Zeitschriftenartikel: „ISA 540 (revised)“

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Gow, Chien-Hung, Min-Shu Hsieh, Yi-Nan Liu, Yi-Hsuan Lee und Jin-Yuan Shih. „Clinicopathological Features and Survival Outcomes of Primary Pulmonary Invasive Mucinous Adenocarcinoma“. Cancers 13, Nr. 16 (15.08.2021): 4103. http://dx.doi.org/10.3390/cancers13164103.

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Pulmonary invasive mucinous adenocarcinoma (IMA) has unique histological patterns. This study aimed to comprehensively evaluate the clinicopathological features, prognosis, and survival outcomes of IMAs. We retrospectively identified 77 patients with pulmonary IMA and reviewed their clinical and pathological features. Another 520 patients with non-IMA-type ADC were retrieved for comparison with patients with IMA. A new two-tier grading system (high-grade and low-grade IMAs) modified from the pancreatic intraepithelial neoplasia classification system was used for survival analyses. Compared to patients with non-IMA-type ADC, patients with IMA tended to have never smoked (p = 0.01) and had early-stage IMA at initial diagnosis (p < 0.001). For stage I–II diseases, the five-year overall survival (OS) rates were 76% in IMAs and 50% in non-IMA-type ADCs, and a longer OS was observed in patients with IMA (p = 0.002). KRAS mutations were the most commonly detected driver mutations, which occurred in 12 of the 28 (43%) patients. High-grade IMAs were associated with a shorter recurrence-free survival (RFS) for stage I–IIIA diseases (p = 0.010) than low-grade IMAs but not for OS. In conclusion, patients with stage I and II IMA had better OS than those with non-IMA-type ADC. A new two-tier grading system might be useful for predicting RFS in stage I–IIIA IMAs.

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Jacobs, J. L., und C. T. Stephens. „FACTORS AFFECTING THE REGENERATION OF PEPPER (CAPSICUM ANNUUM L.)“. HortScience 25, Nr. 9 (September 1990): 1120G—1120. http://dx.doi.org/10.21273/hortsci.25.9.1120.

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Several growth hormone combinations and silver nitrate concentrations were examined for their effect on regeneration of different pepper genotypes. Primary leaf explants from in vitro seedlings were cultured on a revised Murashige and Skoog medium supplemented with auxin, cytokinin and 1.6% glucose. Combinations of different concentrations of indole-3-acetic acid (IAA), 0-5 mg/l, and 6-benzylaminopurine (BAP), 0-5 mg/l, were tested to determine the most effective medium for shoot primordium formation. Experiments with IAA and BAP did not result in a specific growth hormone combination appropriate for regeneration of all genotypes tested. Of the silver nitrate concentrations tested, 10 mg/l resulted in the best shoot and leaf differentiation and reduced callus formation. Differences in organogenic response of individual genotypes were evaluated on a single regeneration medium. Whole plants were regenerated from 11 of 63 genotypes examined. Based on these experiments, a reproducible regeneration system for pepper was developed with a total of 500 plants regenerated to date.

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Jacobs, J. L., und C. T. Stephens. „FACTORS AFFECTING THE REGENERATION OF PEPPER (CAPSICUM ANNUUM L.)“. HortScience 25, Nr. 9 (September 1990): 1120g—1120. http://dx.doi.org/10.21273/hortsci.25.9.1120g.

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Several growth hormone combinations and silver nitrate concentrations were examined for their effect on regeneration of different pepper genotypes. Primary leaf explants from in vitro seedlings were cultured on a revised Murashige and Skoog medium supplemented with auxin, cytokinin and 1.6% glucose. Combinations of different concentrations of indole-3-acetic acid (IAA), 0-5 mg/l, and 6-benzylaminopurine (BAP), 0-5 mg/l, were tested to determine the most effective medium for shoot primordium formation. Experiments with IAA and BAP did not result in a specific growth hormone combination appropriate for regeneration of all genotypes tested. Of the silver nitrate concentrations tested, 10 mg/l resulted in the best shoot and leaf differentiation and reduced callus formation. Differences in organogenic response of individual genotypes were evaluated on a single regeneration medium. Whole plants were regenerated from 11 of 63 genotypes examined. Based on these experiments, a reproducible regeneration system for pepper was developed with a total of 500 plants regenerated to date.

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Carlson, Travis J., Anne J. Gonzales-Luna, Kimberly Nebo, Hannah Y. Chan, Ngoc-Linh T. Tran, Sheena Antony und Kevin W. Garey. „795. Impact of Revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America Guideline on the Classification of Clostridioides difficile Infection Severity“. Open Forum Infectious Diseases 7, Supplement_1 (01.10.2020): S441. http://dx.doi.org/10.1093/ofid/ofaa439.985.

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Abstract Background The Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) revised their Clostridioides difficile infection (CDI) severity classification criteria in 2017 to include a serum creatinine (SCr) value above a threshold (≥ 1.5 mg/dL) rather than a relative increase from baseline (≥ 1.5 times the premorbid level). To date, these criteria have not been validated and may overestimate the number of severe CDI cases in patients with underlying renal insufficiency. Methods This multicenter, retrospective cohort study included all patients ≥ 18 years of age with CDI diagnosed in two large health systems in the Houston, Texas area between 2016 and 2018. Patients were assessed for presence of acute kidney injury (AKI) and chronic kidney disease (CKD), defined per the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, and IDSA/SHEA CDI severity classification criteria per the 2010 and 2017 CDI guidelines. The primary outcome was all-cause inpatient mortality. Results The study cohort consisted of 770 CDI episodes from 12 hospitals. A large proportion of episodes occurred in patients with preexisting CKD (36.5%) and concomitant AKI (29.6%). Eighty-two episodes (10.6%) showed discordant results when applying the 2017 revised severity classification criteria due to the identification of patients with preexisting CKD. However, the 2017 severity classification criteria were better correlated with all-cause mortality (OR, 5.40; 95% CI, 1.84-15.86; P = 0.002) than were the 2010 severity classification criteria (OR, 3.12; 95% CI, 1.35-7.19; P = 0.008) as the 2017 SCr criterion was an independent predictor of mortality (OR, 3.66; 95% CI, 1.66-8.05; P = 0.001) while the 2010 SCr criterion was not (OR, 1.47; 95% CI, 0.71-3.08; P = 0.30). Conclusion Our findings support the inclusion of the 2017 IDSA/SHEA CDI severity classification criteria in future CDI guideline updates. Disclosures Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)

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TUNAKAN DALGIÇ, Ceyda, Aytül Zerrin Sin und Fatma Ömür Ardeniz. „Retrospective Analysis of Autoimmune Diseases and Immunologic Characteristics of the Adult Primary Immune Deficiency Cohort: 17 Years Experience of the Tertiary Referral Immunology Center in Turkey“. Asthma Allergy Immunology 19, Nr. 1 (30.04.2021): 12–23. http://dx.doi.org/10.21911/aai.545.

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ABSTRACT Objective: Primary immunodeficiencies (PIDs) consist of genetically heterogeneous disorders. The spectrum can include infectious diseases, malignancy, allergy, and autoimmunity. We aimed to analyze the frequency and variety of autoimmune diseases (ADs) in PIDs and describe their clinical and laboratory features. Materials and Methods: Ninety-two patients with PID followed by Ege University Medical Faculty between 2000 and 2017 were enrolled in this retrospective, cross-sectional study. All patients’ medical records were reviewed using the demographic information, type of PIDs and ADs, ADs-related autoantibodies, and basic and immunologic laboratory findings. ADs were diagnosed using clinical and complementary paraclinical findings by an immunologist and/or a subspecialist related to the affected organ or system. Results: We evaluated 50 male and 42 female PID patients with a mean age of 40.92 (18-86). Twenty-nine (32 %) patients (15 females/14 males) with a mean age of 43.8 (19-78) had ADs. In our study group, the most commonly detected type of PID with AD is common variable immune deficiency (CVID) (n=17); followed by combined immune deficiency (CID) (n=3), CTLA4 deficiency (n=2), selective IgA deficiency (sIgAD) (n=2), specific IgG subgroup deficiency (n=1), autoimmune polyglandular syndrome (APS) with hypogammaglobulinemia (n=1), dyskeratosis congenita (DC) (n=1), Osler-Rendu-Weber (ORW) syndrome with CVID-like PID (n=1), and cartilage-hair hypoplasia (CHH) (n=1). According to systematic assessments, ADs resulted in endocrinologic 14%, dermatologic 10.8%, rheumatologic 9.7%, gastroenterological 9.7%, hematological 8.6%, and neurologic disorders 1%. The frequency of ADs was higher in CVID cases than other types of PIDs (p <0.05). Basic and immunologic laboratory findings of the PIDs with and without ADs were analyzed and compared; however, no statical significant difference was obtained between the groups. Conclusion: We have analyzed the frequency and variety of ADs in a adult PID cohort in Turkey. Patients presenting with multiple ADs should be screened for having an underlying PID. Keywords: Primary immune deficiency, autoimmunity, autoantibody, immunologic parameters, frequency

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Turgeon, Michael K., Adriana C. Gamboa, Rachel M. Lee, Jeffrey Maniko, Lillias Maguire, Maryam Mohammed, Jennifer Holder-Murray et al. „A United States Rectal Cancer Consortium study of inferior mesenteric artery versus superior rectal artery ligation: How high do we need to go?“ Journal of Clinical Oncology 38, Nr. 4_suppl (01.02.2020): 47. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.47.

