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Trials Sep 2023Pancreaticoduodenectomy (PD) nowadays serves as a standard treatment for patients with disorders of the pancreas, intestine, and bile duct. Although the mortality rate...
The effect of perioperative of dexamethasone on postoperative complications after pancreaticoduodenectomy (PANDEX): a study protocol for a pragmatic multicenter randomized controlled trial.
BACKGROUND
Pancreaticoduodenectomy (PD) nowadays serves as a standard treatment for patients with disorders of the pancreas, intestine, and bile duct. Although the mortality rate of patients undergoing PD has decreased significantly, postoperative complication rates remain high. Dexamethasone, a synthetic glucocorticoid with potent anti-inflammatory and metabolic effects, has been proven to have a favorable effect on certain complications. However, the role it plays in post-pancreatectomy patients has not been systematically evaluated. The aim of this study is to assess the effect of dexamethasone on postoperative complications after PD.
METHODS
The PANDEX trial is an investigator-initiated, multicentric, prospective, randomized, double-blinded, placebo-control, pragmatic study. The trial is designed to enroll 300 patients who are going to receive elective PD. Patients will be randomized to receive 0.2 mg/kg dexamethasone or saline placebo, administered as an intravenous bolus within 5 min after induction of anesthesia. The primary outcome is the Comprehensive Complication Index (CCI) score within 30 days after the operation. The secondary outcomes include postoperative major complications (Clavien-Dindo≥3), postoperative pancreatic fistula (POPF), post-pancreatectomy acute pancreatitis (PPAP), infection, and unexpected relaparotomy, as well as postoperative length of stay, 30-day mortality, and 90-day mortality.
DISCUSSION
The PANDEX trial is the first randomized controlled trial concerning the effect of dexamethasone on postoperative complications of patients undergoing PD, with the hypothesis that the intraoperative use of dexamethasone can reduce the incidence of postoperative complications and improve short-term outcomes after PD. The results of the present study will guide the perioperative use of dexamethasone and help improve the clinical management of post-pancreatectomy patients.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05567094. Registered on 30 September 30 2022.
Topics: Humans; Pancreatectomy; Pancreaticoduodenectomy; Acute Disease; Prospective Studies; Pancreatitis; Postoperative Complications; Intestines; Dexamethasone; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37660052
DOI: 10.1186/s13063-023-07571-y -
Diagnostic and Interventional Radiology... Jul 2023To investigate the relationship between hepatic steatosis (HS), pancreatic steatosis (PS), and coexisting HS and PS and the Coronavirus disease-2019 (COVID-19) pneumonia...
PURPOSE
To investigate the relationship between hepatic steatosis (HS), pancreatic steatosis (PS), and coexisting HS and PS and the Coronavirus disease-2019 (COVID-19) pneumonia total severity score (TSS) and prognosis, assessed through computed tomography (CT), and to evaluate the degree of effectiveness of the three steatosis conditions on TSS and prognosis.
METHODS
This retrospective study involved 461 patients (255 male and 206 female, median age of 53 years) with COVID-19 who underwent unenhanced chest CT. HS, PS, and coexisting HS and PS, assessed through CT, were compared with patient demographics, comorbidities, TSS, hospitalization and intubation requirements, and mortality rates. The parameters were compared using Mann-Whitney U and chi-square tests. The parameters of three groups of patients with only HS, only PS, and both HS and PS were compared using the Kruskal-Wallis test.
RESULTS
Results revealed that TSS ( < 0.001 for all) and hospitalization rates ( < 0.001 for all except for HS [ = 0.004]) were higher in patients with HS, PS, and both than in those without. Intubation ( = 0.003) and mortality rates ( = 0.018) were significantly higher solely in patients with PS. However, TSS, hospitalization, and diabetes mellitus were significantly higher than in age-standardized analyses for PS. In a comparison between only HS, only PS, and coexisting HS and PS in 210 patients, the highest TSS was in the coexistence group ( < 0.001).
