Epidemiological, clinical and microbiological characteristics of patients with biliary tract diseases with positive bile culture in a tertiary hospital.

PURPOSE: The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. PATIENTS AND METHODS: From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. RESULTS: Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. CONCLUSION: Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.

Changes in characteristics of gastroenterology center inpatients in Japan because of rapidly aging society.

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

Impact of COVID-19 Infection on Pancreato-Biliary Diseases Requiring Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Viral infections are known to impact the pancreato-biliary system; however, there are limited data showing that the same is true of COVID-19. Endoscopic retrograde cholangiopancreatography (ERCP) can safely be performed in patients with COVID-19 infection, but outcomes of patients with COVID-19 infections and concomitant pancreatic and biliary disease requiring endoscopic intervention are unknown. AIMS: This study aims to evaluate the severity of pancreaticobiliary diseases and post-ERCP outcomes in COVID-19 patients. METHODS: Patients with pancreato-biliary disease that required inpatient ERCP from five centers in the United States and South America between January 1, 2020, and October 31, 2020 were included. A representative cohort of patients from each month were randomly selected from each site. Disease severity and post-ERCP outcomes were compared between COVID-19 positive and COVID-19 negative patients. RESULTS: A total of 175 patients were included: 95 COVID positive and 80 COVID negative. Mean CTSI score for the patients who had pancreatitis was higher in COVID-positive cohort by 3.2 points (p < .00001). The COVID-positive group had more cases with severe disease (n = 41) versus the COVID-negative group (n = 2) (p < .00001). Mortality was higher in the COVID-19 positive group (19%) compared to COVID-negative group (7.5%) even though the COVID-19-negative group had higher incidence of malignancy (n = 17, 21% vs n = 7, 7.3%) (p = 0.0455). CONCLUSIONS: This study shows that patients with COVID infection have more severe pancreato-biliary disease and worse post-ERCP outcomes, including longer length of stay and higher mortality rate. These are important considerations when planning for endoscopic intervention. CLINICALTRIALS: gov: (NCT05051358).

Aetiological Spectrum of Pancreaticobiliary Diseases in Adult Nigerians on Magnetic Resonance Cholangiopancreatography.

BACKGROUND: Imaging is vital for assessing pancreaticobiliary diseases. AIM: The aim of the study was to investigate the spectrum and pattern of pancreaticobiliary diseases in adult Nigerians using magnetic resonance cholangiopancreatography (MRCP). METHODS: This was a retrospective, descriptive cross-sectional study. The electronic radiological records of 110 adult Nigerians who had undergone MRCP were reviewed. The MRCP images were evaluated for bile duct dilatation, intraluminal filling defects, strictures, calculi, and other abnormalities. RESULTS: There were 45 males (40.9%) and 65 females (59.1%) aged 18-83 years, with a mean age of 51.93 ± 15.22 years. Jaundice (59.1%) and right hypochondrial pain (31.8%) were the most common presenting complaints. Gallstones (32.7%), common bile duct strictures (15.5%), choledocholithiasis (11.8%), pancreatic head carcinoma (10.9%), and gallbladder carcinoma (2.7%) were the most frequent abnormalities. There was biliary obstruction in 56.4% of participants, mostly at the distal and proximal common bile duct. Other findings include hepatomegaly (23.6%), hepatic cysts (6.4%), hepatic steatosis (0.9%), duodenal wall thickening (1.8%), and ascites (5.5%). MRCP was normal in 25 (22.7%) participants. CONCLUSION: Gallstones were the predominant pathology of the various pancreaticobiliary diseases, while Pancreatic head and gallbladder carcinoma were the most common malignant diseases.

The real incidence of biliary tract complications after adult liver transplantation: the role of the prospective routine use of cholangiography during post-transplant follow-up.

