death in the next few months.The main group of drugs for relieving these effects is beta-blockers (BB). This drug class has a wide range of applications: treatment of angina, arrhythmias, hypertension, MI, heart failure. Currently, there is a large evidence for the possibility and feasibility of using BB in patients undergoing surgery.In this article, the authors highlights the issues of prescribing BB in patients with comorbid pathology in the perioperative period. The analysis and comparison of studies on various aspects of BB use in the perioperative period performed. Currently, there is a mixed opinion about the benefits and risks of perioperative therapy of BB, which causes the high relevance of this issue for discussion.

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Pei, Sung-Nan, Kuan-Chih Huang, Ming-Chung Wang, Ching-Yuan Kuo, Ming-Chun Ma, Chun-Kai Liao, Lee Anne Rothwell, Hong Qiu, and Yanfang Liu. "Risk Factors Associated with Earlier Relapse and Death and Treatment Response in Patients with Follicular Lymphoma in Taiwan." Blood 132, Supplement 1 (November 29, 2018): 5338. http://dx.doi.org/10.1182/blood-2018-99-112347.

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Abstract Background: Follicular Lymphoma (FL) has been relatively uncommon in Asia. Information on prognostic risk factors are scarce in the Asian population. We evaluated patients with FL in a tertiary medical center in Taiwan to gain better understanding of real world treatment and risk factors affecting outcome. Purpose: To evaluate clinical outcomes and risk factors associated with outcome in patients with FL in Taiwan. Methods: We conducted a retrospective cohort study using electronic medical records from Kaohsiung Chang Gung Memorial Hospital, a major regional hospital in southern Taiwan, from 01 January 2008 to 31 December 2017. Newly diagnosed patients with FL were enrolled from 01 Jan 2008 to 31 Dec 2013. All eligible patients were followed-up until study end, loss to follow-up or until death, whichever occurred first. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Risk factors of EFS and OS were identified using Cox proportional hazards model. A significant association was set at p<0.01. Results: A total of 67 patients with newly diagnosed FL were included in the cohort analysis, accounting for 13.7% (67/489) patients with B cell non-Hodgkin lymphoma during the enrolment period. Median follow-up time was 60 months. At diagnosis, median age was 58 years (range 28-95), 56.7% (38/67) of patients were female, and 68.7% (46/67) had Stage III-IV disease. There were 37.3% (25/67) of patients with bone marrow involvement and 22.4% (15/67) with involvement of more than one extra-nodal site. The percentage of patients with low, intermediate and high-risk FL was 32.8%, 25.4%, 38.8%, respectively by FLIPI-1, and 13.4%, 44.8%, 26.9% by FLIPI-2. 72% (48/67) of patients received first-line treatment with regimens that included rituximab, cyclophosphamide, vincristine, prednisolone ± doxorubicin. Of these, 54.2% (26/48) of patients demonstrated complete response and 37.5% (18/48) had a partial response. A further 22.4% (15/67) patients received other treatments and 6.0% (4/67) patients did not receive any treatment. Progression of disease within 24 months after commencing treatment occurred in 32.8% of patients. The 5-year EFS and OS for all patients were 48.6% and 76.2%, respectively (Figure). A higher relapse rate was associated with the presence of B symptoms (HR 6.1; 95% confidence interval [CI] 2.8-13.2), ECOG score ≥2 (HR 5.7; 95% CI 1.7-19.6), FLIPI-2 score ≥3 (HR 5.5; 95% CI 1.4-20.6), large cell transformation (HR 4.1; 95% CI 1.66-10.6), elevated β2 microglobulin (HR 4.0; 95% CI 1.8-9.1), age >70 years (HR 3.6; 95% CI 1.7-7.5), involvement of more than one extra-nodal site (HR 3.5; 95% CI 1.6-7.6) and elevated LDH (HR 2.5; 95% CI 1.3-5.1) (Table 2). Conclusion: Most patients with FL in this tertiary center in Taiwan were at an advanced disease stage at diagnosis. While the majority responded to conventional chemotherapy, one-half of patients progressed within 5 years. Involvement of extra-nodal sites, B symptoms, older age (>70) higher FLIPI-2 score, elevated β2 microglobulin and ECOG score ≥2 were identified as risk factors for earlier relapse and death. Disclosures Pei: Janssen Research & Development, LLC: Research Funding. Huang:Janssen Research & Development, LLC: Employment. Rothwell:Janssen Research & Development, LLC: Employment, Equity Ownership. Qiu:Janssen Research & Development, LLC: Employment, Equity Ownership. Liu:Janssen Research & Development, LLC: Employment, Equity Ownership.

