Chronic Alcohol Abuse Research Articles

Linear Monotonic Inter-electrode Associations as Quantitative EEG for Alcoholism Diagnosis

Alcohol use disorders (AUDs) are associated with alterations in EEG patterns that reflect underlying neural dysfunctions, such as impaired cognitive processing, reduced neural connectivity, and disrupted brain rhythms. These EEG alterations can be indicative of several brain disorders, including cognitive deficits, mood disorders, and neurodegenerative diseases, which are often exacerbated by chronic alcohol abuse. Cognitive impairment in alcoholic subjects is caused due to altered functional connectivity between brain regions that can be quantified using statistical measures such as correlation. This paper proposes novel Quantitative EEG (QEEG) features comprising the band-wise absolute value of inter-electrode correlations as a measure of brain functional connectivity to classify alcoholic and non-alcoholic EEG. The EEG signal is first decomposed into five frequency sub-bands. In each sub-band, the absolute value of the linear Pearson product-moment correlation coefficient is computed between time-series EEG recorded by electrode pairs placed over different brain regions. To reduce the dimensionality of the feature vector, an ensemble feature selection approach is adopted, utilizing ANOVA and Chi-square, in conjunction with greedy forward feature selection wrapper algorithm. Four classifiers, namely SVM, KNN, ANN and RF are utilized for the classification. Among them, the SVM classifier achieves the best classification accuracies of 100% on validation with test data and 99.58% on cross-validation with train data, respectively.

Involvement of BRD4 in Alcoholic Liver Injury: Autophagy Modulation via Regulation of the SIRT1/Beclin1 Axis

Alcoholic liver disease (ALD) caused by chronic alcohol abuse involves complex processes from steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma, posing a global health issue. Bromodomain protein 4 (BRD4) typically serves as a “reader” modulating the functions of transcription factors involved in various biological processes and disease progression. However, the specific mechanisms underlying alcoholic liver injury remain unclear. In this study, we detected aberrant BRD4 expression in the alcohol-induced ALD mouse model of chronic and binge ethanol feeding developed by the National Institute on Alcohol Abuse and Alcoholism, consistent with the in vitro results in Aml-12 mouse hepatocytes. Blocking and inhibiting BRD4 restored the impaired autophagic flux and lysosomal functions in alcohol-treated Aml-12 cells, whereas BRD4 overexpression reduced the expression levels of autophagy marker and lysosomal genes. Furthermore, mouse BRD4 knockdown, mediated by a short hairpin RNA carried by the adeno-associated virus serotype 8, significantly attenuated the alcohol-induced hepatocyte damage, including lipid deposition and inflammatory cell infiltration. Mechanistically, BRD4 overexpression in alcoholic liver injury inhibited the expression of sirtuin (SIRT)1 in Aml-12 cells. Chromatin immunoprecipitation and dual-luciferase reporter assays revealed that BRD4 functions as a transcription factor and suppressor, actively binding to the SIRT1 promoter region and inhibiting its transcription. SIRT1 activated autophagy, which was suppressed in alcoholic liver injury via Beclin1 deacetylation. In conclusion, our study revealed that BRD4 negatively regulated the SIRT1/Beclin1 axis and that its deficiency alleviated alcohol-induced liver injury in mice, thus providing a new strategy for ALD treatment.

Влияние различных факторов риска на формирование вторичных органических психических расстройств у лиц пожилого возраста с алкогольной зависимостью, сформированной в среднем и пожилом возрасте