Biliary tract complications (BTCs) still burden liver transplantation (LT). The wide reporting variability highlights the absence of systematic screening. From 2000 to 2009, simultaneous liver biopsy and direct biliary visualization were prospectively performed in 242 recipients at 3 and 6 months (n = 212, 87.6%) or earlier when indicated (n = 30, 12.4%). Median follow-up was 148 (107-182) months. Seven patients (2.9%) experienced postprocedural morbidity. BTCs were initially diagnosed in 76 (31.4%) patients; 32 (42.1%) had neither clinical nor biological abnormalities. Acute cellular rejection (ACR) was present in 27 (11.2%) patients and in 6 (22.2%) BTC patients. Nine (3.7%) patients with normal initial cholangiography developed BTCs after 60 (30-135) months post-LT. BTCs directly lead to 7 (2.9%) re-transplantations and 14 (5.8%) deaths resulting in 18 (7.4%) allograft losses. Bile duct proliferation at 12-month biopsy proved an independent risk factor for graft loss (P = 0.005). Systematic biliary tract and allograft evaluation allows the incidence and extent of biliary lesions to be documented more precisely and to avoid erroneous treatment of ACR. The combination 'abnormal biliary tract-canalicular proliferation' is an indicator of worse graft outcome. BTCs are responsible for important delayed allograft and patient losses. These results underline the importance of life-long follow-up and appropriate timing for re-transplantation.

Biliary and duodenal complications after « en bloc¼ liver-small bowel transplantation in children. A single center cohort study.

BACKGROUND: The technique of « en bloc¼ liver and small bowel transplantation (L-BT) spares a biliary anastomosis, but does not protect against biliary complications. We analyze biliary and duodenal complications (BDC) in our pediatric series. METHODS: Between 1994 and 2020, 54 L-BT were performed in 53 children. The procurement technique included in situ vascular dissection and pancreatic reduction to the head until 2009 (group A). Thereafter, the whole pancreas was recovered (group B). RESULTS: Nine BDCs occurred in 8/53 (15%) patients (7 in group A and 1 in group B): leak of the donor's duodenal stump (2), stenosis of the extra-pancreatic bile duct (5), and intra-pancreatic bile duct stenosis (2). Median delay for diagnosis of stricture was 8 months (4-168). Interventional radiology was successful in one child only, the others required reoperations. Two patients died, of biliary cirrhosis or cholangitis, 15-month and 12-year post-L-BT. One was listed and liver re-transplanted 13 years post-L-BT. At last follow-up, two patients only had normal liver tests and ultrasound. CONCLUSION: BDC after L-BT can cause severe morbidities. Pancreatic reduction might increase this risk. Early surgical complications or chronic pancreatic rejection might be co-factors. Early diagnosis and treatment are key to the long-term prognosis.

Aeromonas dhakensis is not a rare cause of Aeromonas bacteremia in Hiroshima, Japan.

Aeromonas dhakensis, a newly recognized species, is often misidentified as A. hydrophila, A. veronii, or A. caviae by commercial phenotypic tests. Limited data about A. dhakensis are available in Japan. We retrospectively analyzed the patients with monomicrobial Aeromonas bacteremia at Hiroshima University Hospital from January 2011 to December 2017, and species re-identification was conducted using rpoD and gyrB gene sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Of the 19 strains from blood isolates, A. caviae (n = 9, 47.4%), A. dhakensis (n = 4, 21.1%), A. hydrophila (n = 3, 15.8%), and A. veronii (n = 3, 15.8%) were re-identified. A. dhakensis was phenotypically misidentified as A. hydrophila (n = 3, 75%) or A. sobria (n = 1, 25%). A. dhakensis was also misidentified as A. caviae (n = 2, 50%), A. hydrophila (n = 1, 25%), and A. jandaei (n = 1, 25%) in MALDI-TOF MS system. Malignancies (n = 12, 63.2%) and liver cirrhosis (n = 7, 36.8%) were common comorbidities. Biliary tract infection was the most frequent source of Aeromonas bacteremia (n = 11, 57.9%). The major source of A. dhakensis bacteremia was also biliary tract infection (n = 3, 75%), and the 14-day infection-related mortality of A. dhakensis was 25%. A. dhakensis isolates showed similar clinical characteristics, antimicrobial susceptibility, and mortality with those of other Aeromonas species isolates. This study demonstrated that A. dhakensis is not a rare cause of Aeromonas bacteremia, but is often misidentified as A. hydrophila in Hiroshima, Japan. Further studies should be conducted to identify the geographical distribution and clinical impact of A. dhakensis in Japan.

