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Cleveland Clinic Journal of Medicine Mar 2024
Topics: Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Pancreas Transplantation; Kidney; Pancreas
PubMed: 38429002
DOI: 10.3949/ccjm.91a.23042 -
Diabetology & Metabolic Syndrome Feb 2024The effect of age on outcomes after simultaneous pancreas-kidney transplantation (SPK) among type II diabetes (T2DM) recipients remains inconclusive. This study aimed to...
The effect of age on outcomes after simultaneous pancreas-kidney transplantation (SPK) among type II diabetes (T2DM) recipients remains inconclusive. This study aimed to analyze the relationship between the age at time of transplantation and mortality, graft loss and metabolic profiles of T2DM SPK recipients. A retrospective cohort consisting of T2MD SPK recipients in a single transplant center was established. The baseline clinical characteristics and outcomes were collected and analyzed based on the age groups divided by 55-year-old. Time-to-event data analysis was performed using Kaplan-Meier method, and competing risk method was adopted to calculate the cumulative incidence of graft loss. A mixed regression model was applied to compare metabolic outcomes including glycated hemoglobin (HbA1c), fasting blood glucose, triglyceride, cholesterol, low-density lipoprotein, and higher estimated glomerular filtration rate (eGFR). 103 T2DM SPK recipients were included, of which 35 were > = 55 years old and 68 were < 55 years old. Baseline characteristics were comparable between age groups. The results indicated that comparable 5-year survival outcomes between groups with functioning grafts perioperatively. Additionally, no relationship of age with graft loss, complications and metabolic outcomes was detected.
PubMed: 38424556
DOI: 10.1186/s13098-024-01295-y -
The Lancet Regional Health. Europe Apr 2024Open partial pancreatoduodenectomy (OPD) represents the current gold standard of surgical treatment of a wide range of diseases of the pancreatic head but is associated...
BACKGROUND
Open partial pancreatoduodenectomy (OPD) represents the current gold standard of surgical treatment of a wide range of diseases of the pancreatic head but is associated with morbidity in around 40% of cases. Robotic partial pancreatoduodenectomy (RPD) is being used increasingly, yet, no randomised controlled trials (RCTs) of RPD versus OPD have been published, leaving a low level of evidence to support this practice.
METHODS
This investigator-initiated, exploratory RCT with two parallel study arms was conducted at a high-volume pancreatic centre in line with IDEAL recommendations (stage 2b). Patients scheduled for elective partial pancreatoduodenectomy (PD) for any indication were randomised (1:1) to RPD or OPD with a centralised web-based tool. The primary endpoint was postoperative cumulative morbidity within 90 days, assessed via the Comprehensive Complication Index (CCI). Biometricians were blinded to the intervention, but patients and surgeons were not. The trial was registered prospectively (DRKS00020407).
FINDINGS
Between June 3, 2020 and February 14, 2022, 81 patients were randomly assigned to RPD (n = 41) or OPD (n = 40), of whom 62 patients (RPD: n = 29, OPD: n = 33) were analysed in the modified intention to treat analysis. Four patients in the OPD group were randomised, but did not undergo surgery in our department and one patient was excluded in the RPD group due to other reason. Nine patients in the RPD group and 3 patients in the OPD were excluded from the primary analysis because they did not undergo PD, but rather underwent other types of surgery. The CCI after 90 days was comparable between groups (RPD: 34.02 ± 23.48 versus OPD: 36.45 ± 27.65, difference in means [95% CI]: -2.42 [-15.55; 10.71], p = 0.713). The RPD group had a higher incidence of grade B/C pancreas-specific complications compared to the OPD group (17 (58.6%) versus 11 (33.3%); difference in rates [95% CI]: 25.3% [1.2%; 49.4%], p = 0.046). The only complication that occurred significantly more often in the RPD than in the OPD group was clinically relevant delayed gastric emptying. Procedure-related and overall hospital costs were significantly higher and duration of surgery was longer in the RPD group. Blood loss did not differ significantly between groups. The intraoperative conversion rate of RPD was 23%. Overall 90-day mortality was 4.8% without significant differences between RPD and OPD.
INTERPRETATION
In the setting of a very high-volume centre, both RPD and OPD can be considered safe techniques. Further confirmatory multicentre RCTs are warranted to uncover potential advantages of RPD in terms of perioperative and long-term outcomes.