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47 Background: The optimal level of pedicle ligation during proctectomy for rectal cancer, either at the origin of the inferior mesenteric artery (IMA) or the superior rectal artery (SRA), is still debated. Reasons for IMA ligation include facilitating a tension-free anastomosis and improved clearance of regional lymph nodes. Our aim was to determine if SRA ligation portends inferior outcomes. Methods: The US Rectal Cancer Consortium database (2007-2017) was reviewed for pts with primary, non-metastatic rectal adenocarcinoma who underwent treatment with low anterior resection or abdominoperineal resection. Primary outcomes were anastomotic leak rate and lymph node (LN) harvest. Secondary outcomes were locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS). Results: Of 877 pts, median age was 59 years (IQR52-67) and 62% were male (n = 541). 86% received an IMA ligation (n = 755) while 14% SRA (n = 122). 12% were pathologic stage 0 (n = 101), 33% stage I (n = 281), 24% stage II (n = 206), and 31% stage III (n = 269). Median follow-up was 34 mos. SRA ligation was more common in stage III disease (43vs30%, p = 0.005) while IMA ligation was more often performed with a minimally invasive approach (70vs42%, p < 0.001). SRA ligation was associated with a nearly identical anastomotic leak rate compared to IMA (9vs8%, p = 1.0). Similarly, the median number of LNs removed was the same between both ligation groups (15vs15, p = 0.38). On multivariable analysis accounting for an open approach, advanced pathologic stage, and positive resection margin status, SRA ligation was not associated with increased anastomotic leak rate or reduced LRFS, RFS, or OS (all p > 0.1). Conclusions: If a tension-free anastomosis is feasible, SRA ligation is not associated with either a worse technical outcome or inferior lymph node harvest. Furthermore, all cancer survival metrics are similar between SRA and IMA ligation. Given that either approach is safe and feasible from both a technical and oncologic standpoint, this study questions the routine practice of IMA ligation.

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Cremer, A., P. Demetter, M. De Vos, J. F. Rahier, F. Baert, T. Moreels, E. Macken, E. Louis, S. Vermeire und D. Franchimont. „DOP37 Neoplastic lesions outside diseased area in inflammatory bowel disease patients: A national cohort study“. Journal of Crohn's and Colitis 14, Supplement_1 (Januar 2020): S074—S075. http://dx.doi.org/10.1093/ecco-jcc/jjz203.076.

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Abstract Background Patients with inflammatory bowel diseases (IBD) are at increased risk of dysplasia and colitis-associated cancer (CAC). The presentation of (pre)neoplastic lesions (low-grade dysplasia (LGD), high-grade dysplasia (HGD) or colorectal cancer (CRC) is reported to vary depending if the lesions are located inside disease area (IDA) or outside diseased area (ODA). The primary aim was to analyse the characteristics and prognostic of IDA compared with ODA neoplastic lesions in a large cohort of IBD patients. Methods We performed a multicentre retrospective pathological data collection from 7 tertiary referral regional or academic IBD centres in Belgium. Clinical, endoscopic and pathological data were retrieved through retrospective electronic chart review. From the IBD pathology databases, 1183 colorectal lesions were identified in 541 IBD patients: 415 developed dysplasia (77%) and 126 CRC (23%) during their follow-up. Biopsies and surgical specimen were centrally reviewed by an expert IBD pathologist to confirm the diagnosis of dysplasia and/or CRC. Results Demographic and clinical variables of the study population are summarised in Table 1. More patients with IDA lesions had HGD (9%) or CAC (27%) during their follow-up compared with the group of patients with ODA lesions (3% of HGD and 11% of CRC) (p < 0,0001). Mortality was higher in patients with IDA than in those with ODA lesions (p < 0.05). When comparing IBD patients with IDA lesions and CAC (=111) to those with ODA lesions and sporadic CRC (n = 15), median age at IBD diagnosis was lower (29 (IQR:22–49) vs. 41(IQR:28–54) years; p = 0.0001). Characteristics of the 1183 neoplastic lesions are summarised in Table 2. IDA lesions were more frequently non-visible, non-polypoid and ≥ 1 cm than ODA lesions (p < 0.0001). ODA sporadic CRC was more frequently located in the right colon compared with IDA CAC (5/16 (31%) vs. 21/133 (16%), p < 0.01). Conclusion Neoplastic lesions outside the diseased area were more likely to be visible, polypoid, < 1cm, in the right colon and diagnosed at endoscopy than inside disease area lesions. A lower prevalence of HGD and Cancer were reported with neoplastic lesions outside the diseased area.

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Rausch, Caitlin R., Adam DiPippo, Prithviraj Bose und Dimitrios P. Kontoyiannis. „Breakthrough Invasive Fungal Infections (bIFI) Are Uncommon in Patients with Newly Diagnosed Acute Leukemia Receiving Primary Antifungal Prophylaxis“. Blood 136, Supplement 1 (05.11.2020): 31–32. http://dx.doi.org/10.1182/blood-2020-142559.

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Introduction: Mold-active primary antifungal prophylaxis (PAP) is widely recommended in neutropenic patients (pts) with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) who undergo remission-induction chemotherapy (RIC). Posaconazole (PCZ) prophylaxis resulted in fewer invasive fungal infections (IFIs) when compared to fluconazole and was associated with a survival advantage in this population (Cornely et al, 2007). Similarly, pts with acute lymphoblastic leukemia (ALL) undergoing RIC are also at risk of IFI due to prolonged neutropenia. Although PCZ is the preferred agent for PAP, the incorporation of targeted agents into acute leukemia therapy calls for more individualized choices in PAP. Other mold-active agents including voriconazole (VCZ) and isavuconazole (ISA) or the echinocandins are alternatives which may be preferred in individual settings due to variations in toxicity, patient co-morbidities, drug interactions, and cost. Little contemporary data exists to compare the incidence of breakthrough IFI (bIFIs) in pts with AML or ALL receiving PCZ, VCZ, or ISA as prophylaxis during RIC. Methods: We reviewed the medical records of all consecutive pts with newly diagnosed AML/MDS or ALL treated at our institution from 3/2016-7/2019. Included pts received high-intensity chemotherapy, or a lower-intensity venetoclax (VEN)-containing regimen, for RIC. Therapy with high-dose (> 1g/m2/day) cytarabine (HiDAC), continuous cytarabine plus an anthracycline (3+7), or HyperCVAD was considered high-intensity therapy. Patients receiving PCZ, VCZ, or ISA for > 5 days beginning during induction therapy were included. Baseline evidence of prior mold infection and treatment with a concomitant echinocandin were not allowed. Echinocandin use preceding mold-active PAP was allowed, however prior use of an amphotericin B product was not. bIFI were defined according to ECMM criteria (Cornely et al, 2019). Results: We identified 232 pts with AML/MDS (n=186), ALL (n=43), and biphenotypic leukemia (n=3). Among the AML/MDS pts, 31% (n=57) received a lower-intensity VEN-containing regimen, while 69% (n=129) received a high-intensity regimen with or without VEN. Nearly all pts with ALL and biphenotypic leukemia received high-intensity RIC with HyperCVAD or a HiDAC containing regimen. Of the 232 pts, PCZ (n=111), VCZ (n=84), or ISA (n=37) were used as PAP, respectively (Table 1). Most pts (n=157; 68%) received an echinocandin for a median of 6 days (range, 0-38), prior to transitioning to a mold-active triazole. Ten (4.3%) pts had a bIFI (6 proven, 1 probable, 3 possible) during induction therapy while receiving PAP (Table 2) including 9 (4.8%) pts with AML/MDS and 1 (2.3%) patient with ALL. An equal number of pts with bIFI were receiving lower-intensity, VEN-based therapy, or high-intensity therapy. Among the 84 pts receiving VCZ, 4 (4.8%) had a bIFI (4 proven); 3 pts (2.7%) receiving PCZ had a bIFI (2 proven, 1 possible); 3 pts (8.1%) receiving ISA had a bIFI (1 probable, 2 possible). C. glabrata (n=3), and C. krusei, Cryptococcus spp. and Fusarium spp. (one each) accounted for the 6 proven bIFIs. One patient had both C. glabrata and C. krusei fungemia. The probable bIFI was pneumonia with a positive Aspergillus GM from BAL. The 3 possible bIFI were pneumonia (n=2) and sinusitis (n=1). Eight pts (80%) were neutropenic (ANC < 500 cells/mm3) for >14 days at the time of bIFI, 1 pt was neutropenic for >7 days, and 1 pt had ANC > 500 cells/mm3. Seven pts with bIFI received a prior echinocandin for a median of 3 days (range, 0-15) prior to initiation of triazole PAP. Seven pts were neutropenic for < 7 days (n=2), 7-14 days (n=3), or > 14 days (n=2) at the time of azole initiation. bIFI occurred after a median of 20 days (range, 5-72) of azole PAP and a median of 24 days (range, 12-71) from the initiation of RIC. One patient with bIFI deceased within 42 days of starting RIC and did not achieve a response after RIC (bIFI-related mortality: 0.44%). Conclusion: The incidence (<5%) and mortality (< 0.5%) due to bIFI in a contemporary cohort of pts with newly diagnosed acute leukemia receiving PAP is low. bIFI occurred late in induction therapy and most often in pts with > 14 days of neutropenia. Prophylaxis with VCZ, PCZ, or ISA, with or without a prior echinocandin, appear to be comparable options for PAP in pts with newly diagnosed AML or ALL undergoing RIC. Disclosures Bose: CTI BioPharma: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Celgene Corporation: Honoraria, Research Funding; Constellation Pharmaceuticals: Research Funding; Kartos Therapeutics: Honoraria, Research Funding; Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Promedior, Inc.: Research Funding; Pfizer, Inc.: Research Funding; NS Pharma: Research Funding; Blueprint Medicines Corporation: Honoraria, Research Funding. Kontoyiannis:Gilead Sciences: Honoraria; United Medical: Honoraria; Astellas Pharma: Consultancy; Cidara Therapeutics: Consultancy; Amplyx Pharmaceuticals: Consultancy; Mayne Pharma: Consultancy; Pharma Pharmaceutical Industries: Consultancy; Merck & Co.: Consultancy, Honoraria. OffLabel Disclosure: Voriconazole and isavuconazole are approved for the treatment of invasive fungal infections rather than the prevention, as discussed in this abstract.

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Ray, Justin J., Jennifer Koay, Paul D. Dayton, Daniel J. Hatch, Bret Smith und Robert D. Santrock. „Multicenter Early Radiographic Outcomes of Triplanar Tarsometatarsal Arthrodesis With Early Weightbearing“. Foot & Ankle International 40, Nr. 8 (05.05.2019): 955–60. http://dx.doi.org/10.1177/1071100719847700.