Endoscopic treatment of biliary complications after liver transplantation.

BACKGROUND: biliary complications are an important cause of morbidity and mortality after liver transplantation. Endoscopic retrograde cholangiopancreatography (ERCP) is a therapeutic option, which is less invasive than surgical management. MATERIALS AND METHODS: the endoscopic management with ERCP of patients with biliary complications after liver transplantation in the Complexo Hospitalario Universitario de A Coruña between 2012 and 2018 was reviewed. RESULTS: there were 232 liver transplant recipients and biliary complications occurred in 70 (30.1 %) patients. Anastomotic strictures, most of them choledocho-choledochal, constituted the most frequent complication in 43 (61.4 %) patients. Biliary leak occurred in 16 (22.9 %) patients, non-anastomotic strictures in six (8.6 %) and choledocholithiasis in five (7.1 %). ERCP was performed in 39/43 patients with anastomotic strictures, achieving clinical success in 36 (92.3 %). All patients with a biliary leak were treated with CPRE, with a clinical resolution in 10/16 (62.5 %). ERCP was successful in 3/5 patients (60 %) with bile duct stones. In non-anastomotic strictures, ERCP was not effective in any case. Regarding complications, five (7.7 %) patients presented mild-moderate bleeding after biliary sphincterotomy. CONCLUSION: in our study, ERCP is useful in most biliary anastomotic strictures, early biliary leaks and choledocholithiasis after liver transplantation. The rate of ERCP complications in these patients was low and none were lethal.

Prognosis of liver abscess with no identified organism.

BACKGROUND: There are limited studies focusing on liver abscess with negative microbiological cultures. This study evaluated the clinical and prognostic differences of patients with culture-negative liver abscess (CNLA) compared to those with a positive culture (CPLA) and compared these factors between K. pneumoniae liver abscess (KLA) and E. coli liver abscess (ELA). METHODS: A retrospective study of the patients who admitted with a liver abscess at two tertiary hospitals in Korea from 2012 to 2016 was performed. RESULTS: Among a total of 402 patients with liver abscess, 61.2% had positive cultures. K. pneumoniae (n = 133) was the most common cause, followed by E. coli (n = 74). Patients with CPLA were significantly older (p = 0.02) and more frequently had cholelithiasis or biliary tract disease (p = 0.001) compared to patients with CNLA. In-hospital mortality (p = 0.63) and recurrence (p = 0.77) were no different between the two groups. The length of hospital stay was significantly longer in patients with CPLA (p = 0.03) compared with those with CNLA. Subgroup analysis for patients who received 3rd generation cephalosporins empirically showed that in-hospital mortality (p = 0.18) and recurrence (p = 0.27) were not also significantly different. Cholelithiasis, or biliary tract disease (p = 0.001), liver disease (p = 0.001), malignancy (p = 0.0001), and ESBL production (p = 0.0001) were found more frequently in patients with ELA compared with those with KLA. CONCLUSIONS: The prognosis of the CNLA patients was similar to that of the CPLA patients, although the length of hospital stay was shorter in the CNLA patients. The epidemiologic and clinical characteristics of the ELA patients are somewhat different than those of the KLA patients.

Biliary Tract Disease in Girls and Young Women With Rett Syndrome.

