Derivation of sex and age-specific reference intervals for clinical chemistry analytes in healthy Ghanaian adults.

OBJECTVIES: This study is aimed at establishing reference intervals (RIs) of 40 chemistry and immunochemistry analytes for Ghanaian adults based on internationally harmonized protocol by IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). METHODS: A total of 501 healthy volunteers aged ≥18 years were recruited from the northern and southern regions of Ghana. Blood samples were analyzed with Beckman-Coulter AU480 and Centaur-XP/Siemen auto-analyzers. Sources of variations of reference values (RVs) were evaluated by multiple regression analysis (MRA). The need for partitioning RVs by sex and age was guided by the SD ratio (SDR). The RI for each analyte was derived using parametric method with application of the latent abnormal values exclusion (LAVE) method. RESULTS: Using SDR≥0.4 as threshold, RVs were partitioned by sex for most enzymes, creatinine, uric acid (UA), bilirubin, immunoglobulin-M. MRA revealed age and body mass index (BMI) as major source of variations of many analytes. LAVE lowered the upper limits of RIs for alanine/aspartate aminotransferase, γ-glutamyl transaminase and lipids. Exclusion of individuals with BMI≥30 further lowered the RIs for lipids and CRP. After standardization based on value-assigned serum panel provided by C-RIDL, Ghanaian RIs were found higher for creatine kinase, amylase, and lower for albumin and urea compared to other collaborating countries. CONCLUSIONS: The LAVE effect on many clinical chemistry RIs supports the need for the secondary exclusion for reliable derivation of RIs. The differences in Ghanaian RIs compared to other countries underscore the importance of country specific-RIs for improved clinical decision making.

Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data.

BACKGROUND: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists. SCOPE AND APPROACH: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review. KEY FINDINGS AND CONCLUSIONS: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

Active fractions of mannoproteins derived from yeast cell wall stimulate innate and acquired immunity of adult and elderly dogs.

Nutritional intervention in older dogs aims to increase lifespan and improve life quality as well as delay the development of diseases related to ageing. It is believed that active fractions of mannoproteins (AFMs) obtained through extraction and fractionation of yeast cell walls (Saccharomyces cerevisiae) may beneficially modulate the immune system. However, studies that have evaluated this component and the effects of ageing on the immune system of dogs are scarce. This study aimed to evaluate the immunological effects of AFMs in adult and elderly dogs. Three extruded iso-nutrient experimental diets were formulated: without addition of AFM (T0); with AFM at 400 mg/kg (T400); and with AFM at 800 mg/kg (T800). Thirty-six beagle dogs were used, and six experimental treatments, resulting in combinations of age (adult and elderly) and diet (T0, T400, and T800), were evaluated. On days zero, 14, and 28, blood samples were obtained for leucocyte phenotyping and phagocytosis assays. On days zero and 28, a lymphoproliferation test, quantification of reactive oxygen (H2O2) and nitrogen (NO) intermediate production, evaluation of faecal immunoglobulin A (IgA) content, and a delayed cutaneous hypersensitivity test (DCHT) were performed. Statistical analyses were performed with SAS software. Repeated measure variance analyses were performed, and means were compared by the Tukey test. Values of P ≤ 0.05 were considered significant, and values of P ≤ 0.10 were considered tendencies. Dogs fed T400 tended to have higher neutrophilic phagocytic activity than dogs fed T800 (P = 0.073). Regarding reactive oxygen intermediates, bacterial lipopolysaccharide (LPS)-stimulated neutrophils from animals that were fed T400 had a tendency to produce more H2O2 than those from animals fed the control diet (P = 0.093). Elderly dogs, when compared to adult dogs, had lower absolute T and B lymphocyte counts, lower auxiliary T lymphocyte counts, and higher cytotoxic T lymphocyte counts (P < 0.05). A significant effect of diet, age, and time with saline inoculation was noted for the DCHT. There was no effect of diet or age on faecal IgA content in dogs. This study suggests beneficial effects of mannoproteins on the specific and nonspecific immune responses in adult and elderly dogs.

Spirulina supplementation in a mouse model of diet-induced liver fibrosis reduced the pro-inflammatory response of splenocytes.

