Ingestion of Lactobacillus helveticus WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice.

Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.

The relationship between famine exposure in early life and left atrial enlargement in adulthood.

BACKGROUND: Increased left atrium diameter (LAD) is associated with an elevated risk of cardiovascular diseases. The relationship between nutrition status and left atrial enlargement (LAE) is still unclear. The present study aimed to investigate the association of famine exposure in early life with LAE in adulthood. METHODS: Participants were divided into non-exposed, fetal, early, middle and late childhood exposed groups according to birth data. LAE was defined when LAD was ≥3.9 cm in women and ≥4.1 cm in men, or ≥2.3 cm m-2 by a sex-independent cut-off normalised for body surface area. Multivariate logistic regression was performed to calculate the odds ratio (OR) and confidence interval (CI) between famine exposure and LAE. RESULTS: In total, 2522 [905 male, mean (SD) age 59.1 (3.65) years] subjects were enrolled, including 392 (15.5%) LAE subjects. The prevalence of LAE in non-exposed, fetal, early, middle and late childhood exposed groups was 55 (10.8%), 38 (11.2%), 88 (18.1%), 102 (16.7%) and 109 (19.0%), respectively. Compared to the non-exposed group, the ORs for LAE were in fetal (OR = 0.956, 95% CI = 0.605-1.500, P = 0.847), late (OR = 1.748, 95% CI = 1.208-2.555, P = 0.003), middle (OR = 1.647, 95% CI = 1.140-2.403, P = 0.008) and early (OR = 1.630, 95% CI = 1.116-2.399, P = 0.012) childhood exposed groups after adjusting potential cofounders. When stratified by gender, smoking, body mass index, hypertension and diabetes, we found that the effect of famine exposure on LAE was only modified by diabetes (Pinteraction  = 0.007). CONCLUSIONS: Famine exposure during childhood stage might increase the risk of LAE in adults, and this effect interacts with diabetes.

Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study.

The receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/osteoprotegerin system is dysregulated in hyperparathyroid bone diseases. The introduction of denosumab preceding elective surgery as an alternative option when surgery is not possible immediately. INTRODUCTION: The effects of denosumab on vascular calcification in patients with chronic renal failure and low bone mass have been a subject of interest. Therefore, this investigation aimed to determine the short-term changes in vascular calcification after denosumab treatment using a serial electrocardiography-gated computed tomography (CT) to measure coronary artery calcification (CAC) in patients with secondary hyperparathyroidism (SHPT) and low bone mass. METHODS: This 6-month study enrolled patients with SHPT and low bone mass (T-score < - 2.5) owing to dialysis. The 2 groups administered denosumab at a dose of 60 mg (denosumab group), and conventional treatment (control group) had 21 patients each. All patients underwent CT scans at baseline and at the follow-up examination at 6 months to determine the bone mineral density and CAC. RESULTS: The control group demonstrated a significant increase in Agatston scores (187.79 ± 72.27) (P = 0.004). However, no significant change was noted in the denosumab group (P = 0.41). In the denosumab group, only the baseline serum alkaline phosphatase levels correlated negatively with changes in the CAC score (P = 0.01); the baseline alkaline phosphatase levels were the deciding biomarkers for non-responsive CAC scores by Berry Criteria after denosumab treatment (P = 0.02). The denosumab group demonstrated significantly increased bone mineral density in the femoral neck and lumbar spine (P < 0.01). CONCLUSION: The findings provide evidence that denosumab may suppress the progression of CAC and also regress osseous calcification in severe cases of high bone turnover.

Severe hypophosphatemia induced by denosumab in a patient with osteomalacia and tenofovir disoproxil fumarate-related acquired Fanconi syndrome.

