Specific Etiology Research Articles

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<0.0001), have a witnessed arrest (44.6%, p<0.0001) and have an initial shockable rhythm (48.2%, p<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.

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.

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.

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).

Rapid-onset methemoglobinemia from traditional-medicine-induced potassium nitrate poisoning: successful treatment with methylene blue—a case report

BackgroundPotassium nitrate poisoning is a rare but potentially serious condition that can result in methemoglobinemia and subsequent cyanosis. This case report presents a unique instance of rapid-onset methemoglobinemia resulting from the ingestion of a traditional medicine preparation containing potassium nitrate, known as “kalmi shora.”Case presentationA 14-year-old Pakistani boy reported to the emergency department with a history of sudden-onset headache, drowsiness agitation, irritability, and generalized cyanosis. Pulse oximetry showed a concerning oxygen saturation level of 58%, whereas arterial blood gas analysis revealed a normal partial pressure of oxygen (90 mmHg). The profile of abrupt onset of symptoms, generalized cyanosis, and the discrepancy between the partial pressure of oxygen and oxygen saturation readings necessitated a comprehensive assessment including inquiries into potential toxins. The peculiar appearance of the blood, resembling chocolate in color, further indicated the possibility of methemoglobinemia. The patient was successfully treated with methylene blue, leading to a prompt resolution of symptoms.ConclusionThis case highlights the significance of considering toxin exposures, such as traditional-medicine-induced poisoning, in emergency settings. The report contributes to the medical literature by highlighting the potential risks associated with traditional remedies and emphasizes the critical role of prompt diagnosis and intervention in optimizing patient outcomes. Recognition of the specific etiology of methemoglobinemia, in this case, traditional medicine ingestion, is essential for effective management in emergency medicine.

Secondary hypogammaglobulinemia: diagnosis and management of a pediatric condition of clinical importance.

Secondary hypogammaglobulinemia, or low serum immunoglobulins, is associated with a variety of medications or medical conditions and may be symptomatic and lead to increased infectious risk. There is limited data regarding the study of acquired, or secondary, hypogammaglobulinemia (SHG) in pediatrics. The data to date has suffered from methodologic issues including retrospective study design, lack of baseline immunoglobulin measurements, and limited longitudinal follow-up. There is emerging research on the impact of B-cell depleting therapies, specifically rituximab and chimeric antigen T-cells, along with other autoimmune and malignant disease states, in the development of SHG in pediatric patients. This review will also summarize other relevant pediatric conditions related to SHG. The clinical relevance of SHG in pediatrics is increasingly appreciated. Improved understanding of the specific etiologies, risk factors, and natural history of SHG have informed screening and management recommendations.

Appropriate use of wearable defibrillators with multiparametric evaluation to avoid unnecessary defibrillator implantation

IntroductionWearable cardioverter-defibrillators (WCD) have emerged as a valuable tool in the management of patients at risk for life-threatening arrhythmias. These devices offer a non-invasive and temporary solution, providing continuous monitoring...

Study of Number of Cotyledons of Placenta in Different Gestational Age Groups of Healthy Pregnant Mother of Bangladesh

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: The placenta has drawn attention as an important indicator of intrauterine condition of fetus and maternal diseases. The study of number of cotyledons of placenta in different gestational age groups of healthy pregnant mother of Bangladesh is cross sectional descriptive study. &amp;lt;i&amp;gt;Aim of the study&amp;lt;/i&amp;gt;: The aim of the study was to study the variation of number of cotyledons of placenta in deferent state of gestational ages of healthy pregnant mother. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt;: This cross sectional descriptive study was conducted in the Department of Anatomy, Mymensingh Medical College, Mymensingh, from January 2018 to December 2018. This study was performed on 80 human placentae. &amp;lt;i&amp;gt;Result&amp;lt;/i&amp;gt;: The mean (± SD) number of cotyledon of the placenta was 18.56 (±2.15) in group A, 21.21 (±3.11) in group B and 23.75 (±3.45) in group C. The mean number of cotyledon of the placenta was maximum in group C (23.75) and was minimum in group A (18.56). It was also observed that the mean number of cotyledon of the placenta increased with gestational age. The mean difference of the number of placental cotyledons between groups A and C was statistically moderately significant (p &amp;lt; 0.05) but between A and B and B and C was statistically non-significant (p &amp;gt; 0.05). &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt;: The placental examination becomes important as it will help in understanding the specific etiologies of adverse outcome. This study has shown that the mean number of cotyledon of the placenta increased with gestational age.