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Background:Hallux valgus is a multiplanar deformity of the first ray. Traditional correction methods prioritize the transverse plane, a potential factor resulting in high recurrence rates. Triplanar first tarsometatarsal (TMT) arthrodesis uses a multiplanar approach to correct hallux valgus in all 3 anatomical planes at the apex of the deformity. The purpose of this study was to investigate early radiographic outcomes and complications of triplanar first TMT arthrodesis with early weightbearing.Methods:Radiographs and charts were retrospectively reviewed for 57 patients (62 feet) aged 39.7 ± 18.9 years undergoing triplanar first TMT arthrodesis at 4 institutions between 2015 and 2017. Patients were allowed early full weightbearing in a boot walker. Postoperative radiographs were compared with preoperative radiographs for hallux valgus angle (HVA), intermetatarsal angle (IMA), tibial sesamoid position (TSP), and lateral round sign. Any complications were recorded.Results:Radiographic results demonstrated significant improvements in IMA (13.6 ± 2.7 degrees to 6.6 ± 1.9 degrees), HVA (24.2 ± 9.3 degrees to 9.7 ± 5.1 degrees), and TSP (5.0 ± 1.3 to 1.9 ± 0.9) from preoperative to final follow-up ( P < .001). Lateral round sign was present in 2 of 62 feet (3.2%) at final follow-up compared with 52 of 62 feet (83.9%) preoperatively. At final follow-up, recurrence was 3.2% (2/62 feet), and the symptomatic nonunion rate was 1.6% (1/62 feet). Two patients required hardware removal, and 2 patients required additional Akin osteotomy.Conclusion:Early radiographic outcomes of triplanar first TMT arthrodesis with early weightbearing were promising with low recurrence rates and maintenance of correction.Level of Evidence:Level IV, retrospective case series.

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Farrell, D. J., G. Daggard und T. K. S. Mukkur. „Nested Duplex PCR To Detect Bordetella pertussis and Bordetella parapertussis and Its Application in Diagnosis of Pertussis in Nonmetropolitan Southeast Queensland, Australia“. Journal of Clinical Microbiology 37, Nr. 3 (1999): 606–10. http://dx.doi.org/10.1128/jcm.37.3.606-610.1999.

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A duplex PCR to detect Bordetella pertussis andBordetella parapertussis was developed with the insertion sequences IS481 (B. pertussis) and IS1001 (B. parapertussis) and evaluated with specimens from 520 consecutive patients presenting with possible pertussis. No culture-positive–PCR-negative results occurred, giving the method a sensitivity of 100%. For B. pertussis, 58 of 520 patients (11.2%) were positive by PCR compared to 17 of 520 patients positive (3.3%) by culture. For B. parapertussis, 7 of 520 patients (1.3%) were positive by PCR compared to 2 of 520 patients positive (0.4%) by culture. Two patients were positive for both B. pertussis and B. parapertussis. Patient records were reviewed to determine the validity of PCR-positive–culture-negative results. Forty-two of 49 patients who could be evaluated fulfilled the criteria for a case definition of pertussis, with 32 patients being <1 year of age and having classical pertussis symptoms. The seven patients who did not fulfil the criteria were aged 7 to 55 years and had a persistent cough for >2 weeks. The method was also used to investigate a classroom outbreak in whichB. pertussis culture was positive for 5 of 28 patients. All five culture-positive specimens were confirmed by PCR, and an additional eight were positive by PCR. Of 25 patients from a suspected pertussis outbreak in a girls’ dormitory, seven of seven specimens were negative for B. pertussis, although 13 of 25 patients were positive for B. pertussis immunoglobulin M (IgM) (2 of which produced equivocal IgA results, with 23 of 25 patients being negative). Five symptomatic patients were subsequently found to be positive (by IgM and particle agglutination assays) forMycoplasma pneumoniae, demonstrating the value of PCR in rapidly excluding B. pertussis infection in an outbreak situation. Twenty-two of 71 (30.1%) throat swabs were positive by PCR compared to 2 of 71 (2.8%) throat swabs positive by culture, indicating that a reassessment of the use of throat swabs should be considered, particularly for older patients, in contact tracing, and in situations in which specimen collection is difficult.

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Rosiñol, L., S. Montoto, J. Bladé, M. T. Cibeira, M. Rozman, E. Nadal, E. Giné, M. Aymerich, J. Esteve und E. Montserrat. „Monoclonal Gammopathy of Undertermined Significance (MGUS): Clinical Predictors of Malignant Transformation in 434 Patients with a Long Follow-Up from a Single Institution.“ Blood 104, Nr. 11 (16.11.2004): 4838. http://dx.doi.org/10.1182/blood.v104.11.4838.4838.

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Abstract Background: MGUS is a common disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenström’s macroglobulinemia (WM) or primary amyloidosis (AL). Although about one fourth of these individuals will evolve into a malignant disease with a transformation rate of 1% per year, there are not well-established predictors of outcome. Aim: To identify predictor features of malignant transformation in a large series of patients with MGUS and prolonged follow-up. Patients and methods: Four hundred and thirty-four patients (200 M/234 F; median age 66 years) diagnosed with MGUS in a single institution from September 1970 to January 2001 with a minimum follow-up of one year were included in the study. All patients had an M-protein size < 30g/L. Bone marrow aspirates were reviewed independently by two of the authors and the proportion of bone marrow plasma cells (BMPC) were estimated from a 500 cell-count by each observer. The median follow-up was 5.2 years (range: 1–28.8 years) with 84 patients followed for more than 10 years. Results: The type of M-protein was IgG in 67.2% of the cases, IgA in 18.8%, IgM in 11.9%, light chain in 1% and biclonal in 1%. The light chain was kappa type in 56.4% of the patients. The median M-protein size was 15.6 g/L (<10 g/L in 10.8%, 10–20 g/L in 61.7%, and > 20g/L in 27.4%). The median percentage of BMPC in 305 reviewed samples was 4.6% (range: 0.4–25). After a median follow-up of 5.2 years, 50 patients (11.5%) have evolved into a malignant monoclonal gammopathy (44 MM, 5 WM and 1 AL). The median time to progression was 5.4 yrs (range: 1.4 – 16.9). The risk of transformation was 15.4% (95% CI: 10.5–20.3) and 34% (95% CI 22.6–45.3) and 34% (95% CI: 22.6–45.3) at 10 and 20 years, respectively. The variables associated with a higher risk of transformation were IgA-type (p=0.003), kappa light chain (p=0.009), the amount of M-protein (<15 vs >15 g/L, p=0.005) and the percentage of BMPC (<5% vs >5%, p=0.007). Conclusions: In this series of patients with MGUS, the type (i.e. IgA or kappa) and size of M-protein (>15g/L) as well as the percentage of bone marrow plasma cells (>5%) significantly predicted malignance transformation.

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Wu, Daniel Yiang, und Eddy Kwok Fai Lam. „The metatarsaus adductus effect by the syndesmosis procedure for hallux valgus correction“. Bone & Joint Open 2, Nr. 3 (01.03.2021): 174–80. http://dx.doi.org/10.1302/2633-1462.23.bjo-2020-0195.r1.

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Aims The purpose of this study is to examine the adductus impact on the second metatarsal by the nonosteotomy nonarthrodesis syndesmosis procedure for the hallux valgus deformity correction, and how it would affect the mechanical function of the forefoot in walking. For correcting the metatarsus primus varus deformity of hallux valgus feet, the syndesmosis procedure binds first metatarsal to the second metatarsal with intermetatarsal cerclage sutures. Methods We reviewed clinical records of a single surgical practice from its entire 2014 calendar year. In total, 71 patients (121 surgical feet) qualified for the study with a mean follow-up of 20.3 months (SD 6.2). We measured their metatarsus adductus angle with the Sgarlato’s method (SMAA), and the intermetatarsal angle (IMA) and metatarsophalangeal angle (MPA) with Hardy’s mid axial method. We also assessed their American Orthopaedic Foot & Ankle Society (AOFAS) clinical scale score, and photographic and pedobarographic images for clinical function results. Results SMAA increased from preoperative 15.9° (SD 4.9°) to 17.2° (5.0°) (p < 0.001). IMA and MPA corrected from 14.6° (SD 3.3°) and 31.9° (SD 8.0°) to 7.2° (SD 2.2°) and 18.8° (SD 6.4°) (p < 0.001), respectively. AOFAS score improved from 66.8 (SD 12.0) to 96.1 (SD 8.0) points (p < 0.001). Overall, 98% (119/121) of feet with preoperative plantar calluses had them disappeared or noticeably subsided, and 93% (113/121) of feet demonstrated pedobarographic medialization of forefoot force in walking. We reported all complications. Conclusion This study, for the first time, reported the previously unknown metatarsus adductus side-effect of the syndesmosis procedure. However, it did not compromise function restoration of the forefoot by evidence of our patients' plantar callus and pedobarographic findings. Level of Clinical Evidence: III Cite this article: Bone Jt Open 2021;2(3):174–180.

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Ruacho, Guillermo, Marika Kvarnström, Agneta Zickert, Vilija Oke, Johan Rönnelid, Susanna Eketjäll, Kerstin Elvin, Iva Gunnarsson und Elisabet Svenungsson. „Sjögren Syndrome in Systemic Lupus Erythematosus: A Subset Characterized by a Systemic Inflammatory State“. Journal of Rheumatology 47, Nr. 6 (15.09.2019): 865–75. http://dx.doi.org/10.3899/jrheum.190250.

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Objective.An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls.Methods.We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively.Results.SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ–induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons).Conclusion.The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset.

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Dixon, Michael K., Jose Cadena und Elizabeth Walter. „1428. Comparing Outcomes of Diabetic Foot Infections Requiring Amputation, Negative vs. Positive Margins“. Open Forum Infectious Diseases 6, Supplement_2 (Oktober 2019): S521. http://dx.doi.org/10.1093/ofid/ofz360.1292.

