Etiological Spectrum Research Articles

Epidemiological Characteristics of Pathogens in Bronchoalveolar Lavage Fluid in Children With Lower Respiratory Tract Infections: A Retrospective Analysis.

The COVID-19 pandemic has significantly altered the etiological spectrum and epidemiological characteristics of pediatric respiratory diseases, and a profound understanding of these changes is crucial for guiding clinical treatment. The purpose of this study is to analyze the etiological patterns and epidemiological features of pathogens in bronchoalveolar lavage fluid (BALF) from children with pediatric lower respiratory tract infections (LRTIs) after the COVID-19 pandemic, with the aim of providing effective therapeutic evidence for clinical practice. This study enrolled pediatric patients diagnosed with LRTIs who were treated and underwent BALF pathogen detection at our hospital from June 1, 2023, to June 1, 2024. Demographic characteristics and clinical outcomes of the patients, along with the results of BALF pathogen detection, were meticulously collected and subsequently analyzed. A total of 682 children with LRTIs who underwent BALF examinations were included in this study. In pediatric LRTIs, winter was the peak season for disease onset. Regarding diagnostic categories, lobar pneumonia and bronchopneumonia were the most common diseases, representing 62.5% and 27.1% of diagnosed cases, respectively. The vast majority of pediatric patients showed complete recovery in clinical symptoms or imaging findings within 2 weeks after receiving treatment. The BALF examination results revealed that the five most frequently identified pathogens were Mycoplasma pneumoniae (83.1%), followed by Streptococcus pneumoniae (21.3%), Haemophilus influenzae (16.6%), Staphylococcus aureus (11.7%), and Human Respiratory Syncytial Virus (11.3%). The etiological spectrum of pediatric LRTIs is complex, necessitating targeted clinical treatments tailored to the predominant pathogens.

Etiological Profile of Obstructive Jaundice and Acute Cholangitis: Three-year Data from a Tertiary Care Center in Eastern India.

Obstructive jaundice (OJ) and acute cholangitis (AC) are common presentations of biliary obstruction. In Eastern India, data regarding the causes of OJ and AC are scarce. This study aimed to determine the etiological spectrum of OJ and AC in a tertiary center in Eastern India. The data of consecutive patients admitted to the Department of Gastroenterology from January 2021 to December 2023 with a diagnosis of OJ with or without AC was collected from the hospital's computerized database. The data were analyzed for different etiologies of OJ and AC. The results were compared with the various etiologies of OJ reported in previous publications from different centers across India. Totally 772 patients were admitted during this period with a diagnosis of OJ with or without AC. There were 368 male and 404 female patients with a male-to-female ratio of 0.91. In 454 (58.8%) and 309 (41.2%) cases, the etiology of OJ was benign biliary obstruction (BBO) and malignant biliary obstruction (MBO), respectively. The etiologies of BBO-associated OJ were choledocholithiasis (51%) and distal biliary stricture (9%). The causes of MBO-associated OJ were gallbladder cancer (GBC) (21%), periampullary malignancy (10.2%), cholangiocarcinoma (CCA) (5.3%), and carcinoma head of the pancreas (3.4%). Acute cholangitis was observed in 203 (26.2%) with OJ; 23% and 10% of cases of BBO-associated OJ and MBO-associated OJ had AC, respectively. BBOs that presented with AC were choledocholithiasis (50.24%) and distal biliary stricture (14.77%). Similarly, MBOs that presented with AC were GBC (16.74%), periampullary malignancy (10.34%), CCA (6.4%), and carcinoma head of the pancreas (0.0098%). Among the etiologies of AC and OJ, BBOs were more common than MBOs. The most common cause of OJ was choledocholithiasis. Gallbladder cancer was the second most common cause of OJ and the most common cause of malignancy-associated OJ. The most common benign and malignant etiologies of AC were choledocholithiasis and GBC, respectively. Sahu SK, Nath P, Mallick B, et al. Etiological Profile of Obstructive Jaundice and Acute Cholangitis: Three-year Data from a Tertiary Care Center in Eastern India. Euroasian J Hepato-Gastroenterol 2024;14(2):187-190.

Swiss Consensus on Prenatal and Early Postnatal Urinary Tract Dilation: Practical Approach and When to Refer.