CONCLUSION
The TSS and hospitalization rates correlate with HS, PS, and coexisting HS and PS, whereas intubation and mortality rates only correlate with PS. However, TSS correlates with coexisting HS and PS at the highest rate.
Topics: Humans; Male; Female; Middle Aged; COVID-19; Prognosis; Retrospective Studies; Fatty Liver
PubMed: 36960637
DOI: 10.4274/dir.2022.221730 -
Transplant International : Official... 2023The COVID-19 pandemic increased morbidity and mortality worldwide, particularly in the Kidney and Kidney-Pancreas Transplant Recipient (KTR/KPTR) population. Aiming at... (Observational Study)
Observational Study
The COVID-19 pandemic increased morbidity and mortality worldwide, particularly in the Kidney and Kidney-Pancreas Transplant Recipient (KTR/KPTR) population. Aiming at assessing the absolute and relative excess mortality (EM) in a Portuguese KTR/KPTR cohort, we conducted a retrospective observational study of two KTR/KPTRs cohorts: cohort 1 (; = 2,179) between September/2012 and March/2020; cohort 2 (; = 2067) between March/2020, and August/2022. A correlation between relative and absolute EM and age, sex, time from transplantation and cause of death was explored. A total of 145 and 84 deaths by all causes were observed in and , respectively. The absolute EM in versus was 19.2 deaths (observed/expected mortality ratio 1.30, = 0.006), and the relative EM was 1.47/1,000 person-months (95% CI 1.11-1.93, = 0.006). Compared to the same period in the general population, the standardized mortality rate by age in was 3.86 (95% CI 2.40-5.31), with a peak at 9.00 (95% CI 4.84-13.16) in C. The higher EM identified in this population was associated, mainly, with COVID-19 infection, with much higher values during the second seasonal COVID-19 peak when compared to the general population, despite generalized vaccination. These highlight the need for further preventive measures and improved therapies in these patients.
Topics: Humans; Cohort Studies; COVID-19; Kidney; Pancreas Transplantation; Pandemics; Portugal; Transplant Recipients; Retrospective Studies
PubMed: 37850156
DOI: 10.3389/ti.2023.11655 -
Frontiers in Immunology 2024Salmonid alphavirus (SAV) causes pancreas disease (PD), which negatively impacts farmed Atlantic salmon. In this study, fish were vaccinated with a DNA-PD vaccine...
Salmonid alphavirus (SAV) causes pancreas disease (PD), which negatively impacts farmed Atlantic salmon. In this study, fish were vaccinated with a DNA-PD vaccine (DNA-PD) and an oil-adjuvanted, inactivated whole virus PD vaccine (Oil-PD). Controls were two non-PD vaccinated groups. Fish were kept in one tank and challenged by cohabitation with SAV genotype 2 in seawater. Protection against infection and mortality was assessed for 84 days (Efficacy study). Nineteen days post challenge (dpc), subgroups of fish from all treatment groups were transferred to separate tanks and cohabited with naïve fish (Transmission study 1) or fish vaccinated with a homologous vaccine (Transmission study 2), to evaluate virus transmission for 26 days (47 dpc). Viremia, heart RT-qPCR and histopathological scoring of key organs affected by PD were used to measure infection levels. RT-droplet digital PCR quantified shedding of SAV into water for transmission studies. The Efficacy study showed that PD associated growth-loss was significantly lower and clearance of SAV2 RNA significantly higher in the PD-DNA group compared to the other groups. The PD-DNA group had milder lesions in the heart and muscle. Cumulative mortality post challenge was low and not different between groups, but the DNA-PD group had delayed time-to-death. In Transmission study 1, the lowest water levels of SAV RNA were measured in the tanks containing the DNA-PD group at 21 and 34 dpc. Despite this, and irrespective of the treatment group, SAV2 was effectively transmitted to the naïve fish during 26-day cohabitation. At 47 dpc, the SAV RNA concentrations in the water were lower in all tanks compared to 34 dpc. In Transmission study 2, none of the DNA-PD immunized cohabitants residing with DNA-PD-vaccinated, pre-challenged fish got infected. In contrast, Oil-PD immunized cohabitants residing with Oil-PD-vaccinated, pre-challenged fish, showed infection levels similar to the naïve cohabitants in Transmission study 1. The results demonstrate that the DNA-PD vaccine may curb the spread of SAV infection as the DNA-PD vaccinated, SAV2 exposed fish, did not spread the infection to cohabiting DNA-PD vaccinated fish. This signifies that herd immunity may be achieved by the DNA-PD vaccine, a valuable tool to control the PD epizootic in farmed Atlantic salmon.