Background. Alcohol slows down the work of the brain and central nervous system, leads to deterioration of memory and concentration, cognitive disorders, and the formation of organic mental disorders. Due to the retirement of elderly people, some of them resort to taking alcohol as an adaptogen to alleviate various social, mental and psychological disorders, which can lead to the emergence of new or exacerbation of existing somatic disorders, the formation of alcoholism, as well as organic mental disorders. Aim. To investigate the risk factors (RF) for the formation of secondary organic mental disorders (SOMD) in elderly people with alcohol dependence (AD), formed in middle and old age. Patients and methods. The study included only male patients for the purity of the study aged 60 to 74 years (average age 67.5±7.2), who were divided into 2 groups depending on the age of occurrence of AD: group 1 – 21 people (36.2%), AD occurred at the age of 51.6±1.2 years, and the symptoms of SOMD at 61.8±2.1 years; group 2 – 37 people (63.8%), AD occurred at the age of 64.5±2.5 years, and SOMD at 71.3±2.8 years. The following methods were used: questionnaire – using the developed "Anamnestic chart", clinical (anamnesis collection), statistical (parametric and nonparametric). Results. The main factors of the formation of SOMD in people with formed AD in middle and old age are combinations of various RF, as well as a monofactor in the form of chronic alcohol abuse, the proportion of which varies depending on the age of AD formation. Conclusion. When AD is formed in old age, combinations of RF have a greater influence on the development of SOMD. And in the formation of AD in middle age, both alcohol, as an exogenous mono-damaging factor, and a combination of RF contribute to the formation of SOMD. Hereditary burden of alcoholism affects the progrediency of alcoholism, but does not play a role in the rate of formation of SOMD. The formation of alcoholism in middle age is combined with a relatively slow rate of formation of SOMD and a smaller number of associated somatic pathology, and when formed in old age – with a relatively fast rate of development of SOMD and a large number of associated somatic pathology.

A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact.

Hepatocellular carcinoma (HCC) poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale. Hepatitis C virus (HCV) infection remains one of the major risk factors for HCC development. HCC is a heterogeneous disease, and the development of HCC caused by HCV is intricate and involves various factors, including genetic susceptibility, viral factors, immune response due to chronic inflammation, alcohol abuse, and metabolic dysfunction associated with fatty liver disease. In this review, we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection. We also discuss the potential translational implications, including novel biomarkers and drugs for treatment. A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases. Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV. The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease, especially during the initial stages when genetic alterations are uncommon. The enduring "epigenetic memory" of gene expression is believed to be regulated by epigenetic mechanisms, indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment. Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution. By facilitating a more profound understanding of these aspects, this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.

Eruptive Xanthomas – A Case Report with a Review of the Literature

Eruptive xanthomas are most often the result of impaired lipid metabolism. They can be caused by a primary dysregulation in lipid metabolism (familial hyperlipoproteinemias) or by an increase in serum lipids from concomitant diseases (diabetes mellitus, obesity, chronic renal failure, nephrotic syndrome, pancreatitis, hypothyroidism, rarely hyperthyroidism, alcohol abuse, cholestasis or biliary cirrhosis, monoclonal gammopathy, multiple myeloma and leukemia) or from the use of certain medications (beta-blockers, estrogens, retinoids, protease inhibitors, cyclosporine, the antimycotic Miconazole and the antipsychotic Olanzapine (secondary hyperlipoproteinemias). Early diagnosis and adequate therapy of the skin changes and the comorbid underlying disease prevent serious life-threatening complications. A case of a 34-year-old man with papular yellowish lesions on the elbows is presented. The patient has accompanying diseases of diabetes mellitus, alcohol addiction, liver cirrhosis, chronic acute pancreatitis and chronic cholecystitis. The clinical diagnosis of eruptive xanthomas was confirmed by histopathological examination revealing foam cells in the dermis. Laboratory blood tests revealed an accelerated ESR and elevated blood glucose, transaminases, uric acid, total cholesterol, and triglycerides. Hepatoprotective and antidiabetic therapy combined with a dietary regimen improved the patient's condition and laboratory parameters. A partial reversal of skin lesions occurred. An overview of the epidemiology, etiopathogenesis, clinical picture, laboratory tests, differential diagnosis, dietary regimen, and treatment of eruptive xanthomas are presented.

Mediastinitis and septic shock complicating spontaneous esophageal rupture “Boerhaave’s syndrome”: a case report

Boerhaave’s syndrome, also known as spontaneous esophageal rupture, is a rare but life-threatening condition characterized by a tear in the esophagus. It is most commonly caused by a sudden increase in intraesophageal pressure, often due to severe vomiting or retching.Early diagnosis of Boerhaave’s syndrome is crucial for improving patient outcomes. The classic triad of symptoms includes severe chest pain, vomiting, and subcutaneous emphysema (air under the skin). However, not all patients present with this triad, and the diagnosis can be challenging, especially in patients without the typical symptoms.In this case report, we present the clinical details of a 52-year-old male patient who presented to the emergency department (ED) with severe abdominal pain and vomiting for several days. The patient had a history of chronic alcohol abuse and a recent episode of vigorous vomiting.

Neighborhood socioeconomic disadvantages associated with increased rates of revisions, readmissions, and complications after total joint arthroplasty.

