Letteratura scientifica selezionata sul tema "914.19/6/0380924 b"

Abstract Iron overload is a potentially life-threatening consequence of multiple blood transfusions. Effective iron chelation therapy reduces morbidity and saves lives. Many patients are unable to comply with current treatments, deferoxamine (DFO) or deferiprone (L1), because they cannot tolerate the parenteral infusion regimen required for DFO, because of adverse events (AEs), or because they do not respond to treatment. The objective of the ESCALATOR trial is to evaluate the effectiveness of deferasirox, an investigational once-daily oral iron chelator in advanced clinical development, in reducing liver iron concentration (LIC) in patients with β-thalassemia unable to be properly treated with DFO and/or L1. During a 1-year treatment period, patients will receive deferasirox at a daily dose of 20 mg/kg. Reduction of LIC is the primary endpoint, as assessed by biopsy at baseline and study end. Secondary efficacy variables include serum ferritin (SF) and other potential surrogate markers of iron overload such as concentration of labile plasma iron (LPI) in a subgroup of patients. Safety assessments include AEs and comprehensive laboratory evaluations. To date, 232 patients have initiated treatment at seven centers in five countries (Egypt, Saudi Arabia, Lebanon, Oman, Syria). Demographics, relevant medical history and baseline iron burden parameters are described in the table. Importantly, baseline SF values were significantly correlated with LIC (R=0.63; P<0.0001). The last patient’s last visit will be in June 2006. Age 2 to <16 years (n=159) Age ≥16 years (n=73) All patients (n=232) Mean ± SD; †n=14 Female:male, n 79:80 35:38 114:118 Race (caucasian:oriental:other), n 59:81:19 11:41:21 70:122:40 BMI*, kg/m2 17.4 ± 2.6 21.6 ± 3.2 18.7 ± 3.4 Weight*, kg 29.4 ± 9.9 54.7 ± 9.7 37.3 ± 15.3 Hepatitis B or C, n 43 29 72 Splenectomy, n 46 53 99 Transfusions in previous year*, n 15.5 ± 4.5 14.3 ± 3.7 15.1 ± 4.3 Total volume transfused in previous year*, mL 5265 ± 2469 7446 ± 2953 5873 ± 2784 Years on chelation therapy*, n 6.2 ± 3.5 12.7 ± 4.8 8.2 ± 4.9 Proportion of life on transfusion therapy*, % 89.3 ± 13.9 89.0 ± 14.1 89.2 ± 14.0 Liver pathology grading (modified HAI scale) Grade 0–6 143 64 207 Grade 7–12 4 0 4 Grade 13–18 0 0 0 LIC, mg Fe/g dw Mean ± SD 17.1 ± 8.5 20.0 ± 10.0 18.0 ± 9.1 Median (min, max) 16.6 (2.9, 38.2) 19.0 (2.9, 48.9) 17.5 (2.9, 48.9) SF, ng/mL Mean ± SD 3957 ± 2342 4564 ± 4117 4148 ± 3019 Median (min, max) 3356 (914, 13539) 3335 (956, 23017) 3346 (914, 23017) LPI†,μmol/L Mean ± SD - - 1.03 ± 0.80 Median (min, max) - - 0.82 (0, 2.65) The ESCALATOR study cohort is a highly challenging population with varied chelation response and transfusion history. The magnitude of LIC and SF, which were well correlated, reflects the severity of iron overload in patients unable to maintain adequate chelation using DFO or L1. This study will provide important insights into the clinical management of iron overload with the well tolerated, once-daily oral iron chelator deferasirox in this difficult-to-treat population.

Abstract Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection results in poor outcome in patients with hematologic malignancies. Moreover, the efficacy of anti-SARS-CoV-2 mRNA vaccines appears lower in immunocompromised patients, including recipients of allogeneic stem cell transplantation (Allo-HSCT). In this population, data are scarce regarding factors predicting the response to mRNA vaccines. Methods This retrospective study aimed to decipher which factors, including immune status at time of vaccine and recipient/donor blood groups, might influence the antibody response after two injections (V1 and V2) of BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of allografted patients with no previous symptomatic nor asymptomatic COVID-19 infection. Possible previous asymptomatic COVID-19 infection was investigated in pre-V1 samples by testing for anti-nucleocapsid (N) antibodies (anti-SARS-CoV-2 immunoassay, Roche Elecsys®, Rotkreuz, Switzerland). Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested post-V2 (Roche Elecsys®). As recommended by the manufacturer, titers ≥0.8 U/mL were considered positive, the highest value being >250 U/mL. Blood samples were also collected before V1 and at distance from V2 to evaluate, by flow cytometry, total lymphocyte (Ly) counts and quantitative Ly subsets (CD3, CD4 and CD8 T cells, B and NK cells). Statistical analyses were performed on R (version 4.0.3). Patient characteristics were compared by using the Χ² test for discrete variables and the Wilcoxon test for continuous variables. Generalized linear models were used to conduct multivariate analyses. Results Samples were available from 117 Allo-HSCT patients who had been vaccinated between January 20 and April 17, 2021. Patient characteristics are provided in Table 1. The average interval from Allo-HSCT day 0 (D0) to V1 (D0-V1) was 654 (IQR: 372-1367) days (d). S-antibody response rate post-V2 was 82.9% for the entire cohort. Non-humoral responders (NHR) post-V2 (n = 20) had a lower D0-V1 interval (median 271 vs 914 d, p <10 -5) and a lower pre-V1 median total Ly count (0.62 vs 1.61x10 9/L, p < 10 -4). Lymphocyte subsets possibly predictive of antibody response were then investigated. NHR were associated with lower median CD3 (0.39 vs 0.97 x10 9/L, p = 0.01), CD4 (0.13 vs 0.35 x10 9/L, p=<10 -3), and B-cell (0.00 vs 0.28 G/L, p <10 -6) counts. NK and T CD8 counts were not statistically different between NHR and HR (respectively p=0.14 and p=0.06). No influence either was observed when considering the age of donors (p=0.39) or recipients (p=0.55), underlying disease (p=1), Allo-HSCT conditioning (p=0.11), blood groups (donor, p=0.55; receiver, p=0.39) or a previous history of graft versus host disease (GVHD; 83.1 vs 83.6%, p=1). Conversely, ongoing immunosuppressive (IS)/chemotherapy treatment and a haploidentical source of graft were associated with lower responses to vaccination (respectively 62.5 vs 90.5%, p<10 -3, and 69.4 vs 88.6% for patients with matched donors, p=0.02). In multivariate analysis (Fig.1) also including D0-V1 interval, donor source, current IS/chemotherapy treatment and TCD4 Ly count, only B cell aplasia remained statistically associated with lack of antibody response after two vaccine injections (OR 0.01, 95%CI [0.00 - 0.10], p <10 -3). The possible modification in terms of lymphocyte counts between pre-V1 and post-V2 times has been also investigated showing that only CD4 lymphocytes counts improved significantly (0.31 vs 0.34 x10 9/L, p=0.01) between this interval. Conclusion B cell aplasia appears as a major predictor of anti SARS-CoV-2 mRNA vaccine failure after Allo-HSCT. It may be suggested from this result that a close immune monitoring should be proposed after allotransplant to propose the vaccine at the most appropriate time, meaning after of B cell detection, regardless of the delay from Allo-SCT or the presence of an IS/chemotherapy treatment. The possibility for these patients to have mounted a cellular response should also be considered, which was not investigated here. Figure 1 Figure 1. Disclosures Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Oncopeptides: Honoraria; Amgen: Honoraria; Janssen: Honoraria.

