Specific Etiology Research Articles

Clinical Actionability of Genetic Findings in Cerebral Palsy

ImportanceSingle gene variants can cause cerebral palsy (CP) phenotypes, yet the impact of genetic diagnosis on CP clinical management has not been systematically evaluated.ObjectiveTo evaluate how frequently genetic testing results would prompt changes in care for individuals with CP and the clinical utility of precision medicine therapies.Data SourcesPublished pathogenic or likely pathogenic variants in OMIM genes identified with exome sequencing in clinical (n = 1345) or research (n = 496) cohorts of CP were analyzed. A systematic literature review for evidence of effective therapies for specific genetic etiologies was performed.Study SelectionNonstandard interventions that led to a detectable improvement in a defined outcome in individuals with variants in the gene of interest were included.Data Extraction and SynthesisLiterature was evaluated using PRISMA guidelines. A diverse, expert working group was established, scoring rubrics adapted, and scoring consensus built with a modified Delphi approach.Main Outcomes and MeasuresOverall clinical utility was calculated from metrics assessing outcome severity if left untreated, safety and practicality of the intervention, and anticipated intervention efficacy on a scale from 0 to 3.ResultsOf 1841 patients with CP who underwent exome sequencing, 502 (27%) had pathogenic or likely pathogenic variants related to their phenotype. A total of 243 different genes were identified. In 1841 patients with identified genetic etiologies of CP, 140 (8%) had a genetic etiology classified as actionable, defined as prompting a change in clinical management. Also identified were 58 of 243 genes with pathogenic or likely pathogenic variants with actionable treatment options: 16 targeting the primary disease mechanism, 16 with specific prevention strategies, and 26 with specific symptom management. The level of evidence was also graded according to ClinGen criteria; 45 of 101 interventions (44.6%) had evidence class D or below. The potential interventions have clinical utility with 98 of 101 outcomes (97%) being moderate-high severity if left untreated and 63 of 101 interventions (62%) predicted to be of moderate-high efficacy. Most interventions (72 of 101 [71%]) were considered moderate-high safety and practicality.Conclusions and RelevanceThe findings indicate that actionable genetic findings occurred in 8% of individuals referred for genetic testing with CP. Evaluation of potential efficacy, outcome severity, and intervention safety and practicality indicates moderate-high clinical utility of these genetic findings. Genetic sequencing can identify precision medicine interventions that provide clinical benefit to individuals with CP. The relatively limited evidence base underscores the need for additional research.

Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association.

Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist's perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.

ILAE neonatal seizure framework to aide in determining etiology.

To employ the neonatal seizure framework developed by the International League Against Epilepsy (ILAE) Neonatal Task force to assess its usefulness in determining the etiology of neonatal seizures. The members of the ILAE Neonatal Task Force evaluated 157 seizures from 146 neonates to determine internal validity and associations between semiology and a specific etiology. Provoked neonatal electrographic and electroclinical seizures were due to multiple etiologies. For electroclinical seizures, unilateral clonic seizures were typically seen with vascular etiologies, focal tonic seizures and sequential seizures with genetic etiologies, and myoclonic seizures with inborn errors of metabolism. Electrographic seizures were often seen in hypoxic-ischemic encephalopathy or vascular etiologies. These data suggest that the ILAE neonatal seizure classification may be used as a bedside tool to aid and guide workup to determine the etiology of seizures.

Abnormal spirometry in individuals with a smoking history and no known obstructive lung disease: current understanding and clinical implications.

