Predominant Manifestation Research Articles

Dermatological manifestations and associated factors in patients with Graves\' disease in Dakar

: The dermatological manifestations of Graves' disease exhibit a polymorphic nature. Our objective was to delineate the diverse cutaneous, mucosal, and pharyngeal manifestations associated with Graves' disease and to assess the influence of the received treatments.: This cross-sectional study involved the prospective collection of data conducted between March 1st and August 31st, 2021. We enrolled patients aged 18 years or older diagnosed with Graves' disease and under follow-up care at two referral endocrinology units.: Out of the 288 enrolled patients, 210 (72.9%) presented dermatological manifestations. The average age was 38.27 years, and the sex ratio was 0.117. Notably, 44.7% (n=84) of patients reported a history of voluntary skin bleaching. The predominant dermatological manifestations included palmar and/or plantar hyperpigmentation (55.7%), dry and brittle hair (47.6%), non-scarring alopecia (45%), axillary depilation (36.2%), hand wetness (22.8%), skin xerosis (18.6%), pruritus (17%), eyebrow tail sign (16.2%), palmar and/or plantar keratoderma (14.3%), brittle nails (9%), pretibial myxedema (1.4%), and one case of lichenoid toxidermia related to thiamazole. Notably, pruritus showed a statistically significant correlation with the use of oral phytotherapy (p=0.04784). Among former patients, cutaneous hyperpigmentation was statistically associated with carbimazole (p=0.03721) and propranolol (p=0.009850).: The primary dermatological feature in Graves' disease is characterized by the prevalence of cutaneous hyperpigmentation. The persistence of these manifestations for some patients may be attributed to the treatments administered.

Distinguishing seizures in autoimmune limbic encephalitis from mesial temporal lobe epilepsy with hippocampal sclerosis: Clues of a temporal plus network

ObjectiveDiagnosing autoimmune limbic encephalitis (ALE) in adults with new-onset seizures can be challenging, especially when seizures represent the predominant manifestation and MRI findings are not straightforward. By comparison with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), this study aimed to identify ictal electro-clinical features that might help clinicians recognize ALE-related seizures. MethodsThis retrospective, multi-centre study analysed the ictal semiology and EEG correlate of 116 video-EEG-captured seizures in 40 ALE patients and 45 ones recorded in 21 MTLE-HS subjects. The proportion of patients presenting each clinical feature on at least one occasion was compared between the study groups. Latent class analysis (LCA) was also performed. ResultsIctal features were overall more numerous in ALE than in MTLE-HS (33 vs 22), and LCA confirmed the intrinsic variability of ALE-related seizures. Hyperventilation served as a trigger only in ALE (4/40). Awareness impairment (p = 0.032), limb dystonic posturing (p = 0.009) and manual automatisms (p < 0.001) were significantly less common in ALE cases. Conversely, piloerection was observed only in ALE subjects, although it did not reach statistical significance (p = 0.289), as was the case for déjà-vu (p = 0.084), and sensory symptoms (p = 0.079). Regarding EEG, the type of ictal pattern differed significantly (p = 0.007). SignificanceThis study shows that, despite the wide overlap with MTLE-HS, some ictal electro-clinical features could help clinicians suspect the autoimmune origin of adult-onset seizures. Moreover, autoimmune limbic seizures apparently shared similarities with ‘temporal plus’ epilepsy, which could partly account for the poor surgical outcomes and provide an interesting conceptual framework for future research.

Clinical features, treatment, and outcome of granulocyte colony stimulating factor-induced sweet syndrome.