Denosumab, a novel agent that inhibits osteoclasts, reduces the risk of fracture in patients with osteoporosis. However, worsening of hypophosphatemia and other symptoms may be induced by denosumab in patients with pre-existing hypophosphatemic osteomalacia. A 58-year-old man with hepatitis B presented with diffuse bone pain and muscle weakness. Denosumab was prescribed by the orthopedist according to documented low bone mass and spine compression fracture. After administering denosumab, the patient's bone pain worsened, and he later developed a right tibia stress fracture. His condition was diagnosed as adult-onset hypophosphatemic osteomalacia complicated by multiple bone fractures, which resulted from Fanconi syndrome with proximal tubulopathy due to tenofovir disoproxil fumarate (TDF) treatment for his hepatitis B. Denosumab use leads to aggressive hypophosphatemic osteomalacia and the complication of stress fractures, because of its effects on bone resorption. Physicians should be aware that in patients with chronic hepatitis B monoinfection who are administered TDF therapy, bone pain or fracture is possible but preventable by timely monitoring of serum phosphate levels. Denosumab should not be used in patients with untreated osteomalacia or vitamin D deficiency, as it may lead not only to hypocalcemia but also to hypophosphatemia in these patients.

Cost Analysis and Determinants of Living Donor Liver Transplantation in Taiwan.

BACKGROUND: Liver transplantation (LT) has become established therapy for end-stage liver disease and small-cell hepatocellular carcinoma (HCC), relying mainly on living donor LT (LDLT) in Taiwan. The cost of LDLT varies in different countries depending on the insurance system, the costs of the facility, and staff. In this study we aimed to investigate cost outcomes and determinants of LDLT in Taiwan. METHODS: From January 2014 to December 2015, 184 LDLT patients were enrolled in a study performed at the Kaohsiung Chang Gung Memorial Hospital. Patients' transplantation costs were defined as expense from immediately after surgery to discharge during hospitalization for LDLT. Antiviral therapy and hepatitis B immunoglobulin (HBIG) for prevention of hepatitis B virus (HBV) were included, but direct-acting antiviral (DAA) therapy for hepatitis C (HCV) was excluded. RESULTS: The median total, intensive care unit (ICU), and ward costs of LT were US$64,250, $43,357, and $16,138 (currency ratio 1:30), respectively. HBV significantly increased the total cost of LT, followed by postoperative reintubation and bile duct complications. CONCLUSION: The charges associated with anti-HBV viral therapy and HBIG increase the cost of LDLT. Disease severity of liver cirrhosis showed less importance in predicting cost. Postoperative complications such as reintubation or bile duct complications should be avoided to reduce the cost of LT.

Correlation Between Blood Transfusion and Blood Glucose Levels in Adult Living Donor Liver Transplantation.

BACKGROUND: To evaluate the effect of dextrose contained in banked blood products on the changes of blood glucose levels in adult living donor liver transplantation patients retrospectively. METHODS: Four hundred seventy-seven patients were divided into a non-blood transfusion (BT) group (G1) and a BT group (G2). The changes in blood glucose levels during the operation were compared using a Mann-Whitney U test, and a P value less than .05 was regarded as significant. RESULTS: No significant changes were detected in blood glucose levels after anesthesia, during dissection phase, in the anhepatic phase, or after reperfusion between the groups. Estimated blood loss for G1 (n = 89) and G2 (n = 388) were 718 ± 514 and 5804 ± 877 mL respectively, G1 had no blood transfusion but G2 had received 4350 ± 6230 mL leukocyte-poor red blood cell transfusion, the pre- and end operation hemoglobin for G1 and G2 were 13.2 ± 2.0, 10.2 ± 1.9 and 10.1 ± 1.6, 10.2 ± 1.9 mg/dL respectively, indicating that they were not under or over transfused. CONCLUSION: When banked blood products are used to replace ongoing blood loss, the dextrose contained in citrate-phosphate-dextrose-adenine seems to have no effect on the changes in the blood glucose levels of the recipients.

Comparison of Core Temperature Changes Between Pediatric Patients Lying on Regular Operating Room Linen Drapes and Water-Repellent Sheepskin Rug in Living Donor Liver Transplantation.

OBJECTIVES: The aims of this study were to compare the core temperature changes between pediatric patients lying on regular operating room linen drapes and a water-repellent sheepskin rug during living donor liver transplantation (LDLT) and to evaluate the effectiveness of using a water-repellent sheepskin rug in preventing profound hypothermia due to fluid overflow from the abdominal cavity during LDLT. PATIENTS AND METHODS: The operative records of pediatric patients who underwent LDLT from June 1994-September 2003 were reviewed retrospectively. The nasopharyngeal temperature (NT) changes during the LDLT procedure between patients lying on regular operating room drapes (GI) and water-repellent sheepskin rug (GII) were compared and analyzed using the Mann-Whitney U test. A P value <.05 was regarded as significant. RESULTS: Thirty-two patients were included in GI and 56 in GII. Profound hypothermia was not observed in any recipients lying on a water-repellent sheepskin rug (GII). The NT after induction and the following 4 hours into the LT procedure were significantly higher in GII than GI. CONCLUSION: Pediatric patients lying on water-repellent sheepskin preserved their core temperature better in comparison to patients lying on linen drapes. The use of a water-repellent sheepskin rug seems to be effective in preventing profound hypothermia related to physical contact with abdominal fluid overflow during the LDLT.