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Santra, Sutanuka, and Prabha Shrivastava. "A study on prevalence of cardiovascular disease related risk factors among tribal population in a block of West Bengal." International Journal Of Community Medicine And Public Health 6, no. 12 (November 27, 2019): 5302. http://dx.doi.org/10.18203/2394-6040.ijcmph20195489.

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Background: Non communicable diseases (NCDs) refer to chronic diseases of long duration and generally with slow progression. NCDs are affecting Indian population, both in urban and rural areas. Cardiovascular disease (CVD), one of the major NCDs is the leading cause of death worldwide. The rising prevalence of behavioral and anthropometric risk factors for these lifestyle diseases is postulated to be the cause for the alarming increase of NCDs including CVD. Prevalence of cardiovascular diseases is also increasing in tribal population. Objective of this study was to assess the prevalence of risk factors associated with cardiovascular diseases among the tribal population aged 18 years and above.Methods: A community based, observational, descriptive study was conducted at Kharagpur-II block of Paschim Medinipur district, West Bengal from August 2013 to July 2014 among 540 tribal population aged 18 years and above selected by cluster random sampling method.Results: About 64% individuals were addicted to tobacco product. Prevalence of current smoking and tobacco chewing was 9.1% and 60.2% respectively. Prevalence of current alcohol consumption was 48.9%. About 91% individuals took extra salt with meal. Prevalence of overweight and obesity was 7.8% and 3.5% only according to WHO recommended classification for Asian population. However, higher level of physical activity was found among the study population.Conclusions: The study revealed high prevalence of extra salt intake, tobacco and alcohol consumption among the study population which may endanger their life by increasing the risk of cardiovascular disease.

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Robertson, Julia, James Dalton, Siouxsie Wiles, Marija Gizdavic-Nikolaidis, and Simon Swift. "The tuberculocidal activity of polyaniline and functionalised polyanilines." PeerJ 4 (December 20, 2016): e2795. http://dx.doi.org/10.7717/peerj.2795.

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Tuberculosis is considered a leading cause of death worldwide. More than 95% of cases and deaths occur in low- and middle-income countries. In resource-limited countries, hospitals often lack adequate facilities to manage and isolate patients with infectious tuberculosis (TB), relying instead on personal protective equipment, such as facemasks, to reduce nosocomial transmission of the disease. Facemasks impregnated with an antimicrobial agent may be a cost-effective way of adding an extra level of protection against the spread of TB by reducing the risk of disease transmission. Conducting polymers, such as polyaniline (PANI), and their functionalised derivatives are a novel class of antimicrobial agents with potential as non-leaching additives to provide contamination resistant surfaces. We have investigated the antimicrobial action of PANI and a functionalised derivative, poly-3-aminobenzoic acid (P3ABA), against mycobacteria and have determined the optimal treatment time and concentration to achieve significant knockdown ofMycobacterium smegmatisandMycobacterium tuberculosison an agar surface. Results indicated that P3ABA is a potential candidate for use as an anti-tuberculoid agent in facemasks to reduce TB transmission.

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Huang, Chen, Jiahuan Peng, Priscilla Ming Yi Lee, Ce Wang, Kecheng Wei, Minhong Liang, Guoyou Qin, Yongfu Yu, and Jiong Li. "Sibling Death in Childhood and Early Adulthood and Risk of Early-Onset Cardiovascular Disease." JAMA Network Open 7, no. 1 (January 8, 2024): e2350814. http://dx.doi.org/10.1001/jamanetworkopen.2023.50814.