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Abstract Background This was a retrospective, observational cohort study of patients with diabetes and lower extremity osteomyelitis requiring amputation. Patients were categorized as having negative margins (without residual osteomyelitis or with joint disarticulation), or positive margins (with residual osteomyelitis). Health outcomes were compared between groups. The primary outcomes were relapse of infection at one year and reintervention at one year. Secondary outcomes include mortality at 30 days, 90 days, and 1 year; treatment failure at one year; and a composite of relapse of infection at one year, reintervention at 1 year, and death at 1 year. Methods CPRS ICD-10 codes were reviewed from patients at Audie L. Murphy VA with amputation for osteomyelitis between July 2, 2015 and July 13, 2017. Pathology reports were reviewed for the presence or absence of residual osteomyelitis, and outcomes were determined by chart review. Patient characteristics were recorded, such as age, serum albumin, presence of diabetes, hemoglobin A1c, organism on culture, peripheral vascular disease, and occurrence of a peripheral vascular intervention. Results The ALMVA is a 500-bed medical center with an active BMT program. Clinical data from 146 patients were obtained and analyzed. There were no significant differences in primary or secondary outcomes relative to patients with positive margins or negative margins. A lack of consistency in margin reporting by Pathology was seen. Albumin level and number of patients with residual osteomyelitis were significantly different between the two groups (table). Conclusion There were no significant differences in outcomes between amputations with positive margins and those with negative margins. Based on current IDSA guidelines, treatment varies significantly for patients with positive or negative margins, with the former requiring 6 weeks of parenteral antibiotic therapy. Extended courses of parenteral antibiotics increase risk for treatment-associated morbidity, and more evidence is needed to support these recommended durations. A quality improvement project is underway with the ID, Podiatry and Pathology departments to resolve issues related to obtaining and processing surgical samples, as well as interpreting and reporting margin results. Disclosures All authors: No reported disclosures.

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Colby, Geoffrey P., Li-Mei Lin, Risheng Xu, Narlin Beaty, Matthew T. Bender, Bowen Jiang, Judy Huang, Rafael J. Tamargo und Alexander L. Coon. „Utilization of a Novel, Multi-Durometer Intracranial Distal Access Catheter: Nuances and Experience in 110 Consecutive Cases of Aneurysm Flow Diversion“. Interventional Neurology 6, Nr. 1-2 (2017): 90–104. http://dx.doi.org/10.1159/000456086.

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Background: Coaxial catheter support systems provide a safe and stable foundation in endovascular treatment of intracranial aneurysms. Increasingly, robust distal intracranial support is sought during complex neurointerventions. The AXS Catalyst 5 distal access catheter (Cat5) is a new intracranial catheter designed for improved trackability and stability. We report the first experience using Cat5 for aneurysm treatment by flow diversion. Methods: A single-center aneurysm database was reviewed for cases of aneurysm treatment with the Pipeline embolization device (PED) that utilized Cat5. Data were collected for patient demographics, aneurysm characteristics, procedural details, catheter positions, vessel tortuosity, and catheter related complications. Results: One hundred and ten cases of aneurysm flow diversion were successfully performed using Cat5. Patient age ranged from 21 to 86 years (mean 57 ± 12.5 years) with 84% women. Aneurysm size ranged from 2 to 28 mm (mean 5.7 ± 5.0 mm), with 97% in the anterior circulation. Twenty-four aneurysms (22%) were located beyond the ICA termination. Significant cervical carotid tortuosity was present in 26% of cases, and moderate to severe cavernous tortuosity (cavernous grade ≥2) in 45% of cases. Cat5 was tracked to the intended distal position in all cases with 100% technical success of PED implantation. No iatrogenic catheter-related vessel injury occurred, and major neurological morbidity occurred in 1 patient (1%). Summary: The Cat5 is a novel, multi-durometer cranial distal access catheter designed for use in tri-axial systems. We have demonstrated the utility of Cat5 in 110 successful cases of flow diversion with a wide range of complexity. This catheter is a new tool in the neurointerventionalist's armamentarium to achieve robust and atraumatic distal access.

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Stupp, R., R. Goldbrunner, B. Neyns, U. Schlegel, P. Clement, G. G. Grabenbauer, M. E. Hegi, J. Nippgen, M. Picard und M. Weller. „Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients (pts) with newly diagnosed glioblastoma (GBM)“. Journal of Clinical Oncology 25, Nr. 18_suppl (20.06.2007): 2000. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.2000.

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2000 Background: To evaluate safety, toxicity, and efficacy of the combination of the cyclic RGD pentapeptide cilengitide (EMD121974), an inhibitor of integrins avβ3 and avβ5, in addition to standard temozolomide (TMZ) and radiotherapy (RT). Methods: 52 pts (PS 0–1: 92%, 2: 8%; median age 57 yrs) after tumor resection (n=43/83%) or biopsy (n= 9/17%) were treated with standard TMZ/RT (Stupp et al. NEJM 2005). In addition cilengitide (500 mg i.v., 2x/week) was started one week before TMZ/RT and given throughout for the duration of chemotherapy or until progression. The primary endpoint was progression free survival rate at 6 months (target: 65%). Pts were followed with MRI every 2 months. Histopathologic diagnosis and MRI imaging were independently reviewed, O6-Methylguanine- DNA methyltransferase (MGMT) promotor methylation status was assessed in 45 (86.5%) pts. Results: 46 pts (92%) completed RT, = 90% of concomitant TMZ was received by 42 pts and cilengitide by 45 pts. 20 pts (3 ongoing) completed 6 cycles of maintenance TMZ and cilengitide. Observed hematological grade 3 and 4 toxicities were: lymphopenia (28/52, 53.8%), thrombocytopenia (7/52 pt. 13.4%) and neutropenia (5/52, 9.6%). Treatment related non-hematologic grade 3/4 toxicities were reported for n=3/52 (5.7%) patients: constitutional symptoms (asthenia, fatigue, anorexia, n=3); elevated liver function tests (n=1), deep venous thrombosis and pulmonary embolism (n=1). One patient with a history of sigmoid diverticulosis experienced sigmoid perforation (grade 2). In total, 34/52 (65.4% [95% CI, 50.9–78.0%]) of the pts were progression free at 6 months. Pts with MGMT gene-promotor methylation in the tumor were more likely to reach 6 months PFS endpoint. Conclusions: The study reached its primary endpoint. The combination of the integrin inhibitor RGD peptide Cilengitide and TMZ/RT was well tolerated, PFS at 6 months is encouraging. MGMT gene promoter methylation correlates with outcome. At the time of ASCO, updated results and survival estimates after a minimum follow-up of at least 1 year will be available. [Table: see text]

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Singh, Piksi, Lee Tripcony und James Nicklin. „Analysis of Prognostic Variables, Development of Predictive Models, and Stratification of Risk Groups in Surgically Treated FIGO Early-Stage (IA–IIA) Carcinoma Cervix“. International Journal of Gynecologic Cancer 22, Nr. 1 (Januar 2012): 115–22. http://dx.doi.org/10.1097/igc.0b013e31822fa8bb.

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ObjectivesThe objectives of the study were to evaluate clinicopathologic prognostic variables in surgically treated International Federation of Obstetrics and Gynecology early-stage (IA–IIA) cervical cancer, develop prognostic models, and note the role of adjuvant treatment, patterns of failure, and salvage survival (SS) in each group.MethodsRecords of 542 patients who received primary surgical treatment for International Federation of Obstetrics and Gynecology (IA–IIA) cervical cancer were reviewed. Ninety-eight patients who relapsed after primary treatment were identified and matched for stage and age with a control group. Clinicopathologic prognostic variables were identified and used to develop a prognostic model with 3 risk groups for overall survival (OS) and relapse-free survival (RFS). The roles of adjuvant treatment, relapse sites, and SS were also noted in the groups.ResultsThe 5-year OS was 70% for the whole group, 97% in the control group, and 44% in the relapse group. There was a statistically significant decrease in survival in patients 70 years or older, those with positive lymphovascular space invasion (LVSI), and in patients with positive LVSI and increasing depth of invasion in both univariate and multivariate analyses (P < 0.001). Positive lymph node status and tumor size of 31 mm or greater showed only a trend toward lower OS and RFS, respectively, in multivariate analysis. An additive model using regression coefficients from multivariate Cox model stratified patients into low-, medium-, and high-risk groups. Relapse-free survival and OS were significantly different in all 3 groups (P < 0.001). Salvage survival was better in low-risk group relative to medium- and high-risk groups, (P = 0.05) as well as between the medium- and high-risk groups (P = 0.03). More distant and locoregional relapses were noted in the medium- and high-risk groups, and SS was better with a local versus locoregional or distant recurrence (P < 0.001).ConclusionsIn this study, age 70 years or older and positive LVSI were found to be statistically significant prognostic factors for both OS and RFS. Positive lymph nodes status showed only a trend toward lower OS. Positive LVSI status had significant adverse prognostic effects on RFS and OS in tumors with increasing depth of invasion. Additive prognostic model helps identify predictors and stratify patients into low-, medium-, and high-risk groups for survival. Many of these factors can be identified preoperatively and may assist in decision to offer primary surgery or alternative therapies in patients with potentially operable cervix cancer. Prognostic model can be used as a tool to design clinical trials and select the group of patients who are the appropriate target for a trial.

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Boyanov, M., D. Bakalov, V. Karamfilova, A. Gateva, Y. Assyov, E. Zaharieva, K. Atanassova, G. Sheinkova, A. Tsakova und Z. Kamenov. „Primary Hyperparathyroidism – A Contemporary Picture Based on 100 Patients from the Last Decade“. Acta Medica Bulgarica 48, Nr. 2 (01.07.2021): 5–12. http://dx.doi.org/10.2478/amb-2021-0016.