FUNDING
Federal Ministry of Education and Research (BMBF: 01KG2010).
PubMed: 38420108
DOI: 10.1016/j.lanepe.2024.100864 -
Transplantation Direct Mar 2024Hispanic patients receive disproportionately fewer kidney transplants (KT) than non-Hispanic White (NHW) patients. In this observational study, we evaluated disparities...
BACKGROUND
Hispanic patients receive disproportionately fewer kidney transplants (KT) than non-Hispanic White (NHW) patients. In this observational study, we evaluated disparities in completing evaluation steps to KT among Hispanic patients.
METHODS
Using medical records of Hispanic and NHW patients initiating evaluation at 4 transplant centers from January 2011 to March 2020, we performed sequential Cox models to compare Hispanic versus NHW patients reaching each step of the evaluation process until receiving a KT.
RESULTS
Among all 5197 patients (Hispanic n = 2473; NHW n = 2724) initiating evaluation, Hispanic patients had 8% lower risk to be approved by the kidney pancreas (KP) committee than NHW patients (adjusted hazard ratio [aHR], 0.92; 95% confidence intervals (CI), 0.86-0.98; = 0.015). Among 3492 patients approved by the KP committee, Hispanic patients had 13% lower risk to be waitlisted than NHW patients (aHR, 0.87; 95% CI, 0.81-0.94; = 0.004). Among 3382 patients who were waitlisted, Hispanic patients had 11% lower risk than NHW patients to receive KT (aHR, 0.89; 95% CI, 0.81-0.97; = 0.011). Among all patients initiating evaluation, Hispanic patients had a 16% lower risk than NHW patients to reach KT (aHR, 0.84; 95% CI, 0.76-0.92; = 0.0002).
CONCLUSIONS
Our study found that disproportionately fewer Hispanic patients were approved by the KP committee, were waitlisted, and received a KT, particularly a living donor kidney transplant, than NHW patients. Closer oversight of the evaluation process may help patients overcome challenges in access to KT.
PubMed: 38414978
DOI: 10.1097/TXD.0000000000001595 -
Diabetes Care Jun 2024Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement...
OBJECTIVE
Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery.
RESEARCH DESIGN AND METHODS
We included patients undergoing pancreatic surgery and solid organ transplantation (liver, pancreas, islets of Langerhans, kidney) requiring an ICU stay after surgery. We used a Dexcom G6 sensor, placed in the infraclavicular region, for real-time CGM. Arterial blood glucose measured by the amperometric principle (ABL 800; Radiometer, Copenhagen, Denmark) served as a reference value and for calibration. Blood glucose was also routinely monitored by a StatStrip bedside glucose meter. Sensor accuracy was assessed by mean absolute relative difference (MARD), bias, modified Bland-Altman plot, and surveillance error grid for paired samples of glucose values from CGM and acid-base analyzer (ABL).
RESULTS
We analyzed data from 61 patients and obtained 1,546 paired glucose values from CGM and ABL. Active sensor use was 95.1%. MARD was 9.4%, relative bias was 1.4%, and 92.8% of values fell in zone A, 6.1% fell in zone B, and 1.2% fell in zone C of the surveillance error grid. Median time in range was 78%, with minimum (<1%) time spent in hypoglycemia. StatStrip glucose meter MARD compared with ABL was 5.8%.
CONCLUSIONS
Our study shows clinically applicable accuracy and reliability of Dexcom G6 CGM in postoperative ICU patients and a feasible alternative sensor placement site.
Topics: Humans; Male; Blood Glucose; Middle Aged; Female; Critical Illness; Aged; Abdomen; Organ Transplantation; Feasibility Studies; Adult; Monitoring, Physiologic; Continuous Glucose Monitoring
PubMed: 38412005
DOI: 10.2337/dc23-1663 -
Annals of Surgery Jul 2024The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally...
OBJECTIVE
The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).
BACKGROUND
Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking.
METHODS
The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines.
RESULTS
Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ).
CONCLUSIONS
The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.