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ImportanceSibling death is a highly traumatic event, but empirical evidence on the association of sibling death in childhood and early adulthood with subsequent risk of incident cardiovascular disease (CVD) remains limited.ObjectiveTo evaluate the association between sibling death in the early decades of life and subsequent risk of incident early-onset CVD.Design, Setting, and ParticipantsThis population-based cohort study included 2 098 659 individuals born in Denmark from 1978 to 2018. Follow-up started at age 1 year or the date of the first sibling’s birth, whichever occurred later, and it ended at the first diagnosis of CVD, the date of death, emigration, or December 31, 2018, whichever came first. Data analyses were conducted from November 1, 2021, through January 10, 2022.ExposuresThe death of a sibling.Main Outcomes and MeasuresThe outcome was early-onset CVD. Cox models were used to estimate hazard ratios (HRs) with 95% CIs.ResultsThis study included 2 098 659 individuals (1 076 669 [51.30%] male; median [IQR] age at death of sibling, 11.48 [4.68-21.32] years). During the median (IQR) follow-up of 17.52 (8.85-26.05) years, 1286 and 76 862 individuals in the bereaved and nonbereaved groups, respectively, were diagnosed with CVD. Sibling death in childhood and early adulthood was associated with a 17% increased risk of overall CVD (HR, 1.17; 95% CI, 1.10-1.23; cumulative incidence in bereaved individuals, 1.96% [1.61%-2.34%]; cumulative incidence in nonbereaved individuals at age 41 years, 1.35% [1.34%-1.37%]; cumulative incidence difference: 0.61% [95% CI, 0.24%-0.98%]). Increased risks were also observed for most type-specific CVDs, in particular for myocardial infarction (HR, 1.66; 95% CI, 1.12-2.46), ischemic heart disease (HR, 1.52; 95% CI, 1.22-1.90), and heart failure (HR, 1.50; 95% CI, 1.00-2.26). The association was observed whether the sibling died due to CVD (HR, 2.54; 95% CI, 2.04-3.17) or non-CVD (HR, 1.13; 95% CI, 1.06-1.19) causes. The increased risk of CVD was more pronounced for individuals who lost a twin or younger sibling (HR, 1.25; 95% CI, 1.15-1.36) than an elder sibling (HR, 1.11; 95% CI, 1.03-1.20).Conclusions and RelevanceIn this cohort study of the Danish population, sibling death in childhood and early adulthood was associated with increased risks of overall and most type-specific early-onset CVDs, with the strength of associations varying by cause of death and age difference between sibling pairs. The findings highlight the need for extra attention and support to the bereaved siblings to reduce CVD risk later in life.

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Abusanad, Atlal M., Omar Iskanderani, Marwan R. Al-hajeili, Reem Ujaimi, and Rolina Alwassia. "Survival in patients with brain metastasis secondary to breast cancer from Saudi Arabia." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e14018-e14018. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e14018.