Low socioeconomic status based on neighborhood of residence has been suggested to be associated with poor outcomes after total joint arthroplasty (TJA). The area deprivation index (ADI) is a scale that ranks (zero to 100) neighborhoods by increasing socioeconomic disadvantage and accounts for median income, housing type, and family structure. We sought to examine the potential differences between high (national median ADI = 47) and low ADI among TJA recipients at a single institution. Specifically, we assessed: (1) 30-day emergency department visits/readmissions; (2) 90-day and 1-year revisions; as well as (3) medical and surgical complications. A consecutive series of primary TJAs from September 21, 2015, through December 29, 2021, at a tertiary healthcare system were reviewed. A total of 3,024 patients who had complete ADI data were included. Patients were divided into groups below the national median ADI of 47 (n = 1,896) and above (n = 1,128). Multivariable regressions to determine independent risk factors accounting for ADI, race, age, sex, American Society of Anesthesiologists Classification grade, body mass index, diabetes, congestive heart failure (CHF), chronic obstructive pulmonary disease, hypertension, chronic kidney disease, alcohol abuse, substance abuse, and tobacco use. The primary outcomes of interest include evaluation of the independent association of ADI with total postoperative complications (at 30days, 90days, and 1year) after adjusting for multiple relevant cofactors. After adjusting for multiple relevant cofactors, at 90days, ADI > 47 (OR, 1.36, 95% CI 1.00-1.83, P = 0.04), men versus women (OR, 0.73, 95% CI 0.54-0.99, P = 0.039), and CHF (OR, 1.90, 95% CI 1.18-3.06, P = 0.009) were independently associated with increased total complications. The ADI was not associated with increased total complications at 30days or 1-year (All P > 0.05). Our findings of higher complications of the ADI > 47 cohort at 90days, reaffirm the complex relationship between ADI, patient demographics, and additional socioeconomic parameters that may influence postoperative outcomes and complications after TJA. This study utilizing ADI demonstrates potential areas of intervention and further investigation for assessing arthroplasty outcomes.

The Importance of Evaluating Sudomotor Function in the Diagnosis of Cardiac Autonomic Neuropathy.

Cardiac autonomic neuropathy (CAN) is a disorder affecting the autonomic nerves that regulate the cardiovascular system, leading to irregular heart rate and blood pressure control. It is commonly associated with diabetes mellitus but can also result from other conditions such as autoimmune disorders, chronic kidney disease, alcohol abuse, and certain medications. Screening for CAN is essential, particularly in individuals with poor glycemic control, cardiovascular risk factors, or complications. Early identification of CAN is vital for timely intervention to prevent or manage cardiovascular complications effectively. Regular screening helps detect CAN before symptoms emerge, enabling early intervention to slow or halt its progression. This study examined the relationship between sudomotor function and cardiovascular reflex tests. This was a cross-sectional study conducted between June 2019 and June 2020. The study included 271 subjects aged 18 years and above who provided informed consent, were diagnosed with type 2 diabetes mellitus (T2DM), and were overweight or obese. Exclusion criteria encompassed patients with other types of diabetes, pregnant women, those with recent neoplasm diagnoses, stroke sequelae, history of myocardial infarction, or pelvic limb amputations. The assessment of cardiac autonomic neuropathy involved conducting an electrocardiogram and evaluating the QTc interval in the morning before taking medication. Additionally, cardiovascular reflex tests (CART) were conducted, including assessments of heart rate variability during deep breathing, the Valsalva maneuver, and changes in orthostatic position. Simultaneously, the diagnosis of CAN was assessed by performing a sweat test using a Sudoscan assessment (Impeto Medical, Moulineaux, France). Results: More than half of the participants (52%, n=143) were female. Significant differences in statistical measures were noted between females and males regarding age, systolic blood pressure, fasting blood glucose, A1c level, total cholesterol, triglycerides, gamma-glutamyl transferase, and bilirubin levels. Within the CAN-diagnosed group (CAN+), 40.92% were classified as mild cases (n=90), 47.27% as moderate cases (n=104), and 11.81% as severe cases (n=26). Among the CAN+ group, 54% (n=119) were women. Electrochemical skin conductance was lower in the CAN+ group than the CAN- group in hands (67.34±15.51 μS versus 72.38±12.12 μS, p=0.008) and feet (73.37±13.38 μS versus 82.84 ±10.29 μS, p<0.001). The Sudoscan-CAN score significantly correlated with Ewing scores (r= 0.522, p<0.001). In multiple linear regression analysis, the Sudoscan-CAN score remained significantly associated with age, high BMI, long-standing diabetes, and Ewing score. Sudoscan demonstrates potential in identifying patients with an increased risk of CAN. Its integration into clinical practice can improve patient outcomes through early detection, risk stratification, and personalized treatment approaches. Its non-invasive, portable, and user-friendly features render it suitable for utilization in outreach programs or resource-constrained settings as part of screening efforts designed to pinpoint high-risk individuals for additional assessment.

