Definite Cause Research Articles

Evaluation of demographic, clinical, and aetiological data of patients admitted to cardiology clinics and diagnosed with left ventricular hypertrophy in Turkish population (LVH-TR)

Background Left ventricular hypertrophy (LVH) is potentially modifiable cardiovascular risk factor often overlooked in clinical practice. For this reason, we planned to LVH-TR (Left Ventricular Hypertrophy in Turkish Population) trial to determine the aetiological causes and demographic characteristics of LVH patients. Methods Our study was a multicentre, national, observational study and included 886 patients who applied to the cardiology clinics in 22 centres between February 2020 and August 2021. In the initial evaluation, the Fabry disease (FD) and cardiac amyloidosis (CA) algorithm was followed in patients whose definitive etiologic cause(s) could not be identified. Results The most common aetiological causes of LVH in our study were hypertension with a rate of 56.6%, heart valve disease with 8.2%, and hypertrophic cardiomyopathy with 7.5%. Athlete’s heart was detected in eight patients, LV non-compaction was detected in four patients. The rate of LVH of unknown cause was 18.8%. FD was suspected in 143 patients, and CA was suspected in 16 patients. There were 43 (4.85%) patients with low α-galactosidase A enzyme levels. GLA gene mutation analysis was positive in 1.58% of all patients, and these patients were diagnosed with FD, and 15 (1.69%) patients were diagnosed with CA by endomyocardial biopsy method. Conclusion In the aetiology of LVH, the rate of LVH of unknown cause was high. FD and CA should be considered primarily in this patient group. Early diagnosis of the disease by following the schemes leading to FD and CA was essential in starting treatment before the progression of the disease.