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e14018 Background: Breast cancer (BC) is the most common malignancy in women from Saudi Arabia. Nearly one-third of the patients present with metastatic disease. Data on the incidence, pattern and outcome of brain metastasis (BM) in breast cancer patients is yet to be reported to inform the practice and help in assessing the current standard of care. Methods: A retrospective cohort study between the years 2015 and 2020 that included BC patients with BM was conducted. Demographic data, tumor clinico-pathological features, treatment modalities and outcomes were obtained. Survival, factors influencing survival time and the risk of death were examined. A p-value of less than 0.05 was considered statistically significant. Results: 111 patients with BM due to BC were included in the analysis. All are female with a mean age 50.28 ± 11.61 years. IDC histology (93%), grade III (71%), tumor > T2 (64%) and N-positive (60%) BC accounted for the majority. Human epidermal growth factor receptor2 (HER2)-positive/Hormone receptors (HR)-negative was 21%, HER2-positive/HR-positive was 16%, HR-positive/HER2-negative was 31%, TNBC was 22.5% and unknown subtype in 10%. 60% had metastatic disease on presentation with 41% had both skeletal and visceral metastases. Brain lesions > three were reported in nearly half of the cohort. Whole brain radiotherapy (WBRT), surgical resection and SRS were reported in 84%, 16% and 22%, respectively. The mean survival time was 3.31 years with a maximum of 4.23 years and a minimum of 2.39 years. Patients with HR-positive and HER2-positive BC had a significant longer survival (p=0.039, 0.033 respectively). Neither tumor size nor nodal status in BC patients with BM influenced survival time. The presence of visceral metastasesincreased the likelihood of death in BC patients with BM up to 6 folds (p=0.031). The relationship between risk of death, treatment modalities, and response of BM is shown. Conclusions: Although BM secondary to BC represents a therapeutic challenge with an expected unfavorable impact on survival, mortality was associated with the presence of extra-cranial metastases, particularly visceral metastases in this cohort. Longer survival was seen with specific subtypes (HR-positive and HER2-positive), suggesting advancement in systemic treatments against them. [Table: see text]

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Piechocki, Marcin, Tadeusz Przewłocki, Piotr Pieniążek, Mariusz Trystuła, Jakub Podolec, and Anna Kabłak-Ziembicka. "A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients—A Review: Part I—Epidemiology, Risk Factors, and Atherosclerosis-Related Diversities in Elderly Patients." Journal of Clinical Medicine 13, no. 5 (March 3, 2024): 1471. http://dx.doi.org/10.3390/jcm13051471.

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Atherosclerosis is a generalized and progressive disease. Ageing is a key risk factor for atherosclerosis progression that is associated with the increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity and quality of life, and it is associated with reduced life expectancy. Although there is evidence on coronary artery disease management in the elderly, there is insufficient data on the management in older patients presented with atherosclerotic lesions outside the coronary territory. Despite this, trials and observational studies systematically exclude older patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment and referral for endovascular or surgical interventions. Therefore, we attempted to gather data on the prevalence, risk factors, and management strategies in patients with extra-coronary atherosclerotic lesions.

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Zage, Peter, Kathy Scorsone, and Linna Zhang. "The role of c-Met inhibition for neuroblastoma treatment." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 10041. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.10041.

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10041 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood. Many children present with high-risk disease characterized by rapid tumor growth, resistance to chemotherapy, and widespread metastasis, and novel therapies are needed. Previous studies have identified a role for the HGF/c-Met pathway in the pathogenesis of neuroblastoma. We hypothesized that EMD1214063 would be effective against neuroblastoma tumor cells and tumors in preclinical models via inhibition of HGF/c-Met signaling. Methods: We determined the expression of c-Met in a panel of neuroblastoma tumor cells and neuroblastoma cell viability after treatment with EMD1214063 using MTT assays. Analyses were performed for changes in cell morphology, cell cycle progression, and cell death via apoptosis after EMD1214063 treatment. To investigate the efficacy of EMD1214063 against neuroblastoma tumors in vivo, neuroblastoma cells were injected orthotopically into immunocompromised mice, and the mice in which tumors developed were treated with oral EMD1214063. Results: All neuroblastoma cell lines were sensitive to EMD1214063, and IC50 values ranged from 2.4 - 8.5 mcM. EMD1214063 treatment inhibited HGF-mediated c-Met phosphorylation in neuroblastoma cells. EMD1214063 induced cell cycle arrest in neuroblastoma tumor cells with high c-Met expression, and induced apoptosis in all tested cell lines. In mice with neuroblastoma xenograft tumors, EMD1214063 inhibited tumor growth. Conclusions: Treatment of neuroblastoma tumor cells with EMD1214063 inhibits HGF-induced c-Met phosphorylation and results in cell death. Furthermore, EMD1214063 induces cell cycle arrrest prior to cell death in neuroblastoma tumor cells with high c-Met expression. EMD1214063 treatment is effective in reducing tumor growth in vivo in mice. Inhibition of c-Met represents a potential new therapeutic strategy for neuroblastoma, and further preclinical studies of EMD1214063 are warranted.