Recent recognition of the importance of abnormal spirometry without obstruction has generated interest in its epidemiology, risk factors, longitudinal outcomes, and clinical implications. Preserved ratio impaired spirometry (PRISm), defined as an forced expiratory volume in 1 s (FEV1)/ forced vital capacity (FVC) ≥0.7 with an FEV1 <80% predicted, has a high prevalence globally (2.4-16.7%) and is more common in individuals with metabolic comorbidities, smoking history, female sex, and higher BMI. PRISm is associated with increased respiratory symptoms and poor clinical outcomes such as increased all-cause mortality and cardiovascular events compared to normal spirometry. Longitudinal studies show substantial subsets of individuals with PRISm will transition to other spirometric categories, including progression to obstruction. Individuals with PRISm are heterogeneous; recent investigations have focused on subtyping PRISm based on spirometric features or pathobiologically-based phenotypes. PRISm is a common spirometric abnormality which is robustly associated with negative outcomes. However, current knowledge gaps with respect to heterogeneity, specific etiologies, and longitudinal progression preclude the development of universal evidence-based diagnostic and management strategies. At present, clinicians are advised to focus on risk factor modification (e.g., diabetes, obesity) and the identification of actionable traits (e.g. emphysema, interstitial lung abnormalities) among patients with PRISm.

Unexplained Illnesses Associated With a Subscription Meal Service, 2022

In recent years, shifting consumer demands have led to changes in the types of foods produced and how consumers obtain them. A growing demand for non–meat-based proteins has led to the development of new plant-based protein products. Simultaneously, there has been an increase in subscription-based meal services. In 2022, a subscription-based meal service, Daily Harvest, launched a new plant-based protein line of products called Crumbles. Shortly, thereafter, consumer complaints of gastrointestinal symptoms were heard, and Daily Harvest recalled the French Lentil and Leek Crumbles, which contained a unique ingredient, tara flour. We obtained case data from the Marler Clark law firm and conducted an epidemiologic investigation of the relationship between illness and consumption of food products distributed by Daily Harvest. We independently reviewed data on 338 people, including 264 people with supplemental food exposure information, and calculated minimal attack rates. Of 264 people who completed the supplemental survey, all (100%) consumed the Lentil and Leek Crumbles. Minimal attack rates were highest for the Lentil and Leek Crumbles (1.4%) followed by the Walnut and Thyme Crumbles (0.45%). Among 213 subscribers, the minimal attack rate was highest for those who purchased three or more units of Lentil and Leek Crumbles (3.7%) compared to those who purchased two units (2.3%) or one unit (1.5%). The strength of the association and the increased risk of illness among persons who consumed Lentil and Leek Crumbles, but not other products that shared ingredients (other than tara flour) with Lentil and Leek Crumbles, suggests that tara flour was likely the source of illness, although a specific etiology remains unknown. This study highlights the value of using nontraditional data to identify sources of illness. Further research is needed to understand the safety of tara flour for human consumption.

Impact of MASLD on Portal Vein Thrombosis Following Hepatectomy for Liver Cancer.

Background: Due to the increasing global prevalence of non-alcoholic fatty liver disease (NAFLD), which is closely linked to metabolic disorders, there has been a rise in the number of patients with NAFLD undergoing hepatectomy. The metabolic disorders, as well as NAFLD, increase venous thrombotic risk. NAFLD was recently updated to a new concept of hepatic steatosis: metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the impact of MASLD on post-hepatectomy portal vein thrombosis (PH-PVT). Methods: A total of 106 patients who underwent hepatectomy for liver cancer were included. Steatotic liver disease (SLD) was diagnosed using a CT L/S ratio of <1.1. SLD was classified as follows: MASLD, SLD associated with metabolic factors without alcohol consumption; MetALD, SLD with metabolic factors and moderate alcohol consumption; Other SLD, alcohol or other specific etiology of SLD; and No SLD, no hepatic steatosis. Results: PH-PVT was detected in 12/106 patients (11.3%); MASLD, 7/20 (35%); MetALD, 1/5 (20%); Other SLD, 1/13 (8%); and No SLD, 3/68 (4.4%). Multivariate analysis showed that the MASLD group (including MASLD and MetALD) (odds ratio [OR], 9.27) and left lateral sectionectomy (OR, 6.22) were significant independent risk factors for PH-PVT. Additionally, the incidence of PH-PVT was significantly higher in patients with MASLD than in those without SLD, along with metabolic factors, excluding alcohol consumption. Conclusions: MASLD and MetALD were identified as independent and significant risk factors for PH-PVT. Consideration was given to the idea that hepatic steatosis and metabolic dysfunction play synergistic roles in PH-PVT development.