Clinical Indicators of Bone Deterioration in Alcoholic Liver Cirrhosis and Chronic Alcohol Abuse: Looking beyond Bone Fracture Occurrence.

Although previous studies indicated that chronic alcohol abuse (CAA) and alcoholic liver cirrhosis (ALC) are associated with increased bone fragility, understanding bone fragility determinants is still modest in these individuals. We used a comprehensive individualized clinical fracture risk assessment approach (vertebral osteodensitometry, femoral osteodensitometry and geometry, and serum bone turnover biomarkers) to compare adult male patients with ALC who have not previously had femoral or vertebral fractures (n = 39), patients with CAA (without liver cirrhosis, n = 78) who have not previously had femoral or vertebral fractures and healthy age- and sex-matched controls (n = 43). Our data suggested that intertrochanteric bone mineral density was significantly lower in ALC and CAA patients than in controls. Also, the trabecular bone score was considerably lower in ALC patients compared with CAA and control individuals. The most significant inter-group differences in femoral geometry were noted on the femoral shaft. Patients with ALC and CAA have a higher 10-year risk of major osteoporotic fractures compared to the controls. Analysis of bone turnover biomarkers showed increased osteoprotegerin and beta-C-terminal telopeptide serum concentrations and decreased insulin growth factor-1 concentrations in patients with ALC compared to CAA and control groups. Our data revealed that bone alterations are present in patients with ALC and CAA even if they did not sustain a nontraumatic bone fracture, but it is also indicative that current bone-assessing clinical methods are not entirely reliable. Thus, future studies should focus on developing a reliable integrative clinical tool that can be used to accurately predict and prevent bone fracture occurrences in patients with ALC and CAA.

Blood neutrophil to lymphocyte ratio is associated with 90-day mortality and 60-day readmission in Gram negative bacteremia: a multi-center cohort study

IntroductionThe Neutrophil-Lymphocyte Ratio (NLR) in blood has demonstrated its capability to predict bacteremia in emergency departments, and its association with mortality has been established in patients with sepsis in intensive care units. However, its potential concerning mortality and readmission in patients with Gram-negative bacteremia (GNB) is unexplored.MethodsThis retrospective cohort study included patients with GNB between 2018 and 2022 from six hospitals in the Capital Region of Denmark. Patients who were immunosuppressed or had missing NLR values on the day of blood culture were excluded. Logistic regression models were used to analyze the association between NLR levels and 90-day all-cause mortality, while the logit link interpretation of the cumulative incidence function was used to assess the association between NLR levels and 60-day readmission. Associations were quantified as odds ratios (OR) with corresponding 95% confidence intervals (CI).ResultsThe study included 1763 patients with a median age was 76.8 years and 51.3% were female. The median NLR was 17.3 and 15.8% of patients had a quick sequential organ failure assessment score of two or three. Urinary tract infection (UTI) was the most frequent focus and Escherichia coli the most frequent pathogen. Statistically significant differences in median NLR were found by age group and pathogen, and for patients with or without hypertension, liver disease, chronic obstructive pulmonary disease, dementia, and alcohol abuse. 378 patients (21.4%) died before 90 days. 526 (29.8%) patients were readmitted to the hospital within 60 days. For each doubling of the NLR, the OR for all-cause 90-day mortality was 1.15 (95% CI, 1.04–1.27) and 1.12 (95% CI, 1.02–1.24) for 60-day readmission. Analysis of subgroups did not show statistically significant differences between groups in relation to the association between NLR and mortality. The discriminatory ability of NLR for mortality was limited and comparable to blood neutrophil or lymphocyte count, producing receiver operating characteristic curves with an area under the curve of 0.59 (95% CI, 0.56–0.63), 0.60 (95% CI, 0.56–0.65) and 0.53 (95% CI, 0.49–0.56), respectively.ConclusionBlood neutrophil-lymphocyte ratio was associated with 90-day all-cause mortality and 60-day readmission in patients with GNB. However, the ratio has limited ability in predicting mortality or readmission.

