UNASSIGNED: To determine the clinical spectrum, neuroimaging findings, and outcome of Acute Disseminated Encephalomyelitis (ADEM) in children.
UNASSIGNED: We conducted a descriptive cross sectional study of all children aged 6 months to 18 years, diagnosed with ADEM at Aga Khan University Hospital, Karachi from January 2018 till December 2022.
UNASSIGNED: This retrospective study enrolled 30 cases of ADEM, with a mean age of 6.43 ± 4.079, including 13 males and 17 females. The average hospital stay was 7.29 ± 4.379 days. The most common clinical features were fever, headache, and altered consciousness, while motor deficit was observed in 15 (53.5%) patients. Abnormal cerebrospinal fluid was found in 14 (46.6%) patients. Brain MRI identified bilateral and multifocal lesions in 22 (78.6%) patients, with brainstem lesions detected in 7 (25%) patients. Treatment included IV methylprednisolone (22; 73%), IVIG (9; 30%), or both (6; 20%). Clinical improvement was observed in 25 (89.3%) patients, with residual weakness present in eight (26%) patients at discharge. There was one reported death. Long-term complications included motor deficits, seizures, poor scholastic performance, and behavioral issues.
UNASSIGNED: The clinical presentation of ADEM is variable, but the most common symptoms are fever, headache, and altered consciousness. Despite generally favorable outcome, long-term monitoring revealed that patients may experience motor deficits, seizures, cognitive impairment, and academic difficulties.

UNASSIGNED: SARS-CoV-2 infection presentation in children is usually milder than in adults but can be severe and fatal as well. Data on the pediatric population regarding severity and clinical presentation are still limited, and there is a need to have a better understanding of clinical features, severity, and laboratory parameters.
UNASSIGNED: To document clinical and laboratory characteristics and outcomes of children with SARS-CoV-2 in a low-middle-income country and to evaluate clinicodemographic factors and biochemical markers associated with severity and mortality.
UNASSIGNED: A hospital-based cross-sectional study was conducted among 112 COVID-19-positive children at a designated Level-3 center in North India. Clinical characteristics, laboratory parameters, and severity of COVID-19 cases as well as factors associated with the severity of the disease, were analyzed by descriptive statistics and a Chi-square test.
UNASSIGNED: The adolescent age group (age 12-18 years) was affected most (64.3%). Male patients accounted for 56.3% of total cases. Fever was the most common symptom (41.1%) followed by cough. Presenting complaints were highest from the respiratory system (32.1%) followed by the gastrointestinal (8.9%) and the neurological system (7.1%). Majority of patients had mild disease (87%) while 13% had the moderate-severe disease. Spo2 < 95% (P = 0.00001), neutrophilia (P < 0.000001), lymphopenia (P < 0.000001), elevated values of C-reactive protein (P < 0.00001), Interleukin-6 (P = 0.002), D- dimer (P = 0.00014) and respiratory symptoms as presenting complaints (P < 0.000001) were found to be significantly associated with severity of disease.
UNASSIGNED: The male and adolescent age group was affected most. Presenting complaints were highest from the respiratory system. Unusual presentation may have gastrointestinal or neurological presentation. Most children with COVID-19 had mild disease. Moderate to severe disease was not uncommon. Factors including neutrophilia, lymphopenia, elevated lab values of C-reactive protein, D-dimer, and interleukin-6 had a significant association with the severity of the disease. These biomarkers can help predict the severity of the disease.

BACKGROUND: The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this study, we aimed to analyse all published clinical data of patients with M. malmoense isolation to investigate the clinical spectrum, relevance, and outcomes of infections with this uncommon mycobacterium.
METHODS: A systematic review of PubMed, Web of Science, Embase, and Scopus was performed to identify all clinical data about M. malmoense. Random effects meta-analyses of proportions were calculated for clinical relevance, treatment success, and mortality, as well as for other clinical characteristics. A logistic regression analysis, investigating predictors of mortality, as well as Kaplan-Meier survival analyses, were performed.
RESULTS: One hundred and eighty eight patients with individual data from 112 articles and 671 patients with pooled data from 12 articles were included in the meta-analyses. Of patients with individual data, pulmonary infection was the most common manifestation (n = 106/188, 56.4%). One third (n = 61/188, 32.4%) suffered from isolated extra-pulmonary and 21/188 (11.2%) from disseminated disease. In 288 patients with pooled data and pulmonary affection, clinical relevance was high with 68% (95% CI 44-85%) of patients fulfilling criteria for clinical disease. Macrolide and rifamycin-containing regimens were associated with improved survival (adjusted OR 0.12, 95% CI 0.03-0.42, p = 0.002, and 0.23, 95% CI 0.04-0.86, p = 0.03, for lethal events, respectively).
CONCLUSIONS: In this study, we provide a detailed clinical description of M. malmoense infections. The pathogen is of high clinical relevance for the individual patient with more than 2 out of 3 patients having relevant disease and >40% of manifestations being extra-pulmonary or disseminated. Macrolide and rifamycin-containing regimens are associated with improved survival.