Sweet syndrome (SS) is a rare dermatological adverse reaction caused by granulocyte colony-stimulating factor (G-CSF), but the characteristics of G-CSF-induced SS are unclear. This study aims to elucidate the characteristics of G-CSF-induced SS and offer guidance for its prevention and management. We collected relevant case reports of G-CSF-induced SS by searching pertinent databases until June 30, 2024, and synthesized the data for retrospective analysis. A total of fifty patients were analyzed, with a median age of 44 years (1.7-77). The onset of SS occurred between 2 and 90 days post-administration, with a median onset time of 7 days. The predominant cutaneous manifestations included papules/plaques (74.0%), nodules (32.0%), and vesicles/bullae (24.0%). Fever presented in 74.0% of cases, while extra-cutaneous symptoms appeared in 32% of patients. Skin biopsy revealed key findings such as dermal diffuse neutrophil infiltration (97.8%), leukocytoclasis (19.1%), and dermal papillary edema (27.7%). Following both the cessation of G-CSF and systemic corticosteroids treatment, patients showed symptomatic improvement at a median interval of 7 days (2-70). Clinicians should remain vigilant for the risk of SS during G-CSF administration. Skin biopsy plays a crucial role in confirming SS diagnosis. G-CSF-induced SS exhibits a favorable response to corticosteroids, and re-administration of G-CSF should be avoided due to the risk of symptom recurrence.

Clinical profile, laboratory characteristics and prognostic factors in patients with miliary tuberculosis

BackgroundMiliary tuberculosis (TB) is a severe form of pulmonary TB. It is uncommon in immunocompetent patients. In this study, we aimed to investigate features of miliary TB (clinical, biological, and radiological) and to determine factors associated with unfavorable outcomes in a population of patients in the South East Tunisia where TB remains endemic. MethodsThis is a retrospective study including patients diagnosed with miliary TB between 2006 and 2023. Factors independently associated with poor prognosis were determined by multivariate logistic regression analysis. ResultsMiliary tuberculosis (TB) accounted for 1.8% (n = 36) of all TB cases diagnosed during the study period. A notable female predominance was observed, comprising 66.6% of the cohort. The median age of patients was 47.5 ± 11.33 years. The predominant clinical manifestations included cough (88.8%), loss of appetite (77.7%), and fever (58.3%). Radiologically, a typical miliary pattern was present in 83.3% of patients, although only 36.1% had positive sputum samples on direct smear microscopy. Notably, all patients tested negative for HIV serology. Extrapulmonary TB involvement was documented in 55.5% of cases. All patients were treated with first-line anti-TB medications, and the outcome was favorable in 77.7% (n = 28) of patients. However, 16.6% (n = 6) of patients succumbed to the disease. Factors significantly associated with unfavorable outcomes included age ≥65 years (odds ratio (OR) = 0.39; p = 0.03), diabetes (OR = 0.13; p = 0.046), presence of fever (OR = 2.89; p = 0.01), and oxygen saturation ≤92% at admission (OR = 3.2; p = 0.001). ConclusionOur study identified advanced age, diabetes, fever at baseline, and low oxygen saturation on admission as significant predictors of poor prognosis in patients with miliary tuberculosis. These findings highlight the need for early identification and targeted management of high-risk individuals to improve clinical outcomes.

Eosinophil-Related Disorders With Myelitis as the Predominant Clinical Manifestation: A Case Report.

Eosinophil-Related Disorders With Myelitis as the Predominant Clinical Manifestation: A Case Report.

Clinical characteristics and risk factors for antituberculosis drug-induced hypersensitivity.

The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs. A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020. Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016-1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145-2.913), existing liver disease (OR = 2.464, 95% CI: 1.822-3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681-16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs. Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre-existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity.

Molecular investigation of MEFV gene polymorphisms among patients with familial mediterranean fever-like symptoms.

The diagnosis of familial Mediterranean fever (FMF) is primarily based on clinical standards. The purpose of this study was to investigate the relevance of Mediterranean fever (MEFV) genetic testing in the diagnosis of FMF as well as to identify the most frequent variant alleles and their relationship to clinical symptoms in Egyptian patients. Egyptian patients with a clinical suspicion of having FMF were studied in order to determine MEFV genotypes. Each patient was meticulously evaluated through an extensive collection of their medical history, a thorough clinical examination, and a series of laboratory tests, encompassing CBC, ESR, and CRP measurements. The MEFV variant screening procedure included the use of reverse dot blot hybridization. The average age of our patients when they were given a diagnosis was 22.8 ±1.404 years old. The predominant clinical manifestations identified were abdominal pain, fever, and arthralgia. Molecular interrogation of the MEFV gene unveiled that a significant proportion of the cohort, constituting 72 individuals (60%), displayed heterozygosity, whereas a smaller fraction, comprising 12 subjects (10%), demonstrated homozygosity and an equivalent number (10%) exhibited compound heterozygosity. Pertaining to the distribution of allele variants, E148Q emerged as the most prevalent, succeeded by M694I, accounting for 12.5% of the cases, and M680I (G/A), representing 10.41%. This notable prevalence of heterozygous genotypes among the Egyptian demographic, preliminarily identified as potential FMF cases, underscores the imperative for molecular diagnostics to enhance the precision of FMF identification.

