Human Dectin-1 deficiency impairs macrophage-mediated defense against phaeohyphomycosis.

Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, ß-glucan-binding receptor, Dectin-1. The patient's PBMCs failed to produce TNF-α and IL-1ß in response to ß-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1ß and TNF-α production, which enhanced fungal killing in an interdependent manner. Deficiency of either Dectin-1 or CARD9 was associated with more severe fungal disease, recapitulating the human observation. Because these data implicated impaired Dectin-1 responses in susceptibility to phaeohyphomycosis, we evaluated 17 additional unrelated patients with severe forms of the infection. We found that 12 out of 17 carried deleterious CLEC7A mutations associated with an altered Dectin-1 extracellular C-terminal domain and impaired Dectin-1-dependent cytokine production. Thus, we show that Dectin-1 and CARD9 promote protective TNF-α- and IL-1ß-mediated macrophage defense against C. cassiicola. More broadly, we demonstrate that human Dectin-1 deficiency may contribute to susceptibility to severe phaeohyphomycosis by certain dematiaceous fungi.

Update on endoscopic ultrasound-guided liver biopsy.

Endoscopic ultrasound guided liver biopsy (EUS-LB) has emerged as a minimally-invasive alternative to the traditional (percutaneous or transjugular) liver biopsy techniques for the diagnosis of liver parenchymal diseases. Po-tentially, EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure. Additionally, EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy. Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield, increased acquisition of complete portal tracts, and longer specimen length as compared to the traditional approaches. EUS-LB is associated with lesser post-procedural pain and shorter recovery time, while providing lower risk of complications when compared to traditional liver biopsy. Innovations in needle types, needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique. This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB, and compares EUS-LB with traditional methods of liver biopsy.

Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol. AIM: To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF. METHODS: A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups. RESULTS: A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (P = 0.05), patients on Ursodiol (P < 0.001), and patients on dual therapy (P = 0.003). The highest incidence of cirrhosis was found among patients treated with Ursodiol alone, compared to untreated patients (P < 0.001) or patients on Ursodiol and CFTR modulators (P = 0.01). CONCLUSION: CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Top Ten Tips Palliative Care Clinicians Should Know About End-Stage Liver Disease.

End-stage liver disease (ESLD) is an increasingly prevalent condition with high morbidity and mortality, especially for those ineligible for liver transplantation. Patients with ESLD, along with their family caregivers, have significant needs related to their quality of life, and there is increasing attention being paid to integration of palliative care (PC) principles into routine care throughout the disease spectrum. To provide upstream care for these patients and their family caregivers, it is essential for PC providers to understand their complex psychosocial and physical needs and to be aware of the unique challenges around medical decision making and end-of-life care for this patient population. This article, written by a team of liver and PC experts, shares 10 high-yield tips to help PC clinicians provide better care for patients with advanced liver disease.

Bariatric Surgery in Patients with Cirrhosis: Careful Patient and Surgery-Type Selection Is Key to Improving Outcomes.

PURPOSE: Previous reports suggest an increased mortality in cirrhotic patients undergoing bariatric surgery (BS). With advancements in management of BS, we aim to study the trends, outcomes, and their predictors in patients with cirrhosis undergoing BS. MATERIALS AND METHODS: A retrospective study was performed using the National Database from 2008 to 2013. Outcomes of BS in patients with cirrhosis were studied. In-hospital mortality, length of stay, and cost of care were compared between patients with no cirrhosis (NC), compensated cirrhosis (CC), and decompensated cirrhosis (DC). Multivariable logistic regression analysis was performed to study the predictors of mortality. RESULTS: Of the 558,017 admissions of patients who underwent BS during the study period, 3086 (0.55%) had CC and 103 (0.02%) had DC. An upward trend of vertical sleeve gastrectomy (VSG) utilization was seen during the study period. On multivariate analysis, mortality in CC was comparable with those in NC (aOR 1.88; CI 0.65-5.46); however, it was higher in DC (aOR 83.8; CI 19.3-363.8). Other predictors of mortality were older age (aOR 1.06; CI 1.04-1.08), male (aOR 2.59; CI 1.76-3.81), Medicare insurance (aOR 1.93; CI 1.24-3.01), lower income (aORs 0.44 to 0.55 for 2nd to 4th income quartile vs. 1st quartile), > 3 Elixhauser Comorbidity Index (aOR 5.30; CI 3.45-8.15), undergoing Roux-en-Y gastric bypass as opposed to VSG (aOR 3.90; CI 1.79-8.48), and centers performing < 50 BS per year (aOR 5.25; CI 3.38-8.15). Length of stay and hospital cost were also significantly higher in patients with cirrhosis as compared with those with NC. CONCLUSION: Patients with compensated cirrhosis can be considered for bariatric surgery. However, careful selection of patients, procedure type, and volume of surgical center is integral in improving outcomes and healthcare utilization in patients with cirrhosis undergoing BS.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review