Long-Term Outcomes following Acute Upper Gastrointestinal Bleeding Remain Poor: A Single-Center Comparison over Two Distinct Time Periods within the Last 15 Years in Finland

Introduction: Acute upper gastrointestinal bleeding (AUGIB) is a common and life-threatening condition. This study aimed to compare the causes and long-term outcomes of AUGIB over two distinct periods in the last 15 years. Methods: This population-based study included consecutive patients who underwent emergency upper endoscopy for visible bleeding in 2006 and 2016. Our primary focus was on long-term mortality up to 5 years after the endoscopy, although short-term mortality was also reported. Results: A total of 832 patients (median age 67 [12–96] years, 37% female) were included, with peptic ulcer disease (48%), esophagitis (20%), and variceal bleeding (15%) being the most common diagnoses. The incidence of AUGIB increased with age, reaching 8.31 cases per 1,000 person-years among those aged 80 years or older. Mortality rates at 30 days, 90 days, 1 year, and 5 years were 13%, 16%, 27%, and 47%, respectively. The standardized mortality ratio was high in all age groups, with particularly elevated rates observed among younger patients compared to the standard population. Variceal bleeding, liver cirrhosis, and chronic alcohol abuse were associated with the highest mortality. Only two short-term deaths were attributed to failed hemostasis. The primary causes of death were malignancies, liver failure, and cardiac failure. No improvement in outcomes was observed between the two time periods. Conclusion: Although the treatment of AUGIB may be relatively straightforward, the outcomes following treatment remain poor. High mortality can be attributed to the presence of coexisting conditions and patients’ lifestyle.

Droplet Microfluidics with Capillary Electrophoresis for Glycan Biomarker Analysis.

Several glycoproteins are validated biomarkers of various diseases such as cancer, cardiovascular diseases, chronic alcohol abuse, or congenital disorders of glycosylation (CDG). In particular, CDG represent a group of more than 150 inherited diseases with varied symptoms affecting multiple organs. The distribution of glycans from target glycoprotein(s) can be used to extract information to help the diagnosis and possibly differentiate subtypes of CDG. Indeed, depending on the glycans and the proteins to which they are attached, glycans can play a very broad range of roles in both physical and biological properties of glycoproteins. For glycans in general, capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) has become a staple. Analysis of glycans with CE-LIF requires several sample preparation steps, including release of glycans from the target glycoprotein, fluorescent labeling of glycans, and purification of labeled glycans. Here, we describe the protocol for glycan sample treatment in a microfluidic droplet system prior to CE-LIF of labeled glycans. The microfluidic droplet approach offers full automation, sample, and reagent volume reduction and elimination of contamination from external environment.

Huangqi Gegen decoction ameliorates alcohol-induced cognitive dysfunction via attenuating oxidative stress and enhancing blood-brain barrier integrity in rats through the Keap1-Nrf2/HO-1 signaling pathway.

Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism. Wistar rats were orally administered 50% ethanol for 10 weeks, followed by treatment with HGD at doses of 16, 32, or 64 mg/kg/day for an additional 6 weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap1, Nrf-2, HO-1, and NQO-1 were tested by PCR and western blot. Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-1, Occludin, and Claudin-5. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-1β, IL-6, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-2, HO-1, and NQO-1 while down-regulating Keap1 expression. These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction.

Long-Term Survival Analysis of 5619 Total Ankle Arthroplasty and Patient Risk Factors for Failure.

Total ankle arthroplasty (TAA) has higher complication and failure rates compared to other surgical joint replacement procedures despite technological advances. This study aimed to find the long-term survivability of the TAA procedure and identify the patient risk factors for failure with one of the largest cohorts of patients in the literature. This retrospective cohort study involving cases between 2007 and 2018 analyzed patients who received an index primary TAA procedure in Korea. A total of 5619 cases were included in the final analysis. The TAA failure was defined as either a case with revision arthroplasty or a case with TAA implant removal and arthrodesis performed after primary TAA. During the study period, the 5-year survival rate was 95.4% (95% CI, 94.7-96.1%), and the 10-year survival rate was 91.1% (95% CI, 89.1-93.1%). A younger age (<55 years, adjusted hazard ratio [AHR], 1.725; 55-64 years, AHR, 1.812; p < 0.001 for both), chronic pulmonary disease (AHR, 1.476; p = 0.013), diabetes (AHR, 1.443; p = 0.014), and alcohol abuse (AHR, 1.524; p = 0.032) showed a significantly high odds ratio for primary TAA failure in Cox regression analysis. The 10-year TAA survivorship rate was 91.1%. A younger age, chronic pulmonary disease, diabetes, and heavy alcohol consumption are risk factors for TAA.