Prognostic factors and treatment outcomes in pediatric autoimmune encephalitis: a multicenter study.

The last few decades have increased our understanding of autoimmune encephalitis (AE). In both the pediatric and adult populations, it proves to be a disease of dramatic acute onset of heterogeneous clinical manifestations, notably encephalopathy with neuropsychiatric symptoms, seizures, and extrapyramidal symptoms. More often, it is triggered by a viral infection in the pediatric age groups, as suggested by the preceding febrile symptoms in over half of cases, and more ostensibly, NMDAR encephalitis post herpes encephalitis. An underlying neoplasm may be present in certain types (i.e., NMDAR encephalitis). The rising rate of antibody detection and subsequent confirmation has been boosted by improved live cellular assay detection methods. The corresponding clinical phenotypes, common underlying malignancies, and histopathological findings have helped improve our management regarding intervention and choice of immunotherapy. New assessment tools such as the Clinical Assessment Scale in Autoimmune Encephalitis (CASE score) have helped improve the objective assessment of impact on cognitive functions (1). Early intervention with immunotherapy (and tumor removal in proven underlying neoplasms) has improved overall outcomes in most presenting patients. But nearly 40% of cases fail to respond to the first tier of treatment (2). The complex interplay between pathogenic autoantibodies, T-cells, B-cells, and cytokines has led to the emergence of additional immunotherapy agents (i.e., tocilizumab and bortezomib). In this retrospective observational study of pediatric AE conducted at two tertiary care centers, we observed the clinical characteristics, autoantibody yield, treatment modalities used, and disability scores during presentation and follow-up. Our secondary aim was to delineate prognostic factors for poor outcomes. Neuropsychiatric symptoms, encephalopathy, and seizures were the predominant manifestations in most of our patients. Younger age groups, refractory seizures, profound encephalopathy, and refractory disease harbored higher disability scores. The group that received combined immunotherapy has shown mitigation of disability score from severe to mild during long-term follow-up, signifying the role of multifaceted immunotherapy in pediatric refractory AE. Early implementation of combined immunotherapy in refractory cases significantly improved longterm disability scores, in spite of lingering residual effects on neurologic functions, notably cognition, behavior, and speech.

Formation of a Large Cold Groundwater Mantle Helium Anomaly and High Temperature Geothermal Resources in Response to Bimodal Magmatism Near Roosevelt Hot Springs and Utah FORGE, Milford Valley, Southwest Utah

AbstractA large mantle helium anomaly and separate domains of high heat flow are the predominant manifestations of bimodal magmatic activity in the Milford valley. The mantle helium anomaly (1.9–2.6 R/Ra) covers 270 km2 and is subdivided into two separated domains: a cold shallow groundwater regime and high temperature hydrothermal activity. The zone of anomalous heat flow covers &gt;100 km2 and is also subdivided into two adjacent domains, comprising hydrothermal activity at Roosevelt Hot Springs (RHS) (3–7 W/m2) and conductive heat flow (100–180 mW/m2). While the transfer of heat and mantle helium at RHS are coupled, heat and helium transfer are decoupled in the adjacent cold groundwater regime to the west. Both the mantle helium and geothermal anomalies are attributed to recent mafic‐felsic magmatic intrusions of &gt;400 km3, however, the absence of volcanic eruptions &lt;500,000 years indicates magmas stall before rising to shallow crustal level &lt;10 km depth. Deep level magmatism produces a felsic composition melt, which is inferred to be responsible for the widespread and near uniform range of diluted mantle helium values. A thick and impermeable mass of crystalline granitic basement rock at the mid‐crustal level divides the ascent of mantle helium into separate flow paths. It may also impede the rise of buoyant magma trapping thermal energy that facilitates partial melting, slow cooling, and development of a thick thermal aureole. Partitioning of convective and conductive thermal regimes and independent flow paths supplying deeply derived helium characterize the development of a large long‐lived magma‐related geothermal system.

