Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C)

\ua9 2024 Bellos et al.Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, “burdenMC,” which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2

Effect of amyloidosis on long-term survival in kidney transplantation

Amyloidosis is characterized by the accumulation of an amorphous material in various organs and tissues secondary to a variety of inflammatory, immune, infectious, and hereditary diseases. Since 1975, our transplantation team has performed 1470 renal transplantations. Between 1985 and July 2004, among 1159 kidney transplantations, 953 (82.3%) were from living donors and 206 (17.7%) from cadaveric donors. There were 32 recipients (28 men, 4 women; mean age, 31.4 +/- 1.7 years; range, 21 to 48 years) with amyloidosis, including, 28 (87.5%) who received grafts from living donors and 4 (12.5%) from cadaveric donors. Amyloidosis was secondary to familial Mediterranean fever in 22 (68.7%) patients and rheumatoid arthritis in 1 (3.1%). The remaining 9 (28.1%) patients had primary amyloidosis. The mean follow-up time was 51.2 +/- 5.7 months (range, 2-124 months). Mean HLA mismatch rate was 2.2 +/- 1. Twenty-six (81.2%) patients are alive at this time with functioning grafts, and a mean serum creatinine value of 2.1 +/- 1.5 ng/dL. The 1- and 5-year patient and graft survival rates were 90.6% and 84.3%, and 81.2% and 68.7%, respectively. We conclude that patients with amyloidosis may undergo kidney transplantation safely expecting outcomes similar to those patients who receive transplantations for other reasons

DElayed COloRectal cancer care during COVID-19 Pandemic (DECOR-19): Global perspective from an international survey

Background: The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer care during the pandemic. Methods: The impact of coronavirus disease 2019 on preoperative assessment, elective surgery, and postoperative management of colorectal cancer patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in colorectal cancer care. Respondents were divided into 2 comparator groups: (1) “delay” group: colorectal cancer care affected by the pandemic and (2) “no delay” group: unaltered colorectal cancer practice. Results: A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the delay (745, 70.9%) and no delay (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to coronavirus disease 2019 units, units fully dedicated to coronavirus disease 2019 care, and personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology, and prolonged chemoradiation therapy-to-surgery intervals. In the delay group, 48.9% of respondents reported a change in the initial surgical plan, and 26.3% reported a shift from elective to urgent operations. Recovery of colorectal cancer care was associated with the status of the outbreak. Practicing in coronavirus disease-free units, no change in operative slots and staff members not relocated to coronavirus disease 2019 units were statistically associated with unaltered colorectal cancer care in the no delay group, while the geographic distribution was not. Conclusion: Global changes in diagnostic and therapeutic colorectal cancer practices were evident. Changes were associated with differences in health care delivery systems, hospital's preparedness, resource availability, and local coronavirus disease 2019 prevalence rather than geographic factors. Strategic planning is required to optimize colorectal cancer care

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C)

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, “burdenMC,” which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5–5.3, P < 10−6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Abstract Background This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic. </jats:sec

Delayed colorectal cancer care during covid-19 pandemic (decor-19). Global perspective from an international survey

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care