OBJECTIVE: Galactose mutarotase (GALM) deficiency was first reported in 2019 as the fourth type of galactosemia. This study aimed to investigate the clinical and genotypic spectra of GALM deficiency.
METHODS: This was a questionnaire-based retrospective survey conducted in Japan between February 2022 and March 2023.
RESULTS: We identified 40 patients with GALM deficiency in Japan (estimated prevalence: 1:181,835). Four of 38 patients (10.5%) developed cataracts, which resolved with lactose restriction in 3 out of 4 patients. Transient transaminitis was the most common symptom (23.1%). All of the patients followed lactose restriction; discontinuation of the restriction after infancy did not cause any complications. Moreover, none of the participants experienced long-term complications. Two variants, GALM NM_138801.3: c.294del and c.424G>A, accounted for 72.5% of the identified pathogenic variants. The patients showed moderately elevated blood galactose levels with lactose intake; however, the elevation was lower than that observed in galactokinase deficiency.
CONCLUSIONS: GALM deficiency is characterized by a similar but milder phenotype and lower blood galactose elevation than in galactokinase deficiency. Diagnosis and initiation of lactose restriction in early infancy should be essential for prevention of cataracts, especially in cases of irreversible opacity.

OBJECTIVE: The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients.
METHODS: A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis.
RESULTS: The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5 h after treatment initiation, peaked after 8 h, and subsided after 18 h. Patients with severe JHR experienced a longer recovery time (26 h). Patients with general paresis (OR = 6.825), ocular syphilis (OR = 3.974), pleocytosis (OR = 2.426), or a high CSF-VDRL titre (per log2 titre increase, OR = 2.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided.
CONCLUSIONS: Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy.

BACKGROUND: Brucellosis is a severe zoonotic disease that is often overlooked, particularly in impoverished countries. Timely identification of focal complications in brucellosis is crucial for improving treatment outcomes. However, there is currently a lack of established indicators or biomarkers for diagnosing these complications. Therefore, this study aimed to investigate potential warning signs of focal complications in human brucellosis, with the goal of providing practical parameters for clinicians to aid in the diagnosis and management of patients.
METHODS: A multi-center cross-sectional study was conducted in China from December 2019 to August 2021. The study aimed to investigate the clinical characteristics and complications of patients with brucellosis using a questionnaire survey and medical record system. The presence of warning signs for complications was assessed using univariate and multivariate logistic regression models. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used for variable screening and model evaluation.
RESULTS: A total of 880 participants diagnosed with human brucellosis were enrolled. The median age of the patients was 50 years [interquartile range (IQR): 41.5-58.0], and 54.8% had complications. The most common organ system affected by complications was the osteoarticular system (43.1%), with peripheral arthritis (30.0%), spondylitis (16.6%), paravertebral abscess (5.0%), and sacroiliitis (2.7%) being the most prevalent. Complications in other organ systems included the genitourinary system (4.7%), respiratory system (4.7%), and hematologic system (4.6%). Several factors were found to be associated with focal brucellosis. These factors included a long delay in diagnosis [odds ratio (OR) = 3.963, 95% confidence interval (CI) 1.906-8.238 for > 90 days], the presence of underlying disease (OR = 1.675, 95% CI 1.176-2.384), arthralgia (OR = 3.197, 95% CI 1.986-5.148), eye bulging pain (OR = 3.482, 95% CI 1.349-8.988), C-reactive protein (CRP) > 10 mg/L (OR = 1.910, 95% CI 1.310-2.784) and erythrocyte sedimentation rate (ESR) elevation (OR = 1.663, 95% CI 1.145-2.415). The optimal cutoff value in ROC analysis was > 5.4 mg/L for CRP (sensitivity 73.4% and specificity 51.9%) and > 25 mm/h for ESR (sensitivity 47.9% and specificity 71.1%).
CONCLUSIONS: More than 50% of patients with brucellosis experienced complications. Factors such as diagnostic delay, underlying disease, arthralgia, eye pain, and elevated levels of CRP and ESR were identified as significant markers for the development of complications. Therefore, patients presenting with these conditions should be closely monitored for potential complications, regardless of their culture results and standard tube agglutination test titers.