Neuroretinitis: a comprehensive review on aetiologies, clinical manifestations, and treatment options.

Neuroretinitis connotes a descriptive clinical entity of optic disc oedema in association with macular exudates in a star configuration. Accordingly, it does not indicate a specific aetiology, although cat scratch disease caused by Bartonella henselae is the most common cause. Historically, the recognition of neuroretinitis dates to the early 20th century with the eventual understanding that the optic disc is the primary target of disease with secondary macular involvement. Neuroretinitis can be broadly divided into four categories: infectious, inflammatory, autoimmune and mimickers. The intention of this article is to review the various aetiologies of neuroretinitis with a focus on the etiopathogenesis, clinical manifestations, and management of B. henselae associated neuroretinitis and recurrent idiopathic neuroretinitis.

Role of Serum Ferritin and Prediction of Neurological Outcome in Acute Ischemic Stroke Patients

Background: Stroke, also known as cerebrovascular accident (CVA), is an abrupt onset of neurological deficiency caused by a specific vascular aetiology. Aim: This study aimed to assess the role of serum ferritin in acute ischaemic stroke patients to correlate serum ferritin and neurological scales on the day of admission and during follow-up and to predict neurological outcomes. Methods: This prospective observational study included 100 patients who presented with acute ischaemic stroke clinically and with radiological imaging in the General Medicine and Neurology departments of Saveetha Medical College and Hospital for 18 months. Functional disability was assessed for all patients after 3 months based on the correlation of serum ferritin levels with the neurological scales, and the outcome was estimated. Results: The mean age of the patients was 59.45 ± 14.39. The serum ferritin level and Canadian Stroke Scale score during admission on day 7th and day 30th, were significantly different (p &lt; 0.01). Serum ferritin levels were positively associated with the Glasgow Coma Scale score at admission and on the 7th and 30th days after admission. Ferritin levels were significantly higher in the moderate category under all circumstances (p &lt; 0.01). Patients with mRS scores of 2, 3, and 4 were compared with serum ferritin levels and found to be significantly associated with serum ferritin levels. Conclusion: This study found that patients with higher serum ferritin levels experienced increased stroke severity and lower GCS and mRS scores, which correlated with increased morbidity.

Persistent Chronic Active T-Cell-Mediated Rejection After Kidney Transplantation Is Associated With Poor Allograft Survival.

Histopathological findings of chronic active T-cell-mediated rejection (CA-TCMR) have been reported to potentially improve with treatment. However, whether this improvement is associated with a better renal prognosis remains unclear. This study was performed to analyze the impact of the histological response to therapy on kidney allograft survival in patients with CA-TCMR. The data of patients diagnosed with CA-TCMR between January 2018 and May 2023 were retrospectively reviewed. A composite graft endpoint was defined as a two-fold increase in the serum creatinine level or the development of end-stage kidney disease. Thirty-seven patients with CA-TCMR underwent 46 follow-up biopsies. Eleven patients who were diagnosed with CA-TCMR at the last biopsy were classified as the persistent group, while the remaining 26 patients were classified as the transient group. Both before and after treatment, there were no significant changes in serum creatinine, estimated glomerular filtration rate, or proteinuria in either group. However, the transient group showed a significant reduction in interstitial fibrosis and tubular atrophy without a specific etiology (IFTA). This improvement was attributed to better histopathological Banff scores after treatment. Patients with persistent CA-TCMR had significantly worse graft survival than those with transient CA-TCMR (p = 0.002), even after adjusting for significant clinical factors (hazard ratio: 11.4; 95% CI: 1.1-120.0; p = 0.043). Our findings suggest that the persistence of histopathologic evidence of CA-TCMR after treatment is a significant risk factor for allograft loss compared with transient CA-TCMR.

