A safe, efficacious, and clinically applicable immunosuppressive regimen is necessary for islet xenotransplantation to become a viable treatment option for diabetes. We performed intraportal transplants of wildtype adult porcine islets in 25 streptozotocin-diabetic cynomolgus monkeys. Islet engraftment was good in 21, partial in 3 and poor in 1 recipient. Median xenograft survival was 25 days with

Clinical islet transplantation has relied almost exclusively on intraportal administration of pancreatic islets, as it has been the only consistent approach to achieve robust graft function in human recipients. However, this approach suffers from significant loss of islet mass from a potent immediate blood mediated inflammatory response (IBMIR) and a hypoxic environment. To avoid these negative aspects

Capitalizing on the Concept of Local Immune Suppression by Inhalation for Lung Transplant Recipients Over the past 30 years lung transplantation has become a commonly performed therapy providing an opportunity to improve longevity and regain quality of life (1). Improved surgical techniques and the use of oral calcineurin inhibitors have resulted in early post-operative benefits but medium and long-term

Surgery residency requires tremendous sacrifice. So does parenthood. Add them together, and the sacrifices can become overwhelming. In recognition of the difficult position of resident parents, the American Board of Medical Specialties (ABMS) recently issued an updated policy on parental leave, which states that member boards must allow 6 weeks of parental leave without exhausting other leave or extending

Importance Low surgical volume in the US Military Health System (MHS) has been identified as a challenge to military surgeon readiness. The Uniformed Services University of Health Sciences, in partnership with the American College of Surgeons, developed the Knowledge, Skills, and Abilities (KSA) Clinical Readiness Program that includes a tool for quantifying the clinical readiness value of surgeon

Importance The optimal staging for gastric cancer remains a matter of debate. Objective To evaluate the value of 18F-fludeoxyglucose–positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. Design, Setting, and Participants This multicenter prospective

In their analysis using the Knowledge, Skills, and Abilities metric and TRICARE claims, Dalton et al1 noted decreasing numbers of general surgery cases in military treatment facilities (MTFs) between fiscal years 2015 and 2019. They link this decrease to a simultaneous increase in purchased care in the civilian setting. These findings have implications for the expeditionary readiness of surgical teams

Accurate preoperative staging of gastric cancer is essential, because the median survival for advanced gastric cancer is only 3 months in population studies.1 Metastasis is most common in the liver and peritoneum and less so in the lungs, bones, and distant lymph nodes. The most commonly used staging methods are computed tomography (CT) scanning of the chest, abdomen, and pelvis with intravenous or

In the age of minimally invasive surgery (MIS), it is essential to provide suitable training methods to ensure efficient, safe practice, and optimal patient outcomes.1 Practical intraoperative training in surgery is based on the quality of communication between the instructor and the trainee and traditionally has been conducted on-site. Minimally invasive surgery is hindered because instructions can

To the Editor We read with great interest the results from the study by de Boniface et al,1 which indicated a significantly higher comorbidity burden in patients using mastectomy irrespective of postoperative radiotherapy, compared with those treated with breast-conserving surgery with radiotherapy in patients with early-stage breast cancer. Moreover, after stepwise adjustment for all covariates, overall

In Reply We thank Lin and colleagues for the comments on our study comparing survival following breast conservation vs mastectomy.1 As the authors confirm, whole-breast radiotherapy was a requirement for all individuals in our study undergoing breast-conserving surgery, and those in whom it was omitted (n = 2390) were excluded from analysis.1 Although we agree that the register we used does not give

Background There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after LVAD implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve one-year survival and increase the likelihood of RV AMCS weaning. Methods A multi-center retrospective database of 826 consecutive patients

Background Transmission of latent human cytomegalovirus (HCMV) via organ transplantation with post-transplant viral reactivation is extremely prevalent and results in substantial adverse impact on outcomes. Therapies targeting the latent reservoir within the allograft to mitigate viral transmission would represent a major advance. Here, we delivered an immunotoxin (F49A-FTP) that targets and kills

Introduction Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition. Methods All patients who were followed post-HT for ATTR-CA at our center

Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplantation Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome caused by germline fumarate hydratase (FH) mutations and characterized by uterine and cutaneous leiomyomas and renal cell cancer. Currently, there is no generally approved method to differentiate FH-deficient uterine leiomyomas from other leiomyomas. Here, we analyzed 3 antibodies (S-(2-succino)-cysteine [2SC]

Maintenance of systemic homeostasis by kidney requires the coordinated response of diverse cell types. Use of single-cell RNA sequencing (scRNAseq) for patient samples remains fraught with difficulties. The ability to characterize immune and parenchymal cells during transplant rejection (some of which may be present at very small numbers due to injury) will be invaluable in defining transplant pathologies

The importance of PD-1/PD-L1 interaction to alloimmune response is unknown in intestinal transplantation. We tested whether PD-L1 regulates allograft tissue injury in murine intestinal transplantation. PD-L1 expression was observed on the endothelium and immune cells in the intestinal allograft. Monoclonal antibody treatment against PD-L1 led to accelerated allograft tissue damage, characterized by

The statin family of therapeutics are widely used clinically as cholesterol lowering agents, and their effects to target intracellular mevalonate production is a key mechanism of action. In this study, we performed full transcriptomic RNA sequencing and qPCR to evaluate the effects of mevalonate on the immunoregulatory phenotype of endothelial cells (EC). We find that mevalonate-dependent gene regulation

Diversity in medicine improves patient outcomes and decreases health disparities.1-3 Despite ongoing diversity, equity, and inclusion initiatives, however, several groups remain underrepresented in medicine (URIM). In 2021, Zhu et al4 reported racial disparities among Black and Hispanic academic surgeons with little change over the past 12 years. Among medical schools in the US, the proportion of female

We recommend that vaccination for COVID-19 should be a requirement for waitlist activation for solid organ transplant (SOT). We also recommend that such vaccination be required of the primary member of the in-home support team. We argue that these requirements are consistent with current standard practices that draw on a well-established established ethical framework. As a result, these recommendations

Chronic lung allograft dysfunction (CLAD) is the most important long-term complication after lung transplant (LTx), and clinical experience suggests significant variability in its management. We sought to capture azithromycin practices among LTx providers internationally. A survey was distributed via the International Society for Heart and Lung Transplantation and completed by 103 respondents (15 countries)

Background: The development of noninvasive approaches for the early diagnosis of acute cellular rejection (ACR), an important complication of cardiac transplantation, is of great importance in clinical practice. We conducted a nontargeted transcriptomic study focused on identifying serum miRNAs to evaluate their diagnostic accuracy for detecting rejection episodes. Methods: We included consecutive

Background Infections are the most common complication in recipients of durable left ventricular assist devices (LVAD) and are associated with increased morbidity, mortality, and expenditures. The existing literature examining factors associated with infection in LVAD recipients is limited and principally comprises single-center studies. This scoping review synthesizes all available evidence related

Background We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS). Methods In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9915 adult candidates on MCS underwent HTx from 1/1/2010 to 3/31/2019. Multi-organ, re-transplant, and congenital heart

Knowledge of living donor liver transplantation (LDLT) for autoimmune liver diseases (AILDs) is scarce. This study analyzed survival in LDLT recipients registered in the European Liver Transplant Registry with autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC) and the non-autoimmune disorder alcohol-related cirrhosis. In total, 29 902 individuals enrolled between

Importance It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes among patients with locally advanced gastric cancer. Data from a multicenter, randomized clinical trial (Chinese Laparoscopic Gastrointestinal Surgical Study [CLASS]–01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal

Importance Previous studies have shown high rates of mistreatment among US general surgery residents, leading to poor well-being. Lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) residents represent a high-risk group for mistreatment; however, their experience in general surgery programs is largely unexplored. Objective To determine the national prevalence of

Importance There are discrepancies in guidelines on preparation for colorectal surgery. While intravenous (IV) antibiotics are usually administered, the use of mechanical bowel preparation (MBP), enemas, and/or oral antibiotics (OA) is controversial. Objective To summarize all data from randomized clinical trials (RCTs) that met selection criteria using network meta-analysis (NMA) to determine the