Nurture growth: Ketogenic diet therapy and growth velocity in infants under 12 months with epilepsy − A systematic review and infant data study

Ketogenic diet therapy (KDT) is well established for the treatment of early epileptic encephalopathies and specific aetiologies; however, the impact on growth in infancy remains controversial. Our aim was to examine the influence of early KDT on growth velocity and height percentiles completing two tasks. First, we systematically reviewed the literature on growth in infants younger than 12 months. Second, we analysed data from our prospective database, including infants <12 months (n = 63) treated with KDT. The literature review (n = 7) remains descriptive and includes growth percentiles and z-scores as growth velocity was not described. Studies up to 2010 used fasting, calorie restrictions, and ratios >3:1. In individual cases, significant growth delays were found; other authors did not find any changes in growth parameters. Study endpoints in our own cohort included z-scores of growth velocity, standard deviation (SD) of height, weight, BMI, deviation from individual height percentile, and daily macronutrient intake. The median z-score of growth velocity was 1.03 (first year of life). After three months, median daily intake of protein and energy was 1.68 g/kg and 85 kcal/kg. Until the age of one year, neither growth velocity nor individual growth percentiles decreased. Infants showed distinct growth improvements at three months, likely due to continuous nutritional monitoring and reduction in seizures. In the second year of life, z-scores of growth velocity decreased in patients still receiving KDT (from 1.03 at 12 months to −1.5 at 24 months). Furthermore, younger age at epilepsy onset and at KDT start correlated with slower growth velocities in the first year of life.With appropriate nutritional intake and monitoring, KDT does not reduce growth in the first year of life. Future directions might be to study the impact of KDT on growth velocity and growth hormones throughout childhood.

International treatment outcomes of neonates on extracorporeal membrane oxygenation (ECMO) with persistent pulmonary hypertension of the newborn (PPHN): a systematic review

BackgroundPPHN is a common cause of neonatal respiratory failure and is still a serious condition and associated with high mortality.ObjectivesTo compare the demographic variables, clinical characteristics, and treatment outcomes in neonates with PHHN who underwent ECMO and survived compared to neonates with PHHN who underwent ECMO and died.MethodsWe adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of PPHN in neonates who underwent ECMO, published from January 1, 2010 to May 31, 2023, with English language restriction.ResultsOf the 5689 papers that were identified, 134 articles were included in the systematic review. Studies involving 1814 neonates with PPHN who were placed on ECMO were analyzed (1218 survived and 594 died). Neonates in the PPHN group who died had lower proportion of normal spontaneous vaginal delivery (6.4% vs 1.8%; p value > 0.05) and lower Apgar scores at 1 min and 5 min [i.e., low Apgar score: 1.5% vs 0.5%, moderately abnormal Apgar score: 10.3% vs 1.2% and reassuring Apgar score: 4% vs 2.3%; p value = 0.039] compared to those who survived. Neonates who had PPHN and died had higher proportion of medical comorbidities such as omphalocele (0.7% vs 4.7%), systemic hypotension (1% vs 2.5%), infection with Herpes simplex virus (0.4% vs 2.2%) or Bordetella pertussis (0.7% vs 2%); p = 0.042. Neonates with PPHN in the death group were more likely to present due to congenital diaphragmatic hernia (25.5% vs 47.3%), neonatal respiratory distress syndrome (4.2% vs 13.5%), meconium aspiration syndrome (8% vs 12.1%), pneumonia (1.6% vs 8.4%), sepsis (1.5% vs 8.2%) and alveolar capillary dysplasia with misalignment of pulmonary veins (0.1% vs 4.4%); p = 0.019. Neonates with PPHN who died needed a longer median time of mechanical ventilation (15 days, IQR 10 to 27 vs. 10 days, IQR 7 to 28; p = 0.024) and ECMO use (9.2 days, IQR 3.9 to 13.5 vs. 6 days, IQR 3 to 12.5; p = 0.033), and a shorter median duration of hospital stay (23 days, IQR 12.5 to 46 vs. 58.5 days, IQR 28.2 to 60.7; p = 0.000) compared to the neonates with PPHN who survived. ECMO-related complications such as chylothorax (1% vs 2.7%), intracranial bleeding (1.2% vs 1.7%) and catheter-related infections (0% vs 0.3%) were more frequent in the group of neonates with PPHN who died (p = 0.031).ConclusionECMO in the neonates with PPHN who failed supportive cardiorespiratory care and conventional therapies has been successfully utilized with a neonatal survival rate of 67.1%. Mortality in neonates with PPHN who underwent ECMO was highest in cases born via the caesarean delivery mode or neonates who had lower Apgar scores at birth. Fatality rate in neonates with PPHN who underwent ECMO was the highest in patients with higher rate of specific medical comorbidities (omphalocele, systemic hypotension and infection with Herpes simplex virus or Bordetella pertussis) or cases who had PPHN due to higher rate of specific etiologies (congenital diaphragmatic hernia, neonatal respiratory distress syndrome and meconium aspiration syndrome). Neonates with PPHN who died may need a longer time of mechanical ventilation and ECMO use and a shorter duration of hospital stay; and may experience higher frequency of ECMO-related complications (chylothorax, intracranial bleeding and catheter-related infections) in comparison with the neonates with PPHN who survived.

