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Journal of Human Genetics Aug 2023Opportunities for genetic counseling and germline BRCA1/2 (BRCA) testing are increasing in Japan owing to cancer genomic profiling testing and companion diagnostics... (Review)
Review
Opportunities for genetic counseling and germline BRCA1/2 (BRCA) testing are increasing in Japan owing to cancer genomic profiling testing and companion diagnostics being covered by national health insurance for patients with BRCA-related cancers. These tests are useful not only to judge whether platinum agents and PARP inhibitors are indicated but also to reveal an autosomal-dominant inherited cancer syndrome: hereditary breast and ovarian cancer. In individuals with germline BRCA variants, risk of cancers of the breast, ovary, pancreas, and prostate is significantly increased at various ages of onset, but the stomach, uterus, biliary tract, and skin might also be at risk. For women with pathogenic BRCA variants, breast awareness and image analyses should be initiated in their 20s, and risk-reducing procedures such as mastectomy are recommended starting in their 30s, with salpingo-oophorectomy in their late 30s. For male BRCA pathogenic variant carriers, prostatic surveillance should be applied using serum prostate-specific antigen starting in their 40s. For both sexes, image examinations ideally using endoscopic ultrasound and magnetic resonance cholangiopancreatography and blood testing should begin in their 50s for pancreatic surveillance. Homologous recombination pathway-associated genes are also causative candidates. Variant pathogenicity needs to be evaluated every 6-12 months when results are uncertain for clinical significance. Genetic counseling needs to be offered to the blood relatives of the pathogenic variant carriers with suitable timing. We review the recommended cross-organ BRCA risk management in Japan.
Topics: Humans; Male; Female; BRCA1 Protein; Ovary; Japan; Breast Neoplasms; BRCA2 Protein; Mastectomy; Risk Management; Ovarian Neoplasms; Pancreas; Prostatic Neoplasms
PubMed: 37088789
DOI: 10.1038/s10038-023-01153-1 -
Journal of Investigative Surgery : the... Dec 2023Our objective is to compare the early outcomes associated with passive (gravity) drainage (PG) and active drainage (AD) after surgery. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Our objective is to compare the early outcomes associated with passive (gravity) drainage (PG) and active drainage (AD) after surgery.
METHODS
Studies published until April 28, 2022 were retrieved from the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science databases.
RESULTS
Nine studies with 14,169 patients were identified. Two groups had the same intra-abdominal infection rate (RR: 0.55; = 0.13); In subgroup analysis of pancreaticoduodenectomy, active drainage had no significant effect on postoperative pancreatic fistula (POPF) rate (RR: 1.21; = 0.26) and clinically relevant POPF (CR-POPF) (RR: 1.05; = 0.72); Active drainage was not associated with lower percutaneous drainage rate (RR: 1.00; = 0.96), incidence of sepsis (RR: 1.00; = 0.99) and overall morbidity (RR: 1.02; = 0.73). Both groups had the same POPF rate (RR: 1.20; = 0.18) and CR-POPF rate (RR: 1.20; = 0.18) after distal pancreatectomy. There was no difference between two groups on the day of drain removal after pancreaticoduodenectomy (Mean difference: -0.16; = 0.81) and liver surgery (Mean difference: 0.03; = 0.99).
CONCLUSIONS
Active drainage is not superior to passive drainage and both drainage methods can be considered.
Topics: Humans; Abdomen; Pancreas; Drainage; Pancreatectomy; Postoperative Complications; Pancreaticoduodenectomy
PubMed: 37733388
DOI: 10.1080/08941939.2023.2180115 -
Radiographics : a Review Publication of... Aug 2023
Topics: Humans; Ascariasis; Pancreas; Pancreatitis; Biliary Tract Diseases
PubMed: 37471244
DOI: 10.1148/rg.230049 -
Diabetes/metabolism Research and Reviews Feb 2024Fulminant type 1 diabetes (FT1D) is a novel type of type 1 diabetes that is caused by extremely rapid destruction of the pancreatic β cells. Early diagnosis or... (Review)
Review
Fulminant type 1 diabetes (FT1D) is a novel type of type 1 diabetes that is caused by extremely rapid destruction of the pancreatic β cells. Early diagnosis or prediction of FT1D is critical for the prevention or timely treatment of diabetes ketoacidosis, which can be life-threatening. Understanding its triggers or promoting factors plays an important role in the prevention and treatment of FT1D. In this review, we summarised the various triggering factors of FT1D, including susceptibility genes, immunological factors (cellular and humoural immunity), immune checkpoint inhibitor therapies, drug reactions with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome, pregnancy, viral infections, and vaccine inoculation. This review provides the basis for future research into the pathogenetic mechanisms that regulate FT1D development and progression to further improve the prognosis and clinical management of patients with FT1D.