The article by Heiderscheit et al1 is the latest to investigate biases, discrimination, and bullying in surgery. This is an important study that leveraged the captive audience of surgical residents who took the 2019 American Board of Surgery In-Training Examination. The authors concluded that lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) surgical residents

Rosenberg and colleagues1 first proposed the use of nonabsorbable oral antibiotic preparation (OAB) for colorectal surgery in 1971. In a randomized clinical trial, they demonstrated a reduction in surgical site infection and anastomotic leak rates after combined mechanical bowel preparation (MBP) and 1 or 2 nonabsorbable oral antibiotics (phthalylsulphathiazole and phthalylsulphathiazole and neomycin

Liver transplantation is a necessary life-saving procedure for end-stage liver disease. Deceased donors contribute 95% of the organs required for liver transplantation across the US and Europe. However, the scarcity of deceased donors has made live donor liver transplantation (LDLT) the predominant modality (90%) in Asia. Morbidity and mortality of the donor are understandably the most feared repercussions

To the Editor The ICAN trial has provided level 1 evidence favoring intrathoracic anastomosis after a total or hybrid minimally invasive esophagectomy.1 We commend the authors on a robust study design for a purely surgical trial. The quality control of the surgical technique before participation and later during the trial is meticulous and may lay the standard for future surgical trials.

To the Editor With interest we have read the randomized clinical trial by van Workum et al.1 In their article, the authors show a reduction in anastomotic leakage rate from 31.7% to 12.3% with the introduction of an intrathoracic anastomosis. They conclude that “intrathoracic, as opposed to cervical, anastomosis resulted in better outcome for patients treated with transthoracic MIE [minimally invasive

In Reply With great interest we read the Letters from Nittala et al and de Steur et al, and we thank them for their thoughtful comments on our study.1 In the Letter by Nittala et al, the generalizability of the results of the ICAN trial to the subgroup of midesophageal tumors is questioned. For the ICAN trial, we believed it was important that we only included patients in which both types of anastomoses

Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable

Vaccine-induced immune thrombosis and thrombocytopenia (VITT) syndrome is a new entity, characterised by severe thrombocytopenia and multiple sites of thrombosis1. The presumed mechanism is driven by anti-platelet factor 4 (PF4) antibodies causing platelet activation1. Donors with VITT syndrome have a particular relevance for liver transplantation (LT), due to the associated risk of passenger lymphocyte

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS

Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommended for morbidly obese transplant recipients. Here, we delineated the effects of obesity and bariatric surgery on alloimmunity and transplant outcomes in diet-induced obese (DIO) mice

Hispanic patients receive disproportionately fewer living donor kidney transplants (LDKTs) than non-Hispanic Whites (NHWs). The Northwestern Medicine Hispanic Kidney Transplant Program (HKTP), designed to increase Hispanic LDKTs, was evaluated as a nonrandomized, implementation-effectiveness hybrid trial of patients initiating transplant evaluation at two intervention and two similar control sites

BACKGROUND Mobile health (mHealth) technology has been proposed as a method of improving post-discharge surveillance. Little is known about how mHealth has been used to track patients after surgery and whether its use is associated with differences in postoperative recovery. METHODS Three databases (PubMed, MEDLINE and the Cochrane Central Registry of Controlled Trials) were searched to identify studies

Despite decennia of research and numerous successful interventions in the preclinical setting, renal ischemia reperfusion (IR) injury remains a major problem in clinical practice, pointing towards a translational gap. Recently, two clinical studies on renal IR injury (manifested either as acute kidney injury or as delayed graft function), identified metabolic derailment as a key driver of renal IR

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first

T cells must be activated and become effectors first before executing allograft rejection, a process that is regulated by diverse signals and transcription factors. In this study, we studied the basic leucine zipper ATF-like transcription factor (BATF) family members in regulating T cell activities in a heart transplant model and found that mice deficient for both BATF and BATF3 (Batf−/−Batf3−/− mice)