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Paccosi, Elena, Michele Costantino, Alessio Balzerano, Silvia Filippi, Stefano Brancorsini, and Luca Proietti-De-Santis. "Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival." International Journal of Molecular Sciences 22, no. 18 (September 17, 2021): 10070. http://dx.doi.org/10.3390/ijms221810070.

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Neuroblastoma, the most common extra-cranial solid tumor of early childhood, is one of the major therapeutic challenges in child oncology: it is highly heterogenic at a genetic, biological, and clinical level. The high-risk cases have one of the least favorable outcomes amongst pediatric tumors, and the mortality rate is still high, regardless of the use of intensive multimodality therapies. Here, we observed that neuroblastoma cells display an increased expression of Cockayne Syndrome group B (CSB), a pleiotropic protein involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division, and were recently found to confer cell robustness when they are up-regulated. In this study, we demonstrated that RNAi-mediated suppression of CSB drastically impairs tumorigenicity of neuroblastoma cells by hampering their proliferative, clonogenic, and invasive capabilities. In particular, we observed that CSB ablation induces cytokinesis failure, leading to caspases 9 and 3 activation and, subsequently, to massive apoptotic cell death. Worthy of note, a new frontier in cancer treatment, already proved to be successful, is cytokinesis-failure-induced cell death. In this context, CSB ablation seems to be a new and promising anticancer strategy for neuroblastoma therapy.

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Wang, Haotong, Ruoyu Miao, Alex Jacobson, Saveli Goldberg, David C. Harmon, Gregory Cote, Francis J. Hornicek, et al. "Osteosarcoma prognostic nomograms for predicting the 10-year probability of mortality and recurrence." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 11020. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.11020.

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11020 Background: The multidisciplinary approach in treatment of osteosarcoma has been well established and well adopted nationwide. This study combined the clinical prognostic factors at initial presentation into a nomogram to predict local control (LC), metastasis free survival (MFS), and overall survival (OS) for patients with non-metastatic bone osteosarcoma. Methods: We reviewed 397 osteosarcoma patients treated from 1995 to 2014. Patients with metastatic disease at diagnosis or limited follow up were excluded, resulting in 283 cases for analysis. Clinical and pathologic variables were recorded. Predictive variables included age at diagnosis, gender, previous radiation history, site, tumor size, histologic subtype, histologic grade, extra-osseous extension (EOE), lymphovascular invasion (LVI), necrosis rate and margin. The multivariate Cox proportional hazards regression was used to analyze survival outcomes and risk variables. Results: At 10 years, LC was 70.4% (95% confidence interval, CI: 64.0%-76.7%), MFS was 64.7% (95% CI: 58.1%-71.3%), and OS was 61.5% (95% CI: 54.9%-68.1%). Multivariate Cox model identified age (p = 0.033), site (p = 0.020), EOE (p = 0.017), LVI (p = 0.011), and margin (p = 0.039) were correlated with LC; age (p = 0.028), tumor size (p < 0.001), histologic grade (p = 0.039), and LVI (p = 0.014) were correlated with MFS; whereas age (p < 0.001), prior radiation history (p = 0.010), tumor size (p = 0.002), histologic subtype (p = 0.012), EOE (p = 0.002), and LVI (p = 0.001) were associated with OS. The nomograms were drawn on the basis of the Cox regression model and were internally validated using bootstrapping, with predictive accuracy of ±7.2% for 10-year LC, ±7.4% for 10-year MFS, and ±7.5% for 10-year OS. Conclusions: Nomograms have been developed to predict the 10-year local-control failure, recurrence and death. We suggest that this tool at presentation may be useful for individualized risk evaluation, patient counseling, and making clinical decisions.