S1941 Acute Pancreatitis Following a Lower Extremity Angioplasty

Introduction: Acute pancreatitis affects a significant population globally. Usual etiologies are gallstones, alcohol, hypertriglyceridemia, medications; less frequent are trauma, hypercalcemia, infections, toxins, ischemia, anatomic anomalies, vasculitis, and idiopathic. Pancreatitis post coronary intervention is an uncommon cause with only 19 published cases in the last two decades. Being cognizant of this etiology is important given the increasing number of patients undergoing angiography. Case Description/Methods: An 81-year-old female with hypertension, diabetes, peripheral arterial disease, prior cholecystectomy underwent left lower extremity angioplasty at an outside center. Within a few hours, she started having severe epigastric pain radiating to her back, nausea, vomiting and loose bloody stool. She presented to the emergency department 24 hours after symptom onset. Epigastric tenderness was present on exam. Labs revealed leukocytosis (24,450/µL),elevated lipase (1410 U/L), elevated creatinine (1.3 mg/dL), lactate (3.1 mmol/L), calcium 9.4 mg/dL and triglycerides 161 mg/dL. Incidentally, found to be positive for COVID-19. Normal common bile duct diameter seen on sonogram. CT angiogram of the abdomen/pelvis showed acute pancreatitis, duodenal and central small bowel enteritis (Figure). She was not on any medications known to cause pancreatitis and denied alcohol use. Patient improved with analgesics and intravenous fluids. She had no recurrence of bloody stools and hemoglobin remained stable. On day 4, she was able to tolerate a regular diet, and leukocyte count and creatinine normalized. Patient did not have any COVID respiratory symptoms, and was discharged. Discussion: Given the temporal association to angioplasty and no other identifiable cause, acute pancreatitis was presumed to be due to the contrast used during angioplasty. Other possibilities included cholesterol embolism but no peripheral signs of cholesterol embolism were seen. Patient was an asymptomatic COVID-19 case. Although, there are case series of pancreatitis due to COVID, those were found in very sick symptomatic patients. On review of literature, cholesterol embolism was identified as a definite cause only on autopsy or laparotomy (Table). Other possible mechanisms are: high viscosity of the contrast media leading to ischemia and necrosis, contrast causing NF-κB activation followed by epithelial damage, and vasospasm. Pancreatitis after coronary angiography is rare, nonetheless, an important differential especially if there is a temporal relationship.Figure 1.: CT scan (abdomen) of our patient demonstrating acute pancreatitis. Table 1. - Current literature reports on acute pancreatitis after coronary angiography/angioplasty S. NO. YEAR AUTHOR PROCEDURE ETIOLOGY TIME BETWEEN PROCEDURE AND SYMPTOM ONSET CONTRAST USED VOLUME OF CONTRAST(mL) 1 1994 Orvar et al1 Angiography Cholesterol emboli detected on autopsy 14 hours Not Mentioned 80-160 2 1994 Orvar et al1 Angiography Cholesterol emboli detected on autopsy Immediately Not Mentioned 80-160 3 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 4 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 5 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 6 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 7 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 8 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 9 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 10 1994 Orvar et al1 Angiography Contrast-Induced Not Mentioned Not Mentioned 80-160 11 1994 Orvar et al1 Angiography Cholesterol emboli detected on autopsy Not Mentioned Not Mentioned 80-160 12 1994 Orvar et al1 Angiography Cholesterol emboli detected on autopsy Not Mentioned Not Mentioned 80-160 13 2013 Gorges et al2 Angiography Contrast-Induced 1 hour Iopamidol 120 14 2014 Abstract 343, Journal of Hospital Medicine3 Angioplasty Contrast-Induced Not Mentioned Not Mentioned Not Mentioned 15 2017 Hajimaghsoudi et al4 Angiography Contrast-Induced 48 hours Visipaque(Iodixanol) 100 16 2020 Rafiq et al5 Angioplasty Contrast-Induced Immediately Ioversal 150 17 2020 Mui et al6 Angioplasty Contrast-Induced Immediately Omnipaque(Iohexol) 120 A total of 19 cases were identified. However, only seventeen cases have been shown in the table. Due to inability to get permission for reuse, the remaining 2 cases have not been shown. 1 - Orvar K, Johlin FC. Atheromatous embolization resulting in acute pancreatitis after cardiac catheterization and angiographic studies. Arch Intern Med 1994;154:1755–61 2 - Gorges R, Ghalayini W, Zughaib M. A case of contrast-induced pancreatitis following cardiac catheterization. J Invasive Cardiol 2013;25:E203–4. 3 - An Unusual Source of Abdominal Pain.Abstract published at Hospital Medicine 2014, March 24-27, Las Vegas, Nev.. Abstract 343 Journal of Hospital Medicine, Volume 9, Suppl 2. https://shmabstracts.org/abstract/an-unusual-source-of-abdominal-pain/ 4 - Hajimaghsoudi M, Zeinali F, Mansouri M, et al. Acute necrotizing pancreatitis following coronary artery angiography: a case report. ARYA Atheroscler 2017;13:156–8. 5 - S1558 A Rare Case of Pancreatitis Secondary to Coronary Angiogram Dye. Rafiq, Rehan; Rafiq, Ahmad.The American Journal of Gastroenterology: October 2020 - Volume 115 - Issue - p S791doi: 10.14309/01.ajg.0000708280.94586.25 6 - Mui JJ, Shamavonian R, Thien KCP. Acute pancreatitis following coronary angiography: case report and review of contrast-induced pancreatitis. Int Surg J 2020;7:870-2

Inconsistent discharge diagnoses for young cardiac arrest episodes: insights from a statewide registry.

Administrative coding of out-of-hospital cardiac arrest (OHCA) is heterogeneous, with the prevalence of noninformative diagnoses uncertain. To characterize the prevalence and type of non-informative diagnoses in a young cardiac arrest population. Hospital discharge diagnoses provided to a statewide OHCA registry were characterised as either 'informative' or 'noninformative.' Informative diagnoses stated an OHCA had occurred or defined OHCA as occurring due to coronary artery disease, cardiomyopathy, channelopathy, definite noncardiac cause, or no known cause. Noninformative diagnoses were blank, stated presenting cardiac rhythm only, provided irrelevant information or presented a complication of the OHCA as the main diagnosis. Characteristics of patients receiving informative versus noninformative diagnoses were compared. Of 1479 patients with OHCA aged 1 to 50 years, 290 patients were admitted to 15 hospitals. Ninety diagnoses (31.0%) were noninformative (arrest rhythm=50, blank=21, complication=10 and irrelevant=9). Two hundred diagnoses (69.0%) were informative (cardiac arrest=84, coronary artery disease=54, noncardiac diagnosis=48, cardiomyopathy=8, arrhythmia disorder=4 and unascertained=2). Only 10 diagnoses (3.5%) included both OHCA and an underlying cause. Patients receiving a noninformative diagnosis were more likely to have survived OHCA or been referred for forensic assessment (P= 0.011) and had longer median length of stay (9 vs 5 days, P= 0.0019). Almost one third of diagnoses for young patients discharged after an OHCA included neither OHCA nor any underlying cause. Underestimating the burden of OHCA impacts ongoing patient and at-risk family care, data sampling strategies, international statistics and research funding.

