A Peek at LVADs Pumping to Recovery.

Left ventricular assist devices (LVADs) have revolutionized the management of patients with advanced heart failure refractory to medical therapy. Current indications of LVADs include Bridge to Transplantation (BTT), Destination Therapy (DT) for long-term use, Bridge to the Decision (BTD) used as a temporary measure, and lastly Bridge to Recovery (BTR). Here, we briefly review the clinical evidence and the molecular mechanisms behind myocardial recovery following LVAD placement. We also share institutional protocols used at 2 major medical centers in the USA.

Association of scooter-related injury and hospitalization with electronic scooter sharing systems in the United States.

INTRODUCTION: We used interrupted time series (ITS) analysis to determine whether e-scooter shares' introduction in September 2017 increased serious scooter-related injury across the United States. METHODS: Using the National Electronic Injury Surveillance System, we queried emergency department visits involving motorized scooter-related injuries from January 2010-December 2019. Cases originating where e-scooter shares launched between September 1, 2017-December 1, 2019 (intervention period) were considered exposed. The first month of launch (September 2017) was chosen as the time point for pre- and post-intervention analysis. The primary outcome was change in hospitalizations following scooter injury in association with the month/year launch. RESULTS: This analysis includes 2754 unweighted encounters, representing 102614 estimated injuries involving motorized scooters nationwide. Hospitals within 20 miles of e-scooter shares also experienced a significant monthly increase of 0.24 scooter-related injury hospitalizations/1000 product-related injury hospitalizations ([0.17,0.31]) compared to a non-significant change in hospitalizations of 0.02 [-0.05,0.09] for control hospitals. CONCLUSION: An increase in serious motorized scooter injuries coincides with e-scooter shares' introduction in the US. Future works should explore effective polices to improve public safety.

Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

PURPOSE: Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. EXPERIMENTAL DESIGN: We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. RESULTS: Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. CONCLUSIONS: The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR.

Tumor-Specific Effector CD8+ T Cells That Can Establish Immunological Memory in Humans after Adoptive Transfer Are Marked by Expression of IL7 Receptor and c-myc.

The optimal T-cell attributes for adoptive cancer immunotherapy are unclear. Recent clinical trials of ex vivo-expanded tumor-infiltrating lymphocytes indicated that differentiated T effector cells can elicit durable antitumor responses in some patients with cancer, with their antitumor activity tightly correlated with their persistence in the host. Thus, there is great interest in the definition of intrinsic biomarkers that can predict the conversion of short-lived tumor antigen-specific T effector cells into long-lived T memory cells. Long-term persistence of ex vivo-expanded tumor-specific CD8+ T effector clones has been reported in refractory metastatic melanoma patients after adoptive T-cell transfer. By using highly homogeneous clone populations from these preparations, we performed a comparative transcriptional profiling to define preinfusion molecular attributes that can be ascribed to an effector-to-memory transition. Through this route, we discovered that preinfusion T-cell clones that expressed the IL7 receptor (IL7R) and c-myc were more likely to persist longer after adoptive transfer to patients. The predictive value of these two biomarkers was strengthened by using IL7R protein, IL7-induced pSTAT5, and c-myc mRNA expression to prospectively identify human tumor-specific T effector clones capable of engraftment into immunodeficient mice. Overall, our findings reveal IL7R and c-myc expression as intrinsic biomarkers that can predict the fate of CD8+ T effector cells after adoptive transfer.

Persistence of CTL clones targeting melanocyte differentiation antigens was insufficient to mediate significant melanoma regression in humans.