Topics: Animals; Alphavirus; Salmo salar; Pancreatic Diseases; RNA; Water; Viral Vaccines; Vaccines, DNA; Pancreas; DNA; Genotype; Fish Diseases
PubMed: 38515753
DOI: 10.3389/fimmu.2024.1342816 -
Advanced Science (Weinheim,... Sep 2023Type 1 diabetes (T1D) is a complex autoimmune disease that develops in genetically susceptible individuals. Most T1D-associated single nucleotide polymorphisms (SNPs)...
Type 1 diabetes (T1D) is a complex autoimmune disease that develops in genetically susceptible individuals. Most T1D-associated single nucleotide polymorphisms (SNPs) are located in non-coding regions of the human genome. Interestingly, SNPs in long non-coding RNAs (lncRNAs) may result in the disruption of their secondary structure, affecting their function, and in turn, the expression of potentially pathogenic pathways. In the present work, the function of a virus-induced T1D-associated lncRNA named ARGI (Antiviral Response Gene Inducer) is characterized. Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic β cells and binds to CTCF to interact with the promoter and enhancer regions of IFNβ and interferon-stimulated genes, promoting their transcriptional activation in an allele-specific manner. The presence of the T1D risk allele in ARGI induces a change in its secondary structure. Interestingly, the T1D risk genotype induces hyperactivation of type I IFN response in pancreatic β cells, an expression signature that is present in the pancreas of T1D patients. These data shed light on the molecular mechanisms by which T1D-related SNPs in lncRNAs influence pathogenesis at the pancreatic β cell level and opens the door for the development of therapeutic strategies based on lncRNA modulation to delay or avoid pancreatic β cell inflammation in T1D.
Topics: Humans; Insulin-Secreting Cells; Diabetes Mellitus, Type 1; RNA, Long Noncoding; Transcriptional Activation; Inflammation
PubMed: 37382191
DOI: 10.1002/advs.202300063 -
Gastroenterology Research Feb 2024Emphysematous pancreatitis (EP), a severe form of necrotizing infection of the pancreas, is an extremely rare medical emergency with high rates of mortality. It is...
Emphysematous pancreatitis (EP), a severe form of necrotizing infection of the pancreas, is an extremely rare medical emergency with high rates of mortality. It is characterized by intraparenchymal pancreatic or peri-pancreatic air due to either monomicrobial or polymicrobial infection with gas-forming bacteria or due to entero-pancreatic fistula. EP is classified according to timing from disease onset when air bubble signs were detected on computed tomography (CT) scan, as early onset (within 2 weeks from disease onset) or late (more than 2 weeks from disease onset). While most cases of acute pancreatitis are resolved with supportive care alone, clinical outcomes of EP, especially the early onset subtype, are very poor with high rates of morbidity and mortality. These two case reports present the clinical features, diagnostic investigations, and management of two patients admitted to our hospital with early onset fulminant EP, each investigated and managed with different approaches. The first patient underwent a more conservative treatment, with diagnosis being made 52 h following admission, and thus, intensive care unit (ICU) admission and surgery were postponed, while the second patient was diagnosed a few hours following presentation with earlier ICU admission. In this article, we will present the critical importance of early diagnosis of the aforementioned rare entity of severe pancreatitis and will consider the consequences of rapid diagnosis on disease course, morbidity and mortality.