Urinary tract dilations (UTDs) are the most frequent prenatal renal anomaly. The spectrum of etiologies causing UTD ranges from mild spontaneously resolving obstruction to severe upper and lower urinary tract obstruction or reflux. The early recognition and management of these anomalies allows for improved renal endowment prenatally and ultimately better outcome for the child. The role of the general obstetrician and pediatrician is to recognize potential prenatal and postnatal cases addressed to their practice and to refer patients to specialized pediatric nephrology and urology centers with a sense of the urgency of such a referral. The aim of this paper is to offer clinical recommendations to clinicians regarding the management of neonates and children born with prenatally detected UTD, based on a consensus between Swiss pediatric nephrology centers. The aim is to give suggestions and recommendations based on the currently available literature regarding classifications and definitions of prenatal and postnatal UTD, etiologies, prenatal and postnatal renal function evaluation, investigations, antibiotic prophylaxis, and the need for referral to a pediatric nephrologist and/or urologist. The overarching goal of a systematic approach to UTD is to ultimately optimize kidney health during childhood and improve long-term renal function prognosis.

Clinical and genetic characteristics of RANBP2 mutations in children with acute necrotizing encephalopathy.

This study investigated RANBP2 mutations in children with acute necrotizing encephalopathy (ANE) and conducted a systematic review of the differences in clinical characteristics between with or without RANBP2 mutations. Whole-exome sequencing was performed on 19 pediatric ANE patients at Beijing Children's Hospital affiliated to Capital Medical University between 2017 and 2020. A systematic literature review was also conducted on the clinical characteristics and spectrum analysis of RANBP2 mutations. Besides the common mutation site c.1754C > T, new mutation sites were identified, including c.7454G > T, c.7474A > G, c.7807C > T, c.7918C > A, and c.872A > G. These sites are highly conserved. Twenty-four publications describing 38 ANE children were reviewed, of which 22 cases had the RANBP2 mutations. When combined with our study, the data included 54 ANE children aged from 3 months to 120 months, and divided into RANBP2 mutation group (n = 26) and non-mutation group (n = 28). No significant differences were observed in initial presentations, neuroimaging, treatment, or outcomes between these two groups. However, children with RANBP2 mutations had slightly elevated blood ammonia levels and a broader etiological spectrum, especially involving non-influenza pathogens. This study highlights novel RANBP2 mutation sites in ANE children and associates these mutations with higher blood ammonia levels and diverse etiologies.

Demographic Profiles, Etiological Spectrum, and Anatomical Locations of the Post-Hepatic Obstructive Jaundice in Adult Population in Hadhramout Region in Yemen.

Obstructive jaundice is a common health challenge in daily clinical practice caused by a heterogeneous group of benign and malignant conditions in or around extrahepatic bile ducts. This study aimed to investigate the causes of obstructive jaundice, analyze the age and sex distribution, and report the locations of obstruction. This was a retrospective study of electronic records of patients diagnosed with obstructive jaundice in the Hadhramout region in Yemen. This study analyzed the data of 303 patients (mean age: 57 ± 17.99 years; range: 18-95 years); 60.40% (n = 183) were female, and 39.60% (n = 120) were male. The highest prevalence was found in middle-aged adults (n = 112, 36.96%), followed by the old (n = 101, 33.33%). Common bile duct (CBD) stones were the most common cause of obstructive jaundice (n = 175, 57.8%), followed by CBD stricture (n = 58, 19.1%), carcinoma of the head of the pancreas (n = 35, 11.6%), cholangiocarcinoma (n = 21, 6.9%), and external compression of the CBD (n = 2, 0.7%). CBD stones, cholangiocarcinoma, and ampulla of Vater masses were more prevalent in females (30.9%, 3.8%, and 2.2%, respectively) than in males (25.8%, 2.9%, and 1.7%, respectively). In contrast, CBD stricture and carcinoma of the pancreas were more frequent in males, occurring in 12.1% and 7.1% of male patients, respectively, compared to 7.9% and 4.9% in female patients. The primary obstruction site was the CBD (n = 254, 83.8%), followed by the head of the pancreas (n = 30, 9.9%), and the ampulla of Vater (n = 13, 4.3%). Obstructive jaundice predominantly affects middle-aged adults followed by the old-aged patients predominantly in females. The most common cause of obstructive jaundice was CBD stones, followed by CBD stricture, while carcinoma of the head of the pancreas was the most common malignant cause, followed by cholangiocarcinoma. Distal CBD is the most common anatomical location of obstructive jaundice.