DARI DARUSSUFI MENJADI TARUNA RABBANI: SEBUAH STUDI TENTANG PERKEMBANGAN SEBUAH PESANTREN (2000-2020)

This study examines the history of an educational institution regarding the formation of a boarding school in Nagari Koto Sani and its development from Darussufi to Taruna Rabbani. This study uses the historical writing method with four stages, namely: heuristics, source criticism, interpretation and historiography. The result of this research is the formation of Islamic boarding schools in Nagari Koto Sani starting from da'wah activities which were pioneered by Pourku Syekh Muhammad Ali Hanafiah Ar Rabbani. Da'wah activities are carried out by spreading to several areas by carrying out recitation activities assisted by students and friends. Da'wah activities for areas outside the city of Padang were entrusted to Buya Hendra to develop to rural areas in Nagari Koto Sani. The formation of the Islamic boarding school in Nagari Koto Sani began in 2000. The construction of the Islamic boarding school was carried out in mutual cooperation with the main funding source from the recitation congregation. The Islamic boarding school since its inception has undergone four name changes from Darussufi, Tasawuf Rabbani, Rabbani and Taruna Rabbani which were founded on waqf land. The change in the name of the Islamic boarding school does not have a definite cause, but follows the times based on the demands of the needs which then develops formal educational institutions with elementary, junior high, high school levels.
 
 Keywords: Development, Islamic Boarding School, Darussufi, Sufism Rabbani, Rabbani, Taruna Rabbani

Elements That Influence the Development of Attention Deficit Hyperactivity Disorder (ADHD) in Children.

Various factors may have a role in the development of attention deficit hyperactivity disorder (ADHD). Although the specific pathophysiology of this disease is still not entirely understood, it is believed to be caused by a mix of genetic, maternal, dietary, and environmental factors. The effect of these factors can determine the severity of ADHD; for example, some of them are dose-dependent, but there is a typical pattern that all are known to be associated with either early childhood exposure or maternal exposure during pregnancy. Some factors share a similar mechanism of affecting pathways and increasing the risk of ADHD.ADHD is not a disorder that can be detected before symptoms appear in a child, making it more challenging to anticipate even if a child has been exposed to a known trigger. Environmental pollutants were investigated, and it was shown that there was a link between ADHD in childhood and exposure to pollutants throughout childhood or during pregnancy. It is well known that maternal health is a significant factor in the unborn child's development in many health aspects. The central nervous system (CNS) is a primary system that can suffer irreversible damage from health conditions, stress, depression, or specific nutritional deficiency when the pregnant mother is subjected to these conditions. Even though numerous studies have been conducted to investigate the probable causes of ADHD, with some of them having robust findings, no conclusive explanation can be provided to identify a definitive cause or a risk factor.

CD123-directed allogeneic chimeric-antigen receptor T-cell therapy (CAR-T) in blastic plasmacytoid dendritic cell neoplasm (BPDCN): Clinicopathological insights

PurposeBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy associated with overexpression of CD123. Allogeneic chimeric antigen receptor T cells (CAR-T) directed against CD123 in BPDCN have been studied in clinical trials. We performed post-mortem analysis of a patient treated with anti-CD123 CAR-T to elucidate cause of death, development of cytokine release syndrome (CRS), and tissue distribution of UCART123 cells. MethodsA post-mortem multidisciplinary clinicopathologic analysis was performed with digital droplet polymerase chain reaction of isolated blood and tissue ribonucleic acid (RNA) to evaluate tissue distribution of infused CAR-T. Multiparameter flow cytometry for detection of CAR-T was used for whole blood samples. Cytokine levels in plasma were measured using multiplex bead assay. Gene expression profiling on isolated RNA was performed using semi-custom Nanostring immune gene panel and RNA-sequence method. RNA in situ hybridization was performed using CAR-specific probe. ResultsThe patient developed severe clinical CRS refractory to corticosteroids, tocilizumab, and lymphodepletion. Despite significant reduction in BPDCN lesions, the patient passed away on day 9 of CAR-T. Autopsy results show that following lymphodepletion and UCART123 administration, the patient remained severely lymphopenic with few UCART123 cells detected, predominantly localized to spleen. ConclusionsNo definitive cause of death was determined, but we hypothesized that the patient may have succumbed to CAR-T-mediated cardiopulmonary toxicity. UCART123 cells displayed low overall distribution, with predominance in immune organs and tissues. Mechanism of CRS development is still poorly understood in patients receiving CAR-T therapy. Future directions in the field developing CD123-targeted agents in BPDCN are discussed.