Abstract INTRODUCTION: Extracellular vesicles (EVs), including exosomes, shedding vesicles (microvesicles: MVs) and apoptotic bodies, are membrane vesicles of 40-3,000 nm that are released from many cell types, such as red blood cells, platelets, lymphocytes, dendritic cells, endothelial cells and tumour cells. They have a key role not only in the regulation of normal physiological processes, but also in the pathology underlying several diseases. Recently, it was discovered that EVs circulate in bodily fluids of cancer patients and could serve as potential diagnostic biomarkers. However, the presence and role of peripheral circulating EVs in hematological malignancies (HMs) remain unclear. The aim of this study was to investigate EVs in peripheral blood of HM patients, defining the EVs count, size and phenotype. METHODS: Peripheral blood samples were obtained prior to treatment from 87 subjects: 6 Chronic Lymphocytic Leukemia (CLL), 10 Non-Hodgkin's Lymphoma (NHL; 5 follicular, 5 diffuse large B-cell), 6 Waldenstrom's Macroglobulinemia (WM), 6 Hodgkin's Lymphoma (HL), 6 Multiple Myeloma (MM), 5 Acute Myeloid Lukemia (AML), 19 Myeloproliferative Neoplasms [(MPNs; 5 Essential Thrombocythemia (ET), 5 Polycythemia Vera (PV), 5 Primary Myelofibrosis (PMF), 4 Chronic Myelogenous Leukemia (CML)], 5 Myelodysplastic Syndrome (MDS) and 28 healthy controls. EVs were isolated from serum of peripheral blood by ultracentrifugation steps. For calculation of counts, TruCOUNT beads were added immediately prior to analysis by flow cytometry (FACS). For size assessment, Megamix beads with specific size (0.3,0.9, 3.0 micrometer) were used. For phenotype characterization, a panel of specific antibodies (anti CD59, CD61, CD62E, CD19, CD20, CD38, CD138, CD13, CD30) were employed in a FACS analysis. RESULTS: MVs count was significantly higher in patients with CLL, WM, HL, MM, AML and CML (median values 890, 3227, 1218, 914, 656 and 1275 MVs/microliter of serum, respectively) compared to healthy controls (median value 270 MVs/ microliter of serum, ***P<0.001). MV levels in the other HMs, although sligthly higher when compared to healthy controls, did not mantain statistical significance when p value was corrected for the number of malignancies analysed. (Figure) In CLL and MDS, through the number of cases was small, MVs counts directly correlated with Rai stage and R-IPSS risk, respectively. As regards vesicles volume, all HMs generated a distinct population of MVs with smaller size when compared with controls. As expected, MVs were consistently Annexin V positive and expressed a common membrane protein, CD59, an ubiquitous complement regulator. Part of MVs originated from platelets (median value 400 CD61 positive/ microliter of serum) and endothelial cells (median value 60 CD62E positive/ microliter of serum). Interestingly, MV phenotype was disease specific: a relevant amount of MVs expressed surface specific proteins related to malignancy. In particular, we found MVs positive for CD19 and/or CD20 in CLL, WM and NHL, CD38 and/or CD138 in MM, CD13 in AML, MPNs and MDS, CD30 in HL. These markers were not significantly expressed on the surface of healthy subject MVs. CONCLUSIONS: In this study, for the first time, serum MVs in a panel of HMs were analysed. We found that patients with various types of HMs release elevated peripheral blood MV levels selectively displaying markers of the underlying malignancy. MVs could be therefore useful as potential novel biomarkers in HMs. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 305 Introduction: Non-Hodgkin's lymphoma (NHL) are malignant tumors usually sensitive to chemotherapy; this results in prolonged survival and possibly disease eradication in a large proportion of patients. However, despite the general improvement in treatment options, a variable number of patients still shows a refractory disease, i.e. poor or absent response to induction therapy. Prediction and management of refractory disease is a major issue in the biological and clinical research programs for NHL. The present study was undertaken to evaluate on a large series of NHL patients, managed at two Italian centers over the last three decades: i. the actual rate of refractory patients; ii. the main factors associated with refractory disease; iii. the long-term outcome of refractory vs. responsive patients. Patients and Methods: Data have been collected on a series of 3,952 NHL patients, referred and treated at the University Hematology of Torino (S. Giovanni B. and Mauriziano Hospitals) (864 cases) and at the Hematology Division of Ospedali Riuniti di Bergamo (3,088 cases), between 1984 and 2012. There were 1,819 (46%) female patients, 2,056 (52%) were aged less than 60 yrs, B-cell NHL were 3,633 (92%), with 318 (8%) patients diagnosed as T-NHL; main histological subtypes included: 1,809 (45.8%) Diffuse Large Cell Lymphoma (DLCL), 758 (19.2%) follicular lymphoma (FL), 210 (5.3%) mantle-cell lymphoma, the remaining 1,175 (29.7) had other histologies. According to Ann Arbor staging, 2,369 (62%) patients presented with advanced stage disease and 914 out of 2,174 evaluable patients (42%) had an intermediate-high IPI score. Overall, 1,430 out of 3,187 (44.9%) received conventional chemo-radiotherapy supplemented with rituximab. The criteria to identify refractory patients were: stable or progressive disease (fully refractory) or transient response with disease progression within 6 months (early relapse), following first-line chemotherapy. Results: Among 2,543 broadly analysed patients, treated during the last 28 yrs, 649 (25.5%) were classified as refractory, including 14% fully refractory and 11.5% with early relapse or disease progression. The overall incidence of refractory disease was similar in the two Centers, 24.1% in Torino and 26.3% in Bergamo. The rate of refractoriness was as high as 46.9% in the small T-cell subgroup, while the overall incidence was 23.6% for B-cell NHL (p<0.001), with refractory patients more frequently observed among DLCL (26.0%) than in FL (15.1%) (p<0.001). Besides T-cell histology, the following factors had the highest association (p<0.001) with treatment response: i. intermediate-high risk IPI presentation, with 38.5% refractory patients, compared to 16.7% for 0–2 IPI scores; ii. female gender, with a markedly lower incidence (22%) of refractoriness compared to males (28.4%); iii. rituximab addition, that cut the incidence of refractoriness to 19.2% compared to 28.8% for patients treated without rituximab. These factors maintained their independent predictive values in multivariate regression analysis. At a median follow-up of 5.4 yrs., 1,607 (61%) out of 2,543 patients are alive, 11.8% of them were refractory to their first line treatment. Indeed, among 649 refractory patients, 189 (29%) are presently alive, compared to 1,418 alive (75%) among 1,894 responsive patients. Lastly, the overall survival (OS) was significantly poorer for fully refractory (median survival: 1.1 yrs) compared to early relapse patients (2.09 yrs) (p<0.001); both these refractory subgroups had a definitely poorer OS compared to responsive patients, whose median survival was 22.2 yrs (see Figure 1). Conclusions: i. Overall, in this large series of NHL patients who received induction therapy both in the pre- and post-Rituximab era, approximately one fourth displays full refractoriness or early relapse/progression; ii. the introduction of rituximab has markedly reduced the risk of refractory disease, whose incidence is now around 19%; iii. a markedly higher rate of refractory disease is observed with T-subtypes compared to B-cell NHL; iv. intermediate-high IPI score is associated to refractoriness, while female gender significantly reduces the risk of refractory disease; iv. patients responsive to first-line therapy have a very prolonged life expectancy, with a median survival around 22 yrs, whereas the median survival for refractory patients does not exceed 2 yrs. Disclosures: Tarella: Hoffmann-La Roche: Consultancy, Honoraria. Rambaldi:Hoffmann-La Roche: Consultancy, Honoraria.

TK and SM are Co-first authors INTRODUCTION Treatment with chimeric antigen receptor (CAR) T-cells significantly improved outcomes in relapsed/refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). CAR-T activation and anti-tumor cytotoxicity are associated with bystander inflammatory reactions resulting in CRS and/or ICANS. Due to complex cytokine profiles, disease heterogeneity, and variability between commercial CAR-T products, identification of risk factors associated with CRS and/or ICANS has been challenging. In this study, we used plasma proteomic profiling at different timepoints to identify possible inflammatory mediators associated with CRS and ICANS METHODS We prospectively collected plasma samples from patients who received CAR-T cells therapy between 9/2021 to 12/2022 at several time points - before lymphodepletion chemotherapy on day -5 (relative to CAR-T cell infusion), prior to CAR T-cell infusion on day 0, and post CAR T-cell therapy on days 1, 2, 3, and 7. Protein profiling analyses were conducted at Eve Technologies (Calgary, Alberta, Canada) using an assay measuring 71 total cytokines and chemokines. Proteins levels were compared across different time points used Wilcoxon rank test, while features associated with CRS/ICANS were identified using logistic regression. Receiver operating characteristic (ROC) analysis used to identify variables predictive for CRS. Area under the curve (AUC) of at least 0.8 was used and best cutoffs were determined according to Youden index. P-values &lt;0.05 were considered statistically significant. This study was supported in part by The Frederick A. Deluca Foundation. RESULTS Overall, 56 patients with available cytokine assays at all time points were included. The median age was 65 years (IQR: 57-74) and 70% were men. Of all patients, 26 (46%) had diffuse large B-cell lymphoma (DLBCL), 23 (41%) MM, 4 (7%) mantle cell lymphoma, and 3 (6) follicular lymphoma. Ide-cel (39%), liso-cel (36%), and axi-cel (17%) were the most used CAR-T cell products. All patients received lymphodepleting chemotherapy with fludarabine/cyclophosphamide. In total, 35 (63%) patients developed CRS (grade 1, 89%; grade 2, 8%; grade 3, 3%) and 18 (32%) patients developed ICANS (grade 1, 72%; grade 2, 22%; grade 3, 6%). Compared to patients who did not develop CRS, patients with CRS had lower median absolute lymphocyte counts at day -5 (0.02 x10 9/L vs. 0.05, p=0.0146), higher baseline CRP (13 vs. 4 mg/L, p=0.0005), and higher ferritin (914 vs. 442 mg/L, p=0.048). No differences in the type of CAR-T products (p=0.090), percentages of DLBCL or MM (p=0.270) were observed between CRS and no CRS cohorts ( Panel-A). First, we investigated the proteomic profiles at baseline for CRS odds. Hemoglobin (odd ratio [OR]: 0.6, 95%CI: 0.4-0.8) was associated with lower odds for CRS while IL6 (2.0, 1.2-3.3) and stem cell factor (scf 2.2, 1.2-4.2) were associated with higher odds of CRS. We then analyzed the differences in cytokine levels between day 0 and day 3 to select cytokines with significant changes for further analysis ( Panel-B). At day 3, groa (1.9, 1.1-3.3), IL3 (1.6, 1.2-2.1), IL5 (1.5, 1.2-1.9), IL6 (1.7, 1.3-2.3), IL10 (2.0, 1.3-3.0), TNFα (2.0, 1.1-3.6), and mcp2 (2.5, 1.2-5.3) were all associated with higher odds for CRS. Based on ROC analysis at day 3, best cutoff points to estimate CRS (value, sensitivity/specificity) for IL3 (3, 80%/90%), IL5 (197, 74%/85%), IL6 (11, 70%/85%), and IL10 (53, 74%/85%) were identified. Based on that, elevated IL3 (OR:24, 95%CI: 6-105), IL5 (11, 3-40), IL6 (21, 5-95), and IL10 (12, 3-46) were associated with higher odds for CRS. For ICANS, day 3 IL3 (1.5, 1.2-1.9), IL6 (1.2, 1.1-1.5), IL8 (2.1, 1.4-3.3), and IL10 (1.7, 1.3-2.4) were associated with higher odds for ICANS. Best cutoff points to estimate ICANS at day 3 (value, sensitivity/specificity) for IL3 (5, 78%/76%), IL6 (115, 78%/78%), IL10 (130, 81%/80%), and IL8 (21, 83%/81%) were identified. Based on that, elevated IL3 (OR:10, 95%CI: 3-37), IL6 (11, 3-43), IL10 (13, 3-51), and IL8 (19, 4-81) were associated with higher odds for ICANS. CONCLUSIONS In our comprehensive plasma proteomic profiles analysis, we identified cutoffs for IL3, IL6, IL5 and IL10 that may be predictive for CRS and ICANS regardless of CAR-T cell product. Our results are clinically applicable and may be used to recognize patients at risk for CRS and/or ICANS who may be eligible for prophylactic therapies.