Topics: Humans; Pancreatic Neoplasms; Perioperative Care; Pancreatectomy; Carcinoma, Pancreatic Ductal; Delphi Technique; Practice Guidelines as Topic; Neoplasm Staging; Patient Selection
PubMed: 38407228
DOI: 10.1097/SLA.0000000000006248 -
Biomedicines Jan 2024Posttransplant diabetes mellitus (PTDM) is a common complication after kidney transplantation. Pathophysiologically, whether beta-cell dysfunction rather than insulin...
Posttransplant diabetes mellitus (PTDM) is a common complication after kidney transplantation. Pathophysiologically, whether beta-cell dysfunction rather than insulin resistance may be the predominant defect in PTDM has been a matter of debate. The aim of the present analysis was to compare glucometabolism in kidney transplant recipients with and without PTDM. To this aim, we included 191 patients from a randomized controlled trial who underwent oral glucose tolerance tests (OGTTs) 6 months after transplantation. We derived several basic indices of beta-cell function and insulin resistance as well as variables from mathematical modeling for a more robust beta-cell function assessment. Mean ± standard deviation of the insulin sensitivity parameter PREDIM was 3.65 ± 1.68 in PTDM versus 5.46 ± 2.57 in NON-PTDM. Model-based glucose sensitivity (indicator of beta-cell function) was 68.44 ± 57.82 pmol∙min∙m∙mM in PTDM versus 143.73 ± 112.91 pmol∙min∙m∙mM in NON-PTDM, respectively. Both basic indices and model-based parameters of beta-cell function were more than 50% lower in patients with PTDM, indicating severe beta-cell impairment. Nonetheless, some defects in insulin sensitivity were also present, although less marked. We conclude that in PTDM, the prominent defect appears to be beta-cell dysfunction. From a pathophysiological point of view, patients at high risk for developing PTDM may benefit from intensive treatment of hyperglycemia over the insulin secretion axis.
PubMed: 38397919
DOI: 10.3390/biomedicines12020317 -
American Journal of Transplantation :... Feb 2024In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled...
In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.
PubMed: 38387622
DOI: 10.1016/j.ajt.2024.02.014 -
Hepatology (Baltimore, Md.) Jul 2024Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP).
APPROACH AND RESULTS
We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC.
CONCLUSIONS
Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.
Topics: Humans; Genome-Wide Association Study; Liver Neoplasms; Genetic Predisposition to Disease; Carcinoma, Hepatocellular; Male; Female; Middle Aged; North America; Case-Control Studies; Polymorphism, Single Nucleotide; Aged; Genetic Loci; White People
PubMed: 38381705
DOI: 10.1097/HEP.0000000000000800 -
Advanced Science (Weinheim,... Apr 2024Many patients with hepatocellular carcinoma (HCC) respond poorly to radiotherapy despite remarkable advances in treatment. A deeper insight into the mechanism of...
Many patients with hepatocellular carcinoma (HCC) respond poorly to radiotherapy despite remarkable advances in treatment. A deeper insight into the mechanism of sensitivity of HCC to this therapy is urgently required. It is demonstrated that RECQL4 is upregulated in the malignant cells of patients with HCC. Elevated RECQL4 levels reduce the sensitivity of HCC to radiotherapy by repairing radiation-induced double-stranded DNA (dsDNA) fragments. Mechanistically, the inhibitory effect of RECQL4 on radiotherapy is due to the reduced recruitment of dendritic cells and CD8 T cells in the tumor microenvironment (TME). RECQL4 disrupts the radiation-induced transformation of the TME into a tumoricidal niche by inhibiting the cGAS-STING pathway in dendritic cells. Knocking out STING in dendritic cells can block the impact of RECQL4 on HCC radiosensitivity. Notably, high RECQL4 expressions in HCC is significantly associated with poor prognosis in multiple independent cohorts. In conclusion, this study highlights how HCC-derived RECQL4 disrupts cGAS-STING pathway activation in dendritic cells through DNA repair, thus reducing the radiosensitivity of HCC. These findings provide new perspectives on the clinical treatment of HCC.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Nucleotidyltransferases; Humans; Membrane Proteins; Mice; Animals; RecQ Helicases; Signal Transduction; Tumor Microenvironment; Dendritic Cells; Disease Models, Animal; Radiation Tolerance; Cell Line, Tumor
PubMed: 38381090
DOI: 10.1002/advs.202308009