Extensive Spinal Epidural Hematoma as the Cause of Postpartum Headache and Neck Pain After Epidural Anesthesia: a Case-Based Report

Spinal epidural hematomas (SEH) are a rare hemorrhagic event occurring after trauma, epidural anesthesia, or operative inventions. However, in 40–50% of cases, they occur spontaneously. Spontaneous spinal epidural hematomas (SSEH) are rare in occurrence with an estimated incidence of 1 case per million annually. Pregnancy is an independent risk factor. Sudden neck or back pain, often in combination with a rapid onset of neurological symptoms, is the most common presentation of SEH (1). A 36-year-old Caucasian female with rheumatoid arthritis (RA) presented to the emergency department approximately 48 h after an uncomplicated vaginal delivery. She sought medical attention due to constant headaches and neck pain that started during active labor. An MRI of the spine revealed an extensive SEH spreading from C1 to L5. The patient was without neurological symptoms or deficits and was successfully treated conservatively without any sequelae. Even though the definitive cause of this case of SEH will remain unknown, several possible synergistic mechanisms have been identified. These include female gender, full-term pregnancy, physical activity with increased intraabdominal pressure (i.e., Valsalva maneuver), systemic administration of platelet aggregation inhibitor (PAI), and iatrogenic manipulation such as spinal epidural anesthesia. Even though autoimmune and inflammatory disorders have been described in the literature to be rare sources of hemorrhage in the spinal canal, it is unclear whether the patient’s RA should be regarded as an individual risk factor.Key FactsSpinal epidural hematomas are a rare hemorrhagic event characterized by an accumulation of blood between the vertebrae and the dura of the spinal canal, and can be a clinical challenge to diagnose due to the insidious presentation, with symptoms ranging from asymptomatic to non-specific head or neck pain, or neurological deficits.The etiology of spontaneous spinal epidural hematomas remains largely unknown, although there are many predisposing factors, including vascular malformation, anticoagulation therapy, trauma, iatrogenic manipulations, and hypertension.The differential diagnosis to spinal epidural hematomas are several, e.g., meningitis, migraine, subarachnoid or intracranial hemorrhage, pituitary apoplexy, venous sinus thrombosis, and thrombosis, and radiological examination is key to diagnose and map the distribution of the hemorrhage.

Bilateral Vestibular Hypofunction in a Tertiary Dizziness Center: Occurrence and Etiology.

Background:The primary goal of this study was to determine the occurrence of bilateral vestibular hypofunction in a specialized dizziness clinic and to assess the etiology in patients diagnosed with bilateral vestibular hypofunction. Secondary goal was to find out if the diagnosis was already made before the patient was seen at our clinic.Methods:A retrospective cohort study, including patients who visited our specialized dizziness center between January 1, 2008, and December 31, 2018, fulfilling the criteria for bilateral vestibular hypofunction according to the Classification Committee of the Bárány Society (2017). Data were collected regarding symptoms, causes, and vestibular function.Results:In total, 126 patients met our initial inclusion criteria, of which 103 patients met the Classification Committee of the Bárány Society criteria for bilateral vestibular hypofunction, so patients with bilateral vestibular hypofunction comprised 0.9% of the total population seen at our clinic. Mean age was 65.2 years and 49.5% were female. In only 29.1% of patients, the diagnosis was already made elsewhere. A definite cause was identified in 39.8%, the most common cause being ototoxicity.Conclusion:About 1% of the patients visiting our dizziness clinic has bilateral vestibular hypofunction. In our patient population, ototoxicity was the most common cause of bilateral vestibular hypofunction, and in more than 40%, the cause remains unknown. In the majority of the cases, the diagnosis of bilateral vestibular hypofunction was first made at our clinic and not by the referring general practitioner or specialist. When using the Classification Committee of the Bárány Society criteria for bilateral vestibular hypofunction and presbyvestibulopathy, some patients with bilateral vestibular weakness and complaints cannot be categorized in either group.