Бинарные и сложные халькогениды с тетрадимитоподобной слоистой структурой представляют большой практический интерес как топологические изоляторы, термоэлектрические и оптоэлектронные материалы. Их фундаментальные термодинамические функции в совокупности с фазовыми диаграммами важны для разработки и оптимизации методов синтеза и выращивания кристаллов. В работе представлены результаты термодинамического исследования исходных соединений и твердых растворов системы Bi2Se3-Bi2Te3 методом электродвижущих сил (ЭДС). Различные модификации этого метода широко применяются для исследования бинарных и сложных халькогенидов металлов. Исследования проводили измерением ЭДС концентрационных цепей типа:(–) Bi (тв.) | ионная жидкость + Bi3+ | Bi в сплаве (тв.) (+) в интервале температур 300-450 K.В качестве правых электродов были использованы предварительно синтезированные равновесные сплавы Bi2Se3–хTex (х = 0; 0.6; 1.2; 1.8; 2.0; 2.4; 3.0) с 0.5 ат. % избытком теллура. В качестве электролита использовали ионную жидкость (формиат морфолина) с добавлением BiCl3.Полученные экспериментальные данные обработаны с помощью компьютерной программы «Microsoft Office Excel 2003» методом наименьших квадратов и получены линейные уравнения типа E = a + bT. Из полученных уравнений температурных зависимостей ЭДС рассчитаны относительные парциальные молярные функции висмута в сплавах. На основании диаграммы твердофазных равновесий системы Bi–Se–Te были определены уравнения потенциалобразующих реакций, с использованием которых вычислены стандартные термодинамические функцииобразования и стандартные энтропии соединений Bi2Se3, Bi2Te3 и твердых растворов Bi2Se3–xTex вышеуказанных составов. Также вычислены термодинамические функции образования твердых растворов Bi2Se3–xTex из исходных бинарных соединений. 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La obesidad y la diabetes mellitus tipo II (DMT2) han sido declaradas pandemias del nuevo siglo, en virtud de su acelerado crecimiento y presencia en la población mundial. Sin embargo, el enfoque empleado en los tratamientos de estas condiciones ha radicado en la atención farmacológica de las comorbilidades asociadas, sin conseguir efectos positivos en la enfermedad en el largo plazo. En tal sentido, la investigación tuvo como objetivo determinar los parámetros básicos de atención de la obesidad y la DMT2, a través de la atención nutricional no farmacológica mediante una revisión bibliográfica en bases de datos atendiendo el contenido científico de cada estudio analizado. La evidencia científica es consistente es señalar que un tipo de alimentación con unaporte bajo en grasa, contenido moderadamente alto en proteínas, hidratos de carbono de bajo índice glucémico es adecuada para mantener y/o restablecer las condiciones de salud en este tipo de paciente. Palabras Clave: Diabetes, Obesidad, Diabesidad, Nutrición. Referencias [1]M. Mangas, A. Martínez y P. García, «“Tratamiento Farmacológico de la Diabesidad”,» Nutr. Clín. Med, vol. VI, nº 1, pp. 34-4, 2012. [2]L. Altamiro, M. Vásquez, G. Cordero, R. Álvarez, R. Añez, J. Rojas y V. Bermúdez, «Prevalencia de la diabetes mellitus tipo 2 y sus factores de riesgo en individuos adultos de la ciudad de Cuenca- Ecuador,» Avances en Biomedicina, vol. 6, nº 1, pp. 10-21, 2017. [3]A. Forero, J. Hernández, S. Rodríguez, J. Romero, G. Morales y G. Ramírez, «La alimentación para pacientes con diabetes mellitus de tipo 2 en tres hospitalespúblicos de Cundinamarca, Colombia,» Biomédica, nº38, pp. 355-362, 2018. [4]S. Durán, E. Carrasco y M. Araya, «Alimentación y diabetes,» Nutrición Hospitalaría, vol. 27, nº 4, pp. 1031-1036, 2012. [5]J. Hernandez, «Recomendaciones para el tratamiento médico de la obesidad exógena en el nivel primario de atención,» Rev cuba med gen integr, vol. 34, nº 3, pp. 123-144, 2018. [6]M. Acebo, «Obesidad y Salud: ¿En realidad existe el paciente obeso metabólicamente sano?,» Respyn, vol. 16, nº 2, p. 44–55, 2017. [7]T. Suarez, J. Sandoval, M. Galván, G. López, A.Olivo, A. J y M. González, «Nutracéuticos: usos potenciales en el tratamiento de la diabetes,» Educacióny Salud Boletín Científico de Ciencias de la Salud del ICSa, vol. 6, nº 12, p. doi: https://doi.org/10.29057/icsa.v6i12.3101, 2018. [8]R. Orellana, E. Salinas, D. Sánchez, J. Guajardo, E. Díaz y F. Rodríguez, «Tratamiento farmacológico de la diabetes mellitus tipo 2 dirigido a pacientes con sobrepeso y obesidad,» Medicina Interna México, vol. 35, nº4, pp. 525-536, 2019. [9]O. Pereira, «Diabesidad: una epidemia del siglo XXI,» Medisan , vol. 16, nº 2, pp. 295-299, 2012. [10]S. Andino, «Evolución de la diabetes mellitus tipo 2 en pacientes obesos mórbidos después del by pass gástrico. Tesis para la obtención del título de posgrado de Doctor en Medicina,» Universidad Católica de Córdoba , Córdoba- Argentina , 2016. [11]A. Muñoz, M. Jiménez, R. Mora, A. Hidalgo y D. Montoya, «Glucosa: amiga o enemiga,» de Diabetes mellitus: el reto a vencer, vol. 44, México, EditorialesFT, S. A., 2013, pp. 9-24. [12]H. Bays, L. Mandarino y R. DeFronzzo, «Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach,» J Clin Endocrinol Metab, vol.89, nº 2, pp. 463-478, 2014. [13]C. Quintanilla y S. Zúñiga, «El efecto incretina y su participación en la diabetes mellitus tipo 2,» Rev Med Inst Mex Seguro Soc, vol. 48, nº 5, pp. 509-520, 2013. [14]L. Baggio y D. Drucker, «Biology of incretins: GLP-1 and GIP,» Gastroenterology, vol. 132, nº 6, pp. 2131-2157, 2014. [15]Z. Cabrera y J. Díaz, «Sobrepeso - obesidad como factor de riesgo a la nefropatía en pacientes diabéticos del Hospital Víctor Lazarte Echegaray.2015,» Cientifi-k , vol. 5, nº 2, pp. 155-201, 2017. [16]F. Abbasi, J. Chu, C. Lamendola, T. McLaughlin, J. Hayden, G. Reaven y et al, «Discrimination between obesity and insulin resistance in the relationship withadiponectin,» Diabetes, vol. 53, nº 3, pp. 585-590, 2014. [17]M. Navarro, I. Jáuregui y G. Herrero, «Trastornos de la conducta alimentaria y diabetes mellitus: Tratamiento nutricional,» vol. 5, nº 9, pp. 914-1066, 2020. [18]A. Forero, J. Hernández, M. Rodríguez, J. Romero, G. Morales y G. Ramirez, «“La alimentación para pacientes con diabetes mellitus de tipo 2 en tres hospitales públicos de Cundinamarca, Colombia,» Biomédica, vol. 38, pp. 355-62, 2018. [19]S. Ramón y G. Medina, «Conocimientos, actitudes y prácticas nutricionales en diabéticos tipo 2 que integran los clubes de diabéticos urbanos, Cuenca, 2015,» Recimundo, vol. 2, pp. 595-610, 2018. [20]A. Prado, M. Mazacón y T. Estrada, «Aspectos nutricionales en la atención del paciente con diabetes,» Universidad, Ciencia y Tecnología, nº 02, pp. 132-139,2019. [21]D. Cárdenas, C. Bermúdez, S. Echeverri, A. Pérez, M. Puentes, L. López, M. Correia, J. Ochoa, A. Ferreira, M. Texeira, D. Arenas, H. Arenas, M. León y D. Rodríguez, «Declaración de Cartagena. declaración internacional sobre el derecho al cuidado nutricional y la lucha contra la malnutrición Cartagena,» Nutr Hosp, vol. 36, nº 4, pp. 974-980, 2019. [22]M. Manrique, M. de la Maza, F. Carrasco, M. Moreno, C. Albala, J. García, J. Díaz y C. Liberman, «Diagnóstico, evaluación y tratamiento no farmacológicodel paciente con sobrepeso u obesidad,» Rev Méd Chile, vol. 137, pp. 963-971, 2009. [23]A. Laparra, «Revisión sistemática y metaanálisis de los diferentes enfoques dietéticos para el tratamiento de la diabetes tipo 2: Lectura Crítica DARE,» Revista española de nutrición humana y dietética , vol. 21, nº 4, pp. 393-396, 2017. [24]F. Represa, «Comorbilidad, control metabólico y