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Abstract Primary hyperparathyroidism (PHPT) is an endocrine disease, the clinical picture of which has slowly shifted to milder and asymptomatic forms during the last decades. Objective to describe the clinical presentation and the main laboratory and imaging findings in a group of patients with PHPT diagnosed during the last 10 years. Materials and Methods This was a retrospective cross-sectional study with data review from the database of a tertiary endocrine clinic from the last 10 years. Secondary causes for elevated PTH were excluded. The major clinical symptoms and signs of hypercalcemia/HPT were reviewed as well as concomitant diseases and medications. Serum calcium (total, albumin-corrected and ionized; sCa, corrCa, iCa+), phosphates (P), magnesium, creatinine, alkaline phosphatase, beta-crosslinks were measured. The intact parathyroid hormone (iPTH) and 25(OH)-vitamin D were determined by electro-hemi-luminescence (Elecsys, Roche Diagnostics). 24-hour urinary probes for calcium and phosphate were collected. Neck ultrasound (US) was used as the localization study of choice. Almost half of the participants underwent fine-needle aspiration biopsy (FNAB) with cytology and needle-washouts for iPTH. One fourth of the patients were assessed by Single-Photon Emission Tomography (SPECT-CT). Data on bone density (from DXA), fractures and renal stones (from renal US) were collected. Results One hundred patients met the study criteria – 95 were women. Most of them were in their 5th and 6th decades. The median corrected sCa was 2.73 mmol/l, iCa+ – 1.39 mmol/l, P – 0.88 mmol/l, iPTH – 14.5 pmol/l and 25(OH)D – 54.0 nmol/l. Normal sCa was registered in 20 participants (20%), while normal sP – in 67.0%. The neck US located single lesions (parathyroid adenoma) in 81% – behind or below the left inferior pole of the thyroid gland in 33 cases (33%) and contra-laterally in another 33%. FNAB of the suspicious lesion had been performed in 51% of the study subjects. The cytology confirmed the presence of parathyroid cells in 22 cases (43.1%), Bethesda II thyroid nodules in 21 cases (41.2%), Bethesda III nodules in 2 cases (3.9%) and insufficient samples (Bethesda I) in 5 cases (9.8%). SPECT-CT from 27 patients identified a suspicious left parathyroid in 11 cases, a right one – in 6 cases, as well as three ectopic locations. BMD data were available in 66 female patients and showed a higher prevalence of osteoporosis than in the general age-matched population; fractures, however, were not more frequent. Data from renal ultrasound were available in 77% and revealed chronic pyelonephritis without stones in 8 patients and renal stone disease – in 37 patients. Conclusion To our knowledge, this study is the first of its kind in our country during the last two decades. Mild to moderate hypercalcemia was very common, although most patients were oligoor asymptomatic. Renal and bone involvement were surprisingly frequent, with reduced eGFR and low bone mass being more prevalent than in the general population. The most typical location was a single parathyroid lesion within the lower glands. The use of SPECT-CT seems to decline and is replaced by US-guided FNAB with needle washout measurements of iPTH and cytological examination. Although the general picture of PHPT is shifting towards milder and asymptomatic (and probably earlier) forms of the disease, the classical clinical presentation can still be found in everyday practice.

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García, Consuelo González, Ma Sol Durán, Jose Ramón Mayans, Javier De La Rubia, Alfons Soler, Inmaculada Castillo, Paz Ribas et al. „Epidemiological Study of Mutiple Myeloma In Spain: Efectiveness and Survival Analysis“. Blood 116, Nr. 21 (19.11.2010): 5044. http://dx.doi.org/10.1182/blood.v116.21.5044.5044.

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Abstract Abstract 5044 Introduction: Epidemiological studies are the base to evaluate the efficiency of medical interventions in the interest of the public health. Updated epidemiological data and effectivenes in the daily clinical practice are needed in Multiple Myeloma (MM). Materials and Methods: Epidemiological retrospective, longitudinal, multicenter nation wide Spanish study of an historical cohort of patients with MM. Data from patients aged ≥ 18 years, with a MM Stage II or III, who received a treatment on a daily clinical practice (not in clinical trials) for MM in the September'03-August'05 time frame were collected. The study protocol was approved by an Ethics Committee in 2009. Data were collected in 37 Spanish Centres during a 6 months period. Stratified effectiveness and survival analysis were performed (age <65, ≥65; gender; ECOG 0–1 vs 2–3; stage; heavy chain IgA vs IgG; light chain kappa vs lambda, bone lesions or not, plasmacytoma or not, Hb level <10 vs ≥ 10 gr/dL, LDH <130 vs ≥130 U/L, beta2 microglobuline <3.5 vs >3.5, calcium <11 vs ≥ 11 mg/dL, creatinine <1.5 vs ≥ 1.5 mg/dL, plasma cells <10 vs >10%, myelomatous cells <10 vs >10%, induction treatment, dose delayed, full dose). Results: Data from 338 patients' files who fulfill all the study selection criteria were reviewed. Median age at diagnosed was 66 years. A 45% were aged less than 65 years, 34% 65–74 years and 21% ≥ 75. Male/female ratio: 50/50. ECOG performance status were available in 314 patients (93%) in whom the score was 0/1/2/3/4 in a proportion (%) of 25/25/25/20/5 respectively. Secretor MM was present in 95% of the patients. Bone lesions were present in 244 patients (73%). Plasmacytoma was evidenced in 51 (15%). Half of the patients were transplant candidates and it was performed in 128 (38%). Overall response rate were statistically different when using VBAD/VBMCP vs VAD and MP as induction regimens (86% vs 62% vs 50%, p=0,002). It must be noted that most novel treatments were not widely used by the time of the study. Median survival was 56.1 months. Survival rate at 3 years was 60.8%. Variables statistical significant at the discriminant analysis are showed at table 1. A stepwise Cox Model determine Hb level <10 g/dL, LDH <500 and transplant are prognostic factors for survival (table 2). Toxicity was manageable and no differences with those data already published were reported. Conclusion: These epidemiological data suggest the effectivemens of the treatment depends on its individualization based on patients' characteristics and in treatment adherence. LDH is a survival prognostic parameter in MM. No new safety issues appears, despite those already published. Disclosures: De La Rubia: Celgene: Research Funding. Castillo:Celgene: Research Funding. López:Celgene: Employment. Ramirez:Celgene: Research Funding.

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Fernández de Larrea, Carlos, Ignacio Isola, María Teresa Cibeira, Laura Rosiñol, Xavier Calvo, Natalia Tovar, Montserrat Elena et al. „Smoldering Multiple Myeloma: Impact of the Evolving Pattern on Early Progression“. Blood 124, Nr. 21 (06.12.2014): 3363. http://dx.doi.org/10.1182/blood.v124.21.3363.3363.

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Abstract Introduction: Smoldering multiple myeloma (SMM) is a plasma cell dyscrasia defined by the presence of a monoclonal protein (MP) (≥ 30 g/L in serum or >1g/24-hours in urine) and/or plasma cell bone marrow involvement (BMPC) ≥ 10%, in the absence of symptoms due to the gammopathy. The risk of progression to symptomatic disease in patients with SMM is highly variable. Several biomarkers and prognostic index associated with risk of early progression based on tumoral load (M-protein size and percentage of BMPC), M-protein behaviour (evolving vs. non-evolving) and/or immunological status (heavy chain isotype, isotype suppression of uninvolved immunoglobulins and serum free light-chain (FLC) κ/λ ratio) have been recently identified. The identification of patients at risk for early progression is crucial when considering the current possibility of prompt therapeutic intervention. The aim of this study was to analyze the factors associated with early progression to multiple myeloma (MM) in patients diagnosed with SMM and long follow-up in a single institution. Methods: Medical records of the 207 patients (76M/131M; median age 65 years, range 33 to 92) diagnosed with SMM (International Myeloma Working Group criteria, 2003) at our institution between January 1973 and December 2012 were systematically reviewed. Progressive increase in the value of MP was defined as "evolving" when at least 10% increase was observed within the first 6 months from diagnosis when MP was ≥ 30 g/L (Rosiñol et al, Br J Haematol. 2003) or progressive increase in MP in each of the annual consecutive measurements during a period of 3 years in patients with an initial MP < 30 g/L (Rosiñol et al, Mayo Clin Proc. 2007). Immunoparesis was defined as any value below normal in not involved immunoglobulins. Bone marrow aspirates obtained at diagnosis were reviewed independently by 2 observers. Plasma cell percentages were estimated from a 500-cell count by each examiner and the mean values were considered. Results: Sixty-seven patients (33%) accomplished both SMM criteria (MC and BMPCs), while the remaining 140 patients only had one of them. With a follow up of 1,692 years-person, 105 patients had progressed (50.7%) to MM and one case to AL amyloidosis (0.5%). The estimated probability of progression at 2 and 5 years was 19.9% and 44.9% respectively, with a median time to progression (TTP) of 7.3 years (95% CI 3.9 to 10.6). At the time of progression, clinical manifestations were mainly anemia (52%) and skeletal lytic lesions (40%). The presence of renal insufficiency, extramedullary plasmacytomas or hypercalcemia was only identified in 12 patients (5.8%). The median survival after progression was 5 years (95% CI 3.8 to 6.2). Evolving type was recognized in 25% of the patients, and was associated with a probability of progression of 45% and 78.1% at 2 and 5 years and was higher than those with stable MP (HR 4.5; 95% CI 3 to 6.9; p<0.001) (Figure 1). Evolving pattern was more frequently associated with IgA isotype (41.2% vs. 23.8%; p=0.02). Negative impact in median TTP of evolving type was significant in patients either with both diagnostic criteria (MP and BMPCs; 1.3 vs. 6.3 years, p<0.001) and in those with only one of them (3.7 vs. not reached; p<0.001). At the univariate analysis the MP size (< vs. ≥ 30 g/L, median 13.4 vs. 3.1 years, p<0.001), the proportion of BMPCs (< vs. ≥ 20%, 17.2 vs. 2.9 years, p<0.001), the presence or absence of immunoparesis (3.9 vs. 16.9 years, p=0.001) and the evolving pattern (19.4 vs. 3 years, p<0.001) were significantly associated with a higher risk of progression. At the multivariate analysis only the evolving type (HR 4.9, 95% CI 2.8 to 8.7, p<0.001), the proportion of BMPCs (HR 2.5, 95% CI 1.3 to 4.6, p=0.004) and the presence of immunoparesis (HR 1.9, 95% CI 1.03-3.6, p=0.042) retained their statistical significance. Considering these last three variables, a model of risk stratification (Figure 2) was built, ranging from a probability of progression at 2 years of 81.8% for patients with the 3 factors present to only 4% for patients in group 4 (no risk factors). Conclusion: In this series of patients with SMM with long follow up, evolving pattern, proportion of BMPCs and the presence of immunoparesis can accurately predict accurately the risk of early progression to symptomatic disease. Evolving type should be routinely monitored during the follow up of patients with SMM, since it is the most significant predictor for early progression. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Magnano, Laura, Ivan Dlouhy, Olga Balagué, Alfredo Rivas-Delgado, Jordina Rovira, Kennosuke Karube, Blanca Gonzalez et al. „Clinical Impact of the Presence of a Diffuse Large B-Cell Lymphoma (DLBCL) Component in the Outcome of Untreated Patients with Follicular Lymphoma (FL)“. Blood 128, Nr. 22 (02.12.2016): 3043. http://dx.doi.org/10.1182/blood.v128.22.3043.3043.