Methamphetamine-associated pulmonary arterial hypertension.

Methamphetamine use is increasing in popularity globally, and chronic users suffer from various drug toxicities, including the development of pulmonary arterial hypertension. Although it was previously thought to be a possible cause of pulmonary arterial hypertension, as of the sixth World Symposium on Pulmonary Hypertension, methamphetamine use is now recognized as a definite cause of pulmonary arterial hypertension. This review will discuss the history of methamphetamine use, the link between methamphetamine use and pulmonary arterial hypertension, and the clinical characteristics of patients with pulmonary hypertension from methamphetamine use. The mechanism by which methamphetamine abuse leads to pulmonary hypertension is unclear. However, recent studies have suggested that reduced expression of carboxylesterase 1 may be implicated due to maladaptation to the environmental injury of methamphetamine abuse. Based on the report of two recent cohort studies, patients with methamphetamine-associated pulmonary arterial hypertension have a worse functional class, less favorable hemodynamics, impaired health-related quality of life, increased health-care utilization, and attenuated survival, as compared to those with idiopathic pulmonary arterial hypertension. Future studies are needed to better understand the mechanism by which methamphetamine use leads to pulmonary arterial hypertension. Methamphetamine-associated pulmonary arterial hypertension likely represents a more advanced disease state than idiopathic pulmonary arterial hypertension, however, it is treated less aggressively in clinical practice.

A patient with CD4+ T cells deficiency and HIV negative with pulmonary tuberculosis, tuberculous pleuritis and meningitis tuberculosis

Background: CD4+ T cells deficiency generally occurs in human immunodeficiency virus (HIV) patients, leading to some infections such as pulmonary and extrapulmonary tuberculosis. A rare case of decreased CD4+ T cells is idiopathic CD4+ T cell lymphocytopenia, a rare and unexplained immunodeficiency syndrome with no evidence of HIV infection. In this case report, we are reporting a patient with CD4+ T cells deficiency, pulmonary tuberculosis, pleuritis tuberculosis, and meningitis with HIV test negative. Case Presentation: A 58-year-old male was referred to the Emergency Department of Dr. Soetomo General Hospital with a gradual decrease of consciousness following six days of hospitalization at a private hospital. During hospitalization, one liter of fluid was evacuated from the right lung and analyzed, revealing tuberculosis infection. History of diabetes, hypertension, stroke, hepatitis, and cardiovascular disease was denied. The patient also never had chemotherapy or radiation treatment. Based on history taking, physical examination, and laboratory results, this patient has been diagnosed new case of pulmonary tuberculosis with deficiency CD4+ T cells and altered consciousness et causes meningitis tuberculosis with pleurisy tuberculosis. After 32 days of hospitalization with anti-mycobacterium therapy, the patient was improved and was discharged. Conclusion: This case highlights the challenges of having the definitive cause of CD4+ T cells deficiency either active tuberculosis infection or idiopathic CD4+ lymphocytopenia. Therefore, serial analyses of CD4+ T cells are advised on the patient during the treatment with anti-tuberculosis drug.

Structural Cardiac Abnormalities in Patients with Atrial Fibrillation/Flutter and Myocardial Injury