Treatment of liver fibrosis is very limited as there is currently no effective anti-fibrotic therapy. Spirulina platensis (SP) is a blue-green alga that is widely supplemented in healthy foods. The objective of this study was to determine whether SP supplementation can prevent obesity-induced liver fibrosis in vivo. Male C57BL/6J mice were randomly assigned to a low-fat or a high-fat (HF)/high-sucrose/high-cholesterol diet or an HF diet supplemented with 2·5 % SP (w/w) (HF/SP) for 16 or 20 weeks. There were no significant differences in body weight, activity, energy expenditure, serum lipids or glucose tolerance between mice on HF and HF/SP diets. However, plasma alanine aminotransferase level was significantly reduced by SP at 16 weeks. Expression of fibrotic markers and trichrome stains showed no differences between HF and HF/SP. Splenocytes isolated from HF/SP fed mice had lower inflammatory gene expression and cytokine secretion compared with splenocytes from HF-fed mice. SP supplementation did not attenuate HF-induced liver fibrosis. However, the expression and secretion of inflammatory genes in splenocytes were significantly reduced by SP supplementation, demonstrating the anti-inflammatory effects of SP in vivo. Although SP did not show appreciable effect on the prevention of liver fibrosis in this mouse model, it may be beneficial for other inflammatory conditions.

Improvements in clinical characteristics of patients with non-alcoholic fatty liver disease, after an intervention based on the Mediterranean lifestyle: a randomised controlled clinical trial.

Lifestyle interventions remain the cornerstone therapy for non-alcoholic fatty liver disease (NAFLD). This randomised controlled single-blind clinical trial investigated the effect of Mediterranean diet (MD) or Mediterranean lifestyle, along with weight loss, in NAFLD patients. In all, sixty-three overweight/obese patients (50 (sd 11) years, BMI=31·8 (sd 4·5) kg/m2, 68 % men) with ultrasonography-proven NAFLD (and elevated alanine aminotransferase (ALT) and/or γ-glutamyl transpeptidase (GGT) levels) were randomised to the following groups: (A) control group (CG), (B) Mediterranean diet group (MDG) or (C) Mediterranean lifestyle group (MLG). Participants of MDG and MLG attended seven 60-min group sessions for 6 months, aiming at weight loss and increasing adherence to MD. In the MLG, additional guidance for increasing physical activity and improving sleep habits were given. Patients in CG received only written information for a healthy lifestyle. At the end of 6 months, 88·8 % of participants completed the study. On the basis of intention-to-treat analysis, both MDG and MLG showed greater weight reduction and higher adherence to MD compared with the CG (all P<0·05) at the end of intervention. In addition, MLG increased vigorous exercise compared with the other two study groups (P<0·001) and mid-day rest/naps compared with CG (P=0·04). MLG showed significant improvements in ALT levels (i.e. ALT<40 U/l (P=0·03) and 50 % reduction of ALT levels (P=0·009)) and liver stiffness (P=0·004) compared with CG after adjusting for % weight loss and baseline values. MDG improved only liver stiffness compared with CG (P<0·001) after adjusting for the aforementioned variables. Small changes towards the Mediterranean lifestyle, along with weight loss, can be a treatment option for patients with NAFLD.

Dietary curcumin supplementation attenuates inflammation, hepatic injury and oxidative damage in a rat model of intra-uterine growth retardation.

Rats with a normal birth weight (NBW) or intra-uterine growth retardation (IUGR) were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NC and IC groups) from 6 to 12 weeks. The body weight of IUGR rats was lower (P<0·05) than that of the controls. Rats with IUGR showed higher (P<0·05) concentrations of TNF-α, IL-1ß and IL-6; higher (P<0·05) activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in their serum; and increased (P<0·05) concentrations of malondialdehyde (MDA), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHDG) in the liver compared with the NBW rats. The livers of IUGR rats exhibited a lower (P<0·05) superoxide dismutase activity and decreased (P<0·05) metabolic efficiency of the hepatic glutathione redox cycle compared with those of the NBW rats. In response to dietary curcumin supplementation, concentrations of inflammatory cytokines and activities of AST and ALT in the serum and MDA, PC and 8-OHDG in the liver were lower (P<0·05), and the hepatic glutathione redox cycle in the liver was improved (P<0·05) in the IC group than in the IUGR group. These results were associated with lower (P<0·05) phosphorylated levels of the NF-κB pathway and Janus kinase 2 (JAK2) and higher (P<0·05) mRNA expression of genes involved in the nuclear factor, erythroid 2-like 2 (Nfe2l2)/antioxidant response element (ARE) pathway in the liver of the IC rats than that of the IUGR rats. Maternal undernutrition decreased birth weight and led to inflammation, oxidative damage and injury in rats. Curcumin appeared to be beneficial in preventing IUGR-induced inflammation, oxidative damage and injury by activating the expression of the NF-κB, JAK/STAT and Nfe2l2/ARE pathways in the liver.

