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The final paper in this theme issue summarizes concerns related to establishing a national quality assurance system for institutions of higher education in South Africa. Proposes a three-phase approach to establishing a national quality assurance system to include: (1) evaluation of existing institutional self-evaluation systems; (2) establishment of external evaluation; and (3) engagement with globalization issues. (DB)

A South African university's community development program attempted to integrate Checkland's soft-systems method into Kolb's learning-cycle theory. Evaluation revealed shortcomings in the curriculum design, including the assumption of learner autonomy, necessity of assessing students individually, and difficulty of allowing learners to construct their own knowledge. (SK)

Nearly 20 years into the new democracy, student success at South African universities continues to be differentiated along racial lines. The tendency has been to define the problem in terms of student deficit. This article suggests that this is a limited view of a complex problem. The study reported on investigated the case of a South African university's Department of Chemical Engineering and its historical struggle with the success of black students. The study explored students' progression through a design course and the associated pedagogical realities. Using a social realist approach, the study showed that the higher education environment is a complex of necessary contradictions which create a situational logic for agents. In the process of navigating the inconsistencies of a system in which academic development and quality assurance work against each other, it seems that black students get caught in the middle, with deleterious consequences for the country's transformative agenda. [ABSTRACT FROM AUTHOR]

Background: Long-term outcomes of HBV nucleic acid test (NAT)-positive (+) allograft use in seronegative liver transplant (LT) and kidney transplant (KT) recipients remains unknown despite being incorporated into practice by select centers. This study compares long-term outcomes between HBV NAT+ and NAT-negative (-) allografts in seronegative recipients., Study Design: All recipients of an HBV core antibody-positive (HBcAb+) LT or KT were prospectively evaluated at a single transplant center from 6/2015-3/2023 and compared by NAT status. Study endpoints were post-transplant viremia, patient, and graft survival., Results: 144 HBcAb+ LT and 220 HBcAb+ KT were performed including 57 (39.6%) NAT+ LT's and 123 (55.9%) NAT+ KT's with a median follow-up of 36 months. 14.8% of NAT+ and 3.5% of NAT- LTs experienced post-transplant viremia (p=0.004). At the time of last follow-up, 100% of NAT+ and 98.9% of NAT- LT recipients had undetectable HBV DNA (p=0.31). 4.1% of NAT+ and 6.2% of NAT- KTs experienced post-transplant viremia (p=0.12). At the time of last follow-up, 100% of NAT+ and 96.9% of NAT- KT recipients had undetectable HBV DNA (p=0.85). LT and KT patient and graft survival were not different between groups (p>0.05)., Conclusion: With close surveillance, HBV seronegative recipients transplanted with NAT+ allografts can develop viremia which can be cleared with antiviral therapy. This is the first and largest single-center study reporting longer-term experience with HBV NAT+ allografts in seronegative recipients demonstrating the safe expansion of the donor pool., (Copyright © 2025 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

As cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death 1,2 . Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance 3-5 . However, we lack an understanding of metastatic cell states and the mechanisms by which they transition. Here, in a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that, although primary tumours largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Cancer cells lose intestinal cell identities and reprogram into a highly conserved fetal progenitor state before undergoing non-canonical differentiation into divergent squamous and neuroendocrine-like states, a process that is exacerbated in metastasis and by chemotherapy and is associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues compared with their intestinal lineage-restricted primary tumour counterparts. We identify PROX1 as a repressor of non-intestinal lineage in the fetal progenitor state, and show that downregulation of PROX1 licenses non-canonical reprogramming., Competing Interests: Competing interests: K.G. is listed as an inventor on US patent 11,464,874, and US provisional patent applications 63/478,809 and 63/478,829 on targeting L1CAM to treat cancer, submitted by MSKCC. D.P. is on the scientific advisory board of Insitro. J.S. is a consultant for Paige AI. R.Y. has served on the advisory board for Pfizer, Mirati Therapeutics, Revolution Medicine, Loxo@Lilly and Amgen, received a speaker’s honorarium from Zai Lab, and has received research support from Pfizer, Boehringer Ingelheim, Mirati Therapeutics, Daiichi Sankyo, FogPharma and Boundless Bio. J.G.-A. owns stock in Intuitive Surgical. R.C. is a consultant for Sanavia Oncology, S2 Genomics and LevitasBio. The other authors declare no competing interests., (© 2024. The Author(s).)

