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A recent randomized, multicenter trial did not show benefit of a CXCR1/2 receptor inhibitor (Reparixin) when analysis included marginal islet mass (>3,000 IEQ/kg) for allotransplantation and when immunosuppression regimens were not standardized among participating centers. We present a post-hoc analysis of trial patients from our center at the University of Chicago who received an islet mass of over 5,000 IEQ/kg and a standardized immunosuppression regimen of anti-thymocyte globulin (ATG) for induction. Twelve islet allotransplantation (ITx) recipients were randomized (2:1) to receive Reparixin (N = 8) or placebo (N = 4) in accordance with the multicenter trial protocol. Pancreas and donor characteristics did not differ between Reparixin and placebo groups. Five (62.5%) patients who received Reparixin, compared to none in the placebo group, achieved insulin independence after only one islet infusion and remained insulin-free for over 2 years (P = 0.08). Following the first ITx with ATG induction, distinct cytokine, chemokine, and miR-375 release profiles were observed for both the Reparixin and placebo groups. After excluding procedures with complications, islet engraftment on post-operative day 75 after a single transplant was higher in the Reparixin group (n = 7) than in the placebo (n = 3) group (P = 0.03) when islet graft function was measured by the ratio of the area under the curve (AUC) for c-peptide to glucose in mixed meal tolerance test (MMTT). Additionally, the rate of engraftment was higher when determined via BETA-2 score instead of MMTT (P = 0.01). Our analysis suggests that Reparixin may have improved outcomes compared to placebo when sufficient islet mass is transplanted and when standardized immunosuppression with ATG is used for induction. However, further studies are warranted. Investigation of Reparixin and other novel agents under more standardized and optimized conditions would help exclude confounding factors and allow for a more definitive evaluation of their role in improving outcomes in islet transplantation. Clinical trial reg. no. NCT01817959, clinicaltrials.gov

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation.

BackgroundChronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) in pediatric patients are strongly associated with genetic mutations and lead to pan-parenchymal disease refractory to medical and endoscopic treatment. Our aim was to assess pain resolution and glucose control in patients with CP and ARP following total pancreatectomy with islet auto-transplantation (TPIAT).MethodsWe retrospectively analyzed prospectively collected clinical data of 12 children who developed CP and ARP and underwent TPIAT when 21 years old or younger at the University of Chicago between December 2009 and June 2020. Patients with recurrent or persistent abdominal pain attributed to acute or chronic pancreatic inflammation and a history of medical interventions attempted for the relief of pancreatic pain were selected by a multi-disciplinary team for TPIAT. We followed patients post-operatively and reported data for pre-TPIAT, post-operative day 75, and yearly post-TPIAT.ResultsAll 12 patients experienced complete resolution of pancreatic pain. The overall insulin-independence rate after 1 year was 66% (8/12) and 50% (3/6) at 4 years. Shorter duration of CP/ARP pre-TPIAT, higher mass of islets infused, and lower BMI, BMI percentile, and BSA were associated with insulin-independence post-TPIAT.ConclusionsTPIAT is a viable treatment option for pediatric patients with CP and ARP. Pediatric patients undergoing TPIAT for CP achieved resolution of pancreatic-type pain and reduced opioid requirements. The majority were able to achieve insulin-independence which was associated with lower pre-TPIAT BMI and higher islet mass transplanted (i.e., over 2000 IEQ/kg), the latter of which can be achieved by earlier TPIAT.Level of evidenceTreatment study, Level IV.