Low ALT blood levels are associated with lower baseline fitness amongst participants of a cardiac rehabilitation program.

BACKGROUND/OBJECTIVE: Objective assessment tools for patients' frailty are lacking. Such tools would have been highly valuable for assessment of candidates for cardiac rehabilitation programs. Low ALT (Alanine aminotransferase) values were recently shown to be a promising parameter for objective, quantitative frailly assessment. METHODS: This was a retrospective study of patients participating in a cardiac rehabilitation program. RESULTS: Patients with lower ALT activity levels at the initiation of rehabilitation program had lower estimated METs values (6.86 vs. 7.73; p < 0.001), shorter stress test duration (06:41 vs. 07:44 min; p < 0.001), higher resting heart rate (72 ± 13 vs. 70 ± 13 BPM; p = 0.01) and lower heart rate reserve (49 ± 24 vs. 54 ± 24; p < 0.001). Multivariate linear modeling demonstrated that ALT values were Independent determinants of baseline exercise capacity (expressed in METs). CONCLUSION: Lower ALT values, measured prior to the initiation of cardiac rehabilitation programs may indicate frailty of patients and be indicative for poor rehabilitation outcomes. Further, prospective studies should assess the potential correlation between ALT values and rehabilitation efficiency. We aimed to assess the potential correlation between the baseline ALT values and the baseline exercise capacity, as expressed in METs (Metabolic equivalent of tasks). 3806 patients were included in our study.

Citrulline decreases hepatic endotoxin-induced injury in fructose-induced non-alcoholic liver disease: an ex vivo study in the isolated perfused rat liver.

Steatosis can sensitise the liver to various challenges and favour the development of non-alcoholic fatty liver disease (NAFLD). In this context, fructose feeding promotes endotoxin translocation from the gut, contributing to disease progression via an inflammatory process. Citrulline is protective against fructose-induced NAFLD; we hypothesised that this property might be related to its anti-inflammatory and antioxidative action against endotoxin-induced hepatic injuries. This hypothesis was evaluated in a model of perfused liver isolated from NAFLD rats. Male Sprague-Dawley rats (n 30) were fed either a standard rodent chow or a 60 % fructose diet alone, or supplemented with citrulline (1 g/kg per d) for 4 weeks. After an evaluation of their metabolic status, fasted rats received an intraperitoneal injection of lipopolysaccharide (LPS) (2·5 mg/kg). After 1 h, the livers were isolated and perfused for 1 h to study liver function and metabolism, inflammation and oxidative status. In vivo, citrulline significantly decreased dyslipidaemia induced by a high-fructose diet and insulin resistance. In the isolated perfused rat livers, endotoxaemia resulted in higher cytolysis (alanine aminotransferase release) and higher inflammation (Toll-like receptor 4) in livers of fructose-fed rats, and it was prevented by citrulline supplementation. Oxidative stress and antioxidative defences were similar in all three groups. Amino acid exchanges and metabolism (ammonia and urea release) were only slightly different between the three groups. In this context of mild steatosis, our results suggest that fructose-induced NAFLD leads to an increased hepatic sensitivity to LPS-induced inflammation. Citrulline-induced restriction of the inflammatory process may thus contribute to the prevention of NAFLD.

Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicanaextracts.

Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl4-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl4-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl4-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum ß-carotene, ß-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats.

Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats.

The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

Murine models provide insight to the development of non-alcoholic fatty liver disease.

Associated with the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) has become the leading liver disease in North America. Approximately 30 % of patients with NAFLD may develop non-alcoholic steatohepatitis (NASH) that can lead to cirrhosis and hepatocellular carcinoma (HCC). Frequently animal models are used to help identify underlying factors contributing to NAFLD including insulin resistance, dysregulated lipid metabolism and mitochondrial stress. However, studying the inflammatory, progressive nature of NASH in the context of obesity has proven to be a challenge in mice. Although the development of effective treatment strategies for NAFLD and NASH is gaining momentum, the field is hindered by a lack of a concise animal model that reflects the development of liver disease during obesity and the metabolic syndrome. Therefore, selecting an animal model to study NAFLD or NASH must be done carefully to ensure the optimal application. The most widely used animal models have been reviewed highlighting their advantages and disadvantages to studying NAFLD and NASH specifically in the context of obesity.