Emergency neurosurgical hybrid operating platform for acute intracranial hemorrhage (E-HOPE)

BackgroundPrecise diagnosis and rapid treatment for acute complex intracranial hemorrhage (ICH) are crucial. The neurosurgical hybrid operating platform integrates traditional open neurosurgery operating room functionalities with endovascular therapy capabilities and is developing in the neurosurgical practice. However, its effect on the emergent complicated neurovascular cases needs pilot exploration.MethodsIn this prospective study, a total of 103 cases of both spontaneous and non-spontaneous ICH were consecutively recruited between June 2019 and June 2023. Demographic data, including age, gender distribution, and types of hemorrhage, were collected. Surgical interventions were tailored based on DSA, including spontaneous and non-spontaneous hemorrhages. Functional outcomes were assessed using the modified Rankin Scale (mRS) preoperatively and postoperatively.ResultsOver the study period from June 2019 to June 2023, a cohort of 103 ICH cases underwent emergency hybrid surgical treatment utilizing the E-HOPE platform. Among these cases, 88 were classified as spontaneous ICH, while 15 were non-spontaneous. The mean age at diagnosis for the entire cohort was 54.0 ± 3.7 years, with a slight predominance of male patients. Spontaneous ICH encompassed a diverse spectrum of etiologies, including arteriovenous malformations, aneurysms, arteriovenous fistulas, cavernous malformations, moyamoya disease, and cryptogenic hemorrhages. Surgical interventions were tailored to address the specific pathology. Notably, improvements in mRS scores were observed in a majority of cases, with some patients experiencing stabilization or deterioration postoperatively. Non-spontaneous cases (n = 15) were primarily iatrogenic (n = 13) due to tumors adjacent to the internal carotid artery, necessitating stent graft deployment. Surgical approaches, including stent graft deployment and middle meningeal artery embolization, were effective in managing these cases. Postoperative functional outcomes varied depending on the nature of the hemorrhage, with a subset of patients demonstrating improvement in mRS scores while others showed no significant change.ConclusionsEmergency hybrid surgical treatment utilizing the E-HOPE platform offers promising outcomes for ICH patients. Tailored surgical approaches result in favorable postoperative functional outcomes, highlighting the importance of a multidisciplinary approach in managing these complex cases.

Clinical Outcomes of Liver Abscesses in Adults: A 10-Year Experience at a Tertiary Care Center in Northern India.

Purpose Hepatic abscesses remain a significant clinical challenge due to high morbidity and mortality. This research aims to examine the etiological spectrum, management approaches, clinical features, and results in hepatic abscesses in a tertiary care facility in northern India, emphasizing the distinctions among pyogenic liver abscesses (PLAs) and amoebic liver abscesses (ALAs). Methods This retrospective study was done at GSVM Medical College, Kanpur, analyzing 725 patients with hepatic abscesses over a 10-year period. Patients were included based on confirmed diagnoses of ALAs or PLAs through clinical, serological, and microbiological evidence. Data on demographics, clinical presentation, imaging findings, laboratory results, and management approaches were extracted from hospital records.IBMSPSSStatistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York, United States)was employed for statistical analysis, and continuous variables were displayed accordingly as means or medians and categorical variables as frequencies. Subgroup analyses were conducted based on abscess characteristics, including size, location, and etiology. Results Of the 725 patients analyzed, the mean age was 42.7 ± 15.8 years, with men comprising 85.93% of the cohort. ALAs accounted for 82.3% of cases, while PLAs comprised 12%. PLA cases frequently involved Gram-negative pathogens, such as Escherichia coli and Klebsiella pneumoniae, with 64% of PLA patients exhibiting positive pus or blood cultures. Common presenting symptoms included abdominal pain (87%) and fever (84.5%). Significant comorbidities included alcoholism (43.6%) and diabetes mellitus (34.2%). Right lobe involvement was predominant (75.9%), and multiple abscesses were noted in 47.5% of patients. Complications included pleural effusion (53.9%), abscess rupture (16.3%), and systemic inflammatory response syndrome (25.7%). Management strategies comprised antibiotics, percutaneous catheter drainage (74.8%), and needle aspiration (43.4%), with conservative treatment being effective in smaller abscesses. Mortality rates were low, at 1.6% for ALAs and 1.5% for PLAs. Hospital stays were shorter for PLA cases (median: five days) compared to ALAs (median: 7.3 days). Conclusion This study underscores the predominance of ALAs in endemic regions like India and highlights the significant role of Gram-negative bacteria in PLAs. Tailored management strategies, including percutaneous interventions and early antibiotic therapy, were associated with favorable outcomes and low mortality. However, the emergence of antimicrobial resistance in PLAs warrants robust antimicrobial stewardship. Public health measures focused on sanitation and clean water are critical to reducing the prevalence of ALAs.