PubMed: 38463147
DOI: 10.14740/gr1671 -
IScience Jan 2024An altered gut microbiota is associated with type 1 diabetes (T1D), affecting the production of short-chain fatty acids (SCFA) and glucose homeostasis. We previously...
An altered gut microbiota is associated with type 1 diabetes (T1D), affecting the production of short-chain fatty acids (SCFA) and glucose homeostasis. We previously demonstrated that enhancing serum acetate and butyrate using a dietary supplement (HAMSAB) improved glycemia in non-obese diabetic (NOD) mice and patients with established T1D. The effects of SCFA on immune-infiltrated islet cells remain to be clarified. Here, we performed single-cell RNA sequencing on islet cells from NOD mice fed an HAMSAB or control diet. HAMSAB induced a regulatory gene expression profile in pancreas-infiltrated immune cells. Moreover, HAMSAB maintained the expression of β-cell functional genes and decreased cellular stress. HAMSAB-fed mice showed preserved pancreatic endocrine cell identity, evaluated by decreased numbers of poly-hormonal cells. Finally, SCFA increased insulin levels in human β-like cells and improved transplantation outcome in NOD/SCID mice. Our findings support the use of metabolite-based diet as attractive approach to improve glucose control in T1D.
PubMed: 38213620
DOI: 10.1016/j.isci.2023.108694 -
Hepatobiliary & Pancreatic Diseases... Aug 2023Coronavirus disease 2019 (COVID-19) is a global pandemic issue. In addition to the well-known respiratory and fever symptoms, gastrointestinal symptoms have also been... (Observational Study)
Observational Study
BACKGROUND
Coronavirus disease 2019 (COVID-19) is a global pandemic issue. In addition to the well-known respiratory and fever symptoms, gastrointestinal symptoms have also been reported. This study aimed to evaluate the prevalence and prognosis of patients with COVID-19 infection complicated with acute pancreatitis in intensive care unit (ICU).
METHODS
This was a retrospective observational cohort study, and patients aged 18 years or older, admitted into the ICU in a single tertiary center from January 1, 2020, to April 30, 2022 were enrolled. Patients were identified by electronic medical records and reviewed manually. The primary outcome was the prevalence of acute pancreatitis among ICU patients with COVID-19. The secondary outcomes were the length of hospital stay, need for mechanical ventilation (MV), need for continuous renal replacement therapy (CRRT), and in-hospital mortality.
RESULTS
A total of 4133 patients, admitted into the ICU, were screened. Among these patients, 389 were infected by COVID-19, and 86 were diagnosed with acute pancreatitis. COVID-19 positive patients were more likely to present with acute pancreatitis than COVID-19 negative patients (odds ratio = 5.42, 95% confidence interval: 2.35-6.58, P < 0.01). However, the length of hospital stay, need for MV, need for CRRT, and in-hospital mortality were not significantly different between acute pancreatitis patients with and without COVID-19 infection.
CONCLUSIONS
Severe COVID-19 infections may cause acute pancreas damage in critically ill patients. However, the prognosis may not differ between acute pancreatitis patients with and without COVID-19 infection.
Topics: Humans; COVID-19; Cohort Studies; Critical Illness; Prevalence; Acute Disease; Pancreatitis; Prognosis; Intensive Care Units; Retrospective Studies
PubMed: 36973110
DOI: 10.1016/j.hbpd.2023.03.004 -
Narra J Aug 2023A choledochal cyst is a bile duct anomaly that disrupts the transportation of bile from the liver to the gallbladder and small intestine. Choledochal cysts are rare,...