Vitamin A Reduces the Mortality of Animals with Induced Liver Fibrosis by Providing a Multi-level Body Defense System.

Background: Liver diseases remain the most important medical and biological problem. Works devoted to the study of the vitamin A role have shown conflicting results of its effect on the fibrosis development. We tested the hypothesis that an increase of the copper content in the liver, an example of which is Wilson's disease, shifts the balance in the redox system towards pro-oxidants, which leads to the antioxidant systems inhibition, including a decrease in the vitamin A content; this affects the levels of liver function regulation and the development of fibrosis. Methods: In animals with Cu-induced liver fibrosis, neutrophil activity, the immunocompetent cells content, the activity of alanine aminotransferase and γ-glutamylaminotransferase, the content of urea and creatinine in blood serum, as well as the vitamin A content in the liver, copper ions and its regenerative potential were determined. Results: It was found that three consecutive injections of copper sulfate to animals with an interval of 48 h between injections led to the death of 40% of the animals, and 60% showed resistance. The content of vitamin A in "resistant" animals at the beginning of the development of the fibrosis was reduced by 4 times compared to the control, the functional activity of the liver was somewhat reduced, and a connective tissue capsule was formed around the liver lobes in 75% of the animals. If animals with the initial stage of liver fibrosis received daily vitamin A at a dose of 300 IU/100 g of body weight, which was accompanied by its multiple increase in the liver (15 times on day 14), the mortality of animals decreased by almost 7 times, the functional activity of the liver did not differ from control. In the blood of these animals, the number of leukocytes, granulocytes, and monocytes was increased and phagocytic activity was increased. At the same time, the connective tissue capsule was developed more intensively than in animals receiving only copper sulfate, and was detected in 91% of the animals. Fragments of the liver, even more than in the case of fibrosis, lost the ability to regenerate in culture. Conclusion: We came to the conclusion that vitamin A leads to the connective tissue "specialization" formation of the liver and triggers vicious circles of metabolism and includes several levels of regulation systems. Further studies of the vitamin A effect mechanisms on the liver with fibrosis will allow the use of this antioxidant in the treatment.

Sofosbuvir plus velpatasvir for 8 weeks in patients with acute hepatitis C: The HepNet acute HCV-V study.

Background & Aims: EASL guidelines recommend 8 weeks of treatment with sofosbuvir plus velpatasvir (SOF/VEL) for the treatment of acute or recently acquired HCV infection, but only 6- and 12-week data are available. Therefore, the aim of this study was to evaluate the safety and efficacy of a shortened 8-week SOF/VEL treatment for acute HCV monoinfection. Methods: In this investigator-initiated, prospective, multicentre, single-arm study, we recruited 20 adult patients with acute HCV monoinfection from nine centers in Germany. Patients received SOF/VEL (400/100 mg) as a fixed-dose combination tablet once daily for 8 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). Results: The median HCV RNA viral load at baseline was 104,307 IU/ml; the distribution of HCV genotypes was as follows: GT1a/1b/2/3/4: n = 12/1/1/3/3. Thirteen (65%) of the 20 patients were taking medication for HIV pre-exposure prophylaxis. SVR12 was achieved in all patients who complied with the study protocol (n = 18/18 [100%], per protocol analysis), but the primary endpoint was not met in the intention-to-treat analysis (n = 18/20 [90%]) because two patients were lost to follow-up. One serious adverse event (unrelated to study drug) occurred during 12 weeks of post-treatment follow-up. Conclusions: The 8-week treatment with SOF/VEL was well tolerated and highly effective in all adherent patients with acute HCV monoinfection. Early treatment of hepatitis C might effectively prevent the spread of HCV in high-risk groups. Clinical Trial Number: NCT03818308. Impact and implications: The HepNet acute HCV-V study (NCT03818308), an investigator-initiated, single-arm, multicenter pilot study, demonstrates the efficacy and safety of 8 weeks of daily treatment with the fixed-dose combination sofosbuvir/velpatasvir (400/100 mg) in patients with acute hepatitis C virus (HCV) infection. All patients who completed therapy and were followed-up achieved sustained virologic response. Thus, early treatment with SOF/VEL which might effectively prevent the spread of HCV in high-risk groups can be recommended for patients with acute HCV monoinfection.