Epidemiological characteristics and trend of mortality on hand, foot and mouth disease in China, 2008-2022

Objective: To analyze the nationwide epidemiological characteristics and trend of hand, foot and mouth disease (HFMD) fatal cases from 2008 to 2022 and provide evidence for the prevention and control of HFMD. Methods: The information on HFMD fatal cases during 2008 to 2022 was collected from the National Notifiable Disease Surveillance Reporting System of China. Data of the epidemiological characteristics was analyzed by R 4.2.2 software and the changing trends for the case fatality rates, mortality rates and their age-adjusted rates were analyzed by Joinpoint 4.9.10 software. Results: From 2008 to 2022, a total of 3 704 fatal HFMD cases were reported in China. The fatal cases were primarily observed in children aged <3 years (83.42%, 3 090/3 704). The male and female gender ratio was 1.82 ∶1 (2 389 ∶1 315). Regarding the age-adjusted case fatality rates over time, there was a rapid increase from 2008 to 2010 [annual percentage change (APC) =41.97%, P<0.05]. From 2010 to 2016, a steady decline was observed (APC=-28.57%, P<0.05), and the decline accelerated (APC=-39.66%, P<0.05) from 2016 to 2022. Since 2020, less than 10 fatal cases were reported annually nationwide. Among the 2 566 laboratory-confirmed deaths from 2008 to 2022, Enterovirus A71 (EV71) was the predominant pathogen (91.62%,2 351/2 566). There have been noticeable changes in the pathogen composition since 2017, decreasing in EV71 and increasing in the proportion of fatalities caused by Coxsackievirus A16 (CV-A16) and other enteroviruses. Conclusions: From 2008 to 2022, the HFMD case fatality rates and mortality rates continuously declined, peaked in 2010. Since 2017, the decline of HFMD case fatality rates has been noticeably accelerated. Along with the decrease in the proportion of EV71 in HFMD fatal cases, the proportion of other enteroviruses appeared increasing. It is essential to continuously monitor the etiological spectrum of the fatal cases.

Bronchiectasis in African children: Prevalence, etiology, and clinical spectrum at a pediatric tertiary hospital in Cape Town, South Africa

Objectives: The objective of the study was to describe the disease burden, etiology, and clinical spectrum of bronchiectasis in children attending a tertiary hospital in Cape Town, South Africa. Materials and Methods: Data were collected by chart review of all patients aged 3 months to 15 years attending the respiratory clinic at Red Cross War Memorial Children’s Hospital between January 2019 and December 2019. We included children who had a diagnosis of bronchiectasis based on a history of a recurrent (&gt;3 episodes/year) or persistent (&gt;4 weeks) wet or productive cough and a clinical phenotype characterized by any of the following: Exertion dyspnea, recurrent chest infections, growth failure, finger clubbing, and chest deformity associated with radiographic features of bronchiectasis on chest radiograph or chest tomography reported by a pediatric radiologist. Patients with cystic fibrosis were excluded from the study. Results: Of 337 children seen at the respiratory clinic during the study period, 58 (17.2%) had bronchiectasis that was diagnosed at a mean age of 34 months (standard deviation 26), and 32 (55.0%) were female. The most common causes of bronchiectasis were post-infectious 25 (43.1%), and underlying immunodeficiencies 19 (32.8%), including 16/58 (27.6%) who were living with human immunodeficiency virus (HIV) and 3 (5.1%) with primary immunodeficiency. Other causes included aspiration syndrome 8 (13.8%) and anatomical abnormalities 4 (6.9%). Of the participants with post-infectious bronchiectasis, tuberculosis (TB) was the most common organism isolated 16 (64.0%), and most common in children living with HIV (11/16, 68.8%). Cough was common in 48 (82.8%), with wet cough being predominant in 41 (85.4%), course crepitations were found in 37 (63.8%), hyperinflation in 24 (41.4%), finger clubbing in 21 (36.2%), wheeze in 16 (29.3%), and exertional dyspnea in 7 (12.0%). Conclusion: Bronchiectasis is common in South African children, usually resulting from previous pneumonia episodes, with TB being the most common infective cause. The importance of early diagnosis and treatment of underlying causes, especially infectious diseases in low-middle-income settings, to prevent bronchiectasis is highlighted.