Natural disasters significantly contribute to human death and suffering. Moreover, they exacerbate pre-existing health inequalities by imposing an additional burden on the most vulnerable populations. Robust local health systems can greatly mitigate this burden by absorbing the extraordinary patient volume and case complexity immediately after a disaster. This resilience is largely determined by the predisaster local surgical capacity, with trauma, neurosurgical, obstetrical and anaesthesia care of particular importance. Nevertheless, the disaster management and global surgery communities have not coordinated the development of surgical systems in low/middle-income countries (LMIC) with disaster resilience in mind. Herein, we argue that an appropriate peridisaster response requires coordinated surgical and disaster policy, as only local surgical systems can provide adequate disaster care in LMICs.We highlight three opportunities to help guide this policy collaboration. First, the Lancet Commission on Global Surgery and the Sendai Framework for Disaster Risk Reduction set forth independent roadmaps for global surgical care and disaster risk reduction; however, ultimately both advocate for health system strengthening in LMICs. Second, the integration of surgical and disaster planning is necessary. Disaster risk reduction plans could recognise the role of surgical systems in disaster preparedness more explicitly and pre-emptively identify deficiencies in surgical systems. Based on these insights, National Surgical, Obstetric, and Anesthesia Plans, in turn, can better address deficiencies in systems and ensure increased disaster resilience. Lastly, the recent momentum for national surgical planning in LMICs represents a political window for the integration of surgical policy and disaster risk reduction strategies.

(1) Background: The correlation between titers of islet autoantibodies (IAbs) and the loss of transplanted islets remains controversial. We sought to evaluate the prognostic utility of monitoring IAbs in diabetic patients after islet transplantation (ITx); (2) Methods: Twelve patients with Type 1 diabetes mellitus and severe hypoglycemia underwent ITx. Serum concentration of glutamic acid decarboxylase (GAD), insulinoma antigen 2 (IA-2), and zinc transport 8 (ZnT8) autoantibodies was assessed before ITx and 0, 7, and 75 days and every 3 months post-operatively; (3) Results: IA-2A (IA-2 antibody) and ZnT8A (ZnT8 antibody) levels were not detectable before or after ITx in all patients (median follow-up of 53 months (range 24–61)). Prior to ITx, GAD antibody (GADA) was undetectable in 67% (8/12) of patients. Of those, 75% (6/8) converted to GADA+ after ITx. In 67% (4/6) of patients with GADA+ seroconversion, GADA level peaked within 3 months after ITx and subsequently declined. All patients with GADA+ seroconversion maintained long-term partial or complete islet function (insulin independence) after 1 or 2 ITx. There was no correlation between the presence of IAb-associated HLA haplotypes and the presence of IAbs before or after ITx; (4) Conclusions: There is no association between serum GADA trends and ITx outcomes. IA-2A and ZnT8A were not detectable in any of our patients before or after ITx.

Women with breast cancer in low-income and middle-income countries (LMICs) account for 51% of cases globally and often present with advanced disease. Fear of costs contributes to delay in seeking care, as health expenditures are financially catastrophic for families worldwide. Despite efforts to improve affordability of health care in LMICs, the financial burden of indirect costs (eg, transportation and lost wages) is often overlooked. We aimed to identify and quantify the expenditures of patients seeking breast cancer care in a LMIC. Patients receiving breast cancer care free of charge at Hôpital Universitaire de Mirebalais (HUM) in Haiti were interviewed to quantify their costs and assess the effect of these costs on patients and families. These costs included expenses for food, lodging, transportation, childcare, medical costs at other institutions, and lost wages. 61 patients were interviewed during diagnostic, chemotherapy, and surgical visits between March 1, and May 12, 2014. Institutional review board exemption was granted from Boston Children's Hospital and Partners in Health/Zanmi Lasante. The median non-medical out-of-pockent expenses incurred by breast cancer patients at HUM were US$233 (95% CI 170–304) for diagnostic visits, US$259 (95% CI 200–533) for chemotherapy, and US$38 (95% CI 23–140) for surgery. The median total out-of-pockent expense (including medical costs) was US$717 (95% CI 619–1171). These costs forced 52% of participants into debt and 20% to sell possessions. The median percentage of potential individual income spent on out-of-pocket costs was 60%. The median sum of out-of-pocket costs and lost wages was US$2996 (95% CI 1676–5179). In Haiti, 74% of people earn less than US$2 per day. Even when breast cancer treatment is provided for free, out-of-pocket expenses could account for more than 91% of annual earnings at this income level. This financial burden is an overwhelming obstacle for Haiti's poorest citizens, and probably for many patients in LMICs. High-powered, multisite studies are needed to further characterise this burden worldwide. Funders and health-care providers should reduce indirect costs to achieve equitable access to oncology care. Boston Children's Hospital and Partners in Health.