Eye Protection in Liver Transplantation Patients Under General Anesthesia.

BACKGROUND: Opsite (Smith & Nephew, Hull, UK) is widely used in wound care but its use in eye protection against corneal abrasion during major surgery is rarely reported. The purpose of the current study is to compare the effectiveness of using Opsite in eye protection with either wet gauze alone or with wet gauze following application of eye ointment in patients undergoing living donor liver transplantation (LDLT). METHODS: This is a prospective, double-blinded, randomized controlled trial. Forty-one patients undergoing liver transplantation were enrolled. One eye of each patient was protected with sterile gauze soaked with normal saline solution and covered with Opsite. Duratears (ALCON, Fort Worth, Tex, United States) ointment was applied to the other eye before covering it with sterile wet gauze and Opsite (ointment group). The corneal examination was carried out after fluorescein staining before and at the end of surgery by the same doctor. A Student t-test and a χ2 test were used for the statistical analyses. RESULTS: Forty-one patients with 82 eyes were observed in this study. No corneal epithelial defects were found in either the normal saline group or the ointment group. CONCLUSION: Opsite combined with wet gauze with or without additional eye ointment provided 100% protection against corneal abrasion in patients undergoing LDLT.

Anesthesia Management and Fluid Therapy in Right and Left Lobe Living Donor Hepatectomy.

OBJECTIVE: Right lobe living donor hepatectomy poses a greater risk for the donor in relation to blood loss. The aims of this study were to compare anesthetic and intraoperative fluid management in right and left lateral segment living donor hepatectomy. PATIENTS AND METHODS: The anesthesia records of living donor hepatectomy patients were retrospectively reviewed. Donor age and weight, anesthesia time, central venous pressure, blood loss, blood product transfusion, intravenous fluids used, doses of furosemide, and urine output were compared and analyzed between groups using the Mann Whitney U test. RESULTS: Forty-six patients underwent living donor left lateral segment hepatectomy (Group I); while 31 patients underwent right lobe hepatectomy (Group II). The mean blood loss in Group II was significantly higher compared to Group I (118 ± 81 mL vs 68 ± 64 mL), but clinically such amount of blood loss was not high enough to affect the hemodynamics. The fluid management was therefore not meaningfully different between the two groups. No blood transfusions or colloid infusions were required for either group. Urine output, hemoglobin changes, blood urea nitrogen, and serum creatinine pre- and postoperatively were not significantly different between groups. CONCLUSIONS: As long as blood loss is minimal, we found no difference in the anesthetic management and fluid replacements between right and left lateral segment living donor hepatectomy.

The Correlation Between CVP and SVV and Intraoperative Minimal Blood Loss in Living Donor Hepatectomy.

BACKGROUND: Blood loss during liver surgery is found to be correlated with central venous pressure (CVP). The aim of the current retrospective study is to find out the cutoff value of CVP and stroke volume variation (SVV), which may increase the risk of having intraoperative blood loss of more than 100 mL during living liver donor hepatectomies. METHOD AND PATIENTS: Twenty-seven adult living liver donors were divided into 2 groups according to whether they had intraoperative blood loss of less (G1) or more than 100 mL (G2). The mean values of the patients' CVP and SVV at the beginning of the transaction of the liver parenchyma was used as the cutoff point. Its correlation to intraoperative blood loss was evaluated using the χ2 test; P < .001 was regarded as significant. RESULTS: The cutoff points of CVP and SVV were 8 mm Hg and 13% respectively. The odds ratio of having blood loss exceeding 100 mL was 91.25 (P < .001) and 0.36 (P < .001) for CVP and SVV, respectively. CONCLUSION: CVP less than 5 mm Hg, as suggested by most authors, is not always clinical achievable. Our results show that a value of less than 8 mm Hg or SVV 13% is able to achieve a minimal blood loss of 100 mL during parenchyma transaction during a living donor hepatectomy. Measurements used to lower the CVP or increased SVV in our serial were intravenous fluids restriction and the use of a diuretic.