Sowing the seeds for sustainability: A business model innovation perspective on artificial intelligence in green technology startups

In today's data-driven era, ubiquitous concern about environmental issues pushes more startups to engage in business model innovation that promotes environmentally friendly technologies. The goal of these startups is to create technology-based products and services that enhance environmental sustainability. In this context, artificial intelligence promises to be a key instrument to create, capture, and deliver value. However, the existing literature lacks a deep understanding of how startups using AI innovate their business models to achieve a positive environmental impact. Therefore, this paper investigates how green technology startups utilize AI from a business model innovation perspective for environmental sustainability. We conduct a qualitative, exploratory multiple-case study using the Eisenhardt methodology, based on interview data analyzed using qualitative content analysis. We derive five predominant manifestations for AI-driven business model innovation and identify archetypical connections between business model dimensions. Further, we establish three overarching archetypical associations among the cases. In doing so, we contribute to theory and practice by providing a deeper account of how green technology startups attempt to maximize their positive environmental impact through AI. The results of this study also highlight how business model innovation driven by AI can support society in securing a more environmentally sustainable future.

C-Myc-XRCC2-FOS axis promotes the proliferation and the resistance to Doxorubicin of NSCLC

Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80 %-90 % of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.

Hereditary antithrombin deficiency pilot project registry from the American Thrombosis and Hemostasis Network

BackgroundPatients with hereditary antithrombin deficiency (HAD) have an increased risk of venous thromboembolism (VTE). The American Thrombosis and Hemostasis Network (ATHN) 12: HAD Pilot Project established a registry to collect data on patients with HAD. ObjectivesTo inform current practice and serve as a platform to design a multicenter global registry for patients with HAD. MethodsThe HAD registry was designed in 2020 to identify 100 patients with HAD receiving care at ATHN-affiliated centers. Demographics, type of HAD, thrombotic events, risk factors, anticoagulants, and antithrombin (AT) concentrate administration were recorded. ResultsNinety-four patients were included; 65% were females; 51% had type 1 HAD. Mean age at diagnosis was 26 years (SD, 18 years); 61% had VTE: 55% deep vein thrombosis and 27% pulmonary embolisms. Eight patients had arterial thrombosis. Recurrent thrombosis occurred in 58.6% of patients (44.8%) despite anticoagulation. The main risk factor for thrombosis in females was estrogen. Direct oral anticoagulants were prescribed in 30%, heparin in 34%, and warfarin in 32%. There were 139 pregnancies. Low-molecular-weight heparin was administered in 33% and AT concentrate in 19% and 11% prior to and after delivery, respectively. Twelve patients developed thrombosis in pregnancy. Seventy-nine patients underwent 239 surgeries or procedures, mainly gastrointestinal and vascular. Overall, 35% of participants received AT concentrate without adverse events. ConclusionIn ATHN 12, VTE was the predominant manifestation, frequently recurrent. There was a trend toward using direct oral anticoagulants. Low-molecular-weight heparin was administered in one-third of pregnancies and AT concentrate in one-fifth without adverse events. These data should encourage prospective studies to optimize the management of these patients.

Generation of hereditary spastic paraplegia patient-derived induced pluripotent stem cell line UJSi003-A

Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. Patients with HSP experience spastic paralysis in both lower limbs, leading to progressive walking difficulties, increased reflexes, spasms, and extensor plantar responses. We successfully generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) obtained from a patient diagnosed with HSP. The iPSCs exhibited a normal karyotype, expressed pluripotency markers, and differentiated into the three germ layers in vitro.

Genome-wide methylation and gene-expression analyses in thalassemia.