ABSTRACT Introduction and aim. Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. Material and methods. Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. Results. Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review.

INTRODUCTION AND AIM: Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. MATERIAL AND METHODS: Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. RESULTS: Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

Respiratory syncytial virus outbreak on an adult stem cell transplant unit.

BACKGROUND: An increase in respiratory syncytial virus type B (RSV-B) infections was detected on an adult hematology/oncology and stem cell transplant unit during March 2015. This prompted an outbreak investigation. METHODS: Nosocomial cases were defined as RSV-B-positive patients who developed respiratory virus symptoms ≥ 7 days after admission to the unit or were readmitted with symptoms ≤ 7 days since last discharge from the unit. Strict outbreak control measures were implemented to stop the outbreak. RESULTS: During the outbreak, 19 cases of RSV-B were detected, 14 among patients and 5 among health care workers (HCWs). Additionally, 2 HCWs tested positive for respiratory syncytial virus type A and 1 tested positive for influenza B among the 27 symptomatic HCWs evaluated. No specific antiviral therapy was given and all cases recovered without progression to lower respiratory tract infection. After no new cases were identified for 2 weeks, the outbreak was declared over. CONCLUSIONS: High vigilance for respiratory viruses on high-risk inpatient units is required for detection and prevention of potential outbreaks. Multiple respiratory viruses with outbreak potential were identified among HCWs. HCWs with respiratory virus symptoms should not provide direct patient care. Absence of lower respiratory tract infection suggests lower virulence of RSV-B, compared with respiratory syncytial virus type A, among immunocompromised adults.

Associations between Tobacco, Alcohol, and Drug Use with Coronary Artery Plaque among HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study.

BACKGROUND: We characterized associations between smoking, alcohol, and recreational drug use and coronary plaque by HIV serostatus within the Multicenter AIDS Cohort Study (MACS). METHODS: MACS participants (N = 1005, 621 HIV+ and 384 HIV-) underwent non-contrast CT scanning to measure coronary artery calcium; 764 underwent coronary CT angiograms to evaluate plaque type and extent. Self-reported use of alcohol, tobacco, smoked/inhaled cocaine, methamphetamine, ecstasy, marijuana, inhaled nitrites, and erectile dysfunction drugs was obtained at semi-annual visits beginning 10 years prior to CT scanning. Multivariable logistic and linear regression models were performed, stratified by HIV serostatus. RESULTS: Among HIV+ men, current smoking, former smoking, and cumulative pack years of smoking were positively associated with multiple coronary plaque measures (coronary artery calcium presence and extent, total plaque presence and extent, calcified plaque presence, and stenosis >50%). Smoking was significantly associated with fewer plaque measures of comparable effect size among HIV- men; current smoking and calcified plaque extent was the only such association. Heavy alcohol use (>14 drinks/week) was associated with stenosis >50% among HIV+ men. Among HIV- men, low/moderate (1-14 drinks/week) and heavy alcohol use were inversely associated with coronary artery calcium and calcified plaque extent. Few significant associations between other recreational drug use and plaque measures were observed. CONCLUSION: Smoking is strongly associated with coronary plaque among HIV+ men, underscoring the value of smoking cessation for HIV+ persons. Alcohol use may protect against coronary artery calcium and calcified plaque progression in HIV- (but not HIV+) men. Few positive associations were observed between recreational drug use and coronary plaque measures.