Impact of Sarcopenia on Simultaneous Pancreas and Kidney Transplantation Outcomes: A Retrospective Observational Cohort Study.

BACKGROUND: Sarcopenia has been identified as a predictive variable for surgical outcomes. We hypothesized that sarcopenia could be a key measure to identify frail patients and potentially predict poorer outcomes among recipients of simultaneous pancreas and kidney (SPK) transplants. METHODS: We estimated sarcopenia by measuring psoas muscle mass index (PMI). PMI was assessed on perioperative computed tomography (CT) scans of SPK recipients. RESULTS: Of the 141 patients identified between 2010 and 2018, 107 had a CT scan available and were included in the study. The median follow-up was 4 years (range, 0.5-9.1 y). Twenty-three patients had a low PMI, and 84 patients had a normal PMI. Patient characteristics were similar between the 2 groups except for body mass index, which was significantly lower in low PMI group (P < 0.001). Patient and kidney graft survival were not statistically different between groups (P = 0.851 and P = 0.357, respectively). A multivariate Cox regression analysis showed that patients with a low PMI were 6 times more likely to lose their pancreas allograft (hazard ratios, 5.4; 95% confidence intervals, 1.4-20.8; P = 0.015). Three out of 6 patients lost their pancreas graft due to rejection in the low PMI group, compared with 1 out of 9 patients in the normal PMI group. Among low PMI patients who had a follow-up CT scan, 62.5% (5/8) of those with a functional pancreas graft either improved or resolved sarcopenia, whereas 75.0% (3/4) of those who lost their pancreas graft continued to lose muscle mass. CONCLUSION: Sarcopenia could represent one of the predictors of pancreas graft failure and should be evaluated and potentially optimized in SPK recipients.

Attitudes of Israeli medical students towards the medical treatment of uninsured migrants.

BACKGROUND: Undocumented migration to developed countries poses practical concerns, as migrants are not medically insured. This cross-sectional study aims to appraise the attitudes of Israeli medical students towards the uninsured migrant population. METHODS: Participants from five medical schools in Israel completed anonymous questionnaires in Hebrew, based on the "Medical Students' Attitudes Toward the Underserved" (MSATU), which assessed students' attitudes regarding the professional responsibility and societal expectations towards the migrants. It also evaluated students' views of the migrants as eligible for expensive medical procedures. RESULTS: A total of 891 students completed the survey with a median age of 28 years. The majority were Jews (N = 816, 91.6%) and singles (N = 681, 68.5%). Participants in the pre-clinical years were likely to be female and unmarried compared to those in clinical training. They also demonstrated higher scores on professional responsibilities and societal expectations than students in clinical training, but no significant differences were found in their views on expensive medical services. Students of minorities (non-Jews and migrants) scored higher on professional responsibilities and societal expectations. The scores for professional responsibilities and societal expectations decreased as students progressed in their medical training (Spearman coefficient p = 0.04 and p = 0.01, respectively). This trend was more apparent in males rather than females. CONCLUSION: MSATU scores declined as students progressed through medical school, with females maintaining more favorable attitudes than males. Medical schools should attempt to maintain the enthusiasm and idealism that students possess as they enter medical training and provide clinical experience with migrant populations that allows for cross-cultural communication.

Outcomes of multiple myeloma patients receiving bortezomib, lenalidomide, and carfilzomib.

New classes of drugs including the proteasome inhibitors (PI) bortezomib and, more recently, carfilzomib and the immunomodulatory agent lenalidomide have shown improved outcomes for multiple myeloma (MM) patients during the past decade. However, most of the studies reporting outcomes for patients receiving these drugs have relied on older data sets derived from large institutions that included patients not receiving their treatment at those facilities and represented only those eligible for clinical trials or were from sites where treatment options were limited. We have analyzed data from 258 MM patients who have received treatment with at least one of three agents: bortezomib, carfilzomib, and lenalidomide in a single clinic specializing in MM with respect to their responses and other outcomes to treatment regimens including these agents. Response rates were similar between these three drugs when used for the first time and again during subsequent treatment regimens. As expected, the clinical benefit rates (CBRs) were better for patients receiving their first treatment when compared to their use in subsequent treatment regimens. The CBRs were similar during their 2nd, 3rd, and 4th treatments containing these agents. Many patients refractory to these agents showed responses to regimens containing these same drugs when used in different combinations. In addition, patients refractory to one PI often responded to the other PI. The results of this study demonstrate that novel agents can be used repeatedly in novel combinations with significant clinical benefit for patients with MM.

Improved clinical outcomes for multiple myeloma patients treated at a single specialty clinic.

Despite recent advances made in its treatment, multiple myeloma (MM) remains an incurable B cell malignancy. Thus, the objective for treating these patients is to prolong overall survival (OS) and preserve patients' quality of life. We have analyzed data from 264 consecutive MM patients who had their initial visit between July 1, 2004 and December 1, 2014 and have received treatment in a single clinic specializing in MM. We determined their progression-free survival (PFS, OS, and 5-year OS). The PFS for frontline (n = 165 treatments), salvage (n = 980), and all treatments (n = 1145) were 13.9, 4.6, and 5.5 months, respectively. The median OS of all patients was 98 months with a 5-year survival of 74%. The results of this study show a marked improvement in OS for unselected MM patients compared with historical data. There were no significant differences in OS between patients with different International Staging System (ISS) stages. Younger patients (<65 years old) showed a longer OS. The results of this study should help physicians predict outcomes for MM patients and be encouraging for patients with this B cell malignancy.

Augmentation of integrin-mediated mechanotransduction by hyaluronic acid.

Changes in tissue and organ stiffness occur during development and are frequently symptoms of disease. Many cell types respond to the stiffness of substrates and neighboring cells in vitro and most cell types increase adherent area on stiffer substrates that are coated with ligands for integrins or cadherins. In vivo cells engage their extracellular matrix (ECM) by multiple mechanosensitive adhesion complexes and other surface receptors that potentially modify the mechanical signals transduced at the cell/ECM interface. Here we show that hyaluronic acid (also called hyaluronan or HA), a soft polymeric glycosaminoglycan matrix component prominent in embryonic tissue and upregulated during multiple pathologic states, augments or overrides mechanical signaling by some classes of integrins to produce a cellular phenotype otherwise observed only on very rigid substrates. The spread morphology of cells on soft HA-fibronectin coated substrates, characterized by formation of large actin bundles resembling stress fibers and large focal adhesions resembles that of cells on rigid substrates, but is activated by different signals and does not require or cause activation of the transcriptional regulator YAP. The fact that HA production is tightly regulated during development and injury and frequently upregulated in cancers characterized by uncontrolled growth and cell movement suggests that the interaction of signaling between HA receptors and specific integrins might be an important element in mechanical control of development and homeostasis.