BackgroundHigh-sensitivity cardiac troponin (hs-cTnT) is often increased in patients with atrial fibrillation/flutter, portending a poor prognosis. The etiologies for these increases have not been systematically investigated. Our aim was to define prevalence/significance of structural cardiac abnormalities in patients with atrial fibrillation/flutter and high-sensitivity cardiac troponin T (hs-cTnT) increases. MethodsThis is a retrospective observational cohort study of patients with atrial fibrillation/flutter diagnosis with hs-cTnT measurements, echocardiograms, and coronary angiograms. Myocardial injury was defined as hs-cTnT >10 ng/L for women and >15 ng/L for men. Cases with myocardial injury were adjudicated according to the Fourth Universal Definition of Myocardial Infarction. ResultsPatients with definite causes for increased hs-cTnT (n = 875) were tabulated but not evaluated further; common diagnoses were type 1 myocardial infarction, critical illness, and known heart failure. Of the remaining 401, increased hs-cTnT was present in 336 (84%) patients. Of those, 78% had nonischemic myocardial injury, the remaining (n = 75, 22%) had type 2 myocardial infarction. Patients with elevated hs-cTnT had greater left ventricular mass index, left ventricular filling pressures, and right ventricular systolic pressure. They more frequently had significant coronary artery disease (47% vs 31%, P = .016), especially in type 2 myocardial infarction. With logistic regression, age, sex (F), diabetes, left ventricular mass index, e′ medial velocity, and right ventricular systolic pressure were independent determinants of myocardial injury. One-year mortality was higher in patients with myocardial injury. ConclusionsStructural heart abnormalities are common in patients with atrial fibrillation/flutter and increased hs-cTnT. Causes of myocardial injury should be elucidated in each patient to craft appropriate therapies.

Transient respiratory arrest after quadratus lumborum block in a dog

AbstractA 13.9 kg, 4‐year‐old, male cocker spaniel dog was scheduled for cystotomy. Premedication consisted of intravenous medetomidine (5 µg/kg), induction with propofol (1 mg/kg, intravenous) and anaesthesia maintenance with isoflurane in O2 100%. A medetomidine constant‐rate infusion (1 µg/kg/h) was administered throughout. A bilateral quadratus lumborum block with 3 ml of 0.5% bupivacaine (each side) was performed, and intermittent positive‐pressure ventilation was initiated. At the end of the surgery, medetomidine constant‐rate infusion and intermittent positive‐pressure ventilation ceased. The patient remained in apnoea and developed severe hypercapnia (end‐tidal carbon dioxide: 12 kPa). Thirty minutes after isoflurane discontinuation, respiratory muscles movement started. Three days before, the dog underwent a mini‐hemilaminectomy (similar anaesthetic protocol) without complications. Epidural/spinal migration from the right quadratus lumborum block was suspected, although the definitive cause of transient respiratory arrest after bilateral quadratus lumborum block could not be ascertained. We advise caution when performing quadratus lumborum if previous neighbouring spinal surgery was performed.

Olanzapine Induced Pedal Edema: A Prudent and Rare Side Effect: A Case Report

Premarketing trials of olanzapine reported an occurrence of peripheral edema of 3%. Olanzapine belongs to atypical antipsychotics and is considered superior to its traditional congeners. Here we document a case of bilateral pedal edema which was developed secondary to olanzapine use, where all the systemic causes of pedal edema were ruled out. Pedal edema regressed on decreasing the dose of olanzapine and completely gets resolved after stopping the drug. So, we attribute the pedal edema to olanzapine drug therapy. As the definitive cause of pedal edema along with its consequences are not known, so stringent monitoring of this drug’s adverse effects is needed.

Coupled Cluster Benchmarking of Large Noncovalent Complexes in L7 and S12L as Well as the C60 Dimer, DNA-Ellipticine, and HIV-Indinavir.

In this work, we report the benchmark binding energies of the seven complexes within the L7 data set, six host-guest complexes from the S12L data set, a C60 dimer, the DNA-ellipticine intercalation complex, and the largest system of the study, the HIV-indinavir system, which contained 343 atoms or 139 heavy atoms. The high-quality values reported were obtained via a focal point method that relies on the canonical form of second-order Møller-Plesset theory and the domain-based local pair natural orbital scheme for the coupled cluster with single double and perturbative triple excitations [DLPNO-CCSD(T)] extrapolated to the complete basis set (CBS) limit. The results in this work not only corroborate but also improve upon some previous benchmark values for large noncovalent complexes albeit at a relatively steep cost. Although local CCSD(T) and the largely successful fixed-node diffusion Monte Carlo (FN-DMC) have been shown to generally agree for small- to medium-size systems, a discrepancy in their reported binding energy values arises for large complexes, where the magnitude of the disagreement is a definite cause for concern. For example, the largest deviation in the L7 data set was 2.8 kcal/mol (∼10%) on the low end in C3GC. Such a deviation only grows worse in the S12L set, which showed a difference of up to 10.4 kcal/mol (∼25%) by a conservative estimation in buckycatcher-C60. The DNA-ellipticine complex also generated a disagreement of 4.4 kcal/mol (∼10%) between both state-of-the-art methods. The disagreement between local CCSD(T) and FN-DMC in large noncovalent complexes shows that it is urgently needed to have the canonical CCSD(T), the Monte Carlo CCSD(T), or the full configuration interaction quantum Monte Carlo approaches available to large systems on the hundred-atom scale to solve this dilemma. In addition, the performances of cheaper popular computational methods were assessed for the studied complexes with respect to DLPNO-CCSD(T)/CBS. r2SCAN-3c, B97M-V, and PBE0+D4 work well in large noncovalent complexes in this work, and GFN2-xTB performs well in π-π stacking complexes. B97M-V is the most reliable computationally efficient approach to predicting noncovalent interactions for large complexes, being the only one to have binding errors within the so-called 1 kcal/mol "chemical accuracy". The benchmark interaction energies of these host-guest complexes, molecular materials, and biological systems with electronic and medicinal implications provide crucial reference data for the improvement of current and future lower-cost methods.