Diffusion-Weighted Magnetic Resonance Imaging in Liver Graft Rejection.

OBJECTIVE: The purpose of this study is to evaluate the use of diffusion-weighted magnetic resonance imaging (DWMRI) in the assessment of graft rejection after liver transplantation (LT). METHODS: From June 2017 to January 2018, 32 patients were included in the study with a mean age of 52.3 years. All patients underwent LT. The DWMRI was performed using the apparent diffusion coefficient map and measuring the different b-values (b-400, b-600, b-800, and b-1000). These measurements were compared with the histopathology results. Statistical analysis included t test, analysis of variance, and area under the curve for receiver operating characteristic (ROC). RESULTS: There were 17 patients without rejection and 15 patients with liver graft rejection diagnosed by histopathology. The mean (SD) results between the nonrejection and rejection groups were as follows: b-400 = 1.568 (0.265) vs 1.519 (0.119) (P = .089), b-600 = 1.380 (0.181) vs 1.284 (0.106) (P = .039), b-800 = 1.262 (0.170) vs 1.170 (0.086) (P = .035), b-1000 = 1.109 (0.129) vs 1.098 (0.078) (P = .095); B-values × 10-3 mm2/s. Only b-600 (P = .04) and b-800 (P = .04) values have significant differences between the 2 groups. B-600 showed 90.48% sensitivity and 83.33% specificity (ROC area under the curve = 0.784; P < .001), and b-800 showed 90.38% sensitivity and 83.03% specificity (ROC area under the curve = 0.816; P < .001). The values obtained with the apparent diffusion coefficient in b-800 were clearly differentiated between the mild, moderate, and severe degrees of rejection (P < .001). CONCLUSION: Measurement of b-600 and b-800 values using DWMRI may be used for the diagnosis of graft rejection after LT.

Acoustic Radiation Force Impulse Elastography in Post-transplant Recurrent Hepatitis C in Living Donor Liver Transplantation.

OBJECTIVE: The aim of the study was to evaluate the efficacy of liver fibrosis (LF) with acoustic radiation force impulse (ARFI) elastography for post-transplant (post-LT) HCV recurrence. PATIENTS AND METHODS: We enrolled 89 adult recipients of living donor liver transplantation (LDLT) who had HCV, with or without post-LT HCV recurrence and treated or not treated. The post-LT HCV recurrence was diagnosed on the basis of RNA viral load present. ARFI examination was performed every 3 months for all patients, with shear wave velocity (SWV) obtained quantitatively in m/s and correlated with histopathologic fibrosis scoring of liver biopsy (LB). RESULTS: There were 50 (50 of 89) patients without HCV recurrence and 39 (39 of 89) with post-LT recurrence in the 89 patients studied. The recurrent group had significantly higher median SWVs (1.87 ± 0.52 vs 1.37 ± 0.52 m/s, P < .0001), in which 18 (18 of 39) patients had antiviral drug treatment and obtained significant improvement with SWVs from 1.83 ± 0.49 to 1.68 ± 0.56 m/s, P = .043. The correlations of LF staging between ARFI elastography and Ishak histopathologic LF scores showed great significance, P = .045. The HCV RNA titer after antiviral treatment decreased from 3,831,750 to 0, P < .0001, but the RNA titer of nontreated patients remained high and the median SWV increased. The Ishak LF staging in the nontreated group progressed from stage 1 to 2, P = .012 and SWV increased from 1.69 ± 0.54 to 1.91 ± 0.66 m/s, P = .085 at 1-year follow-up. CONCLUSION: ARFI elastography has efficient quantitative LF monitoring correlated with histopathologic staging for post-LT HCV recurrence. It could be an alternative, noninvasive method for frequent LB in the disease follow-up.

Donor-Transmitted Bacterial Infection in Deceased Donor Liver Transplantation: Experience of Southern Taiwan Medical Center.