Risk Factors of Emergency Department Utilization After Outpatient Surgery for Sports-Related Injuries.

The purpose of this study was to identify the most common reasons for and risk factors associated with postoperative emergency department (ED) utilization after orthopaedic procedures for sports-related injuries. Using the 2014 to 2016 New York and Florida State Databases from the Healthcare Cost and Utilization Project, outpatient procedures for sports-related injuries were identified. Patient records were tracked across care settings within each state to determine the rate and reasons of postoperative ED utilization within 90 days after the index surgery. Multiple logistic regression models were used to identify risk factors associated with ED visits at 0 to 7 days, 8 to 30 days, 31 to 90 days postoperatively. A total of 28,192 surgery visits for sports-related injuries were identified, with knee arthroscopy with partial meniscectomy (18.48%) and arthroscopic anterior cruciate ligament reconstruction (17.04%) as the two most common procedures treating sports injuries. The overall postoperative ED utilization rates were 1.6% (0 to 7 days postoperative), 1.3% (8 to 30 days) and 2.1% (31 to 90 days). The main cause of ED visits was markedly different during each postoperative period: mainly musculoskeletal pain (36.3%) during 0 to 7 days, either musculoskeletal pain (17%) or injury (16.6%) during 8 to 30 days, and injury (24.2%) during 31 to 90 days. Sports with the highest ED utilization in descending order were basketball, football, ice/snow sports, walking/running, cycling, and soccer. Relative to open procedures, arthroscopic procedures were 0.71 times as likely to result in a postoperative ED visit. Independent predictors of ED utilization up to 90 days postoperatively included renal failure, chronic pulmonary disease, psychosis, diabetes, and alcohol abuse. Rate of ED utilization after outpatient surgery for sports-related injuries is low (<2.2%), with postoperative musculoskeletal pain and reinjury as the two most common causes, highlighting the importance of postoperative pain management and injury prevention. Arthroscopic procedures showed markedly lower ED utilization compared with open surgery, although not indicative of overall superiority. III, Retrospective Cohort Study.

Anemia Outside the Box: Nonimmune Intramedullary Hemolytic Anemia Driven By Vitamin B12 Deficiency

Introduction: Vitamin B12 and folate deficiencies are common etiologies of macrocytic anemia, mostly encountered with chronic alcohol use, and uncommon for healthy individuals with unremarkable medical history. The pathogenesis of the resulting anemia is described by two possible mechanisms: either ineffective erythropoiesis, driven by vitamin B12 deficiency, or more rarely, via nonimmune intramedullary hemolysis. We present a very rare case of severe vitamin B12 deficiency leading to nonimmune intramedullary hemolysis and highlight the diagnostic evaluation and tailored management. Case Presentation: A 49-year-old female with history of depression, chronic alcohol use and chronic nitrous oxide inhalation, presented with lethargy, hypotension and fevers with visual hallucinations, and was subsequently admitted for acute encephalopathy. Findings on physical examination included diminished proprioception and diminished sensation to fine touch, pinprick and vibration of the lower extremities with distal hyperreflexia of the patellar and Achilles tendon reflexes bilaterally. Lab work was notable for leukopenia and macrocytic anemia with a significant drop in hemoglobin to 9.6 from a baseline of 13.2 within 5 months and MCV of 103. Extensive investigation of encephalopathy was undertaken, of which we note infectious workup, prompted by the septic presentation, which showed Staphylococcus aureus bacteremia. On the other hand, the patient's anemia was concurrently investigated. Hemolysis workup was positive (LDH 394 U/L; direct bilirubin 1.6 mg/dL; haptoglobin&amp;lt;8 mg/dL; reticulocyte count 6.1%); however, schistocytes were low on peripheral smear (Figures 1 and 2). As such, nonimmune intramedullary hemolysis was suspected. Further anemia workup revealed severe vitamin B12 deficiency (75 ng/L), consistent with the physical exam findings, but normal folate levels. Of note, methylmalonic acid levels and homocysteine were also elevated (respectively 4.39 nmol/mL, and 142 umol/L). The constellation of the clinical presentation and all the laboratory findings confirmed a nonimmune intramedullary hemolytic process, elicited by vitamin B12 deficiency. This deficiency was thought to be multifactorial, mainly caused by chronic alcohol abuse, in addition to persistent nitrous oxide use. It was also suggested that hemolysis could be a consequence of drug-induced carboxyhemoglobinemia (level was 9.4%), whereby carboxyhemoglobin can form during the binding and release of nitric oxide from hemoglobin. Treatment was focused on replacing vitamin B12 with 1000 mcg daily intramuscular injections for 7 days, then weekly thereafter for 4 weeks, followed by monthly injections. Improvement of hemoglobin to 11.1 with improvement of neurologic exam findings were noted prior to discharge. Conclusion: Nonimmune hemolytic anemia must be included in the differential diagnosis when evaluating patients with anemia concurrent with vitamin B12 deficiency, mostly encountered with chronic alcohol use. Vitamin B12 supplementation remains the key treatment to correct this rare, but serious outcome of vitamin B12 deficiency.