OBJECTIVE: We reviewed medical records and conducted a nationwide survey to characterize the clinical features and determine the prevalence of biliary tract disease in girls and women with Rett syndrome (RTT). METHODS: Sixty-two individuals with RTT and biliary tract disease were identified from the membership of Rett Syndrome Organization and patient files of the principal investigator. Medical records of 46 individuals were reviewed for presenting features, diagnostic tests, and treatment outcomes of biliary tract disease. We designed a questionnaire that probed the frequency of risk factors and treatment outcomes of biliary tract disease in RTT. The questionnaire was completed by 271 parents whose daughters met the clinical criteria for RTT and/or had MECP2 mutations and participated in the Natural History of Rett Syndrome Study. RESULTS: Presenting symptoms identified by record review included abdominal pain (94%), irritability (88%), weight loss (64%), and vomiting (52%). Biliary dyskinesia, cholecystitis, and cholelithiasis were identified in 90%, 77%, and 70%, respectively, by cholescintigraphy, surgical pathology, and abdominal ultrasound. The prevalence of biliary tract disease was 4.4% (n = 12) in the RTT cohort. Risk factors included older age (P < 0.001) and a positive family history (P < 0.01). Diagnoses included cholecystitis (n = 5), biliary dyskinesia (n = 6), and cholelithiasis (n = 7). Ten individuals underwent surgery; 7 had resolution of symptoms after surgical intervention. CONCLUSIONS: Biliary tract disease is not unique to RTT, but may be under-recognized because of the cognitive impairment of affected individuals. Early diagnostic evaluation and intervention may improve the health and quality of life of individuals affected with RTT and biliary tract disease.

Biliary leakage following pancreaticoduodenectomy: Prevalence, risk factors and management.

BACKGROUND: Few studies investigated biliary leakage after pancreaticoduodenectomy (PD) especially when compared to postoperative pancreatic fistula (POPF). This study was to determine the incidence of biliary leakage after PD, predisposing factors of biliary leakage, and its management. METHODS: We retrospectively studied all patients who underwent PD from January 2008 to December 2017 at Gastrointestinal Surgery Center, Mansoura University, Egypt. According to occurrence of postoperative biliary leakage, patients were divided into two groups. Group (1) included patients who developed biliary leakage and group (2) included patients without identified biliary leakage. The preoperative data, operative details, and postoperative morbidity and mortality were analyzed. RESULTS: The study included 555 patients. Forty-four patients (7.9%) developed biliary leakage. Ten patients (1.8%) had concomitant POPF. Multivariate analysis identified obesity and time needed for hepaticojejunostomy reconstruction as independent risk factors of biliary leakage, and no history of preoperative endoscopic retrograde cholangiopancreatiography (ERCP) as protective factor. Biliary leakage from hepaticojejunostomy after PD leads to a significant increase in development of delayed gastric emptying, and wound infection. The median hospital stay and time to resume oral intake were significantly greater in the biliary leakage group. Non-surgical management was needed in 40 patients (90.9%). Only 4 patients (9.1%) required re-exploration due to biliary peritonitis and associated POPF. The mortality rate in the biliary leakage group was significantly higher than that of the non-biliary leakage group (6.8% vs 3.9%, P = 0.05). CONCLUSIONS: Obesity and time needed for hepaticojejunostomy reconstruction are independent risk factors of biliary leakage, and no history of preoperative ERCP is protective factor. Biliary leakage increases the risk of morbidity and mortality especially if concomitant with POPF. However, biliary leakage can be conservatively managed in majority of cases.

Drug induced liver injury with analysis of alternative causes as confounding variables.

AIMS: Drug-induced liver injury (DILI) is rare compared to the worldwide frequent acute or chronic liver diseases. Therefore, patients included in series of suspected DILI are at high risk of not having DILI, whereby alternative causes may confound the DILI diagnosis. The aim of this review is to evaluate published case series of DILI for alternative causes. METHODS: Relevant studies were identified using a computerized search of the Medline database for publications from 1993 through 30 October 2017. We used the following terms: drug hepatotoxicity, drug induced liver injury, hepatotoxic drugs combined with diagnosis, causality assessment and alternative causes. RESULTS: Alternative causes as variables confounding the DILI diagnosis emerged in 22 published DILI case series, ranging from 4 to 47%. Among 13 335 cases of suspected DILI, alternative causes were found to be more likely in 4555 patients (34.2%), suggesting that the suspected DILI was probably not DILI. Biliary diseases such as biliary obstruction, cholangitis, choledocholithiasis, primary biliary cholangitis and primary sclerosing cholangitis were among the most missed diagnoses. Alternative causes included hepatitis B, C and E, cytomegalovirus, Epstein-Barr virus, ischemic hepatitis, cardiac hepatopathy, autoimmune hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and alcoholic liver disease. CONCLUSIONS: In more than one-third of published global DILI case series, alternative causes as published in these reports confounded the DILI diagnosis. In the future, published DILI case series should include only patients with secured DILI diagnosis, preferentially established by prospective use of scored items provided by robust diagnostic algorithms such as the updated Roussel Uclaf causality assessment method.