Objective: With the growing global incidence of thyroid carcinomas, there is an increasing need for distinct guidelines for isthmus-confined carcinomas. Here, we performed the first systematic review on the topic to date, aiming to provide understanding to isthmusectomy as surgical management for well-differentiated thyroid carcinoma of the isthmus., Methods: We conducted a systematic review following the PRISMA guidelines, analyzing English-language studies from the past decade that report on thyroid isthmusectomy. Exclusion criteria included isthmusectomy performed alongside full thyroidectomy or partial thyroid lobectomy, lack of data on tumor characteristics or survival outcomes, and non-English publications where a translation was unavailable. Our review identified a total of 227 patients from seven studies., Results: The average 5-year overall survival and disease-free survival rates for patients with isthmus-confined PTC who underwent isthmusectomy were 100 % and 93.1 %, respectively. Similar to that of total thyroidectomy. 3.1 % of patients required completion thyroidectomy. Furthermore, isthmusectomy resulted in fewer surgical complications than total thyroidectomy., Conclusions: The scarcity of studies providing detailed tumor characteristics and patient outcomes limits our ability to fully evaluate the safety and efficacy of isthmusectomy for isthmus-confined PTC. Additionally, the variable sample sizes and restricted geographic distribution of the included studies calls into questions the generalizability of their findings. Despite these limitations, the data suggest that isthmusectomy may be a viable surgical option for select patients with small, isthmus-confined PTC. In the absence of a randomized controlled trial on the noninferiority of isthmusectomy, significantly more publications are needed before strong conclusions can be drawn., Competing Interests: Declaration of competing interest All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Moon Usman, Peter Yao, Kathleen Luckett, Katerina Andreadis, MS(,) Remil Thomas, Andy Hickner, Paul J Christos, Andrew Tassler, David Kutler, William Kuhel, and Vicky Banuchi disclose no conflicts., (Copyright © 2023. Published by Elsevier Ltd.)