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Abstract Introduction: Histological transformation into an aggressive lymphoma, usually DLBCL, may occur during the follow-up of FL patients and determines a poor outcome. The presence of a DLBCL component in a FL (FL/DLBCL) is observed in some cases at diagnosis, usually being considered a transformation of a FL with a previously undetected indolent course. The clinical implications of this situation in terms of prognosis and treatment remain unclear. The aim of the present study was to analyze the clinicobiological characteristics and outcome of patients diagnosed with FL/DLBCL in the rituximab era, in comparison with patients diagnosed with pure FL or de novo DLBCL at the same period in a single institution. Patients and Methods: Eight hundred seventy eight patients sequentially diagnosed with either FL, DLBCL or FL/DLBCL between 2002 and 2015 ina single institution were included in the study. The histological distribution was as follows: FL grade 1, 2, 3a, 320 cases (140M/180F; median age, 58 years), FL 3b, 8 cases (4M/4F; median age, 66 years), DLBCL, 510 cases (275M/235F; median age, 65 years) and FL/DLBCL, 40 (16M/24F; median age, 65 years).According to institutional guidelines, the latter were treated as aggressive lymphomas, with no maintenance or further intensification. All FL/DLBCL biopsies were reviewed and the DLBCL component semiquantified. Cell of origin (COO) assessment by gene expression-based assay was determined in 127 cases and NOTCH1-2 mutational status in 216. Results: Main clinicobiological characteristics of the patients according to the histology are listed in the table. Compared to DLBCL cases, FL/DLBCL patients showed more frequently ambulatory performance status, primary nodal origin and advanced stage, with these features being closer to those of FL patients. On the contrary, FL/DLBCL patients had an intermediate position between FL and DLBCL cases regarding B-symptoms, bone marrow infiltration, hemoglobin and serum LDH levels. The proportion of DLBCL component in FL/DLBCL cases ranged from 5 to 95%, with no significant differences in the initial characteristics according to the proportion of DLBCL component. COO was determined in 11 FL/DLBCL, with 8 (73%) being GCB, 2 (18%) ABC, and 1 unclassified. Such distribution in 116 DLBCL with COO available was: 50 (43%) GCB, 50 (43%) ABC and 16 unclassified. NOTCH 1-2 was mutated in 4/39 (10%) FL/DLBCL, whereas this proportion was 1/41 (2%) FL and 11/136 (8%) DLBCL. All FL/DLBCL patients were treated as aggressive lymphoma with no intensification after front-line therapy. The proportion of primary refractoriness in FL/DLBCL patients was significantly higher than in FL and similar to that of DLBCL. Progression free survival (PFS) and overall survival (OS) are showed in the table and figure. Among the 40 FL/DLBCL cases, the amount of DLBCL component did not show prognostic impact, whereas the histological grade did (5-year OS FL grades 1-2-3a/DLBCL, 92% vs. FL grade 3b/DLBCL, 38%; p=0.001). In the different cohorts analyzed (FL+FL/DLBCL, FL+FL/DLBCL+DLBCL, and FL/DLBCL+DLBCL), FL/DLBCL histology did not show independent value for OS in multivariate analyses that included standard prognostic variables, namely, serum β2m and FLIPI or IPI scores. Sequential biopsies were available in 120 cases, with the following distribution according to the primary diagnosis: FL, 60 cases (at relapse: 37 FL and 23 DLBCL), FL/DLBCL, 6 cases (at relapse: 3 FL, 2 FL/DLBCL and 1 DLBCL), and DLBCL, 54 cases (at relapse: 4 FL and 50 DLBCL). Conclusion: Patients with FL/DLBCL, although infrequent, exists and have clinicobiological differentiated features compared to pure FL and DLBCL. When treated with standard immunochemotherapy their outcome is not worse than that of de novo DLBCL. Some clinicobiological characteristics suggest FL/DLBCL to be a specific category rather than a transformation from a FL; however, this warrants further biological studies. Disclosures No relevant conflicts of interest to declare.

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Enninful-Eghan, Henrietta, Renee H. Moore, Rebecca Ichord und Janet L. Kwiatkowski. „Transcranial Doppler Screening Program Is Effective in Preventing Stroke in Children with Sickle Cell Disease“. Blood 112, Nr. 11 (16.11.2008): 714. http://dx.doi.org/10.1182/blood.v112.11.714.714.

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Abstract In the Cooperative Study of Sickle Cell Disease the incidence of stroke in SCD-SS was estimated to be 0.61 per 100 patient-years. Since that study, the use of transcranial Doppler ultrasonography (TCD) has become routine to detect children at high risk of stroke and regular transfusions have been shown to reduce the risk of stroke by over 95% in those with abnormal TCD studies. The impact of TCD screening on the overall incidence of stroke in children with SCD has not been studied extensively. We sought to determine the impact of our TCD screening and treatment protocol on the incidence of first stroke in a cohort of children followed at our Sickle Cell Center. Routine TCD screening was instituted at our Center in Oct, 1998. Our protocol includes annual TCD studies for children with normal TCD results (<170 cm/s), repeat study every 3 to 6 months in those with conditional results (170–199 cm/s), and within 1–4 weeks for children with abnormal results (≥200 cm/s). Chronic transfusion therapy is recommended for patients with confirmed abnormal TCD velocities. In the current study, the rate of stroke in the 8-y period prior to TCD screening (Sept 1, 1990-Aug 31, 1998 – Pre-TCD) was compared to the rate in the 8-y period after TCD screening began (Sept 1, 1998 – Aug 31, 2006 – Post TCD). Eligible subjects were patients less than 22 years old with a diagnosis of SCD-SS or SCD-Sβ0-thalassemia. Subjects with a history of stroke prior to Sept, 1990 or before enrollment in our Center were excluded. Cases of stroke or other neurological event were identified from our clinical database. The study neurologist reviewed all clinical data and radiological studies for each neurological event and classified events into one of the following categories: overt stroke - ischemic (neurological deficit conforming to a vascular territory with neuroimaging studies corresponding to the clinical deficit) or hemorrhagic not overt stroke (other neurological event), and indeterminate. Incidence rates for stroke were calculated and compared between the Pre and Post TCD groups using a test of binomial proportions. Subjects were followed until they had a stroke or neurological event, turned 22 years old, the end of the 8-y period or until the last clinic date. The pre-TCD group included 475 children with a total follow-up time of 3,137 person-years. Twenty-one patients had overt stroke, 3 had other neurologic events (1-seizure, 1-transient ischemic attack/syncope, 1-behavioral changes) and 2 were indeterminate. The post-TCD group included 530 children with 3,578 person-years follow-up. Two patients had overt stroke, 6 had other neurological events [1-diffuse encephalopathy with viral syndrome, 1-febrile seizure, 3-dizzy and/or syncope (one with hgb=2.7), 1-headache with <30 min arm/leg weakness – all with acute punctate infarcts whose location did not correspond to clinical presentation], and 1 was indeterminate. The incidence of overt stroke in the pre-TCD period was 0.67 per 100 person-years, compared with an incidence of 0.06 per 100 person-years in the post-TCD period (p < 0.001). The first stroke case in the post-TCD period was a 3.4 year-old with ACA velocities > 200 cm/s but no abnormal velocities in the ICA/MCA and the second occurred in a 1.2 year-old, prior to the age that screening is started. Thus, our TCD screening and treatment program has been successful in reducing the rate of first overt stroke, although small vessel ischemia, particularly in the setting of an additional insult such as severe anemia, may not be prevented. Further modifications such as the addition of ACA velocity to treatment criteria, earlier screening, or the addition of other neuroimaging studies might further reduce the risk of first stroke.

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Braschi, Caitlyn, John Doucette und Ajai Chari. „Characterization of B12 Deficiency in Patients with Plasma Cell Disorders“. Blood 126, Nr. 23 (03.12.2015): 5330. http://dx.doi.org/10.1182/blood.v126.23.5330.5330.