Bactibilia in diseases of the biliary tract and pancreatic gland in patients older than 80 years: a STROBE-retrospective cohort study in a teaching hospital in Italy.

Bile is a lipid-rich sterile solution produced in the liver that can be infected resulting in bactibilia. A higher incidence of postoperative infectious complications has been seen in patients with bactibilia. Recently, gram-negative bacteria have been linked to a tumor-associated inflammatory status. This study is a retrospective cohort study of 39 patients, who are over 80 years of age only (53.85% males and 46.15% females), hospitalized with diseases of the biliopancreatic system in one teaching hospital in Italy from January 2011 to December 2012 with a follow-up of 5 years. The most common biliary diseases after surgery were pancreatic head cancer (p < 0.0001) and gallbladder cancer (p = 0.0051), while the most common bacteria in the bile were E. coli (p = 0.0180) and Pseudomonas spp. (p < 0.0001). Uni- and multivariate linear correlation analysis revealed that patients with pancreatic head cancer had low survival times compared to patients with other diseases. Moreover, the bacterium type was a positive predictor of survival time compared to other variables. Our data confirm E. coli as a pathogen in patients with gallbladder and pancreatic cancer. Although the influence of bactibilia in developing surgical complications is limited, we consider that its composition is crucial to properly address the antibiotic treatment in biliary tract infections, especially in the elderly.

Acute biliary events during anti-tuberculosis treatment: hospital case series and a nationwide cohort study.

BACKGROUND: Tuberculosis (TB) remains one of the major infectious diseases worldwide. Adverse reactions are common during TB treatment. Few reports, however, are available on treatment-related acute biliary events (ABEs), such as cholelithiasis, biliary obstruction, acute cholecystitis, and cholangitis. METHODS: We first report four pulmonary TB patients who developed ABEs during anti-TB treatment. Abdominal sonography revealed multiple gall stones with dilated intrahepatic ducts in three patients and cholecystitis in one patient. To investigate the incidence of and risk factors for ABEs during anti-TB treatment, we subsequently conducted a nationwide cohort study using the National Health Insurance Research Database of Taiwan. RESULTS: A total of 159,566 pulmonary TB patients were identified from the database between 1996 and 2010, and among them, 195 (0.12%) developed ABEs within 180 days after beginning anti-TB treatment. Logistic regression analysis revealed that the risk factors associated with ABEs are older age (relative risk [RR]: 1.32 [1.21-1.44] per 10-year increment) and diabetes mellitus (RR: 1.59 [1.19-2.13]). CONCLUSIONS: Although infrequently encountered, ABEs should be considered among patients with TB who experience abdominal discomfort with hyperbilirubinemia, especially patients who have older age or diabetes.

Factors associated to prevalence and treatment of carbapenem-resistant Enterobacteriaceae infections: a seven years retrospective study in three tertiary care hospitals.