PURPOSE: Adoptive transfer of autologous tumor infiltrating lymphocytes (TIL) can mediate durable cancer regression in selected patients with metastatic melanoma. However, the tumor antigens associated with these favorable responses remain unclear. We hypothesized that a clinical strategy involving the iterative adoptive transfer of selected autologous antigen-specific T-cell clones could help systematically define immunologic targets associated with successful cancer therapy, without the interpretative ambiguity of transferring polyclonal populations. Here, we evaluated the clinical efficacy of CD8(+) T-cell clones specific for the melanocyte differentiation antigens (MDA), gp100 and MART-1, respectively. EXPERIMENTAL DESIGN: We conducted two consecutive phase II clinical trials involving the adoptive transfer of highly selected autologous antigen-specific CD8(+) T-cell clones against gp100 and MART-1, respectively. Fifteen patients with HLA-A2(+) treatment-refractory metastatic melanoma received highly avid MDA-specific CD8(+) T-cell clones specific for either gp100 (n = 10) or MART-1 (n = 5) with or without intravenous interleukin-2 (IL2) after a lymphodepleting myeloablative preparative regimen. RESULTS: Of the 15 treated patients, we observed immune-mediated targeting of skin melanocytes in 11 patients (73%) and clonal engraftment in eight patients (53%) after cell transfer. There were only transient minor tumor regressions observed, but no objective tumor responses based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria. CONCLUSIONS: Despite successful clonal repopulation and evidence of in vivo antigen targeting, the poor therapeutic efficacy after the adoptive transfer of autologous MDA-specific T cells raises significant concerns regarding future immunotherapy efforts targeting this class of tumor antigens.

Human melanoma metastases demonstrate nonstochastic site-specific antigen heterogeneity that correlates with T-cell infiltration.

PURPOSE: Metastasis heterogeneity presents a significant obstacle to the development of targeted cancer therapeutics. In this study, we sought to establish from a large series of human melanoma metastases whether there exists a determined pattern in tumor cellular heterogeneity that may guide the development of future targeted immunotherapies. EXPERIMENTAL DESIGN: From a cohort of 1,514 patients with metastatic melanoma, biopsies were procured over a 17-year period from 3,086 metastatic tumors involving various anatomic sites. To allow specific tumor cell profiling, we used established immunohistochemical methods to perform semiquantitative assessment for a panel of prototypic melanocyte differentiation antigens (MDA), including gp100, MART-1, and tyrosinase. To gain insight into the endogenous host immune response against these tumors, we further characterized tumor cell expression of MHC I and MHC II and, also, the concomitant CD4(+) and CD8(+) T-cell infiltrate. RESULTS: Tumor cell profiling for MDA expression demonstrated an anatomic site-specific pattern of antigen expression that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral metastases. Hierarchical clustering analysis supported that melanoma metastases have a phylogenetically determined, rather than a stochastic, pattern of antigen expression that varies by anatomic site. Furthermore, tyrosinase expression was more frequently lost in metastatic sites outside of the brain and was uniquely correlated with both endogenous CD8(+) and CD4(+) T-cell infiltrates. CONCLUSION: Site-specific antigen heterogeneity represents a novel attribute for human melanoma metastases that should be considered in future therapy development and when assessing the responsiveness to antigen-specific immunotherapies.

Clostridium difficile infection in the pediatric surgery population.

PURPOSE: The incidence of Clostridium difficile-associated disease (CDAD) in the adult population doubled in the past decade, with increasing morbidity and mortality; however, little research has been performed in the pediatric population. We characterized C difficile infection in the pediatric population, with emphasis on the surgical population. METHODS: At a university-based children's hospital, we reviewed 231 patient (birth to 18 years of age) records containing a diagnosis of CDAD between January 1, 2002, and December 31, 2008. RESULTS: Clostridium difficile-associated disease incidence increased from 250 per 100,000 hospitalizations in 2002 to 580 per 100,000 hospitalizations in 2008. No fatalities or surgical interventions were attributable to CDAD. Eighty-seven percent of patients received antibiotics within 2 months of diagnosis. Fifty-two percent of patients underwent operative intervention within 2 months of diagnosis; of these, 89% percent received previous antibiotic therapy and 57% were immunosuppressed. The most common antecedent procedures were bone marrow biopsy and line placement for myelodysplastic diseases (40%), followed by renal transplant (11%). CONCLUSIONS: Pediatric CDAD incidence doubled during the study period but was not associated with death or operative intervention. A substantial number of CDAD cases were associated with previous operative procedures, particularly in immunosuppressed patients and those who received prior antibiotics.

One-year readmission rates at a high volume bariatric surgery center: laparoscopic adjustable gastric banding, laparoscopic gastric bypass, and vertical banded gastroplasty-Roux-en-Y gastric bypass.