Etiology, Characteristics, and Outcomes of Neonatal Liver Failure: Lessons Learned Over the Last 3 Decades

To evaluate trends in etiology and outcomes of neonatal liver failure (NLF) over 30years retrospectively at a single institution. Inclusion criteria for this retrospective cohort study were babies presenting at a chronological age of ≤28days between 1991 and 2020 with prothrombin time≥20seconds and biochemical liver injury. Demographics, etiology, laboratory investigations, need for extrahepatic organ support, acute kidney injury, and intervention with liver transplant (LT) were recorded. Survival outcomes were measured as discharge from the hospital alive with native liver or LT. The study period was stratified into 3 10-year blocks. Trends were analyzed for hospital admissions, etiology, and survival outcomes. One hundred twenty-six babies met the NLF criteria. Admissions to the hospital increased from 21 in 1991-2000 to 65 in 2011-2020. An increasing trend in infectious and metabolic causes, while a decreasing trend in indeterminate etiology, was noted. Survival with native liver improved from 23.8% in 1991-2000 to 55.4% in 2011-20 (P=.021), and mortality reduced from 52.4% to 35.4% during the same periods (P=.213). Twenty-three (18.2%) neonates received LT. Post-LT survival outcomes were 100% for gestational alloimmune liver disease, 66.6% in the indeterminate group, and 25% for herpes simplex virus. Specific etiologies (gestational alloimmune liver disease, OR=0.07 [0-0.77, P=.048]), presence of acute kidney injury (OR=6.22 [1.45, 29.38, P=.015]) and need for inotropes (OR=6.22 [1.45, 29.38, P=.028]) influenced mortality in multivariable logistic regression analysis. In the last 30years, advances in diagnosis, treatment, and increasing experience with LT have improved survival in NLF.

Esophageal Atresia with Tracheoesophageal Fistula Is Associated with Consanguinity

Objectives and StudyEsophageal atresia with tracheoesophageal fistula (EA-TEF) is a rare congenital malformation. The incidence of TEF is 1.3-4.6 cases per 10,000 live births. The specific etiology of EA-TEF is unknown. Environmental risk factors, such as maternal medication use and alcohol consumption during pregnancy, are suggested. Genetic factors have also been described, especially among syndromic types, such as Down syndrome, but less among non-syndromic types. The aim of the study is to examine the association between non-syndromic EA-TEF and consanguinity. MethodsA retrospective study comparing the incidence of EA-TEF between low-consanguineous Jewish population and high-consanguineous Bedouin population. All patients were treated at Soroka University Medical Center, the only tertiary medical center in southern Israel. ResultsDuring the years 2000-2022, 579,130 children were born in southern Israel, 386,915 (66.8%) were Jewish, and 192,215 were Bedouin Muslims. A total of 96 patients were diagnosed with EA-TEF, 83 of them were non-syndromic. The incidence of EA-TEF was 1.66 cases per 10,000 live births and was statistically higher among the Bedouin population (3 vs. 0.95 cases per 10,000 live births, P<0.001). The consanguinity rate among the Bedouin group was higher compared with the Jewish (67.8% vs 0% P<0.001). There were no differences in other risk factors. ConclusionThe incidence of EA-TEF is exceptionally higher among the Bedouin population that lives in the same geographic region and has the same medical access as the Jewish population, proposing consanguinity as an important/essential risk factor for EA-TEF.

The Approach to Altered Mental Status in the Intensive Care Unit.

Altered mental status (AMS) is a syndrome posing substantial burden to patients in the intensive care unit (ICU) in both prevalence and intensity. Unfortunately, ICU patients are often diagnosed merely with syndromic labels, particularly the duo of toxic-metabolic encephalopathy (TME) and delirium. Before applying a nonspecific diagnostic label, every patient with AMS should be evaluated for specific, treatable diseases affecting the central nervous system. This review offers a structured approach to increase the probability of identifying specific causal etiologies of AMS in the critically ill. We provide tips for bedside assessment in the challenging ICU environment and review the role and yield of common neurodiagnostic procedures, including specialized bedside modalities of diagnostic utility in unstable patients. We briefly review two common etiologies of TME (uremic and septic encephalopathies), and then review a selection of high-yield toxicologic, neurologic, and infectious causes of AMS in the ICU, with an emphasis on those that require deliberate consideration as they elude routine screening. The final section lays out an approach to the various etiologies of AMS in the critically ill.

Comprehensive molecular characterization of collecting duct carcinoma for therapeutic vulnerability

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.