BACKGROUND: The increasing incidence of carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a difficult problem in the current clinical anti-infective treatment. We performed a retrospective analysis of prevalence and treatment for CRE infections patients. METHODS: This study was conducted in three tertiary care hospitals from January 1, 2010 to December 30, 2016. Baseline data, treatment, and outcomes were collected in patients with ventilator-associated bacterial pneumonia (VABP), bacteremia, complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), superficial wound infection (SWI), biliary tract infection (BTI), deep wound infection (DWI) and sterile body fluids infection (SBFI) due to CRE. RESULTS: One hundred twenty-four cases of CRE infection were identified: 31 VABP, 22 bacteremia, 18 cUTI/AP, 16 HABP, 16 SWI, 9 BTI, 7 DWI and 5 SBFI. The patient population had significant immunocompromised (33 of 124, 26.6%) and severe sepsis (43 of 124, 34.7%). The most common CRE pathogens were Klebsiella pneumoniae (84 of 124, 67.7%) and Enterobacter cloacae (24 of 124, 19.4%). And the production of IMP-type carbapenemase was the main antibiotic resistance mechanism. The majority of patients to take monotherapy for empiric therapy and dual therapy for direct treatment. Outcomes were universally poor (28-day mortality was 22.6%, 28 of 124) across all sites of infection. CONCLUSIONS: We identified a large number of cases of CRE infection in 7 years from different parts, most of these pathogens have been confirmed to produce IMP-type carbapenemases. The retrospective analysis of cases of such bacterial infections will help to control future infections of these pathogens. Despite the high mortality rate, we still found that the selection of quinolone antibiotics can be effective in the treatment of CRE producing IMP type enzymes.

Hepatobiliary Dysfunction and Disseminated Intravascular Coagulation Increase Risk of Mortality in Pediatric Hemophagocytic Lymphohistiocytosis.

OBJECTIVES: Hemophagocytic lymphohistiocytosis poses significant challenges due to limited tools to guide clinical decisions in a population at high risk of death. We sought to assess whether disseminated intravascular coagulation and hepatobiliary dysfunction, significant comorbidities seen in critical care settings, would identify hemophagocytic lymphohistiocytosis patients with increased risk of mortality. DESIGN: Retrospective chart review. SETTING: Single-center PICU. PATIENTS: All patients admitted to a tertiary care children's hospital diagnosed with hemophagocytic lymphohistiocytosis from 2005 to 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-three patients were diagnosed with hemophagocytic lymphohistiocytosis with median age of 61 months. The 5-year overall survival was 51% (22/43). Univariate analyses revealed ferritin levels greater than 10,000 (ng/mL), international normalized ratio greater than 1.5, or platelet counts less than 100,000/µL at initiation of dexamethasone were individually associated with mortality. Development of disseminated intravascular coagulation, hepatobiliary dysfunction, or both increased the likelihood of death in hemophagocytic lymphohistiocytosis patients (relative risk; 95% CI) (6; 1.4-34; p < 0.05), (4.1; 1.8-10; p < 0.05), and (7.5; 1.8-42; p < 0.05). Of 12 autopsies performed, 75% had at least one active infection, 66% had chronic lymphopenia, 50% had lymphocyte depletion in the spleen, thymus, or bone marrow, 42% had evidence of microvascular thrombosis, and 92% had evidence of hepatocellular injury. CONCLUSIONS: Hemophagocytic lymphohistiocytosis continues to have high mortality with hemophagocytic lymphohistiocytosis-1994/2004 (dexamethasone/etoposide), the current standard of care for all children with hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis patients who developed disseminated intravascular coagulation, hepatobiliary dysfunction, or both had higher risk of death with mortalities of 60%, 77%, and 77%, respectively. Phenotypic classifications are urgently needed to guide individualized treatment strategies to improve outcomes for children with hemophagocytic lymphohistiocytosis.

Risk factors of ceftriaxone-associated biliary pseudolithiasis in adults: influence of renal dysfunction.