Longitudinal transcriptome analysis reveals distinct gene expression patterns in traditional Chinese medicine syndromes of upper respiratory tract infections.

Wind-cold (WC) and Wind-heat (WH) are common syndromes of upper respiratory tract infections (URTIs) in traditional Chinese medicine (TCM), presenting different clinical features, but the transcriptomic changes associated with these syndromes remained unclear. Patients with WC and WH syndromes were recruited from outpatient unit, pharyngeal swabs were collected for pathogen detection. Peripheral blood samples were obtained on day 1 and day 6, with healthy volunteers as controls. Transcriptome sequencing was performed to identify differentially expressed genes and pathways associated with the two syndromes. Marker genes for each syndrome were identified, and a machine learning classifier was developed. A total of 124 samples from 34 WC, 30 WH patients, and 16 health controls were included in this study. No significant differences in etiological spectrum were observed between the syndromes. Both syndromes showed distinct gene expression profiles compared to health control. Gene enrichment analysis indicated that TGF-β and Wnt/β -catenin pathways were downregulated in the WH. The oxidative phosphorylation pathways were downregulated in WC cohort compared to the WH cohort. As the URTIs improved from day 1 to day 6, oxidative phosphorylation pathway activity returned to normal levels. The marker genes for WC and WH syndromes were identified and a random forest classifier was built, achieving an accuracy of 0.88. WC and WH syndromes demonstrated distinct gene expression profiles, supporting more precise TCM diagnosis. WC syndrome is marked by mitochondrial dysfunction, while WH syndrome is characterized by downregulated TGF-β and Wnt/β-catenin pathways.

Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study.

The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH. In the US multicentre SHUNT-V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy. Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut-off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%. SHUNT-V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child-Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%-100% for LEV and 97.3%-100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%-35% of EGDs could have been avoided with 0%-3.7% of LEV and 0%-2.7% of all significant PH lesions missed. HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal-systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child-Pugh A cirrhosis. The SHUNT-V study was registered at ClinicalTrials.gov (NCT03583996).

Etiological Spectrum of Bone Marrow Biopsy in Patients With Pancytopenia.

Background Pancytopenia is defined as a decrease in all three hematologic cell lines. The condition is not a disease in itself but a common pathway caused by various etiologies that can be infectious, autoimmune, genetic, nutritional, and/or malignant. Determining the cause of pancytopenia is a challenge and is key in determining the proper treatment regimen and estimating prognosis. Objective The aim of this study was to evaluate the etiological spectrum of pancytopenia in patients who underwent bone marrow biopsy at a tertiary care hospital. Methodology This study was conducted at the Internal Medicine and Gastroenterology Departments of Lady Reading Hospital, Peshawar, Pakistan, from January 1, 2023, to December 31, 2023. A total of 120 patients with pancytopenia aged 12 to 60 years who underwent bone marrow biopsy were enrolled. Data on age, gender, clinical presentations, and bone marrow biopsy findings were observed. Results The mean age was 34.97 years. Males were more frequently affected, 74 (61.7%), than females, 46 (38.3%). Pallor, 86 (71.7%), and weakness, 66 (55.0%), were the most frequent presentations of pancytopenia. The etiological spectrum showed that megaloblastic anemia was present in 48 (40%) of the cases, followed by infection-related changes in 20 (16.7%) and aplastic anemia in 20 (16.7%). Conclusion Megaloblastic anemia emerged as the leading cause of pancytopenia in our study, followed by aplastic anemia and infection-related changes.