Approach to non-compressive myeloneuropathy through a rendezvous of 11 cases from an Indian backdrop

IntroductionMyeloneuropathy is a diagnosis ascribed to disorders that concomitantly affect the spinal cord and peripheral nerves. Recognizing this syndrome may sometimes be arduous, even for the most consummate clinicians, because symptomatology can mimic either spinal cord or peripheral nerve disease. Besides, examination findings suggest a predominantly myelopathic or neuropathic picture. This article reports a rendezvous of rare cases of clinically diagnosed myeloneuropathy with different etiological backgrounds and therapeutic responses. MethodsEleven cases of non-compressive myeloneuropathy were admitted to the Department of General Medicine of Burdwan Medical College and Hospital, Burdwan, West Bengal, India, between May 2018 and May 2022. ResultsWe report the cases of 11 patients (6 men and 5 women) who presented with myeloneuropathy of different etiologies (vitamin B12, copper, and vitamin E deficiencies, organophosphate poisoning, chronic alcohol abuse, illicit substances abuse, anti-thyroid peroxidase/anti-thyroglobulin antibody-related neurologic disorder responsive to steroids, Sjögren syndrome, chikungunya infection, paraneoplastic, and hereditary). ConclusionMeticulous historical analysis, careful clinical examination, and apposite utilization and interpretation of biochemical, electrophysiological, and neuroimaging findings are sine-qua-non for an accurate and consistent approach to evaluating a suspected case of myeloneuropathy, facilitating early treatment and recovery. Differential identification of these disorders needs an in-depth perception of the mode of onset of symptoms, the course of progression of the disease, the pattern of myelopathic/neuropathic findings, and recognition of other neurological or systemic manifestations. For untroubled understanding, etiologies of myeloneuropathies should be subdivided into a few broad categories, e.g., metabolic (nutritional), toxic (toxin-induced), infectious, inflammatory (immune-mediated), paraneoplastic, and hereditary disorders.

Deficiency of aldehyde dehydrogenase 2 aggravates ethanol-induced cytotoxicity in N2a cells via CaMKII/Drp1-mediated mitophagy

Chronic alcohol abuse causes brain damage and has been associated with an increased risk of Alzheimer's disease. The toxic metabolite of alcohol, acetaldehyde, which is converted to acetate by aldehyde dehydrogenase 2 (ALDH2), has been shown to induce excessive mitochondrial fragmentation and dysfunction leading to neurotoxicity. However, it is still unclear how alcohol affects mitochondrial function in ALDH2-deficient cells. The present study investigated the association between abnormal mitochondrial dynamics, mitophagy and cytotoxicity in ALDH2-deficient N2a cells treated with ethanol. It was found that ethanol induced dynamin-related protein 1 (Drp1)-mediated mitochondrial fragmentation and impaired mitochondrial function, causing excessive mitophagy and cytotoxicity in ALDH2-deficient N2a cells while inducing Ca2+ influx and activating Ca2+/calmodulin-dependent protein kinase II (CaMKII). Inhibition of Ca2+ overload or CaMKII activation prevented Drp1 phosphorylation and ameliorated ethanol-induced mitophagy and cytotoxicity, indicating that Ca2+-dependent CaMKII activation was critical for mediating Drp1-dependent excessive mitochondrial fission and mitophagy in ALDH2-deficient N2a cells. The results of the present study suggested that prevention of intracellular Ca2+ overload might be beneficial for preventing neurotoxicity associated with alcohol abuse in individuals with defective ALDH2.