calidad de vida en los pacientes diabéticos tipo 2,» Biblioteca Lascasas, 2016. [25]P. Riobó Serván, «“Pautas dietéticas en la diabetes y en la obesidad”,» Nutr. Hosp., vol. 35, nº 4, pp. 109-115, 2018. [26]M. Hernández, M. Batle, B. Martínez, R. San Cristobal, S. Pérez, S. Navas y J. Martínez, «Cambios alimentarios y de estilo de vida como estrategia en la prevención del síndrome metabólico y la diabetes mellitus tipo 2: hitos y perspectivas,» Anales Sis San Navarra , vol. 39, nº 2, pp. 269-289, 2016. [27]R. Li, S. QU , P. Zhang, S. Chattopadhyay , E. Gregg , A. Albright , D. Hopkins y N. Pronk, «Economic evaluation of combined diet and physical activitypromotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the Community Preventive Services,» Ann Intern Med, vol. 163, nº 6, pp. 452-460, 2016. [28]J. López, Envejecimiento y nutrición. Intervención nutricional en pacientes diabéticos, Madrid: Sociedad Española de Geriatría y Gerontología , 2015. [29]I. Brajkovich, M. Izquierdo, R. Nieto y M. Cordero , «Tratamiento no farmacológico: aspectos nutricionales, estilo de vida y actividad física. Cirugía bariátrica,»Revista Venezolana de Endocrinología y Metabolismo, vol. 1, nº 1, pp. 47-57, 2012. [30]O. González, «Manejo nutricional en la diabetes mellitus tipo 2 y obesidad,» Revista Médica, vol. 4, nº1, pp. 22-31, 2014.

The text analyses three versions of “Programa Universidades e Institutos Empreendedores e Inovadores - Future-se”, presented by the Brazilian federal government. The proposition has been targeted by intense criticism, triggering an ample process of mobiliation and rejection by the deliberative organs of the Higher education federal institutions. The methodological procedures were guided by bibliographical revision and documental analysis with a qualitative nature approach. In the analysis, it was identified that, beyond the privatizing character, when proposing self-financing instruments via market resources captation, the program attacks university autonomy, even interfering with the courses formative profile. Entrepreneurship and employability actions, by the proposition, shall guide academic management of graduation and post-graduation courses. The managerialist logic, based in contracts and result indicators, in exchange of special benefits concession, imputes restrictions to the university makings. Despite the grave crisis of economical, political and sanitary order battled in the country, the government sent the Future-se law project to the House of Representatives and it is going to join to the group of measures of dismantlement of the State, idealized by Paulo Guedes. The results point that an agressive process of universitary counter-reform of which the centrality is the public financing dismantlement and the emptying of university autonomy is in order.ResumoO texto analisa as três versões do “Programa Universidades e Institutos Empreendedores e Inovadores - Future-se”, apresentado pelo governo federal brasileiro. A proposta tem sido alvo de intensas críticas, desencadeando um amplo processo de mobilização e rejeição pelos órgãos deliberativos das Instituições Federais de Ensino Superior. Os procedimentos metodológicos pautaram-se por revisão bibliográfica e análises documentais com abordagem de natureza qualitativa. Na análise feita identificou-se que, além do caráter privatizante, ao propor instrumentos de autofinanciamento via captação de recursos no mercado, o programa ataca a autonomia universitária, com interferência inclusive no perfil formativo dos cursos. Ações de empreendedorismo e empregabilidade, pela proposta, devem nortear a gestão acadêmica dos cursos de graduação e pós-graduação. A lógica gerencialista, pautada em contratos e indicadores de resultado, em troca da concessão de benefícios especiais imputa restrições ao fazer universitário. A despeito da grave crise de ordem econômica, política e sanitária enfrentada no país, o governo encaminhou o projeto de lei do Future-se à Câmara de Deputados e se juntará ao conjunto de medidas de desmonte do Estado, idealizada por Paulo Guedes. Os resultados apontam que está em curso um agressivo processo de contrarreforma universitária cuja centralidade é o desmonte do financiamento público e o esvaziamento da autonomia universitária.Palavras-chave: Future-se, Autonomia, Financiamento, Contrarreforma.Keywords: Future-se, Autonomy, Financing, Counter-reform.ReferencesBASTOS, Pedro Paulo Zahluth. Financeirização, crise, educação: considerações preliminares. Texto para discussão. IE/UNICAMP, Campinas, n.2017 mar. 2013.BRASIL. Constituição da República Federativa do Brasil de 1988. Disponível em http://www.planalto.gov.br/ccivil_03/constituicao/constituicao.htm. Acesso em 20/04/2020.BRASIL. Emenda Constitucional n. 95, de 15 de dezembro de 2016. Altera o Ato das Disposições Constitucionais Transitórias, para instituir o Novo Regime Fiscal, e dá outras providências. Disponível em: www.planalto.gov.br/ccivil_03/constituicao/Emendas/Emc/emc95.htm. Acesso em: 10 dez. 2019.BRASIL. CAPES. GEOCAPES – Sistema de Informações Georreferenciadas da CAPES. 2018. Disponível em: https://geocapes.capes.gov.br/geocapes/ Acesso em 20/03/2020.BRASIL. PRESIDÊNCIA DA REPÚBLICA. Lei nº 13.800 de 04 de janeiro de 2019a. Autoriza a administração pública a firmar instrumentos de parceria e termos de execução de programas, projetos e demais finalidades de interesse público com organizações gestoras de fundos patrimoniais; altera as Leis nº s 9.249 e 9.250, de 26 de dezembro de 1995, 9.532, de 10 de dezembro de 1997, e 12.114 de 9 de dezembro de 2009; e dá outras providências. Disponível em: http://www.planalto.gov.br/ccivil_03/_Ato2019-2022/2019/Lei/L13800.htm. Acesso em 10 de jan 2020.BRASIL. PRESIDÊNCIA DA REPÚBLICA. Decreto n° 9.725 de 12 de março de 2019b. Extingue cargos em comissão e funções de confiança e limita a ocupação, a concessão ou a utilização de gratificações. Disponível em: http://www.planalto.gov.br/ccivil_03/_ato2019-2022/2019/decreto/D9725.htm Acesso em 16 de abril 2020.BRASIL. PRESIDÊNCIA DA REPÚBLICA. Decreto n° 9.739 de 12 de março de 2019c. Estabelece medidas de eficiência organizacional para o aprimoramento da administração pública federal direta, autárquica e fundacional, estabelece normas sobre concursos públicos e dispõe sobre o Sistema de Organização e InovaçãoBRASIL. PRESIDÊNCIA DA REPÚBLICA. Decreto n° 9.741 de 29 de março de 2019d. Altera o Decreto n o 9.711, de 15 de fevereiro de 2019, que dispõe sobre a programação orçamentária e financeira, estabelece o cronograma mensal de desembolso do Poder Executivo federal para o exercício de 2019 e dá outras providências. Disponível em: http://www.planalto.gov.br/ccivil_03/_ato2019-2022/2019/decreto/D9711.htm Acesso em 16 de abril 2020.BRASIL. MINISTÉRIO DA EDUCAÇÃO. Portaria n° 1469 de 22 de agosto de 2019e. Fica estabelecido que os secretários da Secretaria de Educação Superior – SESU e da Secretaria de Educação Profissional e Tecnológica – SETEC divulgarão, junto às Instituições Federais de Ensino vinculadas ao Ministério da Educação, os limites de provimento de cargos autorizados nos bancos de professor-equivalente e nos quadros de referência de servidores técnico-administrativos em educação para o exercício de 2020. Disponível em: https://anup.org.br/legislacao/104366-2/ Acesso em 04 mar 2020.BRASIL. PRESIDÊNCIA DA REPÚBLICA. Medida Provisória nº 914 de 24 de dezembro de 2019f. Dispõe sobre o processo de escolha de dirigentes das universidades federais, dos institutos