Clinical profile and etiological spectrum of patients presenting with corneal hydrops over a 12-year period.

To describe the demographics, clinical characteristics, and management of corneal hydrops in patients presenting to a multi-tier ophthalmology hospital network in India. Cross-sectional hospital-based study. Of the total of 3,140,941 new patients presenting between October 2010 and March 2022, patients with a clinical diagnosis of corneal hydrops in at least one eye were included in the study. All the data was collected using an electronic medical record system. 1291 eyes of 1110 patients were diagnosed with corneal hydrops and included in the study and 961 patients (83.69%) had a unilateral affliction. Corneal hydrops was noted to be significantly more common in males (62.43%) and adults (62.7%). The most common age group at presentation was during the second decade of life with 472 (42.52%) patients. They were more commonly from the higher socio-economic status (77.3%) and from the urban geography (44.23%). In the 1291 eyes, 567 (43.92%) eyes had a visual impairment of blindness (> 20/400-20/1200) followed by moderate visual impairment (> 20/70-20/200) in 166 (12.86%) eyes. Overall, the most common etiology was keratoconus in 1,082 (83.81%) eyes followed by primary congenital glaucoma (PCG) in 91 (7.05%) eyes. Surgical intervention to hasten the recovery of hydrops was performed in 7.82% of eyes with ectasia and as a definite management in 7.05% eyes with PCG. Visual rehabilitation was with contact lenses in 29.1% eyes and keratoplasty in 13.94% eyes. Corneal hydrops is predominantly unilateral and is more common in males. Keratoconus was the commonest etiological condition; however, the risk of hydrops was highest in keratoglobus, followed by PMD. Most affected age was the second decade of life and visual impairment was severe in majority (60%). A surgical intervention was performed in a third of the cases.

Cardiomyopathies in 100,000 genomes project: interval evaluation improves diagnostic yield and informs strategies for ongoing gene discovery

BackgroundCardiomyopathies are clinically important conditions, with a strong genetic component. National genomic initiatives such as 100,000 Genome Project (100KGP) provide opportunity to study these rare conditions at scale beyond conventional research studies.MethodsWe present the clinical and molecular characteristics of the 100KGP cohort, comparing paediatric and adult probands with diverse cardiomyopathies. We assessed the diagnostic yield and spectrum of genetic aetiologies across clinical presentations. We re-analysed existing genomic data using an updated analytical strategy (revised gene panels; unbiased analyses of de novo variants; and improved variant prioritisation strategies) to identify new causative variants in genetically unsolved children.ResultsWe identified 1918 individuals (1563 probands, 355 relatives) with cardiomyopathy (CM) in 100KGP. Probands, comprising 273 children and 1290 adults, were enrolled under > 55 different recruitment categories. Paediatric probands had higher rates of co-existing congenital heart disease (12%) compared to adults (0.9%). Diagnostic yield following 100KGP’s initial analysis was significantly higher for children (19%) than for adults (11%) with 11% of diagnoses overall made in genes not on the existing UK paediatric or syndromic CM panel. Our re-analysis of paediatric probands yields a potential diagnosis in 40%, identifying new probable or possible diagnoses in 49 previously unsolved paediatric cases. Structural and intronic variants accounted for 11% of all potential diagnoses in children while de novo variants were identified in 17%.Conclusions100KGP demonstrates the benefit of genome sequencing over a standalone panel in CM. Re-analysis of paediatric CM probands allowed a significant uplift in diagnostic yield, emphasising the importance of iterative re-evaluation in genomic studies. Despite these efforts, many children with CM remain without a genetic diagnosis, highlighting the need for better gene-disease relationship curation and ongoing data sharing. The 100KGP CM cohort is likely to be useful for further gene discovery, but heterogeneous ascertainment and key technical limitations must be understood and addressed.