Survivability of young sudden cardiac arrest by aetiology: insights from a state-wide adjudicated cardiac arrest registry

Abstract Background Identifying factors to improve survival following out-of-hospital cardiac arrest (OHCA) is important. Many OHCA registries do not document the underlying cause of OHCA and therefore cannot provide insights according to specific arrest aetiology. The aim of this study was to assess survivability of OHCA according to arrest aetiology. Methods A state-wide registry identified all patients aged 1 to 50 years who experienced OHCA in Victoria, Australia from April 2019 to April 2023. OHCA was ambulance-defined with cause of OHCA determined by adjudication against autopsy or hospital data. OHCA aetiology was classified into four categories; non-cardiac, coronary, cardiomyopathy or other cardiac (including unascertained cause). Results 2686 patients experienced OHCA (non-cardiac=1305, 48.6%, coronary=585, 21.8%, cardiomyopathy=250, 9.3%, other cardiac=537(282 unascertained), 20.0%), of whom 250 (9.3%) survived. Patients in the coronary group were older (median 45 years [interquartile range 40-48 years], p=0.0001), more likely to be male (83.6%, p&amp;lt;0.0001), have a witnessed arrest (44.6%, p&amp;lt;0.0001) and have an initial shockable rhythm (48.2%, p&amp;lt;0.0001) when compared to other categories. Using the non-cardiac group as the reference group, adjusted odds ratio of survival (95% CI) were 1.65 (0.86-3.19) for cardiomyopathy, 2.51 (1.55-4.07) for other cardiac and 4.03 (2.51-6.49) for coronary causes of OHCA. Conclusion Odds of survival to hospital discharge following OHCA were four times higher in OHCA of coronary aetiology when compared with non-cardiac OHCA. Ongoing research into OHCA according to aetiology is needed to define subgroups, benchmark resuscitation performance more appropriately and identify patterns according to specific aetiologies to improve survival outcomes.

Endoscopic treatment of chronic pancreatitis in children: a retrospective study

Background. Chronic pancreatitis (CP) in children is a relatively rare polyetiological disease of the pancreas, accompanied by progressive inflammation of the parenchyma with gradual loss of its function and/or the occurrence of specific complications. Indications for a particular treatment method for a specific patient with a specific etiology and stage of CP are not clearly defined and largely depend on the experience and technical capabilities of a specific clinic. In recent years, individual centers have accumulated experience in using endoscopic methods for the treatment of CP in children, which seems very promising. Aim. To analyze the results of our experience in endoscopic treatment of CP in children. Materials and methods. From 2018 to June 2023, endoscopic treatment methods were used in 31 children with CP. Indications for endoscopic treatment were frequent episodes of exacerbation of pancreatitis in combination with signs of ductal hypertension with or without Wirsungolithiasis. According to etiology, patients were divided into groups: pancreatic duct anomalies, abnormal pancreaticobiliary junction (APBJ), hereditary CP, acquired duct strictures and idiopathic pancreatitis. The results were assessed by the frequency of episodes of exacerbation of pancreatitis. Results. Endoscopic treatment failed in two patients due to: impossibility of cannulation of the main pancreatic duct in a child operated on for annular pancreas and impossibility of recanalization of posttraumatic duct stricture in the isthmus area. Early complications included post-manipulation pancreatitis (n=2; 6.4%), asymptomatic hyperenzymemia (n=5; 16.1%), stent loss (n=2; 6.4%), stent obstruction with pancreatic precipitates (n=2; 6.4%). The average follow-up period was 2.31±1.32 years. In all groups except APBJ, there was a significant decrease in exacerbation episodes with their complete absence in most patients. Ineffectiveness of endoscopic treatment was noted in one case of a combination of the complete type of divided pancreas and a pathogenic mutation of the gene SPINK1. Thus, endoscopic treatment was effective in 28 (90.3%) children in the early period and in 22 (71%) in the late period due to the return of symptoms in the APBJ group. Conclusion. Endoscopic treatment of chronic pancreatitis in children is effective and can be recommended as first-line therapy. Endoscopic treatment of symptomatic APBJ has a temporary clinical effect.

Body mass index of 23 or greater is relevant to hepatic steatosis and fibrosis in patients with harmful alcohol use.