Topics: Humans; Diabetes Mellitus, Type 1; Insulin-Secreting Cells; Diabetic Ketoacidosis
PubMed: 37814918
DOI: 10.1002/dmrr.3731 -
Nature Communications Feb 2024Studying survivorship and causes of death in patients with advanced or metastatic cancer remains an important task. We characterize the causes of death among patients...
Studying survivorship and causes of death in patients with advanced or metastatic cancer remains an important task. We characterize the causes of death among patients with metastatic cancer, across 13 cancer types and 25 non-cancer causes and predict the risk of death after diagnosis from the diagnosed cancer versus other causes (e.g., stroke, heart disease, etc.). Among 1,030,937 US (1992-2019) metastatic cancer survivors, 82.6% of patients (n = 688,529) died due to the diagnosed cancer, while 17.4% (n = 145,006) died of competing causes. Patients with lung, pancreas, esophagus, and stomach tumors are the most likely to die of their metastatic cancer, while those with prostate and breast cancer have the lowest likelihood. The median survival time among patients living with metastases is 10 months; our Fine and Gray competing risk model predicts 1 year survival with area under the receiver operating characteristic curve of 0.754 (95% CI [0.754, 0.754]). Leading non-cancer deaths are heart disease (32.4%), chronic obstructive and pulmonary disease (7.9%), cerebrovascular disease (6.1%), and infection (4.1%).
Topics: Male; Humans; Cause of Death; Breast Neoplasms; Risk Factors; Causality; Heart Diseases
PubMed: 38374318
DOI: 10.1038/s41467-024-45307-x -
Clinical Transplantation Nov 2023BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited...
BACKGROUND
BK polyomavirus (BKV) infection is a common complication of kidney transplantation. While BKV has been described in non-kidney transplant recipients, data are limited regarding its epidemiology and outcomes in pancreas transplant recipients.
METHODS
We conducted a retrospective cohort study of adults who underwent pancreas transplantation from 2010-2020. The primary outcome was BKV DNAemia. Secondary outcomes were estimated glomerular filtration rate (eGFR) reduction by 30%, eGFR < 30 mL/min/1.73 m , endstage kidney disease, and pancreas allograft failure. Cox regression with time-dependent variables was utilized.
RESULTS
Four hundred and sixty-six patients were analyzed, including 74, 46, and 346 with pancreas transplant alone (PTA), pancreas-after-kidney, or simultaneous pancreas-kidney transplants, respectively. PTA recipients experienced a lower incidence of BKV DNAemia (8.8% vs. 32.9%; p < .001) and shorter duration of DNAemia (median 28.0 vs. 84.5 days). No PTA recipients with BKV DNAemia underwent kidney biopsy or developed endstage kidney disease. Lymphopenia, non-PTA transplantation, and older age were associated with BKV DNAemia, which itself was associated with pancreas allograft failure (adjusted hazard ratio 2.14, 95% confidence interval 1.27-3.60; p = .004). Among PTA recipients, BKV DNAemia was not associated with eGFR reduction or eGFR < 30 mL/min/1.73 m .
CONCLUSIONS
BKV DNAemia was common among PTA recipients, though lower than a comparable group of pancreas-kidney recipients. However, BKV DNAemia was not associated with adverse native kidney outcomes and no PTA recipients developed endstage kidney disease. Conversely, BKV DNAemia was associated with pancreas allograft failure. Further studies are needed to estimate the rate of BKV nephropathy in this population, and further evaluate long-term kidney outcomes.
Topics: Adult; Humans; BK Virus; Pancreas Transplantation; Retrospective Studies; Polyomavirus Infections; Kidney; Kidney Diseases; Pancreas; Kidney Failure, Chronic; Transplant Recipients; Tumor Virus Infections
PubMed: 37705389
DOI: 10.1111/ctr.15135 -
Simultaneous Pancreas and Kidney Transplantation from Donors after Circulatory Death in Switzerland.Journal of Clinical Medicine Jun 2024Simultaneous pancreas and kidney transplantation (SPK) remains the only curative treatment for type I diabetics with end-stage kidney disease. SPK using donors after...