BACKGROUND: Bacterial Infection is the most important source of mortality and morbidity in liver transplantation recipients. Donor transmitted bacterial infection is rare but one of the most important infection sources. This kind of infection is difficult to identify, causing treatment dilemma. PATIENTS AND METHODS: In this article, we retrospectively reviewed our deceased donor liver transplants performed from January 2014 to December 2016. Forty-two recipients in Kaohsiung Chang Gung Memorial Hospital receiving liver grafts from 35 deceased liver donors were evaluated. The demography, donor transmitted infection, and outcomes were evaluated. RESULT: Two patients had probable donor transmitted bacterial infection and 1 patient died of suspected transmitted infection. CONCLUSION: Early identification of donor infection and adequate antibiotic treatment for the donor and recipient are the keys to preventing donor transmitted bacterial infection. Donor infection is not an absolute contraindication for organ donation in the area of organ shortage. Organ procurement organizations or similar authorities may establish the platform for sharing the data about donor and recipient infections.

Donor Outcomes After Liver Donation in Adult to Adult Living Donor Liver Transplantation.

OBJECTIVES: This study aims to investigate postdonation outcomes of adult living donor liver transplantation donors and remnant liver regeneration in different graft types. METHODS: A total of 236 adult living donor liver transplantation donors were classified into different groups: donors with <35% remnant liver volume (group A; n = 56) and donors with remnant liver volume ≥35% (group B, n = 180); left lobe grafts (LLG group; n = 98) including middle hepatic vein (MHV) and right lobe grafts (RLG group; n = 138) without MHV. The 98 LLG group donors were further classified into 2 subgroups based on hepatic venous drainage patterns: MHV-dominant (n = 20) and non-MHV-dominant (n = 78). The demographic data, postoperative laboratory data, complications, graft weight, remnant liver volume, remnant liver growth rate, and remnant liver regeneration rate (RLRR) after partial liver donation were analyzed. RESULTS: The postoperative aspartate aminotransferase, alanine aminotransferase, total bilirubin, intensive care unit stays, and hospitalization stays were higher in A and RLG group donors. All the donor complications in our series were minor complications. The postoperative complication rate was higher in the A and RLG group, but failed to reach statistical significance. There was no significant difference in RLRR between the RLG/LLG and A/B groups. However, the MHV-dominant group had significantly lower RLRR than the non-MHV-dominant group (P < .05). CONCLUSIONS: Small remnant liver volume donors (<35% remnant liver) have higher risks of developing postdonation minor complications. Left lobe liver donation in MHV-dominant donor candidates are a major concern.

MicroRNA-791 is an independent prognostic factor of papillary thyroid carcinoma and inhibits the proliferation of PTC cells.

OBJECTIVE: To investigate the significance and possible mechanism of miR-791 in the pathogenesis of papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: The expression of miR-791 in 80 cases of thyroid carcinoma tissues and 80 cases of paracancerous tissues was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). After miR-791 mimics were transfected into thyroid cancer cells by liposome method, the cell proliferation was detected by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EDU), respectively. Cell cycle was detected by flow cytometry. RESULTS: The expression of miR-791 in thyroid cancer tissue was significantly lower than that of normal thyroid. The mir-719 expression is positively correlated with the prognosis of thyroid carcinoma. After transfection of miR-791 mimics, the proliferation ability of TPC-1 and HTH83 cells was weakened, and the cell cycle was blocked in the G0/G1 phase. Further study on the underlying mechanism found that after overexpression of miR-791, the expressions of Cyclin D1, CKD6 and CDK4 decreased significantly, while the expression of cyclin inhibitor P21 increased significantly. CONCLUSIONS: MiR-791 is lowly expressed in thyroid cancer. MiR-791 may inhibit thyroid cancer cell proliferation by blocking thyroid cancer cells in G0/G1 phase, thus participating in the impediment of thyroid cancer development.

Clinical outcomes associated with anti-coagulant therapy in patients with renal infarction.