Steatotic liver disease, characterized by a combination of metabolic dysfunction, alcohol use, or specific etiologies, is a leading cause of chronic liver disease. However, the role of metabolic dysfunction in chronic liver disease with harmful alcohol use remains unclear. This study aimed to investigate factors associated with hepatic steatosis and fibrosis in patients with harmful alcohol use. Over a 2-year period, we registered patients with harmful alcohol use, defined by an Alcohol Use Disorders Identification Test score of 8 or higher. We retrospectively analyzed background information, blood test results, ultrasound-guided attenuation parameter (attenuation coefficient), and liver stiffness measurement. Hepatic steatosis was defined as attenuation coefficient ≥0.65dB/cm/MHz, and fibrosis as liver stiffness measurement ≥7.5kPa. The study included 131 patients (82% men, median age 59years). Linear regression analysis revealed significant associations with attenuation coefficient for body mass index ≥23 (0.08, p<0.0001) and age (-0.002, p=0.002). Liver stiffness measurement was associated with body mass index ≥23 (2.52, p=0.001), aspartate aminotransferase (0.02, p=0.0189), gamma-glutamyl transpeptidase (0.008, p<0.0001), platelet count (-0.02, p=0.001), and prothrombin international normalized ratio (26.40, p<0.0001). Among the four groups classified by the presence or absence of steatosis and fibrosis, patients with fibrosis, but without steatosis, demonstrated the lowest liver reserve. In contrast, patients with both steatosis and fibrosis showed higher aspartate aminotransferase and gamma-glutamyl transpeptidase levels. Body mass index is associated with both hepatic steatosis and fibrosis in patients with harmful alcohol use.

Topical Therapies for Periorbital Dyschromia: A 30-Year Review of the Literature.

Periorbital dyschromia (POD) is a prevalent dermatologic problem with multifactorial etiology, making treatment outcomes inconsistent and unclear. To evaluate and compose a comprehensive review of topical ingredients proven to be effective in the treatment of POD. Scopus, PubMed, and OVID databases were searched in a span of 30 years through December 31, 2023, to identify articles with original findings of topical therapies for the treatment of POD. Findings of interest were objectively and subjectively measured regarding pigmentation, skin texture, aesthetic improvement, elasticity, hydration, and eye-bag volume. The database searches yielded 339 unique studies. After screening and review, 22 studies were included totaling 13 nonrandomized control trials, 7 randomized clinical trials, 1 retrospective case series, and 1 prospective single-arm study. Studies included all reported statistically significant results with topical therapies inclusive of acids, bark extract, bicyclic monoterpene diols, caffeine, combo ingredient serums, ethyl ximenynate, gentiopicroside, glycosaminoglycans, growth factors, topical PRP, and vitamins. The findings of this review suggest that topical therapies can be effective in the treatment of POD. Future trials should focus on delineating specific etiology of POD and evaluation of therapies specific to their cause.

Risk Factors for Developing Community-Acquired Hand Infections at a Large-Volume Urban Safety Net Hospital.

Hand infections represent a significant burden for both health care systems and their patients. Epidemiological understanding of community-acquired hand infections is limited. This study examined a cohort of hand infection patients at a large urban safety net hospital for characteristics that were associated with protective and/or risk factors for hand infections. We performed a retrospective chart review for all patients who required hand surgery consultation in the emergency department during a 1-year period (2021-2022). County-level population characteristics were obtained through the county-level data sources. We then performed a risk ratio (RR) analysis for demographic and socioeconomic characteristics. A total of 125 patients were included in the study cohort. Cisgender male (RR, 4.654; P < 0.001), Black (RR, 6.062; P < 0.001) and American Indian/Alaska Native (RR, 3.293; P = 0.041) patients were found to be overrepresented in our cohort when compared to county proportions, indicating an association with increased risk of hand infections. Patients between 35 and 49 years of age were also found to have an increased risk (RR, 1.679; P = 0.005). Age over 65 years, retirement, and employment were found to be protective factors (RR, 0.341 [ P = 0.001]; RR, 0.397 [ P = 0.043]; RR, 0.197 [ P < 0.001]). In contrast, unemployment and unstable housing (unhoused or shelter) were found to have strong harmful risk for necessitating hand infection consults (RR, 7.587 [ P < 0.001]; RR, 235.715 [ P < 0.001]; RR, 29.990 [ P < 0.001]). There are clear risk factors at play for hand infection incidence. We found that housing status, employment, race, gender, and age were some of the most important contributors for incidence. This information can assist clinicians and public officials in developing more specific screening algorithms and prevention tools to reduce systematic burden. Further studies are required to elucidate specific etiologies associated with hand infection risk.