Simultaneous pancreas and kidney transplantation (SPK) remains the only curative treatment for type I diabetics with end-stage kidney disease. SPK using donors after circulatory death (DCD) is one important measure to expand the organ pool for pancreas transplantation (PT). After initial doubts due to higher complications, DCD SPK is now considered safe and equivalent to donation after brain death in terms of survival and graft function. We assessed pancreas and kidney graft function, as well as complications of the first three patients who underwent a DCD SPK in Switzerland. Two transplantations were after rapid procurement, one following normothermic regional perfusion (NRP). Intra- and postoperative courses were uneventful and without major complications in all patients. In the two SPK after rapid procurement, pancreas graft function was excellent, with 100% insulin-free survival, and hemoglobin A1C dropped from 7.9 and 7.5 before SPK and to 5.1 and 4.3 after three years, respectively. Kidney graft function was excellent in the first year, followed by a gradual decline due to recurrent infections. The patient, after NRP SPK, experienced short-term delayed pancreatic graft function requiring low-dose insulin treatment for 5 days post-transplant, most likely due to increased peripheral insulin resistance in obesity. During follow-up, there was persistent euglycemia and excellent kidney function. We report on the first series of DCD SPK ever performed in Switzerland. Results were promising, with low complication rates and sustained graft survival. With almost half of all donors in Switzerland currently being DCD, we see great potential for the expansion of DCD PT.
PubMed: 38930054
DOI: 10.3390/jcm13123525 -
The New England Journal of Medicine Aug 2023
Topics: Humans; Adolescent; Diabetes Mellitus, Type 1; Autoimmunity; SARS-CoV-2; COVID-19; Islets of Langerhans; Autoantibodies
PubMed: 37530831
DOI: 10.1056/NEJMc2216477 -
Journal of Immunology (Baltimore, Md. :... Nov 2023Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus...
Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus suppresses T1D development in NOD mice by promoting clonal expansion of N-acetyl-d-glucosamine (GlcNAc)-specific B-1 B cells that recognize pancreatic β cell-derived Ags bearing GlcNAc-containing posttranslational modifications. Early exposure to Lancefield group A cell-wall carbohydrate Ags increased production of GlcNAc-reactive serum Abs and enhanced localization of innate-like GlcNAc-specific B cells to pancreatic tissue during T1D pathogenesis. We show that B-1 B cell-derived GlcNAc-specific IgM engages apoptosis-associated β cell Ags, thereby suppressing diabetogenic T cell activation. Likewise, adoptively transferring GlcNAc-reactive B-1 B cells significantly delayed T1D development in naive recipients. Collectively, these data underscore potentially protective involvement of innate-like B cells and natural Abs in T1D progression. These findings suggest that previously reported associations of reduced T1D risk after GAS infection are B cell dependent and demonstrate the potential for targeting the natural Ab repertoire in considering therapeutic strategies for T1D.
Topics: Mice; Animals; Diabetes Mellitus, Type 1; Mice, Inbred NOD; Glucosamine; Acetylglucosamine; Pancreas
PubMed: 37747293
DOI: 10.4049/jimmunol.2300264 -
Abdominal Radiology (New York) Jun 2024Pancreas transplantation is a complex surgical procedure performed to restore normoglycemia in patients with type 1 diabetes and includes whole/segmental organ... (Review)
Review
Pancreas transplantation is a complex surgical procedure performed to restore normoglycemia in patients with type 1 diabetes and includes whole/segmental organ transplant and islet cell transplantation (ICT). In the United States, simultaneous pancreas-kidney transplant (SPK) is most commonly performed due to the higher occurrence of end-stage renal disease in diabetic patients. Understanding the surgical technique and postoperative anatomy is imperative for effective and accurate surveillance following transplantation. Imaging plays an essential role in patients with pancreatic transplants and is often used to evaluate viability, vascular and parenchymal anatomy, and identify potential complications. Imaging techniques such as ultrasound, color and spectral Doppler, computed tomography (CT), magnetic resonance imaging (MRI), and angiography have a complementary role in the postoperative evaluation following a pancreas transplant. The common complications after a whole organ pancreas transplant include vascular thrombosis, graft rejection, pancreatitis, and infections. Complications can be classified into vascular (partial or complete venous thrombosis, arterial thrombosis, stenosis or pseudoaneurysm), parenchymal (pancreatitis, graft rejection), and bowel-related or miscellaneous causes (bowel obstruction, anastomotic leak, and peripancreatic fluid collections). Islet cell transplantation is an innovative therapy for patients with type 1 diabetes. It involves isolating insulin-producing islet cells from donor pancreas and transplanting into recipients, to provide long-term insulin independence or significantly reduce insulin requirements. In recent years, isolation techniques, immunosuppressive regimens, and post-transplant monitoring advancements have propelled ICT as a viable therapeutic option. This comprehensive review aims to provide insights into the current state-of-the-art imaging techniques discussing both normal and abnormal features following pancreas transplantation.
PubMed: 38900315
DOI: 10.1007/s00261-024-04383-9