Etiological spectrum of pancytopenia in adults based on hematological parameters and bone marrow studies

ABSTRACT Background This study aimed to investigate the demographic, clinical, and diagnostic aspects of adult pancytopenia while exploring its etiological spectrum through hematological parameters and bone marrow studies. Research design and methods This observational study involved 117 adult individuals ranging from 13 to 85 years who presented with pancytopenia. A comprehensive examination of demographic features, hematological parameters, clinical presentations, and physical findings, including liver and spleen characteristics, was conducted. Additionally, serological analyses for HBsAg and Anti HCV were performed. The diagnostic spectrum was determined through bone marrow studies. Results Pancytopenia manifested with varied clinical symptoms, with generalized weakness (72.65%), fever (64.1%), dyspnea (54.70%), bleeding (34.2%), and weight loss (25.6%) being prominent. Physical examination revealed a range of liver and spleen characteristics, with hepatomegaly observed in 32.48% and splenomegaly in 44.4% of cases. Serological findings indicated HBsAg positivity in 8.5% and Anti HCV positivity in 21.37% of cases. The diagnostic distribution encompassed diverse conditions, with aplastic anemia (17.1%), megaloblastic anemia (12.8%), and myelodysplastic syndromes (12.8%) being prevalent. Conclusions This study provides a comprehensive overview of the demographic, clinical, and diagnostic aspects of pancytopenia. The observed prevalence of different diagnoses underscores the necessity of a thorough evaluation, including bone marrow studies, for accurate diagnosis and appropriate management.

The impact of tricuspid regurgitation on the timing of pulmonary valve replacement in adult patients after Tetralogy of Fallot repair

Abstract Background Tricuspid regurgitation (TR) in patients with repaired tetralogy of Fallot (rTOF) is an important finding with a wide spectrum of etiologies. TR represents an important risk factor in adult patients with rTOF, influencing clinical outcomes and the requirement for additional surgical interventions. In this study, we reviewed the long-term outcomes of TR in ACHD patients with rTOF as well as its impact on the timing of surgical pulmonary valve replacement (PVR). Methods This was a retrospective analysis of a single institutional cohort which included 149 ACHD patients with a history of rTOF (transannular patch only) with CMR data, complete follow-up, and a recent (&amp;lt; 1 year) outpatient clinic visit. Results Overall follow-up time was 25.5 years (95% CI 24.5,26.4). Between 2002 and 2021, 93 patients required isolated PVR at a mean time from TOF repair of 16.6 years (95% CI 15.5,17.7) and at a mean age of 17.9 years (95% CI 16.8,19.0). In the whole cohort, significant TR was associated with a two-fold increase in the likelihood of requiring PVR (log-rank p = 0-.0023, HR 2.02; 1.09-4-47). Moderate to severe TR was more frequent in those who underwent VSD closure through a right atriotomy (17 versus 0, p = .0002) and affected time to PVR (13.9 versus 16.3 years, p = .0071), with equal preoperative RVEDVi at CMR. After PVR, RVEDVi normalized in all patients, regardless of the preoperative amount of TR (median 115.3 ml/m2 versus 112.3 ml/m2, p = .7). At a median time of 6.5 years from PVR, 13 patients (13/93, 14%) underwent redo PVR. Conclusions The preoperative severity of tricuspid regurgitation (TR) may have a substantial role on the likelihood of patients needing PVR at a younger age. This, in turn, could result in a reduced duration of freedom from valve failure. Replacing the pulmonary valve too early can effectively increase the lifetime number of procedures, preserving the function of the tricuspid valve at the time of TOF repair is of paramount importance.

Neonatal hypoglycemia: A review with focus on practical challenges and recent updates on management

At birth, a neonate undergoes a transition from the continuous maternal supply of glucose to a variable and intermittent oral glucose intake, which is regulated by the interplay of hormones and metabolic enzyme induction. Because low plasma glucose concentrations are common in the neonatal period, it may be difficult to identify those who have pathologic hypoglycemia. Hence, it is important to formally evaluate such babies by drawing critical samples. Here, we present two cases of neonatal hypoglycemia where the presentation had some similarities, but the comprehensive evaluation revealed a varied etiological spectrum necessitating lifelong management. Through these case studies, authors discuss practical challenges in the diagnosis, management, and follow-up of neonates with endocrine causes of hypoglycemia.

Meningeal Dissemination and Drop Metastasis From Glioma Presenting With Non-Epileptic Myoclonus and Minipolymyoclonus.