Health systems must deliver care equitably to serve the poor. Both L'Hôpital Albert Schweitzer (HAS) and L'Hôpital Bon Sauveur (HBS) have longstanding commitments to provide equitable surgical care in rural Haiti. HAS charges fees that reflect a preference for the rural population near the hospital, with free care available for the poorest. HBS does not charge fees. The two hospitals are otherwise similar in surgical capacity and rural location. Using geography as a proxy for poverty, we analysed the equity achieved under the financial system at both hospitals. We retrospectively reviewed operative case-logs for general surgery and orthopaedic cases at both hospitals from June 1, to Aug 31, 2012. The records were compared by total number of operations, geographic distribution of patients, and number of elective operations. The service areas were defined as the governmental administrative units closest to both hospitals. For HAS, we analysed the number of operations performed on patients from the most poor and least poor regions within the service area; similarly detailed geographic information was not available from HBS. Rates were compared with χ2 tests. The Ethics Committees at both hospitals and the Institutional Review Board at Partners Healthcare approved the study. Patients from the rural service area received 306 operations (86·2%) at HAS compared with 149 (38·1%) at HBS (p<0·0001). Only 16 operations (4·5%) at HAS were performed on patients from outside the service area for elective conditions compared with 179 (47·0%) at HBS (p<0·0001). Within its rural service area, HAS performed fewer operations on patients from the most destitute areas compared with other locations (4·0 operations per 10 000 population vs 10·1 operations per 10 000 population; p<0·0001). Use of fees as part of an equity strategy will likely disadvantage the poorest patients, while providing care without fees might encourage patients to travel from urban areas that contain other hospitals. Health systems striving to serve the poor should continually evaluate and seek to improve equity, even within systems that provide free care. None.

Background. In Haiti, breast cancer patients present at such advanced stages that even modern therapies offer modest survival benefit. Identifying the personal, sociocultural, and economic barriers-to-care delaying patient presentation is crucial to controlling disease. Methods. Patients presenting to the Hôpital Bon Sauveur in Cange were prospectively accrued. Delay was defined as 12 weeks or longer from initial sign/symptom discovery to presentation, as durations greater than this cutoff correlate with reduced survival. A matched case-control analysis with multivariate logistic regression was used to identify factors predicting delay. Results. Of N=123 patients accrued, 90 (73%) reported symptom-presentation duration and formed the basis of this study: 52 patients presented within 12 weeks of symptoms, while 38 patients waited longer than 12 weeks. On logistic regression, lower education status (OR = 5.6, P=0.03), failure to initially recognize mass as important (OR = 13.0, P<0.01), and fear of treatment cost (OR = 8.3, P=0.03) were shown to independently predict delayed patient presentation. Conclusion. To reduce stage at presentation, future interventions must educate patients on the recognition of initial breast cancer signs and symptoms and address cost concerns by providing care free of charge and/or advertising that existing care is already free.

The Food and Drug Administration (FDA) has been regulating human islets for allotransplantation as a biologic drug in the US. Consequently, the requirement of a biological license application (BLA) approval before clinical use of islet transplantation as a standard of care procedure has stalled the development of the field for the last 20 years. Herein, we provide our commentary to the multiple FDA’s position papers and guidance for industry arguing that BLA requirement has been inappropriately applied to allogeneic islets, which was delivered to the FDA Cellular, Tissue and Gene Therapies Advisory Committee on 15 April 2021. We provided evidence that BLA requirement and drug related regulations are inadequate in reassuring islet product quality and potency as well as patient safety and clinical outcomes. As leaders in the field of transplantation and endocrinology under the “Islets for US Collaborative” designation, we examined the current regulatory status of islet transplantation in the US and identified several anticipated negative consequences of the BLA approval. In our commentary we also offer an alternative pathway for islet transplantation under the regulatory framework for organ transplantation, which would address deficiencies of in current system.