A Clinical-Electrographic Profile of Neonatal Seizures and Their Etiologies in a Single Level III Neonatal Intensive Care Unit

Background: Seizures are the most frequent neurological emergency in neonatal period and can be associated with significant mortality and subsequent neuro-developmental disability if not recognized and managed early. Repaid identification of neonatal seizures and evaluation is critically required to identify and treat the underlying etiology. Clinicians face a major challenge in diagnosing and treating neonatal seizure because of inconspicuous clinical presentation, variable electro-clinical correlation. Assessing the combination of clinical presentation, etiological factors, different diagnostic tools, and treatments, can broaden the knowledge and understanding towards neonatal seizure providing better management and outcome. Objective: To study the characteristics of clinical and electrographic profile of neonatal seizure and the relations to their etiologies in neonatal intensive care unit. Methods: This is a descriptive cross sectional retrospective study of electronic health records with ICD- 10 diagnosis of neonatal seizure from birth to 28 days, who were admitted to neonatal intensive care unit at Sheikh Shakhbout Medical City between January 2020 to December 2021. Clinical data obtained including basic demographics: gender, gestational age, mode of delivery, birth weight, and Apgar score. Onset and type seizure, type of antiepileptic drugs administered, EEG findings, brain imaging, results of relevant laboratory tests and etiology of seizure were collected. Results: Total 31 neonates included in the study. Majority were male (71%), term (87%), and birth weight &gt;2,5 kg (90%). Seizure within 24 hours was 58% and semiology was focal clonic in 32% of patient. No events in EEG in 81% and 6% had electrographic seizure (n=2). 94 % were treated with anti-convulsant, 86% of them before EEG. The majority (86%) received phenobarbitone as 1st line treatment and 83% received monotherapy. Leading causes of seizure were HIE (48%) followed by Vascular causes (16%). Seizure within 24 hours caused mainly by HIE (61%) and 60% of neonates with vascular and all infectious and genetic causes had seizure after 24 hours. In vascular causes, (60%) presented with focal clonic seizure. 60% of Multifocal epileptiform activity seen in HIE whereas focal presented more in vascular patient (36%). In HIE cases, 53% had normal brain MRI and 47% were abnormal. All cases with vascular causes had diagnostic abnormal MRI. The majority of HIE cases (87%) and all vascular cases received monotherapy. Conclusion: In this descriptive study of neonatal seizure, certain demographic data, clinical and electrographic characteristics had established links to their etiologies. Clinical events captured during EEG with no electrographic seizure are classified as non-epileptic clinical phenomenon. Diagnostic utility of EEG is required in diagnosis of involuntary movements and avoid unnecessary anti-seizure medications. Understanding the clinical-electrographic profile of neonatal seizure helps in the early recognition of specific etiologies, allowing an early diagnosis by organized diagnostic approach and management.

Big data analysis reveals significant increases in complications, costs, and hospital stay in revision total knee arthroplasty compared to primary TKA.