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Foteinogiannopoulou, K., P. Nicolaou, A. Mala, E. Theodoraki, E. Orfanoudaki, A. Theodoropoulou, K. Karmiris, and I. Koutroubakis. "P768 The prevalence and risk factors for malignancies in patients with inflammatory bowel disease in Crete : a case control study." Journal of Crohn's and Colitis 17, Supplement_1 (January 30, 2023): i896—i899. http://dx.doi.org/10.1093/ecco-jcc/jjac190.0898.

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Abstract Background There is evidence that about 30% of the patients with inflammatory bowel disease (IBD) develop malignancies whichconstitute the second cause of death, after cardiovascular diseases, such as in general population. Methods The aim of this study was to investigate the prevalence and risk factors for malignancies in IBD patients followed in two tertiary centers. It was a retrospective analysis of prospectively recorded data in an established IBD registry for seven years (06/2015 to 06/2022). IBD patients with malignancies were compared with controls-IBD patients without malignancies [matching 1:3 according to sex, IBD diagnosis (Ulcerative Colitis; UC, Crohn’s Disease; CD) and age (±5 years)] so as to elucidate possible risk factors for cancer (CA) development in these individuals. Results From a total of 2.382 IBD patients of the IBD registry in University Hospital and Venizeleio General Hospital of Heraklion in Crete, 107 (4.5 %) were diagnosed with CAs during their follow-up whereas 22 (0.92 %) had a history of CA before IBD diagnosis. Demographic, clinical and therapeutic data for the total of 428 patients (107 with CA and 321 without CA) are presented in Table 1. Among patients with CA, 49 (45.8%) were females, 54 (50.5%) had CD, the median age of CA diagnosis was 61 years (51.3-69.8) and the median IBD duration was 10 years (3-20). Thirty-two (29.9 %) of the CA-IBD patients had known familial history of CA and 28 (26.1 %) were active smokers whereas 46 (42.9 %) were ex-smokers. Twenty-nine patients (27.1 %) were exposed to immunomodulators, 32 (29.9 %) to anti-TNFs, 20 (18.7 %) to other biologics and 16 (14.9 %) to combination treatment. The majority of CA cases were extra-intestinal, only 12 (11.2 %) had colorectal cancer (CRC) and 11 (10.3 %) had a CA recurrence whereas 19 (17.8 %) died from the CA. In the univariate analysis the median IBD duration (OR 0.96, CI 95%0.94- 0.99), inflammatory phenotype in CD (OR 0.46, CI 95% 0.23-0.93) and treatment with other biologics (other than ant-TNFs) (OR 0.50, CI 95%0.29- 0.86) were protective factors, whereas colonic location in CD (OR 3.24, CI 95% 1,49-7,04) found to be a risk factor for CA development(Table 1). No association with disease characteristics, smoking habits, family history of CA and extra intestinal manifestations was found. In the multivariate analysis only CD inflammatory phenotype (OR 0.28, CI 95%0.09-0.58) was a protective factor whereas colonic location (OR 4.8, CI 95% 1.81-12.79) remained a risk factor for malignancies (Table 2). Conclusion The prevalence of malignancy in IBD patients in Crete is 4.5%. It seems that in CD disease phenotype is associated with the development of malignancies. Non association with the used medications was found.

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Mekonnen, Hailemichael Desalegn, Henok Fisseha, Tewodros Getinet, Fisseha Tekle, and Peter R. Galle. "Helicobacter pylori Infection as a Risk Factor for Hepatocellular Carcinoma: A Case-Control Study in Ethiopia." International Journal of Hepatology 2018 (December 2, 2018): 1–7. http://dx.doi.org/10.1155/2018/1941728.