We describe the case of a 36-year-old woman with a past medical history of low grade right frontal lobe glioma and focal epilepsy presenting with subacute, progressive, multifocal myoclonus and neck and back pain. Unlike her typical seizures, the myoclonus exhibited a distinct semiology, involving both positive and negative muscle jerks affecting multiple limb muscles while sparing the face. In addition, neurological examination revealed low-amplitude, arrhythmic movements of the hands and fingers, resembling minipolymyoclonus. There were no other neurological exam findings, including mental status changes, extrapyramidal signs or signs of myelopathy. Brain and spine MRI indicated leptomeningeal and spinal "drop" enhancing lesions, suggesting likely malignant evolution of the glioma. EEG ruled out a cortical origin of the myoclonus. Pharmacological trials with benzodiazepines and other antiepileptic medications were ineffective. The patient's myoclonus was most likely spinal segmental in origin from meningeal spread of glioma. The spinal roots or anterior horns of the spinal cord may have represented a focus of hyperexcitability responsible for generating minipolymyoclonus. Our case expands the etiological spectrum of non-epileptic myoclonus and minipolymyoclonus to encompass meningeal carcinomatosis and drop metastases from glioma. These cases may occur even without overt signs of myelopathy. Recognizing such presentations holds significance due to the poor prognosis associated with meningeal spread of glioma and the limited response of non-epileptic myoclonus to symptomatic treatments.

Prognostic factors and etiological insights in constrictive pericarditis

Abstract Constrictive pericarditis (CP) is an infrequent disease that poses a diagnostic and therapeutic challenge, with mortality often linked to underlying etiological factors. Our unicentric retrospective research aims to elucidate prognostic indicators and unravel the diverse etiological spectrum of this condition. The study is accepted by the Ethical Committee of our Center. Between January 2010 and December 2023, we have identified a total of 112 patients diagnosed with CP, with an average follow-up time of 6.42 years (IQR 1.98 - 11.45). We present the baseline variables of the patients, etiology and prescribed treatments in the table 1, comparing patients who survive with those who do not survive. 66.1% of patients were males and median age was 60.8 years old. We present two Kaplan-Meier curves (Figures 1 and 2) comparing the survival rates between CP etiologies. In Figure 1, all causes are represented separately. In Figure 2, CP related to cardiac surgery, radiotherapy, purulent pericarditis, tuberculous pericarditis, mixed and other causes are combined. Our results suggest a better prognosis in patients with idiopathic CP and worse prognosis in patients with oncological related CP. The significant predictors in the univariate Cox analysis were age, cachexia, ascites, oncology etiology, hemoglobin, sodium, Euroscore II and surgical pericardiectomy. The best predictive model (selected with a lower AIC) to predict mortality throughout follow-up, with a Harrell's C of 0.835, included the variables age, cachexia, oncological cause and hyponatremia as risk factors for mortality and surgical treatment by pericardiectomy as a protective factor (Figure 3). In conclusion, our study suggests that CP etiology has an impact on survival with oncological cause having the worst prognosis. Furthermore, other factors as hyponatremia, cachexia, shock and age at diagnosis have also resulted in indicators of poor outcome.Figure 1.Kaplan meierFigure 3.Predictive model

The Black and African American Connections to Parkinson’s Disease (BLAAC PD) study protocol

Determining the genetic contributions to Parkinson’s disease (PD) across diverse ancestries is a high priority as this work can guide therapeutic development in a global setting. The genetics of PD spans the etiological risk spectrum, from rare, highly deleterious variants linked to monogenic forms with Mendelian patterns of inheritance, to common variation involved in sporadic disease. A major limitation in PD genomics research is lack of racial and ethnic diversity. Enrollment disparities have detrimental consequences on the generalizability of results and exacerbate existing inequities in care. The Black and African American Connections to Parkinson’s Disease (BLAAC PD) study is part of the Global Parkinson’s Genetics Program, supported by the Aligning Science Across Parkinson’s initiative. The goal of the study is to investigate the genetic architecture underlying PD risk and progression in the Black and/or African American populations. This cross-sectional multicenter study in the United States has a recruitment target of up to 2,000 individuals with PD and up to 2,000 controls, all of Black and/or African American ancestry. The study design incorporates several strategies to reduce barriers to research participation. The multifaceted recruitment strategy aims to involve individuals with and without PD in various settings, emphasizing community outreach and engagement. The BLAAC PD study is an important first step toward informing understanding of the genetics of PD in a more diverse population.