Exploration in the Mechanism of Zhisou San for the Treatment of Cough Variant Asthma Based on Network Pharmacology.

Background Cough variant asthma (CVA) has no definitive diagnosis or pathogenic causes, and there is currently no effective and safe treatment. Methods The network pharmacology was employed to investigate possible targets of Zhisou San (ZSS) in CVA treatment. The main chemical constituents of seven herbs in ZSS were collected based on the TCMSP. To explain the main mechanism, we sequentially screened the targets of each active ingredient and constructed the network of “herb-ingredient-target-disease.” The core targets of ZSS were further confirmed by the molecular docking analysis. Furthermore, pulmonary function, histopathology, and biochemical assays in mice were used to investigate the effect of ZSS on the treatment of CVA. Results A total of 137 active ingredients and 86 potential targets for the ZSS in the treatment of CVA were screened, which were connected with the regulation of inflammatory response and immune balance, such as IL-17 signaling pathway, Th17 cell differentiation, TNF signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, T-cell receptor signaling pathway, Th1 and Th2 cell differentiation, and other signaling pathways closely related to the pathogenesis of CVA. Thereinto, 29 core targets contained 8 of the highest scores and could evidently bind to components such as stigmasterol, quercetin, stemoninine B, luteolin, and β-sitosterol predicted by molecular docking. Furthermore, experiments in vivo were conducted for further validation that ZSS had essential effects on lung function and histopathology as well as the inflammatory state in CVA mice, which was significantly related to regulating the Th17/Treg immune balance to reduce inflammation as the important pharmacological mechanism. Conclusion This study revealed that ZSS has multicomponent and multipathway characteristics of ZSS in the treatment of CVA, which was primarily associated with inflammation and Th17/Treg immune balance. This study provides a scientific foundation for systematically elaborating the pharmacological activities and mechanism of ZSS, as well as explaining the reliability of the TCM compatibility theory.

A Rare Case Report of Sirenomelia

Sirenomelia, which is also known as mermaid syndrome, is an extremely rare congenital developmental disorder characterized by anomalies of the lower spine and the lower limbs. Affected infants are born with partial or complete fusion of the legs. Additional malformations may also occur including genitourinary abnormalities, gastrointestinal abnormalities, anomalies of the lumbar-sacral spine and pelvis and absence or underdevelopment (agenesis) of one or both kidneys. Affected infants may have one foot, no feet or both feet, which may be rotated externally. The tailbone is usually absent, and the sacrum is partially or completely absent as well. Additional conditions may occur with sirenomelia including imperforate anus, spina bifida, and heart (cardiac) malformations. The incidence of sirenomelia is 8-1 case/100000[1] births with male to female ratio being 3:1.[2] Sirenomelia has no definite cause, almost all cases occur without any reason.
 Previously, some literatures mentioned that sirenomelia is the severe form of caudal regression syndrome and has many developmental disorders. Recently much literature mentioned sirenomelia is similar but a different disorder. NORD has a different report on caudal regression syndrome.