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Abstract Background: Although vitamin B12 deficiency has been reported in patients with plasma cell dyscrasias (PCDs), no mechanism has been identified. Excess free light chains (FLCs), readily measurable by the serum FLC assay since 2001, could disrupt the renal proximal tubule receptors megalin and cubulin where B12 is reabsorbed. We sought to identify risk factors for B12 deficiency in PCD patients to elucidate a possible mechanism. In particular, we hypothesized that rates of B12 deficiency would be higher in PCD patients with higher FLC burdens. Methods: Of 1482 patients with ICD9 codes for PCDs, 530 met the inclusion criteria of having both serum B12 and FLC values. We reviewed the electronic medical records to obtain clinical data collected in the time preceding the patient's lowest B12 level. Patients were excluded if the lowest B12 was elevated in the setting of known concurrent vitamin B12 replacement therapy. Data from eligible patients were analyzed using chi-square, Student's independent t test, and Spearman's rank-order correlation to identify associations between B12 insufficiency (defined as <250 pg/ml or <350pg/ml and B12 treatment history) and PCD characteristics. This retrospective study was approved by the Mount Sinai IRB. Results: Overall, 26.6% patients were found have vitamin B12 insufficiency. Other than an IgG isotype PCD (P=0.025) there were no significant differences in age, gender, or PCD diagnosis between patients with and without B12 insufficiency (see Table 1). As expected, there was a strong negative correlation between eGFR and involved FLC, r(248) = -0.277, p < 0.001. However, unexpectedly, there was also a significant negative correlation between B12 level and eGFR, rs(487) = -0.106, p = 0.019 such that insufficient B12 was associated with normal eGFR (p = 0.001). There was no correlation between B12 level and involved FLC (p = 0.948) nor B12 level and Bence Jones proteinuria (p = 0.302). Discussion: While our data do not appear to support the proposed mechanism of FLC disruption of renal receptors, B12 deficiency was more common in our sample (26.6%) than the previously reported 13.6% prevalence among PCD patients (Baz et al Cancer 2004). While B12 deficiency and PCDs are both associated with higher age, the prevalence of B12 deficiency among older adults is only 10-15% (Baik et al Annu Rev Nutr 1999). Therefore, prospective studies are needed to explore other characteristics of PCD patients, such as chemotherapy treatment (Tandon et al Indian Pediatr 2015) or aspirin use (van Oijen et al Am J Cardiol 2004), contributing to a high prevalence of B12 deficiency in this population. Detection and treatment of B12 deficiency among PCD patients remains clinically important to reduce ensuing sequelae of neurologic dysfunction and cytopenias, which are complications of PCDs and their treatments. Table 1. Demographics and disease characteristics by B12 status. Vitamin B12 Status Insufficient B12 Normal B12 Total p Gender N %a N %a N %b Male 78 30.2 180 69.8 258 48.7 0.066 Female 63 23.2 209 76.8 272 51.3 Total 141 26.6 389 73.4 530 Age at PCD Diagnosis (median) 61 62 0.857 PCD N %a N %a N %b Multiple myeloma 60 35.9 107 64.1 167 78.4 0.488 Non-multiple myeloma 14 30.4 32 69.6 46 21.6 Total 74 34.7 139 65.3 213 Isotype N %a N %a N %b IgG 50 44.2 63 55.8 113 53.3 0.025 IgA 9 22.5 31 77.5 40 18.9 IgM 3 30.0 7 70.0 10 4.7 Kappa only 4 16.0 21 84.0 25 11.8 Lambda only 8 33.3 16 66.7 24 11.3 Total 74 34.9 138 65.1 212 Renal Function (KDOQI stages) N %a N %a N %b Stage 1-2 52 36.9 89 63.1 141 29.0 0.001 Stage 3 67 29.1 163 70.9 230 47.2 Stage 4 12 16.7 60 83.3 72 14.8 Stage 5 8 18.2 36 81.8 44 9.0 Total 139 28.5 348 71.5 487 a row percent, b column percent Table 2. Light chain burden and relevant labs by B12 status. Vitamin B12 Status Insufficient B12 Normal B12 Total p FLC Burden* N %a N %a N %b Normal FLC 12 34.3 23 65.7 35 16.4 0.354 Not measurable FLC, abnl ratio 23 40.4 34 59.6 57 26.8 Measureable FLC, nl BJP 18 26.1 51 73.9 69 32.4 Measurable FLC, elevated BJP 15 44.1 19 55.9 34 16.0 Massive BJP (>3g/24hr) 6 33.3 12 66.7 18 8.5 Total 74 34.7 139 65.3 213 Labs (medians) Folate, serum 14.0 14.6 0.919 MCV 91.3 92.4 0.055 Hemoglobin 10.9 10.6 0.940 LDH 186 199 0.145 Albumin 3.8 3.9 0.958 *normal = (sFLC<100mg/l), k/l ratio 0.26-1.85; measureable = sFLC ³100mg/l; abnl ratio = k/l ratio<0.26 or >1.85; elevated bence jones protein (BJP) = M-spike or BJP>200mg/24hr arow percent, b column percent Disclosures Chari: Array Biopharma: Consultancy, Other: Institutional Research Funding, Research Funding; Biotest: Other: Institutional Research Funding; Millennium/Takeda: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Berek, Klaus, Gabriel Bsteh, Michael Auer, Franziska Di Pauli, Anne Zinganell, Thomas Berger, Florian Deisenhammer und Harald Hegen. „Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study“. Frontiers in Immunology 12 (17.06.2021). http://dx.doi.org/10.3389/fimmu.2021.675307.

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BackgroundReports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).ObjectiveTo assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.MethodsCSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Qalb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.ResultsOf 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Qalb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.ConclusionsCSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.

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Duan, Yishan, Xinyan Ou, Yusha Chen, Binmiao Liang und Xuemei Ou. „Severe Influenza With Invasive Pulmonary Aspergillosis in Immunocompetent Hosts: A Retrospective Cohort Study“. Frontiers in Medicine 7 (18.01.2021). http://dx.doi.org/10.3389/fmed.2020.602732.

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Background: Influenza was an independent risk factor for invasive pulmonary aspergillosis (IPA). In light of increasing incidence and mortality of influenza associated aspergillosis, our study summarized risk factors, clinical characteristics, and prognostic factors of developing aspergillosis in immunocompetent hosts with influenza to further screen high-risk population and improve outcome.Methods: We reviewed the patient characteristics, laboratory examinations, radiological imaging, and microbiology data of 72 influenza patients with IPA and 84 influenza patients without IPA admitted to West China Hospital.Result: Our study shown that aspergillosis co-infection increased overall mortality of severe influenza from 22.6 to 52.8%, along with higher white blood count (WBC) (10.9 ± 5.0 vs. 8.4 ± 3.3, P = 0.016), Neutrophiles (9.5 ± 5.0 vs. 7.0 ± 3.8, P = 0.023), procalcitonin (PCT) (8.6 ± 15.9 vs. 1.2 ± 2.1, P = 0.009), and a lower CD4+ T cell count (189.2 ± 135.3 vs. 367.1 ± 280.0, P = 0.022) in death group. No impact of age, gender, underlying diseases, immunosuppressive agents and steroids use, CD4+ T cell count on incidence of influenza associated aspergillosis was observed. But influenza associated aspergillosis cases mostly accompanied with more H1N1 subtype (91.7 vs. 79.8%, P = 0.037) and higher level of C-reactive protein (CRP) (117.6 ± 88.1 vs. 78.5 ± 75.2, P = 0.017) and interleukin 6 (IL-6) (133.5 ± 149.2 vs. 69.9 ± 100.0, P = 0.021) than those without aspergillosis.Conclusion: Aspergillosis co-infection in severe influenza patients can lead to a significant increased mortality, which was associated with severe respiratory failure due to mixed infection and immunosuppression. Pulmonary excessive inflammatory response was related with IPA co-infection.

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Ochoa-Urrea, Manuela, Mojtaba Dayyani, Behnam Sadeghirad, Nitin Tandon, Nuria Lacuey und Samden D. Lhatoo. „Electrical Stimulation-Induced Seizures and Breathing Dysfunction: A Systematic Review of New Insights Into the Epileptogenic and Symptomatogenic Zones“. Frontiers in Human Neuroscience 14 (22.01.2021). http://dx.doi.org/10.3389/fnhum.2020.617061.

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Objective: Electrical stimulation (ES) potentially delineates epileptogenic cortex through induction of typical seizures. Although frequently employed, its value for epilepsy surgery remains controversial. Similarly, ES is used to identify symptomatogenic zones, but with greater success and a long-standing evidence base. Recent work points to new seizure symptoms such as ictal central apnea (ICA) that may enhance presurgical hypotheses. The aims of this review are 2-fold: to determine the value of ES-induced seizures (ESIS) in epilepsy surgery and to analyze current evidence on ICA as a new surrogate of symptomatogenic cortex.Methods: Three databases were searched for ESIS. Investigators independently selected studies according to pre-specified criteria. Studies reporting postoperative outcome in patients with ESIS were included in a meta-analysis. For ES-induced apnea, a thorough search was performed and reference list searching was employed.Results: Of 6,314 articles identified for ESIS, 25 were considered eligible to be reviewed in full text. Fourteen studies were included in the qualitative synthesis (1,069 patients); six studies were included in the meta-analysis (530 patients). The meta-analysis showed that favorable outcome is associated with ESIS prior to surgery (OR: 2.02; 95% CI: 1.332–3.08). In addition, the overall estimation of the occurrence of favorable outcome among cases with ESIS is 68.13% (95% CI: 56.62–78.7). On the other hand, recent studies have shown that stimulation of exclusively mesial temporal lobe structures elicits central apnea and represents symptomatogenic anatomic substrates of ICA. This is in variance with traditional teaching that mesial temporal ES is non-symptomatogenic.Conclusions: ES is a tool highly likely to aid in the delineation of the epileptogenic zone, since ESIS is associated with favorable postoperative outcomes (Engel I). There is an urgent need for prospective evaluation of this technique, including effective stimulation parameters and surgical outcomes, that will provide knowledge base for practice. In addition, ES-induced apnea studies suggest that ICA, especially when it is the first or only clinical sign, is an important semiological feature in localizing the symptomatogenic zone to mesial temporal lobe structures, which must be considered in SEEG explorations where this is planned, and in surgical resection strategies.

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Haussen, Diogo C., Andrey Lima, Mikayel Gregoryan, Jonathan Grossberg, Leah Craft, Lawrance Matarutse, Sharion Smith et al. „Abstract T P24: Neurointervention for Acute Ischemic Stroke Caused by Carotid Dissection“. Stroke 46, suppl_1 (Februar 2015). http://dx.doi.org/10.1161/str.46.suppl_1.tp24.