Characteristics, risk factors and outcomes of patients managed for left-sided infective endocarditis: a prospective study in a high-volume center

Abstract Background Although medical and surgical management of infective endocarditis (IE) have improved in the recent decades, the associated mortality remains high. Available prospective data are scarce, and further knowledge from prospective cohorts could help improving the prognosis of patients with IE. Objective To describe the characteristics and outcomes of left-sided IE and to determine the risk factors associated to in-hospital mortality in a high-volume center. Methods From 15 September 2020 to 15 February 2023, all patients with left-sided IE managed in a tertiary center of cardiology were included in this prospective, observational study. The diagnosis of IE was made according to current guidelines and management was collegially discussed by the endocarditis team. Determinants of in-hospital death were assessed using a multivariate logistic regression model including any covariate associated in univariate analysis (p&amp;lt;0.1). Results A total of 185 patients were included during the study period. Median age was 68 [56 – 76] years, 141 (76%) patients were males, and 75 (41%) cases involved a prosthetic valve. Aortic valve, mitral valve and involvement of both valves were observed in 111 (60%), 48 (26%) and 26 (14%) patients, respectively. Multimodal cardiac imaging, including cardiac computed tomography (CT) and/or PET-FDG, was used in 64 (35%) of all cases, and 49/75 (65%) patients with valvular prosthesis. Severe valvular regurgitation was identified in 56 (30%) patients, root abscess and/or false aneurysms in 57 (31%) patients. A pathogen agent was identified in 169 (91%) patients, and the most frequent germs were Staphylococcus (30%), Streptococcus (30%) and Enterococcus (17%). A severe initial presentation requiring intensive care unit (ICU) admission was observed in 42 (23%) patients. Cardiac surgery was performed in 102 (55%) cases, and 41 (22%) patients required an emergent surgery. A total of 37 (20%) patients died during the initial in-hospital phase, mostly from cardiac or neurovascular causes. In a multivariate analysis, hypertension (Odd ratio (OR) = 3.3; 95% confidence interval (CI): 1.4 – 10), bi-valvular endocarditis (OR = 3.1; 95%CI: 1.0 – 9.5), unidentified pathogen (OR = 4.3; 95%CI: 1.7 – 15) and chronic alcoholic abuse (OR = 16.4; 95%CI: 3.7 – 87.9) were independently associated with increased in-hospital mortality (Table). Conclusion Severe initial presentation requiring an ICU admission and/or urgent cardiac surgery was common among patients with left-sided IE. Chronic alcoholic abuse and unidentified pathogen appear as major determinants of in-hospital mortality.Table

Histopathological examination of characteristic brain MRI findings in acute hyperammonemic encephalopathy: A case report and review of the literature.

Acute hyperammonemic encephalopathy is associated with distinct brain MRI findings, namely, hyperintensity in T2-weighted sequences as well as restricted diffusion in diffusion-weighted imaging with accentuation in the insular cortex and cingulate gyrus. The pathophysiology and the histopathological correlates of these characteristic MRI findings are largely unknown. We present a 57-year-old male with a history of chronic alcohol abuse, liver cirrhosis and portal hypertension, and a clinical syndrome (variceal bleeding, depression of consciousness, seizures), elevated plasma ammonia levels, and characteristic brain MRI abnormalities suggestive of acute hyperammonemic encephalopathy. A postmortem histopathological examination revealed extensive hypoxic ischemic encephalopathy without evidence for metabolic encephalopathy. No episodes of prolonged cerebral hypoxemia were documented throughout the course of the disease. We conducted a review of the literature, which exhibited no reports of hyperammonemic encephalopathy in association with characteristic brain MRI findings and a consecutive histopathological examination. This is the first report of a patient with acute hyperammonemic encephalopathy together with characteristic brain MRI findings and a histopathological correlation. Although characteristic MRI findings of acute hyperammonemic encephalopathy were present, a histopathological examination revealed only hypoxic pathology without signs of metabolic encephalopathy.