The role of ProBNP in differentiation of cardiogenic and non-cardiogenic syncope: A diagnostic accuracy study

Objective: The significance of diagnosing the root reason for syncope and taking the required preventive or treatment measures cannot be overlooked when it comes to outcome prediction. This study endeavors to examine the role of proBNP in differentiating cardiogenic and non-cardiogenic syncope in patients presenting to the emergency department (ED). Methods: We prospectively performed a cross-sectional study on patients presenting with acute syncope. All the patients for this investigation were followed up until the definite cause of their syncope (cardiac or non-cardiac) was diagnosed and the screening performance characteristics of proBNP in differentiation of cardiogenic and non-cardiogenic syncope were evaluated. Results: Three hundred patients with syncope were studied (64.7% male). In the end, the cause of syncope was determined to be cardiogenic in 133 cases (44.3%). The area under the ROC curve of proBNP in the differentiation of cardiogenic syncope from non-cardiogenic was estimated to be 78.9 (95% CI: 73.5 – 84.3). The optimal cut-off point for proBNP in this regard was 143.5 pg/mL point. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of proBNP in the mentioned cut-off point were 75.39% (95% CI: 67.61–82.73), 75.44% (95% CI: 68.07–81.62), 71.12% (95% CI: 62.82–78.26), 79.74% (95% CI: 72.46–85.54), 2.46 (95% CI: 1.86–3.25), and 0.25 (95% CI: 0.18–0.34), respectively. Conclusion: The accuracy of proBNP in differentiation of cardiogenic and non-cardiogenic syncope is fair. ProBNP concentration equals to or higher than 143.5 pg/mL can differentiate cardiogenic syncope from non-cardiogenic with 75% sensitivity and 76% specificity. It seems that its use for this purpose should be considered with caution and along with other tools.

A Deadly Spontaneus Hemopneumothorax: A Case Report

Background: Spontaneous hemopneumothorax (SHP) is a subtype of hemopneumothorax in which there is an accumulation of blood and air in the pleural space without trauma or other definitive cause. Spontaneous hemopneumothorax is a rare disease.
 Case presentation: A man, aged 32 years, came with a complaint of sudden shortness of breath due to a right hemopneumothorax patient who was put on a chest tube insertion. It looked like 1500 cc of blood came out accompanied by an air component. Next, the chest tube is connected to the water-sealed drainage. The patient found a decrease in Hb from 15 mg/dl to 12 mg/dl. In the next nine hours, the patient's Hb became 10 mg/dl. As a result of this condition, the patient underwent an emergency thoracotomy to evaluate the source of bleeding, where the patient's source bleeding was found to be an arterial vein malformation (AVM) at the apex of the lung attached to the chest wall. Anatomical and pathological examination showed confirmed arterial vein malformation.
 Conclusion: Spontaneous hemopneumothorax, in this case, is a rare case caused by arterial-vein malformation. The right decision in patient management will determine the outcome and outcome of the treatment given.

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

Predictors and outcomes of in-hospital referrals for forensic investigation after young sudden cardiac death.

Forensic investigations are recommended following sudden cardiac death (SCD) to determine cause of death and identify living relatives at potential risk. Not all young SCD patients are referred to coronial services. The purpose of this study was to identify referral rates, predictors, and outcomes of young SCD patients who die in-hospital following out-of-hospital cardiac arrest (OHCA). A prospective 2-year analysis of in-hospital deaths following OHCA in Victoria, Australia, was conducted using a statewide registry combining data from ambulance, hospital, and forensic resources. OHCA caused 26.3% of all deaths (n = 1301) in Victorians aged 1-50 years. Rates of prehospital and in-hospital referral to coronial services were 95.0% and 59.5%, respectively. Factors independently predicting in-hospital coronial referral were age <40 years, death in the emergency department, and rural status (odds ratios 4.07, 8.91, and 3.43, respectively). Establishing a diagnosis of coronary disease in-hospital substantially reduced odds of coronial referral (odds ratio 0.07). Of 107 SCD patients referred to the coroner from hospitals, 25 (23.3%) had illicit substances identified on toxicologic analysis. Eighty-one patients (75.7%) underwent autopsy, with cause of death determined in 65 cases (80.2%). Sixteen deaths (19.8%) remained unascertained after autopsy and ancillary investigations. More than one-fourth of young Victorian deaths result from OHCA. Approximately half of patients dying in-hospital following OHCA are referred to the coroner. Patients referred are younger, more likely to die in the emergency department, and reside rurally. Forensic assessment identifies high rates of illicit drug use in young SCD patients and provides a definitive cause of death for most patients.