A complex presentation of an uncommon disease: Gas-forming pyogenic liver abscess complicated by septic pulmonary emboli and muscle abscesses, a case report and review of the literature.

Background: Pyogenic liver abscess (PLA) is the most common type of visceral abscess. Its variable clinical presentation depends on patient demography, underlying conditions, causative pathogens as well as the size of the abscess. Most cases are secondary to enteric pathogens that cause focal liver disease. Gas-forming pyogenic liver abscess (GFPLA) is a rare subgroup of PLA characterized by the presence of gas within the abscess. The disease is associated with diabetes mellitus (DM) while Klebsiella penumoniae is the most frequently isolated pathogen. Despite appropriate evaluation and management, secondary complications are common with significant morbidity and mortality that necessitate prompt recognition and management. Case presentation: We present a case of a 46-year-old gentleman from Bangladesh who presented to the emergency department with fever, chills, and right upper quadrant abdominal discomfort. Evaluation revealed elevated inflammatory markers with high blood glucose and a subdiaphragmatic lucency on a plain chest radiograph. The suspected underlying visceral infection was confirmed by abdominal ultrasonography and computed tomography which demonstrated an emphysematous abscess of 8 cm in diameter in the right liver lobe.Because of clinical instability, the patient was admitted to the medical intensive care unit (MICU) where he received appropriate supportive management with antimicrobials and percutaneous drainage of the abscess. Cultures collected from blood, the abscess, and urine grew a sensitive strain of Klebsiella pneumoniae. During his stay in the MICU, he complained of dyspnea. A CT pulmonary angiography was suggestive of septic emboli. A few days later, the patient started to complain of left gluteal pain and an US revealed a deep left gluteal abscess which required drainage. Cultures of the pus grew the same sensitive strain of Klebsiella pneumoniae. After receiving 6 weeks of parenteral antimicrobial therapy a repeated US revealed complete resolution of the abscess in the liver. Outpatient follow up showed favorable recovery. Conclusion: Gas-forming pyogenic liver abscess (GFPLA) is a rare manifestation of pyogenic liver abscess that usually occurs in patients with poorly controlled DM. Despite appropriate evaluation, morbidity remains high therefore timely recognition and anticipation of complications is important.

Brucellar epididymo-orchitis: Symptoms, diagnosis, treatment and follow-up of 50 patients in Iran.

Introduction: Epididymo-orchitis (EO) is a disease of both the epididymis and ipsilateral testis. Brucellar epididymo-orchitis (BEO) is an uncommon localized infection of the testis and epididymis which occurs in about 2-14 % of all patients with brucellosis as a result of urine Brucella removal or due to blood-borne septic metastasis. Methods: Between January 2018 and June 2021, 50 patients with fever, chills, swelling, and pain of the testicle (testicles) were referred to our center. Two approaches were used for the treatment of brucellarepididymo-orchitis among these individuals. Intravenous Gentamicin and Doxycycline were used in seven cases, while Rifampicin was added to this combination for the remaining 43 patients. Intravenous Gentamicin was administered for 7 days and the other drugs were used for 45 days. All patients were followed up for six months by monitoring the symptoms and signs of the disease. Results: None of the patients had been diagnosed with brucellosis before referral to our clinic. 43 patients were successfully treated by. Intravenous Gentamicin, Doxycycline and Rifampicin, whereas seven patients were fully treated using. Intravenous Gentamicin and Doxycycline. The two therapeutic groups were hospitalized for 7.56 ± 3.45 (3-23) and 10.14 ± 1.77 (8-13) days, respectively. Treatment failure, drug side effects, and disease complications were not observed in any of the cases over a 6-month follow-up period. Conclusions: Physicians should be alert regarding Brucellarepididymo-orchitis (BEO) within the differential diagnosis of nonspecific epididymo-orchitis, especially in regions where the disease is endemic. Delay in diagnosis or inappropriate management of BEO may result in complications.

Incidence and Predictors of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients. Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared. Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hypertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness measurement, bilirubin, CC and DC were independent predictors of LRE. Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes.

Sarcopenia-related gut microbial changes are associated with the risk of complications in people with cirrhosis.