Despite significant advancements in total knee arthroplasty (TKA), some patients require revision surgery (R-TKA) due to complications such as infection, mechanical loosening, instability, periprosthetic fractures, and persistent pain. This study aimed to explore the specific causes leading to R-TKA, associated complications, including infection, mechanical failure, and wound issues, as well as costs, mortality rates, and hospital length of stay (LOS) using data from a large national database. Data from the nationwide inpatient sample (NIS), the largest publicly available all-payer inpatient care database in the United States were analysed from 1 January 2016 to 31 December 2019. The study included 44,649 R-TKA cases, corresponding to 223,240 patients, with exclusions for nonelective admissions. Various statistical analyses were used to assess clinical outcomes, including in-hospital mortality, postoperative complications, LOS, and hospitalization costs. Among 2,636,880 TKA patients, 8.4% underwent R-TKA. R-TKA patients had higher rates of chronic conditions, including mental disorders (36.4%) and renal disease (9.9%). Additionally, these patients often experienced instability, necessitating revision surgery. Infection (22.3%) was the primary reason for R-TKA, followed by mechanical loosening (22.9%) and instability. Compared to primary TKA patients, R-TKA patients exhibited higher in-hospital mortality (0.085% vs. 0.025%), longer LOS (3.1 vs. 2.28 days), and higher total charges ($97,815 vs. $62,188). Postoperative complications, including blood transfusion (4.6% vs. 1.3%), acute kidney injury (4.4% vs. 1.8%), venous thromboembolism (0.55% vs. 0.29%), infection, and wound problems, were significantly higher in R-TKA patients. This study provides detailed insights into t LOS, costs, and complications associated with specific etiologies of revision TKA. Our findings emphasize the need for targeted preoperative optimization and patient education. This approach can help reduce the incidence and burden of R-TKA, improve patient care, optimize resource allocation, and potentially decrease the overall rates of complications in revision surgeries. Level III.

5086 Approaching the Enigma: Unveiling a Pituitary Stalk Lesion with Imaging and Hormonal Patterns

Abstract Disclosure: N. Rodriguez-Morales: None. P. Guido: None. Background: Pituitary stalk lesions (PSL) pose a diagnostic dilemma for endocrinologists. Multiple studies have attempted to associate hormonal imbalances and imaging patterns to a specific etiology (1,2). However, the diagnosis remains a mystery on many occasions. We describe a case of secondary hypogonadism and central DI attributed by a PSL. Clinical Case: A 39-year-old male presented with symptoms of hypogonadism and polyuria. Initial workup was consistent with secondary hypogonadism; decreased free and total testosterone levels (1.8 pg/dL and 9 ng/dL, n&amp;gt;35 pg/dL, n&amp;gt;250 ng/dL), LH (0.2 mIU/mL, n&amp;gt;1.5 mIU/mL), and FSH (&amp;lt;0.7 mIU/mL, n&amp;gt;1.6 mIU/mL). The remaining anterior pituitary hormones were within normal limits. The patient was also polyuric (6.5L urine output in 24hr). HgbA1c was normal. Urine Na, urine Osm demonstrated water diuresis (13 mmol/L and 54 mOsm/kg, respectively). A water deprivation test was performed. Initial urine Osm after water restriction was 119 mOsm/kg, which more than tripled to 575 mOsm/kg after administration of desmopressin, diagnostic of central DI. Pituitary MRI showed a well-circumscribed thickening of the pituitary stalk (6x6x5mm), with uniform enhancement. Evaluation for etiology to rule out germ cell tumor, lymphoma, sarcoidosis, opportunistic infection, tuberculosis, Langerhans cell histiocytosis showed a normal serum hCG, HIV, ACE, LDH, AFP. A lumbar puncture demonstrated normal cytology and was negative for AFB. Whole body bone scintigraphy and chest X-ray were normal. Pituitary deficits were treated with hormone replacement (testosterone and desmopressin), and a repeat MRI showed a stable lesion. Conclusion: Noninvasive testing is key to the evaluation of a pituitary stalk lesion. Careful consideration of inflammatory, infectious, and neoplastic etiologies along with attention to pituitary deficits is very important. Our patient most likely has a craniopharyngioma based on data from other case series (1,2). This case serves to bring additional data to the body of literature on this complicated clinical scenario.

Clinical and echocardiographic parameters associated with outcomes in patients with moderate secondary mitral regurgitation

BackgroundSignificant secondary mitral regurgitation (SMR) is known to be associated with worse prognosis. However, data focusing specifically on moderate SMR and associated risk factors are lacking. In the present study,...