BACKGROUND: An increasing importance has been placed on a bariatric program's readmission rates. Despite the importance of such data, there have been few studies that document 1-year readmission rates. There have been even fewer studies that delineate the causes of readmission. The objective of this study is to delineate the rates and causes of readmissions within 1 year of bariatric operations performed in a high-volume center. METHODS: Records for all patients undergoing bariatric operations during a 31-month period were harvested from the hospital electronic medical database. Readmissions for these patients were then identified within the hospital database for the year following the index operation. The electronic medical records of all readmitted patients were reviewed. RESULTS: The overall 1-year readmission rate for 1,939 consecutive bariatric operations was 18.8%. The laparoscopic adjustable gastric band (LAGB) had the lowest readmission rate of 12.69%. Next was the vertical banded gastroplasty-Roux-en-Y gastric bypass (VBG-RYGB) with a rate of 15.4%. The laparoscopic Roux-en-Y gastric bypass (LRYGB) had the highest readmission rate of 24.2%. Leading causes of readmission were abdominal pain with normal radiographic studies and elective operations. Independent factors predicting readmission were found to be LOS > 3 days (odds ratio 1.69 p = 0.004) and having a LRYGB (odds ratio of 1.49 p = 0.003). The previously reported reoperation rate for bowel obstruction of 9.7% had decreased to 3.7% due to changes in operative technique. CONCLUSION: Rates of readmissions for patients undergoing bariatric surgery center at our high-volume center decreased over time and are comparable to other major abdominal operations.

Short-term outcomes for super-super obese (BMI > or =60 kg/m2) patients undergoing weight loss surgery at a high-volume bariatric surgery center: laparoscopic adjustable gastric banding, laparoscopic gastric bypass, and open tubular gastric bypass.

BACKGROUND: We previously reported significantly longer operating room times and a trend toward increased complications and mortality in the super-super obese (body mass index [BMI] > or =60 kg/m(2)) early in our experience with laparoscopic Roux-en-Y gastric bypass. The goal of this study was to re-examine the short-term outcomes for super-super obese patients undergoing weight loss surgery at our high-volume bariatric surgery center well beyond our learning curve. METHODS: The records for all patients who had undergone weight loss surgery at Hackensack University Medical Center from 2002 to June 2006 were harvested from the hospital's electronic medical database. This population was analyzed as 2 groups (those with a BMI <60 kg/m(2) and those with a BMI > or =60 kg/m(2)), as well as by type of operation. Step-wise and univariate logistic regression analyses assessed the effect of BMI on the outcome variables, including mortality, length of surgery, length of hospital stay, and disposition at discharge. RESULTS: A total of 3692 patients were studied. Of these patients, 3401 had a BMI <60 kg/m(2) and 291 had a BMI > or =60 kg/m(2). Of the 291 super-super obese patients, 130 underwent vertical banded gastroplasty-Roux-en-Y gastric bypass, 116 laparoscopic Roux-en-Y gastric bypass, and 45 laparoscopic adjustable gastric banding. The proportion of male patients, black patients, and patients with sleep apnea was increased in the BMI > or =60 kg/m(2) group. The number of co-morbid diseases per patient correlated with age but not BMI. The BMI > or =60 kg/m(2) group required a significantly longer total operating room time (136 versus 120 min). Hospital length of stay was significantly longer only in the laparoscopic Roux-en-Y gastric bypass patients (3 d for the BMI > or =60 kg/m(2) group versus 2 d for the BMI <60 kg/m(2) group). A significantly greater percentage of patients in the super-super obese group were discharged to chronic care facilities. The overall in-hospital mortality rate was 0.15% (5 of 3692) but did not significantly differ between the 2 groups: BMI <60 kg/m(2), rate of 0.12% (4 of 3401 patients), and BMI > or =60 kg/m(2), rate of 0.34% (1 of 291 patients). The type of operation did not significantly affect the disposition at discharge or in-hospital mortality. CONCLUSION: Super-super obese patients required longer total operating room times, a longer hospital length of stay, and were more likely to be discharged to chronic care facilities than were patients with a BMI <60 kg/m(2); however, the in-hospital mortality was similar for both groups.