Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. Results: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). Conclusions People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Background: Lessons learned from the Household Humidifier Disinfectant Tragedy (HHDT) in Korea, which poisoned thousands of citizens over a period of years, necessitated an examination of national poison prevention and surveillance systems. The objectives of this study are to identify essential changes needed in chemical poisoning prevention regulations and surveillance systems for effective poison control by comparing recent trends in international poison control center (PCC) operations, and to delineate the critical elements for establishing a state-of-the-art poison control surveillance system in Korea based on recent advances in PCCs with toxicovigilance. Methods: A comprehensive review of Korea’s regulatory and surveillance systems for chemical health hazards, with a focus on household products under the HHDT, was conducted. A review of toxicovigilance systems in major countries shows that creating an effective national PCC requires key elements: a centralized database of toxic substances and poisoning cases, mandatory or voluntary reporting of poisoning cases, real-time alerts, collaboration among health organizations, and targeted follow-up of poisoned individuals. Results: Significant deficiencies in Korea’s legislation, toxicological data management, and poisoning surveillance systems, explained the inadequate response of the Korean government to the HHDT for nearly 17 years until the end of 2011. Based on a review of PCC toxicovigilance systems in major countries, a national framework with five core components is recommended for establishing a modern comprehensive Korea PCC system with toxicovigilance capacity. The core components include establishment of a centralized database of toxic substances information and clinical poisoning cases, implementation of mandatory or permissive reporting of poisoning cases, real-time alert mechanisms, collaborative systems among health-related organizations, and clinical follow-up of poisoned sub-groups. Conclusion A rationale and framework for a state-of-the-art national Korean PCC with toxicovigilance is justified and offered. This proposed system could assist neighboring countries in establishing their own sophisticated, globally integrated PCC networks.

Background: The purpose of this study was to quantify and compare the biomechanical characteristics of a new locking loop stitch (LLS), developed utilizing the concepts of both running locking stitch and needleless stitch, to the traditional Krackow stitch. Methods: The Krackow stitch with No.2 braided suture and the LLS with 1.3-mm augmented polyblend suture tape were compared biomechanically. The LLS was performed with single strand locking loops and wrapping suture around the tendon, resulting in half the needle penetrations through the graft compared to the Krackow stitch. Twenty bovine extensor tendons were divided randomly into two groups. The tendons were prepared to match equal thickness and cross-sectional area. Each suture-tendon was stitched and preloaded to 5 N for 60 seconds, cyclically loaded to 20 N, 40 N, and 60 N for 10 cycles each, and then loaded to failure. The deformation of the suture-tendon construct, stiffness, yield load, and ultimate load were measured. Results: The LLS had significantly less deformation of the suture-tendon construct at 100 N, 200 N, 300 N, and at ultimate load compared to the Krackow stitch (Krackow stitch and LLS at 100 N: 1.3 ± 0.1 mm and 1.0 ± 0.2 mm, p < 0.001; 200 N: 3.0 ± 0.3 mm and 1.9 ± 0.2 mm, p < 0.001; 300 N: 5.1 ± 0.6 mm and 2.9 ± 0.4 mm, p < 0.001; ultimate load: 12.8 ± 2.8 mm and 5.0 ± 1.2 mm, p < 0.001).The LLS had significantly greater stiffness (Krackow stitch and LLS: 97.5 ± 6.9 N/mm and 117.2 ± 13.9 N/mm, p < 0.001) and yield load (Krackow stitch and LLS: 66.2 ± 15.9 N and 237.9 ± 93.6 N, p < 0.001) compared to the Krackow stitch. There was no significant difference in ultimate load (Krackow stitch: 450.2 ± 49.4 N; LLS: 472.6 ± 59.8 N; p = 0.290). Conclusions The LLS had significantly smaller deformation of the suture-tendon construct compared to the Krackow stitch. The LLS may be a viable surgical alternative to the Krackow stitch for graft fixation when secure fixation is necessary.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy and is a significant and frequent cause of morbidity and mortality during the perioperative period. Although the pathophysiology of ischemic AKI is not completely understood, several important mechanisms of renal IR-induced AKI have been studied. Renal ischemia and subsequent reperfusion injury initiates signaling cascades mediating renal cell necrosis, apoptosis, and inflammation, leading to AKI. Better understanding of the molecular and cellular pathophysiological mechanisms underlying ischemic AKI will provide more targeted approach to prevent and treat renal IR injury. In this review, we summarize important mechanisms of ischemic AKI, including renal cell death pathways and the contribution of endothelial cells, epithelial cells, and leukocytes to the inflammatory response during ischemic AKI. Additionally, we provide some updated potential therapeutic targets for the prevention or treatment of ischemic AKI, including Toll-like receptors, adenosine receptors, and peptidylarginine deiminase 4. Finally, we propose mechanisms of ischemic AKI-induced liver, intestine, and kidney dysfunction and systemic inflammation mainly mediated by Paneth cell degranulation as a potential explanation for the high mortality observed with AKI.
Acute Kidney Injury ; Apoptosis ; Cell Death ; Cell Degranulation ; Endothelial Cells ; Epithelial Cells ; Inflammation ; Intestines ; Ischemia ; Kidney ; Leukocytes ; Liver ; Mortality ; Necrosis ; Negotiating ; Perioperative Period ; Receptors, Purinergic P1 ; Reperfusion ; Reperfusion Injury ; Toll-Like Receptors

OBJECTIVETo review the clinical features and laboratory investigations of ciguatera patients in Hong Kong between 2004 and 2007 in order to show the timely sampling of implicated fish from ciguatera victims and application of validated mouse bioassay for confirming suspected clinical cases of ciguatera.