federais e do Colégio Pedro II. Disponível em: http://www.planalto.gov.br/ccivil_03/_ato2019-2022/2019/Mpv/mpv914.htm Acesso em 04 mar 2020.BRASIL. MINISTÉRIO DA EDUCAÇÃO. Minuta de Projeto de Lei versão do Programa Future-se. Brasília, DF: Ministério da Educação, 19 jul. 2019g. Disponível em: http://estaticog1.globo.com/2019/07/19/programa_futurese_consultapublica.pdf. Acesso em: 4 nov. 2019.BRASIL. MINISTÉRIO DA EDUCAÇÃO. Minuta de Projeto de Lei versão do Programa Future-se. Brasília, DF: Ministério da Educação, 16 out. 2019h. Disponível em: http://estaticog1.globo.com/2019/10/16/minuta_de_anteprojeto_de_lei__futurese__gt__portaria_1701__16102019.pdf. Acesso em: 26 out. 2019.BRASIL. Proposta de Emenda à Constituição n° 186, de 2019i. Altera o texto permanente da Constituição e o Ato das Disposições Constitucionais Transitórias, dispondo sobre medidas permanentes e emergenciais de controle do crescimento das despesas obrigatórias e de reequilíbrio fiscal no âmbito dos Orçamentos Fiscal e da Seguridade Social da União, e dá outras providências. Disponível em: https://www25.senado.leg.br/web/atividade/materias/-/materia/139702. Acesso em 20 mar.2020.BRASIL. Proposta de Emenda à Constituição n° 187, de 2019j. Institui reserva de lei complementar para criar fundos públicos e extingue aqueles que não forem ratificados até o final do segundo exercício financeiro subsequente à promulgação desta Emenda Constitucional, e dá outras providências. Disponível em: https://www25.senado.leg.br/web/atividade/materias/-/materia/139703. Acesso em 20 mar. 2020.BRASIL. Proposta de Emenda à Constituição n° 188, de 2019k. Estabelece medidas de ajuste fiscal aplicáveis ao custeio da máquina pública e outras modificações. Disponível em: https://www25.senado.leg.br/web/atividade/materias/-/materia/139704. Acesso 20 mar 2020. BRASIL. MINISTÉRIO DA EDUCAÇÃO. Minuta do Projeto de Lei versão do Programa Future-se. Brasília, DF: Ministério da Educação. 03 jan. 2020a. Disponível em: http://www.in.gov.br/en/web/dou/-/despacho-236403674 . Acesso em 25 fev.2020BRASIL. PRESIDÊNCIA DA REPÚBLICA. Lei n° 13.978 de 17 de janeiro de 2020b. Estima a receita e fixa a despesa da União para o exercício financeiro de 2020. 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FAKTOR-FAKTOR YANG MEMPENGARUHI MORTALITAS PADA PASIEN DENGAN FRAKTUR COSTA: Literature Review Anna Tri Wahyuni1), Masfuri2), Liya Arista3)1,2,3 Fakultas Ilmu Keperawatan Universitas Indonesia ABSTRAK Cedera paling umum yang terjadi pada trauma tumpul adalah fraktur costa (patah tulang iga/rusuk) dimana mekanisme cedera berpotensi mengancam jiwa. Pasien fraktur costa yang menunjukkan tingkat keparahan trauma lebih dari 90% melibatkan kepala, perut dan ekstremitas. Nyeri yang dirasakan akibat dari fraktur costa berkontribusi pada gangguan pernafasan, peningkatan resiko pneumonia dan gagal nafas yang meningkatkan angka morbiditas dan mortalitas. Pedoman penanganan fraktur costa sangat dibutuhkan untuk terjadinya komplikasi. Studi literature ini bertujuan menganalisis faktor-faktor yang mempengaruhi mortalitas pada pasien fraktur costa. Metode penulisan artikel ini menggunakan literature review yang didapat melalui 5 online database yaitu Sage Publishing, Science Direct, SpringerLink, Pub Med dan Google Scholar. Kriteria inklusi jurnal terkait meliputi: free fulltext, berbahasa Indonesia atau Bahasa asing lainnya, metode penelitian prospective, retrospective, case-control, cohort dan terbit antara tahun 2004-2021. Kata kunci yang yang digunakan dalam pencarian adalah “Respiratory depression OR Respiratory failure AND fraktur ribs AND Mortality”. Dari pencarian artikel diperoleh hasil akhir sebanyak 7 artikel yang relevan dan dilakukan proses review. Artikel tersebut menunjukkan hasil bahwa angka mortalitas dipengaruhi oleh faktor usia, skor keparahan cedera, jumlah patah tulang rusuk, dan implementasi penanganan infeksi. Faktor usia, tingkat keparahan cedera dan jumlah tulang rusuk yang patah menentukan tinggi rendahnya angka mortalitas pasien fraktur costa. Penanganan yang tepat dan manajemen nyeri yang sesuai dapat mempengaruhi penurunan angka morbiditas dan mortalitas pasien dengan fraktur costa. Pengembangan intervensi perawatan pasien fraktur costa terkait manajemen nyeri dan kontrol infeksi menjadi penelitian menarik selanjutnya.Kata kunci : Depresi pernafasan, gagal nafas, fraktur iga, angka kematian, angka kesakitanABSTRACT The most common injury in blunt trauma is a rib fracture, where the mechanism of injury is potentially life-threatening. Patients with rib fracture whose severity of the injury is greater than 90% are associated with damage to the head, abdomen, and extremities. Pain from rib fractures contributes to respiratory failure, increasing the risk of pneumonia and respiratory failure, which increases morbidity and mortality. Recommendations are needed for the treatment of complicated rib fractures. This literature study aims to analyze the factors that influence mortality in rib fracture patients. The method of writing this article uses a literature review sourced from 5 online databases, namely Sage Publishing, Science Direct, SpringerLink, Pub Med, and Google Scholar. The inclusion criteria for related journals included: free full text, in Bahasa or another foreign language, prospective, retrospective, case-control, cohort study method, and published between 2004 and 2021. Keywords used in the search were: "respiratory depression OR respiratory failure AND rib fractures AND death." From the article search results, we obtained 7 relevant articles which are the final results and a review process is carried out. The article showed that mortality was influenced by age, injury severity score, number of rib fractures, and infection control practices. The mortality rate of patient with rib fracture is determined by Factors such as age, severity of injury, and number of rib fractures. Appropriate care and adequate pain management can help reduce morbidity and mortality in patients with rib fractures. Another interesting research is the development of interventions in the treatment of rib fracture patients related to pain management and infection control.Key words: respiratory depression; respiratory failure; rib fracture; mortality; morbidity. Alamat korespondensi: RSUD Dr.Kanujoso Djatiwibowo Jalan MT.Haryono No 656 Ringroad BalikpapanEmail: annazahra30@gmail.com PENDAHULUAN Fraktur costa adalah cedera pada dada karena trauma tumpul, tajam atau kondisi patologis angka morbiditas dan mortilitas. Berdasarkan Western Trauma Association (WTA) sekitar 10% kematian pada orang dewasa muda disebabkan oleh cedera patah tulang rusuk yang melibatkan kepala, perut dan ekstremitas. Sebaliknya, pasien lanjut usia dengan patah tulang rusuk memiliki setidaknya 20% kematian yang secara langsung menyebabkan gagal napas progresif dan pneumonia (Brasel et al., 2017). Risiko pneumonia meningkat sebesar 27%, dan kematian meningkat sebesar 19% untuk setiap fraktur costa lebih dari 2 pada kelompok lanjut usia (Wanek & Mayberry, 2004). Pasien dengan trauma dada atau fraktur costa harusnya dilakukan pemantauan ketat sejak masuk rumah sakit, 24 jam pertama merupakan identifikasi awal adanya komplikasi yang menyebabkan depresi pernafasan. Menurut penelitian Coary, et.al (2020) fraktur costa adalah cedera paling serius pada 55% pasien berusia di atas 60 tahun yang menyebabkan kematian karena 90% dari patah tulang rusuk menunjukkan cedera tambahan pada pemeriksaan sistemik. Trauma langsung