Our understanding of the involvement of the gut microbiota (GM) in human health has expanded exponentially over the last few decades, particularly in the fields of metabolism, inflammation, and immunology. Immunosuppressive treatment (IST) prescribed to solid organ transplant (SOT) recipients produces GM changes that affect these different processes. This review aims at describing the current knowledge

Invasive lobular carcinoma (ILC) of the breast is characterized by the discohesive growth of tumor cells, which is mainly associated with the complete loss of E-cadherin (E-cad) expression. However, some aberrant expression patterns of E-cad protein that are inconsistent with their morphologies have been reported in ILC. We report herein ILC cases expressing a new type of abnormal E-cad protein that

The probability of kidney transplantation for waitlisted candidates varies widely in the United States. The 3-year probability of deceased donor transplantation ranges from 4% to 64.2% - representing a 16 fold variation.(1) This variation is often attributed to geographical differences in the underlying organ supply but may be explained even more by the willingness of transplant programs to accept

While older males are at highest risk for poor COVID-19 outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID-19 (Jan 01, 2020-June 21, 2021) from 56 sites across the United States identified using the National

Hyperlipidemia induces accelerated rejection of cardiac allografts and resistance to tolerance induction using costimulatory molecule blockade in mice due in part to anti-donor Th17 responses and reduced regulatory T cell function. Accelerated rejection in hyperlipidemic mice is also associated with increased serum levels of IL-6. Here, we examined the role of IL-6 in hyperlipidemia-induced accelerated

Overtreatment is medical intervention that is extremely unlikely to help a patient, is misaligned with a patient’s wishes, or both. Its harms to individual patients and families include iatrogenesis, financial burden, anxiety, and time wasted at hospitals and clinics. Overtreatment adds substantially to US health care costs.1 Surgeons have been concerned with reducing overtreatment for decades. Early

Importance Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer. Objective To assess gastric cancer risk among patients who received a diagnosis of hereditary lobular breast cancer (HLBC) owing to a germline loss-of-function variant in CDH1 by establishing prevalence of signet ring cell carcinomas among asymptomatic patients. Design

To the Editor Liver transplant (LT) has already become one of the major approaches to manage advanced liver diseases, including colorectal cancer liver metastasis (CRLM). Dueland et al1 reported their single-institutional retrospective cohort analysis on LT for CRLM, which was compared with those who received portal vein embolization (PVE) with intent to undergo liver resection (LR). Their results

In Reply We would like to thank Aini et al for commenting on our article on liver transplant (LT) in colorectal cancer liver metastases.1 Our results were presented as Kaplan-Maier–estimated overall survival (OS) because not all patients were observed for 5 years or until death. According to Aini et al, patients receiving portal vein embolization (PVE) and liver resection (LR) had a 5-year OS of 54

The rapid transformation of the health care delivery system and surgical services across the US as a result of the COVID-19 pandemic was unprecedented. To limit COVID-19 exposure and transmission between patients and clinicians, millions of elective surgical procedures were suspended and necessity compelled surgeons to adopt telemedicine for preoperative, follow-up, and emergent surgical care visits

The COVID-19 pandemic has had profound effects on the health care workforce; more than 130 million cases of COVID-19 and nearly 3 million deaths have been recorded worldwide as of April 1, 2021.1 To reduce health care resource utilization and increase the expected need for critical care capacity as COVID-19 cases surged, surgical care was dramatically interrupted, with more than 28 million elective

Importance While surgeons often delay pregnancy and childbearing because of training and establishing early careers, little is known about risks of infertility and pregnancy complications among female surgeons. Objective To describe the incidence of infertility and pregnancy complications among female surgeons in the US and to identify workplace factors associated with increased risk compared with

Importance The familial aspect of acute appendicitis (AA) has been proposed, but its hereditary basis remains undetermined. Objective To identify genomic variants associated with AA. Design, Setting, and Participants This genome-wide association study, conducted from June 21, 2019, to February 4, 2020, used a multi-institutional biobank to retrospectively identify patients with AA across 8 single-nucleotide