Background: Patients with renal infarction are vulnerable to thromboembolic complications with poor outcomes. There is limited report concerning the effect of anti-coagulant therapy in this population. Aim: To assess the impact of anti-coagulant therapy on outcomes in patients with renal infarction. Design: A retrospective cohort study of 101 renal infarction patients was conducted. Methods: The association between anti-coagulant therapy, all-cause mortality, thromboembolic complications and renal outcome was evaluated. Demographic data and comorbidities were collected for analysis. Anti-coagulant therapy was treated as a time-dependent variable. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multi-variate Cox proportional hazards models. Results: Fifty-seven (56.4%) patients with renal infarction received anti-coagulant therapy during the study period. The all-cause mortality rate was 7.56 per 100 patient-years. Age (HR 1.05, 95% CI 1.02-1.08) was a risk factor for all-cause mortality and anti-coagulant therapy was associated with a 92% improved survival (HR 0.08, 95% CI 0.02-0.34). Twelve (11.9%) thromboembolic events occurred following renal infarction. Current smoking (HR 10.37, 95% CI 1.60-67.43) had an adverse effect and anti-coagulant therapy (HR 0.14, 95% CI 0.03-0.73) had a significant protective impact on thromboembolic complications. There was no significant association between anti-coagulant therapy and long-term renal outcome in renal infarction patients including the monthly change in the estimated glomerular filtration rate (eGFR), the incidence of eGFR reduction of more than 50% and end-stage renal disease. Conclusion: Anti-coagulant therapy in patients with renal infarction was associated with better survival and reduced thromboembolic complications.

Proteobacteria community compositions correlate with bronchiectasis severity.

BACKGROUND: Proteobacteria contributes to airway inflammation and poor clinical outcomes in bronchiectasis. OBJECTIVE: To compare sputum Proteobacteria compositions according to bronchiectasis severity. METHODS: Sputum samples collected from 106 patients with stable bronchiectasis and 17 healthy subjects were split for 16srRNA sequencing and biomarker measurement. Pairwise changes in Proteobacteria compositions among 22 of 106 patients during stability, exacerbations and convalescence were compared. Patients were stratified based on the Bronchiectasis Severity Index (BSI). RESULTS: Respectively 44, 34 and 28 patients had mild, moderate and severe bronchiectasis. A higher BSI was associated with a greater relative abundance of Proteobacteria and lower Shannon-Wiener diversity index, Simpson diversity index and bacterial richness. Similar findings applied at genera levels. Proteobacteria and Pseudomonas were the major phylum and genus, respectively, contributing to community similarity in moderate-to-severe bronchiectasis. These significant correlations were not observed in those in whom Pseudomonas aeruginosa was not isolated. Proteobacteria abundance correlated with lung function, but not sputum inflammatory biomarkers in severe bronchiectasis. Proteobacteria compositions in severe bronchiectasis were less likely to change significantly during exacerbations and convalescence. CONCLUSION: Proteobacteria compositions (particularly culturable Pseudomonas abundance) were correlated with bronchiectasis severity. Proteobacteria and Pseudomonas contributed most to community similarity in patients with a higher BSI, indicating microbial targets for interventions in severe bronchiectasis.

Fibrosis-4 index predicts cirrhosis risk and liver-related mortality in 2075 patients with chronic HBV infection.

BACKGROUND: Fibrosis-4 index (FIB-4) is a surrogate marker for hepatic fibrosis in hepatitis B virus (HBV) carriers. AIM: To investigate whether FIB-4 index stratifies the risks of adverse liver events. METHODS: A total of 2075 treatment-naïve, noncirrhotic the patients with chronic HBV infection were included. Most of them (82.1%) were HBeAg-negative patients and their baseline FIB-4 levels were explored to stratify the risks of cirrhosis, cirrhosis-related complications and liver-related mortality. RESULTS: During a mean follow-up period of 15.47 years, we found a higher baseline FIB-4 index was associated with increased incidence rates of cirrhosis in addition to the common host and viral factors. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with increased risks of cirrhosis, cirrhosis-related complications and liver-related mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76-8.05), 6.88, (3.68-12.86) and 7.79, (4.54-13.37) respectively. Within the first 3 years of follow-up, FIB-4 remained stable and its kinetics were consistently associated with the develoopment of adverse liver events. Furthermore, FIB-4 index of 1.29 was able to stratify all the risks of adverse liver events even in HBeAg-negative patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000 IU/mL and ALT <40 U/L). Only 1 patient with FIB-4 index <1.29 developed cirrhosis but not other events within 15 years of follow-up. CONCLUSIONS: In noncirrhotic patients with chronic HBV infection, a higher FIB-4 index was associated with increased risks of adverse liver events. FIB-4 index <1.29 is useful for the prediction of the lowest risks of disease progression.