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Background and Aims.Hepatocellular carcinoma is a major cause of cancer death worldwide, accounting for over half a million deaths per year. Its incidence varies with geographic locations and the type of etiologic factors. In Ethiopia, unidentified causes of liver disease are of sizeable proportion. Recent studies have shown an association of H. pylori infection with different spectrums of chronic liver disease. This study was conducted at St. Paul’s Hospital Millennium Medical College in Ethiopia and assesses liver cancer and the association with H. pylori infection.Method.A prospective case-control study conducted on patients with chronic liver disease presenting with a suspicious liver lesion and diagnosed to have HCC in the Gastrointestinal (GI) Clinic of St. Paul’s Hospital MMC from Dec 30, 2016, to Nov 1, 2017 G.C. Descriptive surveys on clinical history and physical examination and laboratory profiles were obtained, and the clinical course of the patients including the type of treatment was followed prospectively. Control cases were taken from adult patients without evidence of liver disease in the internal medicine clinic coming for routine evaluation. After collection data were analyzed using SPSS version 23 and associations were assessed using chi-square test. Binary logistic regression was used to assess the association of HCC with different variables and H. pylori infection. All variables with p-value <0.05 were considered as statistically significant.Results.One hundred twenty patients were analyzed with equal representation of cases and controls. The majority of patients with HCC were male with a mean age of 36 years. Older age adjusted Odds Ratio (AOR) (95%CI, p-value) 1.07(1.03-1.09, <0.001), viral hepatitis B (AOR) (95%CI, p-value) 6.19 (1.92-19.93, 0.002), and H. pylori infection (AOR) (95%CI, p-value) 5.22 (2.04–13.31, <0.001) were statistically significantly associated with HCC.Conclusion.H. pylori infection is associated with HCC in this case-control study. This study supports the emerging evidence of H. pylori association with other extra-gastric manifestations.

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Atoum, Manar Fayiz, Foad Alzoughool, and Huda Al-Hourani. "Linkage Between Obesity Leptin and Breast Cancer." Breast Cancer: Basic and Clinical Research 14 (January 2020): 117822341989845. http://dx.doi.org/10.1177/1178223419898458.

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Many cancers might be influenced by obesity, including breast cancer, the leading cause of cancer death among women. Obesity is a complex state associated with multiple physiological and molecular changes capable of modulating the behavior of breast tumor cells and the surrounding microenvironment. This review discussed the inverse association between obesity and breast cancer among premenopausal breast cancer females and the positive association among postmenopausal. Four mechanisms may link obesity and breast cancer including leptin and leptin receptor expression, adipose chronic inflammation, sex hormone alternation, and insulin and insulinlike growth factor 1 (IGF-1) signaling. Leptin has been involved in breast cancer initiation, development, and progression through signaling transduction network. Leptin functions are strengthened through cross talk with multiple oncogenes, cytokines, and growth factors. Adipose chronic inflammation promotes cancer growth and angiogenesis and modifies the immune responses. A pro-inflammatory microenvironment at tumor site promotes cytokines and pro-inflammatory mediators adjacent to the tumor. Leptin stimulates pro-inflammatory cytokines and promotes T-helper 1 responses. Obesity is common of chronic inflammation. In obese patients, white adipose tissue (WAT) will promote pro-inflammatory mediators that will encourage tumor growth and WAT inflammation. Sex hormone alternation of estrogens is associated with increased risk for hormone-sensitive breast cancers. Estrogens cause tumorigenesis by its effect on signaling pathways that lead to DNA damage, stimulation angiogenesis, mutagenesis, and cell proliferation. In postmenopausal females, and due to termination of ovarian function, estrogens were produced extra gonadally, mainly in peripheral adipose tissues where adrenal-produced androgen precursors are converted to estrogens. Active estradiol leads to breast cancer development by binding to ERα, which is modified by receptor’s interaction of various signal transduction pathways. Hyperinsulinemia and IGF-1 activate the MAPK and PI3K pathways, leading to cancer-promoting effects. Cross talk between insulin/IGF and estrogen signaling pathways promotes hormone-sensitive breast cancer development. Hyperinsulinemia is a risk factor for breast cancer that explains the obesity-breast cancer association. Controlling IGF-1 level and targeting IGF-1 receptors among different breast cancer subtypes may be useful for breast cancer treatment. This review discussed several leptin signaling pathways, highlighting the potential advantage of targeting leptin as a potential target of the novel therapeutic strategies for breast cancer treatment.

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Journal articles on the topic 'Extra non-Cancer death risk'

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