BACKGROUND: Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL) mainly in children. Biliary elimination of CTRX increases in patients with renal dysfunction. However, the influence of renal dysfunction on the incidence of CTRX-associated BPL has not been well investigated. The aim of this study was to investigate the cumulative incidence of CTRX-associated BPL in adults and to assess if renal dysfunction is a risk factor. METHODS: We retrospectively analyzed the medical records of 478 patients treated with CTRX to assess the incidence and risk factors of CTRX-associated BPL. We examined age, sex, body weight, dosage, and duration of CTRX therapy, and the concentrations of serum creatinine, estimated glomerular filtration rate (eGFR), albumin, and serum calcium in all the patients. The cumulative incidence of BPL was calculated using a competing risk model. The multivariate analysis of each variable for the development of BPL was assessed by a Cox proportional hazards model. RESULTS: A total of 362 patients (75.7%) had renal dysfunction (eGFR: < 60 mL/min). The cumulative incidence of BPL in patients with renal dysfunction was significantly higher than that in patients with normal kidney function (4.1 vs. 0.6%, p = 0.017). Renal dysfunction (Hazard ratio (HR) 8.14, 95% CI 1.05-63.0, p = 0.045) and female sex (HR 5.35, 95% CI 1.17-24.5, p = 0.031) were independent risk factors of CTRX-associated BPL, which was confirmed using multivariate analysis (renal dysfunction: HR 7.93, 95% CI 1.04-60.5, p = 0.046) (female sex HR 4.65, 95% CI 1.03-21.1, p = 0.046). CONCLUSIONS: Renal dysfunction is an independent risk factor of CTRX-associated BPL in adults.

Biliary Tract and Liver Complications in Polycystic Kidney Disease.

Polycystic liver disease is a well described manifestation of autosomal dominant polycystic kidney disease (ADPKD). Biliary tract complications are less well recognized. We report a 50-year single-center experience of 1007 patients, which raised a hypothesis that ADPKD is associated with biliary tract disease. We tested this hypothesis using all England Hospital Episode Statistics data (1998-2012), within which we identified 23,454 people with ADPKD and 6,412,754 hospital controls. Hospitalization rates for biliary tract disease, serious liver complications, and a range of other known ADPKD manifestations were adjusted for potential confounders. Compared with non-ADPKD hospital controls, those with ADPKD had higher rates of admission for biliary tract disease (rate ratio [RR], 2.24; 95% confidence interval [95% CI], 2.16 to 2.33) and serious liver complications (RR, 4.67; 95% CI, 4.35 to 5.02). In analyses restricted to those on maintenance dialysis or with a kidney transplant, RRs attenuated substantially, but ADPKD remained associated with biliary tract disease (RR, 1.19; 95% CI, 1.08 to 1.31) and perhaps with serious liver complications (RR, 1.15; 95% CI, 0.98 to 1.33). The ADPKD versus non-ADPKD RRs for biliary tract disease were larger for men than women (heterogeneity P<0.001), but RRs for serious liver complications appeared higher in women (heterogeneity P<0.001). Absolute excess risk of biliary tract disease associated with ADPKD was larger than that for serious liver disease, cerebral aneurysms, and inguinal hernias but less than that for urinary tract infections. Overall, biliary tract disease seems to be a distinct and important extrarenal complication of ADPKD.

[Splenectomy in hemolitic disorders. Influence of Gilbert's disease in the occurrence of biliary complications]. / Esplenectomía en enfermedades hemolíticas. Influencia de la enfermedad de Gilbert en la aparición de complicaciones biliares.

INTRODUCTION: In patients with hemolytic disorders (HD) splenectomy is recommended between 6-12 years. A higher risk of biliary complications (BC) has been described in those with associated Gilbert's disease (GD), but the ideal surgical age has not been stablished yet. Our aim is to quantify the risk of BC in patients with HD and GD to assess the benefit of early splenectomy. MATERIAL AND METHODS: Retrospective study of splenectomies performed in patients with HD between 2000-2017. The incidence of BC, its clinical consequences (admission or invasive treatment) and time of onset were analyzed. Two groups were considered: patients with GD and without GD. Survival curves were obtained and compared with log-rank test. RESULTS: Fourty-four patients underwent splenectomy, 15 of them (34.1%) with HD+GD. The median age at surgery was 10.3 years (range 5.4-14.8). Twenty-nine (65.9%) had BC. Half of the patients with GD had BC before 8 years vs. 10,5 years in the cases without GD (log-rank 3.9, p= 0.05). Patients with GD had more BC (86.7% vs. 55.2%; Chi2= 4.37, p= 0.037). In the HD+GD group, 8 cases (53%) required admission vs.8 patients (31%) in the group HD without GD (Chi2= 2, p= 0.1). Invasive treatment was performed in 2 patients (13%) in the HD+GD group and 2 others (7.6%) in the group HD without GD (Chi2= 0.3, p= 0.6). CONCLUSIONS: In our series, the BC incidence was higher in patients with HD and GD. There was a trend towards an earlier presentation of BC in this group, but neither this data nor its clinical consequences allow us to recommend early splenectomy.