METHODSDiagnosis of the ciguatera victims was based on history of coral fish consumption and clinical presentations stated in official guidelines for clinical diagnosis of ciguatera fish poisoning in Hong Kong. Food remnants of coral fish samples were collected swiftly from ciguatera victims between 2004 and 2007 for ciguatoxins (CTXs) analysis.

RESULTSMajor clinical symptoms in ciguatera patients included gastrointestinal and neurological effects including limb numbness and diarrhoea, which developed at 0.5 to 15 hours after consumption of fish. In most cases, neurological symptoms were more common than gastrointestinal symptoms. A broad range of attack rate (10%-100%) was observed in each ciguatera outbreak. Validated mouse bioassay on ether extracts of the food remnant samples confirmed that all were CTXs-positive (<0.5 - 4.3 MU/20 mg ether extract) and directly linked to the corresponding ciguatera cases.

CONCLUSIONConsistency between clinical and laboratory analysis for ciguatera poisoning illustrates the application of laboratory mouse bioassay in a timely fashion for confirming ciguatera poisoning cases and implementing effective public health measures. With further improvement in laboratory techniques, features of ciguatera fish poisoning cases can be better defined. Further studies are needed to determine the risk of each class of CTXs (Pacific-, Indian- and Caribbean-CTXs) in Hong Kong.

Animals ; Biological Assay ; Ciguatera Poisoning ; blood ; diagnosis ; epidemiology ; Ciguatoxins ; analysis ; Disease Outbreaks ; Fishes ; Gastrointestinal Diseases ; blood ; diagnosis ; epidemiology ; Hong Kong ; epidemiology ; Humans ; Mice ; Nervous System Diseases ; blood ; diagnosis ; epidemiology ; Prevalence ; Public Health ; Risk Factors ; Time Factors

INTRODUCTIONDengue is a major public health problem in Singapore. Age-specific dengue morbidity rates are highest in the young adult population, unlike in many other Southeast Asian countries where dengue is mainly a paediatric disease. Hence, the World Health Organization (WHO) guidelines on dengue diagnosis and management which were developed using the paediatric experiences, may not be suitable for the management of adult dengue infections.

MATERIALS AND METHODSThe Early DENgue (EDEN) infection and outcome study is a collaborative longitudinal study to investigate epidemiological, clinical, viral and host-specific features of early dengue-infected adults, in an effort to identify new early markers for prognostication. Patients presenting with early undifferentiated fever were included in the study. We carried out an interim analysis to look for early indicators of severe disease.

RESULTSDuring the period of this interim study analysis, 455 febrile patients were recruited. Of these, 133 were confirmed as acute dengue cases based on dengue-specific polymerase chain reaction (PCR) results. There were significant clinical and epidemiological differences between dengue and febrile non-dengue cases. Nine per cent of the dengue cases experienced persistent tiredness, drowsiness and loss of appetite beyond 3 weeks of illness. Quantitation of viral loads using the crossover (Ct) value of real-time RT-PCR correlated with the duration of symptoms. More than half of both primary and secondary dengue cases were hospitalised. There was no dengue-related mortality in this study.

CONCLUSIONThe duration of illness and prolonged symptom duration in 9% of the subjects indicate that the burden of dengue illness is substantially different from other non-dengue febrile illness in our study cohort. Our study also highlights the paucity of early prognostic markers for dengue fever in adults.

Adult ; Antibodies, Viral ; analysis ; Dengue ; diagnosis ; epidemiology ; virology ; Dengue Virus ; genetics ; immunology ; isolation & purification ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Male ; Morbidity ; trends ; Prognosis ; RNA, Viral ; analysis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Singapore ; epidemiology

This is the case of a 71 year old male who developed multiple myeloma (MM) and chronic myelogenous leukemia (CML) within a two year period. The patient initially presented with osteolytic lesions of the lumbar spine, and following the initial work-up a diagnosis of multiple myeloma with an IgG kappa paraproteinemia was made and appropriate treatment was given. Two years later the patient developed a progressively worsening leukocytosis which was found to be due to Philadelphia Chromosome (Ph1) positive CML. The occurrence in the same patient of two distinct hematologic malignancies suggests a neoplastic transformation of a pluripotent stem cell. A review of the literature appears to support the existence of a relationship between MM and CML as well as a relationship between MM and the myeloproliferative disorders.
Aged ; Case Report ; Cell Transformation, Neoplastic/pathology ; Hematopoietic Stem Cells/pathology ; Human ; Leukemia, Myeloid, Chronic/*pathology ; Male ; Multiple Myeloma/*pathology