Distribution of Fibrosis-4 index and vibration-controlled transient elastography-derived liver stiffness measurement for patients with metabolic dysfunction-associated steatotic liver disease in health check-up.

The multisociety consensus nomenclature has introduced steatotic liver disease (SLD) with diverse subclassifications, which are metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), alcohol-associated liver disease (ALD), specific etiology, and cryptogenic. We investigated their prevalence, as per the new definition, in individuals undergoing health check-ups. Additionally, we analyzed the distribution of Fibrosis-4 (FIB-4) index and vibration-controlled transient elastography (VCTE)-derived liver stiffness measurement (LSM) for MASLD. In this cross-sectional study, 6530 subjects undergoing a health check-up in Japan were included. Conventional B-mode ultrasound was carried out on all 6530 subjects, and those with MASLD underwent VCTE. The prevalence of SLD was 39.5%, comprising MASLD 28.7%, MetALD 8.6%, ALD 1.2%, specific etiology SLD 0.3%, and cryptogenic SLD 0.7%. Subjects with VCTE-derived LSM ≥8kPa constituted 2.1% of MASLD. FIB-4 ≥1.3 showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value for diagnosing VCTE-derived LSM ≥8kPa were 60.6%, 77.0%, 5.3%, and 98.9%, respectively. The referral rate to specialists was 23.8% using FIB-4 ≥1.30. "FIB-4 ≥1.3 in subjects <65years and FIB-4 ≥2.0 in subjects ≥65years" showed higher PPV (6.7%) and lower referral rate (17.1%) compared with FIB-4 ≥1.3, but the sensitivity (54.5%) did not show adequate diagnostic capability as a noninvasive test for diagnosing VCTE-derived LSM ≥8kPa. Acknowledging the selection bias in hepatology centers, we undertook this prospective health check-up study. Although the FIB-4 index proves to be a convenient marker, it might not perform well as a primary screening tool for liver fibrosis in the general population (UMIN Clinical Trials Registry No. UMIN000035188).

Evaluating the impact of artificial intelligence-based assessment of body composition on primary artificial urinary sphincter placement outcomes.

Sarcopenia, characterized by low muscle mass, and aberrant adiposity changes, including visceral fat accumulation, has been associated with impaired physiologic stress response and wound healing. Artificial urinary sphincter (AUS) placement is the preferred surgical treatment for men with severe post-prostatectomy incontinence. Given the higher rates of maladaptive body composition changes in this older, high comorbidity population, this study explores their impact on AUS outcomes. A retrospective analysis was performed including men who underwent primary AUS placement at the Mayo Clinic from 1999 to 2023 for post-prostatectomy incontinence and had cross sectional imaging available within 12 months prior to AUS implant. Sarcopenia and body composition were assessed from the available computed tomography (CT) scan using an algorithm that measures the area of different tissues at the L3 abdominal cross-section. The study investigated the association between sarcopenia [defined as skeletal muscle index (SMI) <52.4 cm2/m2] and adiposity (defined by total visceral and subcutaneous fat area) with all-cause reoperation, including specific etiologies of device infection/erosion, urethral atrophy, and device malfunction, using Cox proportional hazards models. There were 111 patients who had available imaging within the study timeframe, 61 (55%) of whom were classified as sarcopenic. Follow-up did not differ significantly between the two groups [2.11 (0.53-4.78) vs. 2.52 (0.36-5.80) years, P=0.52]. Sarcopenic patients had a lower body mass index (BMI) (29.1 vs. 32.7 kg/m2; P<0.001). No significant difference in overall device survival was observed between sarcopenic and non-sarcopenic patients (P=0.94) on Cox survival analysis. Sarcopenic patients had higher device infection rates, accounting for 16.7% (3/18) of device failures in the sarcopenic cohort compared to none in the non-sarcopenic cohort. Sarcopenia was prevalent among AUS patients but did not significantly impact overall device survival. These findings suggest that AUS placement may be feasible to perform in well-selected sarcopenic patients.