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

Objectives: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients., Summary Background Data: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated., Methods: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival., Results: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01)., Conclusions: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has seen transplant volume decrease nationwide, resulting in a 2.2-fold increase in waitlist mortality. In particular, solid organ transplant patients are subjected to increased morbidity and mortality from infection. In the face of these challenges, transplant centers need to develop innovative protocols to ensure high-quality care., Methods: A multidisciplinary protocol was developed that included the following: virtual selection meetings, coronavirus disease 2019 negative donors, pretransplant symptom screening, rapid testing on presentation, telehealth follow-up, and weekly community outreach town halls. All orthotopic liver transplants completed between January 2018 and August 2020 were included in the study (n = 344). The cohort was stratified from January 2018 to February 2020 as "pre-COVID-19," and from March 2020 to August 2020 as "COVID-19." Patient demographics and postoperative outcomes were compared., Results: From March 2020 to August 2020, there was a significant decrease in average monthly referrals for orthotopic liver transplantation (29.8 vs 37.1, P = .01). However, listings (11.0 vs 14.3, P = .09) and transplant volume remained unchanged (12.2 vs 10.6, P = .26). Rapid testing was utilized on arrival for transplant, zero patients tested positively preoperatively, and median time from test result until abdominal incision was 4.5 h [interquartile range, 1.2, 9.2]. Simultaneously, telehealth visits increased rapidly, peaking at 85% of all visits. It is important to note that there was no difference in outcomes between cohorts., Conclusion: Orthotopic liver transplant can be accomplished safely and effectively in the COVID-19 era without compromising outcomes through increasing utilization of telehealth, rapid COVID-19 testing, and multidisciplinary protocols for managing immunosuppressed patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Hepatitis C (HCV) disease transmission from the use of HCV antibody-positive and HCV nucleic acid test-negative (HCV Ab+/NAT-) kidneys have been anecdotally reported to be absent. We prospectively analyzed kidney transplant (KT) outcomes from HCV Ab+/NAT- donors to HCV naïve recipients under T-cell depleting early steroid withdrawal immunosuppression. Allografts from 40 HCV Ab+/NAT- donors were transplanted to 52 HCV Ab- recipients between July 2016 and February 2018. Thirty-three (82.5%) of donors met Public Health Service (PHS) increased risk criteria. De novo HCV infection was detected at 3 months post-KT in one recipient (1.9%). This was a case of transmission from a HCV Ab+ NAT+ donor with an initial false-negative NAT completed using sample collected on donor hospital admission (day 2). At the time of HCV diagnosis, a stored donor sample collected during procurement (day 4) was tested and resulted NAT-positive. Subsequently, sustained virologic response (SVR) was achieved with 12 weeks of glecaprevir/pibrentasvir. One death with functioning graft at 261 days post-KT was determined not related to HCV or donor factors. This experience provides evidence of a low transmission rate of HCV from HCV Ab+/ NAT- kidney donors, thereby arguing for increasing utilization., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Given the shortage of available liver grafts, transplantation (LTx) of hepatitis C virus antibody-positive, nucleic acid test-negative (HCV Ab+/NAT-) livers into nonviremic HCV recipients can expand the donor pool. Having previously described the sentinel experience of HCV Ab+/NAT- allografts in nonviremic recipients, we report the growth and extended follow-up of this program for 55 patients compared with recipients of Public Health Services (PHS) increased-risk donor HCV Ab-/NAT- allografts., Study Design: A prospective review of all HCV nonviremic LTx patients receiving HCV Ab+/NAT- organs between March 2016 and August 2018 was performed. All HCV Ab+/NAT- organ recipients underwent HCV testing at 3 months and 1-year post-LTx to determine HCV transmission., Results: Fifty-five HCV nonviremic candidates received HCV Ab+/NAT- organs; 64% male, median age 59 years (range 36 to 69 years) and median Model for End-Stage Liver Disease score of 22.5. Two recipients were excluded due to death before HCV testing. The HCV disease transmission occurred in 5 recipients (9%). Of these, 4 (80%) underwent anti-HCV treatment with eradication of virus. No patient found to be negative at 3 months seroconverted at 1-year follow-up. No patients who received PHS increased-risk donor HCV Ab-/NAT- organs had viremia develop (0 of 57) and there was no difference in graft and renal function, complications, or survival between HCV Ab+/NAT- recipients and PHS increased-risk donor HCV Ab-/NAT- recipients., Conclusions: We report the largest experience with LTx from HCV Ab+/NAT- donors into 55 seronegative recipients with a HCV transmission rate of 9% with no late conversions at 1 year and no difference in function or graft loss compared with PHS increased-risk donor HCV Ab-/NAT- recipients. Due to availability of safe and effective HCV therapies, the use of such organs should be strongly considered to increase the donor organ pool., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy., Conclusion: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682)., (© 2017 by the American Association for the Study of Liver Diseases.)

Background.  Histoplasmosis causes severe disease in patients with defects of cell-mediated immunity. It is not known whether outcomes vary related to the type of immunodeficiency or class of antifungal treatment. Methods.  We reviewed cases of active histoplasmosis that occurred at Vanderbilt University Medical Center from July 1999 to June 2012 in patients with human immunodeficiency virus (HIV) infection, a history of transplantation, or tumor necrosis factor (TNF)-α inhibitor use. These groups were compared for differences in clinical presentation and outcomes. In addition, outcomes were related to the initial choice of treatment. Results.  Ninety cases were identified (56 HIV, 23 transplant, 11 TNF-α inhibitor). Tumor necrosis factor-α patients had milder disease, shorter courses of therapy, and fewer relapses than HIV patients. Histoplasma antigenuria was highly prevalent in all groups (HIV 88%, transplant 95%, TNF-α 91%). Organ transplant recipients received amphotericin B formulation as initial therapy less often than other groups (22% vs 57% HIV vs 55% TNF-α; P = .006). Treatment failures only occurred in patients with severe disease. The failure rate was similar whether patients received initial amphotericin or triazole therapy. Ninety-day histoplasmosis-related mortality was 9% for all groups and did not vary significantly with choice of initial treatment. Conclusions.  Histoplasmosis caused milder disease in patients receiving TNF-α inhibitors than patients with HIV or solid organ transplantation. Treatment failures and mortality only occurred in patients with severe disease and did not vary based on type of immunosuppression or choice of initial therapy.