A choledochal cyst is a bile duct anomaly that disrupts the transportation of bile from the liver to the gallbladder and small intestine. Choledochal cysts are rare, occurring in approximately one out of every 100,000 to 150,000 children in Western countries, with a girls-to-boys ratio of 4:1. Immediate surgery to excise the cyst and construct a biliary-enteric continuity is necessary to treat this condition. This case-report aimed to present a child with choledochal cyst type IVa who underwent a Roux-en-Y hepaticojejunostomy. A 3-year-11-month-old girl with an abdominal mass experienced jaundice, nausea, and vomiting over the past two years, which worsened in the last month. Abdominal ultrasonography indicated intrahepatic biliary dilatation. Abdominal computed tomography scan results confirmed a choledochal cyst type IVa, characterized by fusiform cyst dilatation at the bilateral intrahepatic bile duct, common hepatic duct, cystic duct, and common bile duct. The cyst exerted pressure on the pancreas and small intestine. Before the surgery, the patient was treated with ceftriaxone 100 mg/kg/day and gentamicin 5 mg/kg/day. Roux-en-Y hepaticojejunostomy was performed, involving the complete excision of the extrahepatic bile duct to reconstruct the biliary system. During the surgery, a retroperitoneal cyst measuring 20 cm x 10 cm with a volume of 200 ml was discovered. Following the surgery, the patient showed clinical improvement. Patient follow-ups indicated that no complications such as wound infection, acute pancreatitis, and the formation of pancreatic or biliary fistula occurred. This case highlights that Roux-en-Y hepaticojejunostomy proves to be an effective surgical approach for managing choledochal cyst type IVa in children, helping to prevent further complications.
PubMed: 38450271
DOI: 10.52225/narra.v3i2.201 -
Journal of Cancer Research and Clinical... Nov 2023Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of...
BACKGROUND
Patients with resectable and borderline resectable pancreatic ductal adenocarcinoma increasingly receive neoadjuvant therapy prior to surgery. However, the effect of neoadjuvant therapy on the immune microenvironment remains largely unknown. We analyzed the immune microenvironment in pancreatic cancer tumor tissue samples from patients treated with neoadjuvant therapy compared to patients after upfront surgery to gain knowledge about the immunological environment after therapy.
METHODS
Multispectral imaging was performed on tissue from resected specimens from patients with PDAC who underwent upfront surgery (n = 10), neoadjuvant FOLFIRINOX (n = 10) or gemcitabine + radiotherapy (gem-RT) (n = 9) followed by surgery. The samples were selected by a dedicated pancreas pathologist from both the central part and the invasive front of the tumor (by the resected vein or venous surface) and subsequently analyzed using the Vectra Polaris.
RESULTS
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile, with less regulatory T cells and more CD8 T cells in the tumor tissue compared to patients receiving neoadjuvant gem-RTgem-RT or undergoing upfront surgery. Furthermore, CD163 macrophages were decreased, and a higher CD163 macrophages versus CD163 macrophages ratio was found in patients with neoadjuvant FOLFIRINOX. In all treatment groups, percentage of FoxP3 B cells was significantly higher in tumor tissue compared to adjacent tissue. Furthermore, an increase in regulatory T cells in the tumor tissue was found in patients undergoing upfront surgery or receiving neoadjuvant gem-RT. In the gem-RT group, less CD8 T cells and a higher CD163 macrophages to CD8 ratio were noted in the tumor tissue, suggesting a more immune suppressive profile in the tumor tissue.
CONCLUSION
Patients receiving neoadjuvant FOLFIRINOX display a more pro-inflammatory immune profile compared to patients receiving neoadjuvant gem-RT or undergoing upfront surgery. Furthermore, in all treatment groups, a more immune suppressive microenvironment was found in the tumor tissue compared to the adjacent non-tumorous tissue.
Topics: Humans; Pancreatic Neoplasms; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Fluorouracil; Gemcitabine; Leucovorin; Tumor Microenvironment
PubMed: 37587309
DOI: 10.1007/s00432-023-05219-7