Background & Aims: Sarcopenia and gut dysbiosis are common in individuals with cirrhosis. However, the association between sarcopenia and microbial alterations, and the subsequent impact on cirrhotic outcomes are poorly understood. This study aimed to identify muscle-dependent microbial changes and related risks of cirrhotic complications. Methods: From September 2018 to December 2020, 89 individuals with cirrhosis and 16 healthy volunteers were prospectively enrolled. Muscle and nutritional status, serum amino acids, and fecal microbiota were analyzed. The association between microbial signatures of sarcopenia and cirrhotic complications was investigated. Results: A decline in muscle mass and strength were associated with gut microbial alterations in individuals with cirrhosis. The greatest microbial dissimilarity was observed between those with sarcopenia (both decline in muscle mass and strength) and those with normal-muscle status (p = 0.035). Individuals with sarcopenia had lower serum levels of alanine, valine, leucine, isoleucine, proline, tryptophan and ornithine. Besides, gut microbial functions associated with amino acid biosynthesis were significantly reduced in individuals with sarcopenia and cirrhosis. Depletion of Dialister, Ruminococcus 2, and Anaerostipes were associated with cirrhotic sarcopenia, and significantly correlated with the serum levels of amino acids. Individuals with coexistent depletion of Ruminococcus 2 and Anaerostipes developed more infectious (44.4% vs. 3.0%) and non-infectious (74.1% vs. 3.0%) complications, and more hospitalizations (54 vs. 3) than those with cirrhosis with good microbial signatures (all p <0.001). In contrast, fecal enrichment of Ruminococcus 2 and Anaerostipes independently decreased the risk of 1-year complications. Conclusions: Sarcopenia-related fecal microbial alterations are associated with cirrhotic complications. These findings may facilitate measures to improve the outcomes of individuals with cirrhosis and sarcopenia by modifying gut microbiota. Impact and implications: The composition and biosynthetic functions of gut microbiota are significantly changed in individuals with sarcopenic cirrhosis. Those with a sarcopenia-related poor microbial signature, in which Ruminococcus 2 and Anaerostipes were both depleted, had significantly more infectious and non-infectious complications, as well as more hospitalizations. These findings highlight the therapeutic potential of modifying the gut microbiota of individuals with sarcopenic cirrhosis to improve their clinical outcomes.

Genomic analysis of lean individuals with NAFLD identifies monogenic disorders in a prospective cohort study.

Background & Aims: Lean patients with non-alcoholic fatty liver disease (NAFLD) represent 10-20% of the affected population and may have heterogeneous drivers of disease. We have recently proposed the evaluation of patients with lean NAFLD without visceral adiposity for rare monogenic drivers of disease. Here, we aimed to validate this framework in a well-characterised cohort of patients with biopsy-proven NAFLD by performing whole exome sequencing. Methods: This prospective study included 124 patients with biopsy-proven NAFLD and paired liver biopsies who underwent standardised research visits including advanced magnetic resonance imaging (MRI) assessment of liver fat and stiffness. Results: Six patients with lean NAFLD were identified and underwent whole exome sequencing. Two lean patients (33%) were identified to have monogenic disorders. The lean patients with monogenic disorders had similar age, and anthropometric and MRI characteristics to lean patients without a monogenic disorder. Patient 1 harbours a rare homozygous pathogenic mutation in ALDOB (aldolase B) and was diagnosed with hereditary fructose intolerance. Patient 2 harbours a rare heterozygous mutation in apolipoprotein B (APOB). The pathogenicity of this APOB variant (p.Val1856CysfsTer2) was further validated in the UK Biobank and associated with lower circulating APOB levels (beta = -0.51 g/L, 95% CI -0.65 to -0.36 g/L, p = 1.4 × 10-11) and higher liver fat on MRI (beta = +10.4%, 95% CI 4.3-16.5%, p = 8.8 × 10-4). Hence, patient 2 was diagnosed with heterozygous familial hypobetalipoproteinaemia. Conclusions: In this cohort of well-characterised patients with lean NAFLD without visceral adiposity, 33% (2/6) had rare monogenic drivers of disease, highlighting the importance of genomic analysis in this NAFLD subtype. Impact and Implications: Although most people with non-alcoholic fatty liver disease (NAFLD) are overweight or obese, a subset are lean and may have unique genetic mutations that cause their fatty liver disease. We show that 33% of study participants with NAFLD who were lean harboured unique mutations that cause their fatty liver, and that these mutations had effects beyond the liver. This study demonstrates the value of genetic assessment of NAFLD in lean individuals to identify distinct subtypes of disease.