dan hipoventilasi yang diinduksi nyeri menyebabkan komplikasi pernafasan sehingga menjadi beban morbiditas dan mortalitas. Komplikasi yang sering terjadi adalah pneumotoraks diikuti hemothoraks, kontusio paru dan flail chest.Nyeri adalah suatu pengalaman sensorik yang multidimensional dengan fenomena yang berbeda dalam intensitas (ringan,sedang, berat), kualitas (tumpul, seperti terbakar, tajam), durasi (transien, intermiten,persisten), dan penyebaran (superfisial atau dalam, terlokalisir atau difus) (Bahrudin, 2018). Induksi nyeri pada pasien dengan fraktur costa menyebabkan pasien kesulitan bernafas dimana keparahan memar paru yang mendasarinya signifikan dengan terjadinya hipoksemia atau gangguan pernafasan. Hal ini menyebabkan pasien cenderung membatasi pergerakan dan menjadi tirah baring lama. Kondisi tirah baring lama menyebabkan tubuh mengalami penurunan berbagai fungsi secara sistematis, yang disebut dengan sindroma dekondisi dan rentan terjadinya infeksi (Hashem, Nelliot, & Needham, 2016; Hunter, Johnson, & Coustasse, 2014; Phelan, Lin, Mitchell, & Chaboyer, 2018 dalam Ananta & Fitri, 2020).Fraktur costa atau patah tulang rusuk secara klinis penting disebabkan tiga hal yaitu: sebagai penanda penyakit serius cedera intrathoraks dan perut, sebagai sumber rasa sakit yang signifikan, dan sebagai prediktor untuk kerusakan paru, terutama pada pasien usia lanjut. Organ perut yang paling sering terluka adalah hati dan limpa. Pasien dengan patah tulang rusuk kanan, memiliki 19% hingga 56% kemungkinan cedera hati, sedangkan patah tulang sisi kiri memiliki 22% hingga 28% kemungkinan cedera limpa (Wanek & Mayberry, 2004). Kematian pada orang dewasa dan lansia cenderung terjadi kemudian (≥72 jam setelah masuk) dan biasanya sebagai akibat dari kegagalan multi-organ yang dipicu oleh insufisiensi pernapasan dan pneumonia sehingga tingkat kematian secara keseluruhan, tanpa memandang usia, diperkirakan antara 10 dan 12% (Wanek & Mayberry, 2004). Tingkat mortalitas untuk pasien trauma usia lanjut yang mengalami patah tulang rusuk lebih besar daripada mereka yang tidak mengalami cedera toraks (Coary, et.al, 2020). Penelitian yang dilakukan Marini, et.al, (2021) menyatakan indikator penyebab kematian pada pasien fraktur costa dengan atau tanpa trauma kepala dan cedera organ adalah usia, jenis kelamin, ISS (Injury Severe Score), dan GCS (Glasglow Coma Scale).Berdasarkan uraian diatas maka peneliti ingin menganalisis faktor-faktor yang mempengaruhi angka morbiditas dan mortalitas pada pasien dengan fraktur costa untuk meningkatkan pemahaman tentang penanganan fraktur costa serta mengidentifikasi dari beberapa artikel terkini dalam mengurangi mortalitas. METODE PENELITIAN Metode penulisan artikel ini menggunakan literature review yaitu studi yang berfokus pada hasil penulisan yang berkaitan dengan topik, tema atau variabel penulisan.dan dipakai untuk menghimpun data atau sebuah sintesa sumber-sumber yang berhubungan dengan topik penelitian (Nursalam, 2017). Didapatkan 5 database yang dilakukan melalui pencarian elektronik dari yaitu Sage Publishing, Science Direct, SpringerLink, Pub Med dan Google Scholar. Kriteria inklusi telaah jurnal ini adalah free fulltext, berbahasa Indonesia atau bahasa asing lainnya, dengan metode penelitian prospective, retrospective, case-control, cohort dan terbit tahun 2004-2021. Kata kunci yang yang digunakan dalam pencarian adalah “Respiratory depression OR Respiratory failure AND fraktur ribs AND Mortality”. HASIL DAN PEMBAHASAN Berdasarkan hasil studi literature terdapat banyak faktor yang mempengaruhi terjadinya depresi pernafasan pada pasien fraktur costa yang dapat menyebabkan kematian. Terdapat 17.500 artikel yang muncul setelah dilakukan telusur berdasarkan kata kunci dalam google scholar, 10.000 artikel tidak masuk kriteria inklusi, 350 artikel duplikat dengan database yang lain. Kemudian sisanya disaring kembali berdasarkan hasil abstrak, metode dan hasil temuan sesuai topik peneliti yang diinginkan dan diperoleh 7 artikel yang relevan dan tersedia dalam bentuk fulltext. Beberapa penelitian terkait pencegahan depresi pernafasan pada fraktur costa berfokus pada manajemen nyeri baik secara farmakologis maupun non farmakologis. Penanganan dan pemantauan yang ketat dapat mengurangi komplikasi yang menyebabkan terjadinya depresi pernafasan. Berikut faktor-faktor yang mempengaruhi angka morbiditas dan mortalitas pada fraktur costa menurut Coary, et.al (2020) yaitu: (1) Usia, pasien berusia > 65 tahun memiliki kematian 2-5 kali lebih tinggi dibandingkan usia dibawahnya pada kondisi fraktur costa lebih dari dua. Pasien dengan komorbid sering menjadi faktor penyulit ditambah dengan kondisi paru-paru yang buruk (misal: perokok). Faktor pemulihan menjadi terhambat disebabkan osteoporosis, sistem pernafasan yang buruk, gangguan pertukaran gas dan tergambar dari lama rawat inap. (2) Jumlah patah tulang, dari beberapa penelitian meta-analisis diperoleh hasil jumlah absolut fraktur tulang rusuk yang berjumlah >2 maka dua kali lebih mungkin meninggal dunia dibandingkan pasien dengan 1-2 patah tulang rusuk. (3) Posisi anatomi patah tulang, Fraktur costa bilateral memiliki resiko kematian lebih tinggi dimana segmen flail chest menghasilkan gerak paradox yang menyebabkan pergerakan dinding dada mengarah kedalam saat inspirasi sedangkan tulang rusuk yang sehat bergerak keluar sehingga ventilasi tidak adekuat dan terjadi depresi pernafasan dan kematian. Berbeda dengan penelitian yang dilakukan Brasel et al., (2006) faktor yang paling mempengaruhi kematian adalah faktor usia ditandai dengan Injury Severity Score (ISS) jika dikaitkan dengan peningkatan terjadinya pneumonia. Analisis yang menyatakan komorbiditas mempengaruhi kematian hal ini disertai dengan faktor usia bukan karena faktor komorbiditas murni. Komorbiditas yang biasanya menyertai fraktur costa menurut penelitian adalah komorbiditas yang spesifik seperti gagal jantung kongestif, aritmia, gagal ginjal, penyakit hati, kanker metastatik dan penyakit neurologis.Pada penelitian Bulger et al dalam Wanek & Mayberry, (2004), membandingkan pasien yang berusia minimal 65 tahun keatas dengan usia 18-64 tahun dengan metode cohort pada kasus fraktur costa pada kelompok >65 tahun memiliki dua kali mortalitas dan morbiditas yang tinggi. Risiko pneumonia meningkat sebesar 27%, dan kematian meningkat sebesar 19% untuk setiap fraktur tulang rusuk tambahan pada kelompok lanjut usia.Nyeri adalah keluhan yang paling dirasakan oleh pasien dengan fraktur costa. Oleh sebab itu penanganan manajemen nyeri untuk mengontrol nyeri terus-menerus dan mencegah depresi pernafasan harus diberikan terapi yang agresif dengan pendekatan multimodalitas. Penelitian yang dilakukan oleh Peek, et.al, (2019) dengan membandingkan pemberian analgesik dengan 4 metode yaitu analgesia epidural, analgesia intravena, blok paravertebral dan blok intercostal, diperoleh hasil berdasarkan systematic review dan meta-analysis analgesia epidural signifikan mengurangi rasa sakit dibandingkan intervensi yang lain. Intervensi keperawatan sendiri menekankan pada terapi non farmakologis untuk kontrol nyeri pada pasien fraktur. Terapi nonfarmakologis dengan guided imagery dapat mengurangi intensitas dan skala nyeri pada pasien fraktur. Guided imagery mempengaruhi hampir semua fisiologis sistem kontrol tubuh yaitu pernapasan, denyut jantung, tekanan darah, tingkat metabolisme dalam sel, mobilitas dan sekresi gastrointestinal, fungsi seksual, dan bahkan respon imun (Rossman, 2000). Intervensi ini