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Introduction: Data related to the treatment of patients with acute ischemic stroke caused by carotid artery dissection is scarce. Methods: We retrospectively reviewed our interventional stroke database Sep 2010 - Jan 2014 to investigate the clinical and radiological characteristics of patients presenting with tandem cervical and intracranial occlusions due to cervical carotid dissection. Results: Out of 504 consecutive patients treated with endovascular therapy for acute ischemic stroke during the study period, 12 (2.5%) patients were observed to have cervical carotid artery dissection as the underlying etiology. Mean age was 56±13 years, 75% were male, 50% received IV t-PA, mean NIHSS was 20±5, 75% had CT ASPECTS≥7, and mean time from last known normal to groin puncture was 6±3 hours. There were 4 MCA M1, 1 MCA M2 and 7 ICA-T occlusions. Extracranial carotid stent was used in 58% and angioplasty in 8% of cases. In 33% of the cases, the carotid dissection was not stented due to the fear of hemorrhagic transformation in cases of IV thrombolysis (presumably increased risk if dual antithrombotics used). IA tPA was used in 41% of cases, while Merci in 16%, Penumbra in 58%, and stentretrivers in 50%. Intracranial TICI 2b-3 reperfusion was achieved in 91% of patients, with PH2 hemorrhage in 8% and mRS at 90 days in 45% of cases. Conclusions: Carotid dissections with associated intracranial occlusions are often refractory to IV tPA and present with a high stroke severity. These lesions are amenable to endovascular therapy resulting in high rates of reperfusion with an acceptable safety profile.

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Cardona, Pedro, Helena Quesada, Blanca Lara, Nuria Cayuela, Paloma Mora, Roger Barranco, De Miquel M. Angeles et al. „Abstract WP439: Who Benefits From CT-Angiography Previous Intravenous Thrombolysis?“ Stroke 47, suppl_1 (Februar 2016). http://dx.doi.org/10.1161/str.47.suppl_1.wp439.

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Background: Endovascular treatment (EVT) is an effective treatment in strokes with persistent large artery occlusion despite previous intravenous thrombolisis (IVT) as rescue treatment. Performing computer tomography angiography (CTA) before IVT could allow early activation of neurointerventional teams; however routine CTA could delay unnecessary door-to-needle time of IVT and may be infeasible. Methods: We reviewed stroke code activations between May 2011 and June 2015 in our comprehensive stroke center and divided into groups based on NIHSS and patency of arterial occlusion according to non-enhanced CT on admission (dense artery sign or dot sign) and baseline CTA. We assessed patients treated with IVT and selected to EVT according to results in CTA post-IVT. We analyze percentage of recanalization or migration of thrombus after IVT alone and variables associated to successful treatment. Results: Of 2856 stroke codes registered during the study period 1810 were diagnosis of ischemic strokes. We treated 520 patients with IVT, 202 had a radiological evidence of large artery occlusion (55%M1, 32% M2, 5%TICA, 5%ICA, 3% basilar). Thirty-two percent of patients showed changes in CTA carried out after IVT(17% successfully recanalized, 15% distal migration of thrombus) so they were not selected to endovascular treatment. There were significant difference between M1 and M2 occlusion regarding changes in CTA after IVT (23% vs 70%; p<0.001). In multivariate logistic regression a baseline score NIH<10 was associated with higher percentage of recanalization with rtPA despite signs of large vessel occlusion (78% vs 32%; p:0.001). In receiver operating characteristic analysis higher baseline NIH was associated with persistent occlusion after IVT (area under curve=0.79;95% CI, 0.6-0.9; P:0.001) with optima threshold of 10 ( Sensivity 84%, Specificity 74%). Conclusions: We consider defer CTA angiography until after IVT in stroke code patients with moderate clinical impairment (NIH<10) or M2-segment occlusion, because they achieve a high percentage of arterial recanalization. CTA previous IVT could be unnecessary, provide unreliable information and delay IVT in that clinical group but could be useful to plan EVT in patients with higher NIH scores.

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Awadh, Hesham, Anne-Marie Chaftari, Melissa Khalil, Johny Fares, Ying Jiang, Rita Deeba, Shahnoor Ali, Ray Hachem und Issam I. Raad. „Management of enterococcal central line-associated bloodstream infections in patients with cancer“. BMC Infectious Diseases 21, Nr. 1 (05.07.2021). http://dx.doi.org/10.1186/s12879-021-06328-9.

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Abstract Objective Enterococcus species are the third most common organisms causing central line-associated bloodstream infections (CLABSIs). The management of enterococcal CLABSI, including the need for and timing of catheter removal, is not well defined. We therefore conducted this study to determine the optimal management of enterococcal CLABSI in cancer patients. Methods We reviewed data for 542 patients diagnosed with Enterococcus bacteremia between September 2011 to December 2018. After excluding patients without an indwelling central venous catheter (CVC), polymicrobial bacteremia or with CVC placement less than 48 h from bacteremia onset we classified the remaining 397 patients into 3 groups: Group 1 (G1) consisted of patients with CLABSI with mucosal barrier injury (MBI), Group 2 (G2) included patients with either catheter-related bloodstream infection (CRBSI) as defined in 2009 Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection by the Infectious Diseases Society of America (IDSA) or CLABSI without MBI, and Group 3 (G3) consisted of patients who did not meet the CDC criteria for CLABSI. The impact of early (< 3 days after bacteremia onset) and late (3–7 days) CVC removal was compared. The composite primary outcome included absence of microbiologic recurrence, 90-day infection-related mortality, and 90-day infection-related complications. Results Among patients in G2, CVC removal within 3 days of bacteremia onset was associated with a trend towards a better overall outcome than those whose CVCs were removed later between days 3 to 7 (success rate 88% vs 63%). However, those who had CVCs retained beyond 7 days had a similar successful outcome than those who had CVC removal < 3 days (92% vs. 88%). In G1, catheter retention (removal > 7 days) was associated with a better success rates than catheter removal between 3 and 7 days (93% vs. 67%, p = 0.003). In non-CLABSI cases (G3), CVC retention (withdrawal > 7 days) was significantly associated with a higher success rates compared to early CVC removal (< 3 days) (90% vs. 64%, p = 0.006). Conclusion Catheter management in patients with enterococcal bacteremia is challenging. When CVC removal is clinically indicated in patients with enterococcal CLABSI, earlier removal in less than 3 days may be associated with better outcomes. Based on our data, we cannot make firm conclusions about whether earlier removal (< 3 days) could be associated with better outcomes in patients with Enterococcal CLABSI whose CVC withdrawal is clinically indicated. In contrast, it seemed that catheter retention was associated to higher success outcome rates. Therefore, future studies are needed to clearly assess this aspect.

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Mercer, Alex, Kevin Carroll, Leah Conley und Jonathan Barratt. „MO256THE TREATMENT EFFECT OF RAS BLOCKADE ON PROTEINURIA IN IGA NEPHROPATHY PATIENTS AS A SURROGATE FOR RENAL EVENTS AND DECLINE IN EGFR: AN ANALYSIS OF RANDOMIZED CONTROLLED TRIALS“. Nephrology Dialysis Transplantation 36, Supplement_1 (01.05.2021). http://dx.doi.org/10.1093/ndt/gfab104.0014.

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Abstract Background and Aims Renin-Angiotensin System Blockade (RASB) is the cornerstone of standard-of-care in IgA nephropathy. Randomized controlled trials (RCTs) have shown the treatment benefit of RASB therapy on proteinuria and risk of renal failure. The objective of this study was to describe the relationships between the treatment effect of RASB on proteinuria and (i) risk of renal events, and (ii) decline in eGFR, as an endpoint proximal to renal failure. To this aim, trial level (TL) and simple weighted linear regression (SWR) analyses were conducted on RCTs identified through a systematic literature review, with RASB as the active intervention. Methods A systematic literature review of available peer-reviewed literature from 1990 to 2020 was performed applying the following inclusion criteria: RCT in patients with biopsy-proven IgAN, investigating the effects of RASB as an intervention, sample size >25, measurement of proteinuria at baseline and at >3 months. At least 1 renal event (defined as ≥50% decline in eGFR, CKD Stage 5, dialysis or transplantation) was required for the renal event analysis and similarly, at least 12 months follow-up was required for the decline in eGFR analysis. For the relationship between proteinuria and risk of renal events, 4 studies including 5 comparisons were identified, while 9 studies including 10 comparisons were identified for the analysis of proteinuria vs eGFR decline. Proteinuria change from baseline was calculated from the value closest to 6 months. If annualized change in eGFR was reported, these data were used, otherwise annualized change in eGFR was calculated per year of follow-up. Methods as described by Burzykoski & Buyse (2006) and Joffe & Greene (2008) were used for TL meta-regression analyses; the resulting meta-regression line was displayed with an 80% credible interval band (CB). Given the assumptions made in this analysis, a SWR analysis was also performed; to compensate for potential underestimation of error associated with the regression line, a 99.9% CB was applied in the SWR analysis. Results For RASB treatment effects on renal events, a statistical association was found with treatment effects on proteinuria with a TL slope estimate = 15.30 95% CI (0.57, 38.79), R2 = 0.88 95% CI (0.22, 1.00); using the lower CI of 0.75 for the estimated slope, a 30% treatment effect on proteinuria would be expected to result in at least a 25% reduction in the risk of renal events. As individual subject level data were not available, the correlation between errors on treatment effects for proteinuria and treatment effects for renal events were unknown, resulting in a wide CB on the meta-regression line and a wide CI for the slope estimate. The SWR approach is not hampered by lack of subject level data and gave a slope estimate of 3.5 95% CI (2.1, 5.0) with R2 = 0.97, such that a 30% treatment effect on proteinuria would be expected to result in at least a 64% reduction in the risk of renal events. For treatment effects on annualized eGFR versus effects on proteinuria, the TL slope estimate was -5.1 95% CI (-30.2, 35.0), R2 = 0.89 95% CI (0.15, 1.00); the corresponding SWR slope estimate was -7.6, 95% CI (-12.3, -2.8) with R2 = 0.71. A 30% treatment effect on proteinuria would be expected to result in a 2.6 mL/min (TL analysis) to 3.9 mL/min slower decline (SWR analysis) in annualized eGFR. Conclusion In patients with IgAN, associations were seen between treatment effects of RASB on proteinuria and on the clinically relevant endpoints of renal events and annualized change in eGFR. Consistent with TL analyses of RCTs across a variety of mechanisms of actions, these data, specific to RASB, contribute to the growing evidence base supporting the use of proteinuria as a valid surrogate endpoint in IgAN.

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