INTRODUCCION: En pacientes con enfermedades hemolíticas (EH) se recomienda esplenectomía entre 6-12 años. En aquellos con enfermedad de Gilbert (EG) asociada se ha descrito mayor riesgo de complicaciones biliares (CB), sin establecerse edad quirúrgica óptima. Nuestro objetivo es cuantificar el riesgo de CB en pacientes con EH y EG para valorar el beneficio de esplenectomía temprana. MATERIAL Y METODOS: Estudio retrospectivo de las esplenectomías realizadas en pacientes con EH entre 2000-2017. Se analizó la incidencia de CB, su repercusión clínica (ingreso o tratamiento invasivo) y momento de aparición. Se consideraron dos grupos: pacientes con EG y sin EG. Se obtuvieron curvas de supervivencia y se compararon mediante log-rank test. RESULTADOS: Se realizaron 44 esplenectomías, 15 de ellas (34,1%) en pacientes con EH+EG. La edad mediana en la cirugía fue 10,3 años (rango 5,4-14,8). Veintinueve (65,9%) presentaron CB. El 50% de los pacientes con EG las presentaron antes de los 8 años vs.10,5 años en los casos sin EG (log-rank 3,9; p= 0,05). Los pacientes con EG presentaron más CB (86,7% vs. 55,2%; Chi2= 4,37, p= 0,037). En el grupo EH+EG, 8 casos (53%) necesitaron ingreso vs. 8 (31%) en el grupo sin EG (Chi2= 2, p= 0,1). El tratamiento invasivo fue necesario en 2 pacientes (13%) del grupo EH+EG y 2 pacientes (7,6%) del grupo sin EG (Chi2= 0,3, p= 0,6). CONCLUSIONES: En nuestra serie, la incidencia de CB fue superior en los pacientes con EG. Existió una tendencia a la presentación más temprana de CB en este grupo, pero ni este dato ni su repercusión clínica nos permiten recomendar la esplenectomía temprana.

Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation.

This study aimed to elucidate the impact of epithelial regenerative responses and immune cell infiltration on biliary complications after liver transplantation. Bile duct (BD) damage after cold storage was quantified by a BD damage score and correlated with patient outcome in 41 patients. Bacterial infiltration was determined by fluorescence in situ hybridization (FISH). BD samples were analyzed by immunohistochemistry for E-cadherin, cytokeratin, CD56, CD14, CD4, CD8, and double-immunofluorescence for cytokine production and by messenger RNA (mRNA) microarray. Increased mRNA levels of adherens junctions (P < 0.01) were detected in damaged BDs from patients without complications compared with damaged BDs from patients with biliary complications. Immunohistochemistry showed increased expression of E-cadherin and cytokeratin in BDs without biliary complications (P = 0.03; P = 0.047). FISH analysis demonstrated translocation of bacteria in BDs. However, mRNA analysis suggested an enhanced immune response in BDs without biliary complications (P < 0.01). Regarding immune cell infiltration, CD4+ and CD8+ cells were significantly increased in patients without complications compared with those with complications (P = 0.02; P = 0.01). In conclusion, following BD damage during cold storage, we hypothesize that the functional regenerative capacity of biliary epithelium and enhanced local adaptive immune cell infiltration are crucial for BD recovery. Such molecular immunological BD analyses therefore could help to predict biliary complications in cases of "major" epithelial damage after cold storage.Liver Transplantation 23 1422-1432 2017 AASLD.