juga dapat mempercepat penyembuhan pasien dan mengurangi hari rawat inap (Forward et.al, 2015) Gambar 1. Algorithma fraktur costa (Brasel K.J, et.al, 2016).Western Trauma Association (WTA) menyatakan algorithma penanganan fraktur costa sebagai suatu observasi atau pemantauan ketat pada fraktur costa lebih dari 2 patah tulang (Brasel et.al, 2017). Berdasarkan algoritma diatas maka pasien dengan patah tulang rusuk >2 dengan usia lebih dari 65 tahun jika pada observasi kurang dari 24 jam menunjukkan peningkatan pada depresi pernafasan maka segera pindahkan ke ICU dan pertimbangkan penggunaan ventilator dan operasi rib fixaxion. Penggunaan terapi analgesia epidural digunakan untuk kontrol nyeri dilanjutkan batuk efektif, tehnik relaksasi nafas dalam dan mobilisasi dini (Brasel et.al, 2017). Analisis terkait studi literatur untuk memperkuat hasil analisis terdapat pada masing-masing artikel dibawah ini. Tabel 1. Artikel terkait faktor-faktor yang mempengaruhi terjadinya depresi pernafasan pada pasien dengan fraktur costa.Study citationMetode penelitian Desain PenelitianSampel dan Jumlah sampelHasil temuanA multidisciplinary clinical pathway decreases rib fracture–associated infectious morbidity and mortality in high-risk trauma patientsTodd,et.al,(2006)prospective cohort study Non eksperimental150 pasien dari Februari 2002-Oktober 2004 dengan > 45 tahun dan>4 patah tulang rusuk.Diperoleh hasil usia, skor keparahan cedera, dan jumlah patah tulang rusuk, jalur klinis menurunkan mekanisme hari tergantung ventilator, lama rawat inap, morbiditas infeksi, dan mortalitas dengan (interval kepercayaan 95% [CI] P<0.01).Predicting outcome of patients with chest wall injuryPressley, et.al, (2012)retrospectively reviewedNon eksperimental649 pasien (Juni 2008 hingga Februari 2010) termasuk usia, jumlah patah tulang, cedera bilateral, adanya kontusio paru, klasifikasi memar, LOS, masuk ICU, ventilasi mekanikSebuah sistem penilaian sederhana memprediksi kemungkinan bahwa pasien akan memerlukan ventilasi mekanik dan perawatan yang berkepanjangan. Skor 7 atau 8 memprediksi peningkatan risiko kematian, penerimaanke ICU, dan intubasi. Skor 5 memprediksi lama tinggal yang lebih lama dan periode ventilasi yang lebih lama. Factors Affecting Pneumonia Occurring to Patients with Multiple Rib FracturesByun & Kim., (2013).retrospectively reviewedNon eksperimentalData rekam medis 327 pasien laki-laki rata-rata usia 53 tahun dengan fraktur costa akibat kecelakaan dari Januari 2002- Desember 2008.Faktor yang mempengaruhi pneumonia pada pasien dengan fraktur tulang rusuk multipel dalam analisis multivariat termasuk usia (p=0,004), ISS (p＜0,001), dan skor tulang rusuk(p=0,038). Penggunaan antibiotik tidak berhubungan dengan kejadian pneumonia (p=0,28).Determinants of Mortality in Chest Trauma PatientsEkpe & Eyo, (2014)Retrospective and prospective Non eksperimental149 pasien dengan trauma thoraks 121 laki-laki, 28 perempuan dari Januari 2007-Desember 2011Variabel bebas, umur, jenis kelamin dan jenis cedera dada tidak terbukti berkorelasi dengan mortalitas dengan nilai P >0,05. Namun adanya cedera organ ekstra toraks terkait, skor MEWS saat masuk tinggi> 9, cedera pada interval presentasi lebih dari 24 jam, dan cedera dada yang parah ditandai dengan keterlibatan dada bilateral yang berkorelasi positif dengan mortalitas dengan nilai P <0,05.The number of displaced rib fractures is more predictive for complications in chest trauma patientsChien et.al, (2017)retrospectively reviewedNon eksperimentalJanuari 2013 -Mei 2015 diperoleh data di rumah sakit dengan total pasien 3151. Pasien yang dirawat dengan trauma dada dan patah tulang rusuk, termasuk cedera otak, limpa, panggul atau hatiJumlah patah tulang rusuk yang bergeser bisa menjadi prediktor kuat untuk berkembangnya penyakit paru-paru komplikasi. Untuk pasien dengan kurang dari tiga patah tulang rusuk tanpa perpindahan tulang rusuk dan paru-paru awal atau cedera organ lainnya, manajemen rawat jalan bisa aman dan efisien.Is the number of rib fractures a risk factor for delayed complications? Flores-Funes, et.al, (2020)Retrospective case–control studyNon eksperimentalPasien yang dirawat dengan diagnosis patah tulang rusuk antara 2010 dan 2014, diperoleh 141 pasien.Tidak ada perbedaan dalam karakteristik dasar pasien (usia, jenis kelamin dan Indeks Komorbiditas Charlson) antara kedua kelompok. Perbedaan ditemukan pada jumlah fraktur pada kelompok tanpa komplikasi p>0,05 (tidak signifikan) pada kelompok dengan komplikasi, (p=0,05) dan pada penurunan kadar hemoglobin (p=0,01). Hari rawat inap bervariasi pada setiap kelompok tetapi tanpa signifikansi statistik (p=0,11). Kesimpulan: Jumlah fraktur iga yang paling baik memprediksi munculnya komplikasi (delayed pleuro-pulmonary) dan perdarahan yang lebih besar) adalah patah tulang rusuk 3 atau lebihPredictors of mortality in patients with rib fracturesMarini, et.al, (2021) Retrospective review Non eksperimental1188 pasien patah tulang rusuk dan cedera tambahan yang dirawat selama Januari 2013-Desember 2014; 800 laki-laki dan 388 perempuan Usia, GCS, jenis kelamin laki-laki, dan Injury Severity Score (ISS) tetapi tidak jumlah patah tulang rusuk dan/atau Pulmonary contusion merupakan prediksi kematian. Peningkatan mortalitas pada pasien patah tulang rusuk dimulai pada usia 65-80 tahun tanpa peningkatan lebih lanjut. Jumlah patah tulang rusuk bukan faktor independen peningkatan mortalitas terlepas dari usia. Severe traumatic brain injury adalah penyebab kematian paling umum pada pasien usia 16-65 tahun, dibandingkan dengan komplikasi pernapasan pada pasien berusia 80 tahun atau lebih. Banyak penelitian yang telah dilakukan untuk menentukan faktor prediktor kematian pada pasien fraktur costa. Dari 7 artikel di atas terdapat berbagai bukti yang mempengaruhi kematian akibat fraktur costa dengan metode penelitian yang berbeda.Penelitian Chien, et.al, (2017) dan Flores-Funes, et.al, (2020) menunjukkan hasil yang hampir sama dimana jumlah fraktur costa yang >2 akan meningkatkan angka morbiditas dan mortalitas dikarenakan faktor komplikasi pada paru. Berbeda dengan penelitian yang dilakukan Marini, et.al, (2021) yang menyatakan jumlah dari fraktur costa tidak memprediksi peningkatan mortalitas terlepas dari usia. Menurut peneliti faktor usia menjadi prediktor utama dalam menentukan angka mortalitas pada pasien dengan fraktur costa, dimana peningkatan mortalitas pada pasien patah tulang rusuk dimulai pada usia 65-80 tahun ke atas.Penelitian yang dilakukan Todd et.al,(2006) menghasilkan hipotesa bahwa usia, skor keparahan cedera, dan jumlah patah tulang rusuk, dan implementasi jalur klinis signifikan dengan penurunan lama perawatan di unit perawatan intensif, lama rawat inap di rumah sakit, infeksi pneumonia, dan mortalitas. Maka semakin lanjut usia, tingkat keparahan yang tinggi dan jumlah patah tulang rusuk bilateral atau >2 dapat meningkatkan angka morbiditas dan mortalitas pasien dengan fraktur costa.Penelitian Pressley et.al, (2012) dilakukan dengan melakukan analisis dengan menggunakan trauma dada scoring system dimana skor >7 memprediksi peningkatan risiko kematian, penerimaan ke ICU, dan intubasi. Penilaian scoring system ini dapat digunakan untuk memprediksi kemungkinan pasien akan memerlukan ventilasi mekanik dan perawatan yang berkepanjangan sehingga dapat memperparah penyakit, menimbulkan infeksi oportunistik dan menyebabkan resiko mortalitas.Penelitian Ekpe & Eyo, (2014) menggunakan system MEWS (modified early warning signs) untuk menganalis