Hao-Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype-phenotype correlations, and disease trajectories. We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals. A questionnaire-based study was performed to characterize the phenotype of Hao-Fountain syndrome more clearly, to highlight new traits, and to better distinguish the disease from related neurodevelopmental disorders. In addition to confirming previously described features, we report hyperphagia and increased body weight in a subset of individuals. HAFOUS patients present an increased rate of birth complications, congenital anomalies, and abnormal pain thresholds. Speech impairment emerges as a potential hallmark of Hao-Fountain syndrome. Cognitive testing reports reveal borderline intellectual functioning on average, although some individuals score in the range of intellectual disability. Finally, we created a syndrome-specific severity score. This score neither indicates a sex- nor age-specific difference of clinical severity, yet highlights a more severe outcome when amino acid changes colocalize to the catalytic domain of the USP7 protein.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) and its association with diabetes might lead to mucormycosis, and studies have reported an association between them. This study aims to find the correlation between COVID-19 and diabetic status in patients with mucormycosis and its role in disease progression and prognosis. The objectives of the study are to analyze the clinical range of mucormycosis in those with diabetes and COVID-19 and to correlate the clinical and radiographic findings.
METHODS: A retrospective cohort analysis was carried out at Saveetha Dental College and Hospitals in Chennai (approval number: IHEC/SDC/OMED-2204/23/218). The data collection was done from the institution\'s electronic database from April 2019 to April 2023 which included the patients\' age and gender and COVID-19 and diabetic status and clinical and radiographic features of mucormycosis.
RESULTS: From the data analyzed, 25 patients had a history of mucormycosis with diabetes and COVID-19 infections. The patients\' average age was 47.76, out of which 22 were males and three were females. The chi-squared test showed no significant association between age (0.178), diabetes (0.465), and COVID-19 (0.583). Spearman\'s correlation was done showing an association between mucormycosis, diabetes, and COVID-19. Radiographically, 100% of the patients had involvement of the maxillary sinus, followed by the palate (32%), orbit (28%), nasal floor (24%), ethmoidal sinus (16%), sphenoidal sinus (12%), and frontal sinus (8%).
CONCLUSIONS: The findings of this study point out the importance of considering the presence of systemic comorbidities like diabetes in COVID-19 patients. Early identification, surgical debridement, and antifungal medications are part of the treatment for increased survival.

Protein-truncating variants in α-1,3-glucosyltransferase (ALG8) are a risk factor for a mild cystic kidney disease phenotype. The association between these variants and liver cysts is limited. We aim to identify pathogenic ALG8 variants in our cohort of autosomal dominant polycystic liver disease (ADPLD) individuals. In order to fine-map the phenotypical spectrum of pathogenic ALG8 variant carriers, we performed targeted ALG8 screening in 478 ADPLD singletons, and exome sequencing in 48 singletons and 4 patients from two large ADPLD families. Eight novel and one previously reported pathogenic variant in ALG8 were discovered in sixteen patients. The ALG8 clinical phenotype ranges from mild to severe polycystic liver disease, and from innumerable small to multiple large hepatic cysts. The presence of <5 renal cysts that do not affect renal function is common in this population. Three-dimensional homology modeling demonstrated that six variants cause a truncated ALG8 protein with abnormal functioning, and one variant is predicted to destabilize ALG8. For the seventh variant, immunostaining of the liver tissue showed a complete loss of ALG8 in the cystic cells. ALG8-associated ADPLD has a broad clinical spectrum, including the possibility of developing a small number of renal cysts. This broadens the ADPLD genotype-phenotype spectrum and narrows the gap between liver-specific ADPLD and kidney-specific ADPKD.

Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.