faktor prognosis pada pasien dengan trauma dada. Sebagai variabel bebas, umur, jenis kelamin dan jenis cedera dada tidak terbukti berkorelasi dengan mortalitas dengan nilai P >0,05. Namun adanya cedera organ ekstra toraks terkait, skor MEWS saat masuk tinggi> 9, dimana interval presentasi lebih dari 24 jam dengan cedera dada yang parah ditandai dengan keterlibatan dada bilateral, berkorelasi positif pada mortalitas. Berbeda dengan penelitian sebelumnya Byun & Kim., (2013) dimana faktor umur berpengaruh pada terjadinya infeksi pneumonia dan meningkatkan angka mortilitas dengan atau tanpa diikuti tingkat keparahan pada trauma dada.Berdasarkan analisis diatas terdapat persamaan hasil penelitian dimana rata-rata metode penelitian yang dilakukan dengan menggunakan retrospective review non eksperimental. Peneliti mengamati data rekam medis dari beberapa rentang waktu dengan kriteria inklusi menderita patah tulang rusuk lebih dari dua. Namun, terdapat kriteria yang berbeda-beda pula dimana peneliti memasukkan trauma tambahan seperti brain injury dan cedera pada organ yang lain. Jumlah sampel antara penelitian satu dengan yang lain juga berbeda dari ratusan hingga ribuan data yang dianalisis. Hal ini menyebabkan hasil penelitian yang diperoleh sedikit berbeda antara satu dengan yang lain.Manajemen fraktur costa berfokus pada manajemen nyeri yang adekuat, batuk efektif, relaksasi nafas dalam dan mobilisasi dini (Brasel et al., 2017). Berdasarkan beberapa penelitian manajemen nyeri pada pasien orthopedic terutama pasca operasi adalah dengan guided imagery. The American Holistic Nurses Association menyatakan guided imagery adalah modalitas holistik yang membantu klien dalam menghubungkan pengetahuan batin mereka pada pemikiran, perasaan, dan tingkat penginderaan, mempromosikan penyembuhan bawaan mereka dengan kemampuan bersama-sama memandu klien mengatasi stres; resolusi konflik; masalah pemberdayaan diri; dan persiapan medis-bedah (Integrative & Review, 2016). Oleh sebab itu, guided imagery tepat jika digunakan pada managemen nyeri non farmakologis yang diterapkan dalam intervensi keperawatan.Dalam teori keperawatan Jean Watson tentang Transpersonal Caring mendefinisikan hubungan manusia yang bersifat caring, bersatu dengan orang lain dengan menghargai klien seutuhnya termasuk keberadaannya di dunia (Alligood, 2014). Watson menyatakan kepedulian transpersonal caring adalah dasar dari teori kepedulian manusia dimana fokus dari kepedulian transpersonal adalah pada peduli, penyembuhan, dan keutuhan, bukan pada penyakit, sakit dan patologi yang mencakup 10 faktor karatif dalam konsep utamanya (Integrative & Review, 2016). Sesuai dengan teori Watson, Guided Imagery (GI) menggabungkan kedua sains (melalui praktik berbasis bukti) dan seni (melalui aplikasi untuk berlatih) untuk mengobati rasa sakit pasien menggunakan imaginasi terbimbing dan teknik relaksasi nafas dalam. Kombinasi dengan terapi obat, GI menyediakan rezim pengobatan holistik untuk manajemen nyeri untuk menenangkan pikiran dan merilekskan tubuh mereka, memberikan kesempatan bagi klien untuk menciptakan lingkungan penyembuhan internalnya sendiri (Integrative & Review, 2016).Intervensi keperawatan untuk batuk efektif dan mobilisasi dini termasuk poin penting dalam manajemen perawatan pasien fraktur costa. Batuk efektif adalah suatu metode batuk dengan benar dan pasien dapat mengeluarkan dahak secara maksimal untuk mengeluarkan sekret dari saluran pernapasan bawah (Potter dan Perry, 2006). Mobilisasi sendiri dapat menghasilkan outcome yang baik bagi pasien seperti meningkatkan pertukaran gas, mengurangi angka Ventilator Associated Pneumoia (VAP), mengurangi durasi penggunaan ventilator, dan meningkatkan kemampuan fungsional jangka panjang (Green, Marzano, Leditschke, Mitchell, & Bissett, 2016 dalam Ananta & Fitri, 2020). Oleh sebab itu, kedua intervensi ini perlu diteliti lebih lanjut guna mengembangkan riset terkait manajemen pasien fraktur costa. SIMPULAN Pasien dengan usia lanjut dengan patah tulang rusuk atau fraktur costa biasanya menunjukkan tingkat kelemahan, multi-morbiditas, dan kompleksitas medis yang tinggi (Coary, et.al, 2020). Hal ini tentu menjadi penghambat dalam faktor penyembuhan tulang dan dapat meningkatkan angka mortalitas. Pemaparan hasil analisis menggambarkan faktor usia, cedera tulang rusuk atau costa bilateral lebih dari 2, terjadinya komplikasi dan cedera pada organ lain menyebabkan pasien harus dirawat di ruang ICU lebih lama karena resiko infeksi dan komplikasi yang dapat meningkatkan angka morbiditas dan mortalitas.Terlepas dari faktor usia, tingkat keparahan cedera dan jumlah tulang rusuk yang patah menentukan haluaran pasien yang lebih baik. Penanganan fraktur costa yang tepat yang berfokus pada kontrol kerusakan, manajemen nyeri, fiksasi seleksi, dan kualitas hidup mempengaruhi penurunan angka morbiditas dan mortalitas pasien dengan fraktur costa. Kedudukan dan peran perawat spesialis dalam tugas mengatur asuhan klien dengan kompleksitas tinggi menjadi sangat penting (Masfuri, et.all, 2019) SARAN Penelitian klinis terkait implementasi keperawatan berbasis kasus masih jarang dilakukan. Implementasi keperawatan pada pasien dengan fraktur costa terkait manajemen nyeri dan kontrol infeksi menjadi penelitian yang menarik untuk dilakukan karena hal ini menjadi indikator faktor yang mempengaruhi angka mortalitas pasien dengan fraktur costa. DAFTAR PUSTAKA Alligood Raile Martha,2014, Nursing Theorits and their Work, 8th edition, by Mosby, an imprint of Elsevier IncAnanta Tanujiarso, B., & Fitri Ayu Lestari, D. (2020). Mobilisasi Dini Pada Pasien Kritis Di Intensive Care Unit (Icu): Case Study. 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Importance: Sodium glucose co-transporter-2 (SGLT-2) inhibitors are being used among hospitalized patients, but there is no real-world empiric data on the risk of diabetic ketoacidosis (DKA) in-hospital. Objective: To assess the risk of DKA with SGLT-2 inhibitor use during hospital stay. Design, Setting, Participants: We conducted a multi-centre cohort study of hospitalized patients in 19 hospitals in Canada between January 1, 2015 and December 31, 2021. We included patients over age 18 years with type 2 diabetes mellitus who received an SGLT-2 inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor in hospital. Exposure: SGLT-2 inhibitor Comparator: DPP4-inhibitor Main Outcomes and Measures: The primary outcome was the risk of DKA defined using American Diabetes Association (ADA) DKA criteria (pH &lt;7.30, bicarbonate less than 18 mmol/l and positive ketones). Patients were followed from the date of admission to hospital to date of discharge or occurrence of DKA. Results: We identified 11,098 patients who received an SGLT-2 inhibitor and 67,429 who received a DPP-4 inhibitor. The average age was 67.7 years (SD: 18.3 years), and 47.7% were women. In the matched population, the risk of DKA was 0.06% (N=6 events) over 5.2 hospital days with DPP-4 inhibitors and 0.19% (N=20 events) over 5.4 hospital days with SGLT-2 inhibitors. The relative risk was 3.33 (95% CI 1.33 - 8.30) for SGLT-2 inhibitors compared to DPP-4 inhibitors. Conclusion and Relevance: Among hospitalized patients, the risk of DKA with use of SGLT-2 inhibitors was three-fold higher compared to DPP-4 inhibitors, but the absolute risk of DKA was low. Disclosure S. Sarma: None. B. Hodzic-Santor: None. M. Colacci: None. A.A. Verma: None. F. Razak: None. A. Raissi: None. M.C.H. Lassen: None. M. Fralick: Consultant; singal1, proofdx.