Thalassemia is the most common autosomal genetic disorder in humans. The pathogenesis of thalassemia is principally due to the deletion or mutation of globin genes that then leads to disorders in globin-chain synthesis, and its predominant clinical manifestations include chronic forms of hemolytic anemia. However, research on the epigenetics and underlying pathogenesis of thalassemia is in its nascency and not yet been systematically realized. In this study, we compared the results of RNA-seq and the whole-genome bisulfite sequencing (WGBS) on 22 peripheral blood samples from 14 thalassemic patients and eight healthy individuals revealed a genome-wide methylation landscape of differentially methylated regions (DMRs). And functional-enrichment analysis revealed the enriched biological pathways with respect to the differentially expressed genes (DEGs) and differentially methylated genes (DMGs) to include hematopoietic lineage, glucose metabolism, and ribosome. To further analyze the interaction between the transcriptome and methylome, we implemented a comprehensive analysis of overlaps between DEGs and DMGs, and observed that biological processes significantly enriched the immune-related genes (i.e., our hypermethylated and down-regulated gene group). Hypermethylated and hypomethylated regions of thalassemia-related genes exhibited different distribution patterns. We thus, further identified and validated thalassemia-associated DMGs and DEGs by multi-omics integrative analyses of DNA methylation and transcriptomics data, and provided a comprehensive genomic map of thalassemia that will facilitate the exploration of the epigenetics mechanisms and pathogenesis underlying thalassemia.

CGG/CCG Repeat Expansions in LOC642361/NUTM2B-AS1 in Thai Patients With Oculopharyngodistal Myopathy.

This study characterizes oculopharyngodistal myopathy in 4 Thai patients from 3 families with CGG/CCG repeat expansion in LOC642361/NUTM2B-AS1. Repeat-primed PCR analyzed CGG/CCG repeat size in LOC642361/NUTM2B-AS1 in 4 Thai patients suspected of oculopharyngodistal myopathy (OPDM). Clinical records were reviewed for clinicopathologic features. All patients exhibited strong somatic instabilities of the expanded CGG/CCG repeats, primarily manifesting as oculopharyngeal weakness. Patient 1 had mild finger extensor and intrinsic hand muscle weakness, and although patient 2 lacked limb weakness, both siblings showed electrophysiologic evidence of distal myopathy, indicative of OPDM. Patient 3, the daughter of a sibling with OPDM reported in 2004, lacked limb weakness or leukoencephalopathy on brain MRI. Patient 4, initially misdiagnosed with refractory myasthenia gravis, had generalized muscle weakness. While initially characterized as oculopharyngeal myopathy with leukoencephalopathy (OPML) in a Japanese family, our study suggests a stronger association between CGG/CCG expansion in LOC642361/NUTM2B-AS1 and oculopharyngodistal myopathy (OPDM) rather than OPML. The variable presence or absence of leukoencephalopathy further supports OPDM as the predominant clinical manifestation linked to CGG/CCG expansion in LOC642361/NUTM2B-AS1.

Investigations on cleavage fracture mechanism and surface damage of indium phosphide by molecular dynamics simulation

The quality and undamaged size in the resonant cavity surface directly affect the operational stability and output power of semiconductor lasers. To meet the demand for large-size and high-quality mirror facets, a deep understanding of fracture mechanisms of mechanical cleavage is essential. Nevertheless, 3D models of cleavage fracture are rarely investigated. In this work, a molecular dynamics study on the cleavage mechanisms of indium phosphide is reported through examining the effects of the cleavage gap, scratch depth, and cleavage rate on the cleavage damage morphology. The proposed molecular dynamics approach provides insights into the details of cleavage fracture at the atomic level. The simulation results reveal that the cleavage fracture mechanism includes the deviation of cracks between adjacent cleavage surfaces. The predominant damage manifestations on the cleavage surfaces are mainly characterized by cleavage terraces that begin at the bottom of the scratched groove. The cleavage terraces propagate along the [001] crystal direction on the (110) cleavage surface and deviate from their path. This phenomenon is essentially related to the stress released during the crack propagation process. Compared with the cleavage gap and scratch depth, the cleavage rate significantly affects the critical cleavage load. Additionally, a good correlation between the density of the cleavage terraces and the maximum undamaged length is achieved and reasonably explained. Mastering the correlation between various cleavage conditions and cleavage surface damage will facilitate and guide the fabrication of nanoscale resonant cavity mirrors and advance the development of mechanical cleaving processes.

Severe Organ Impairment Was Common in Elderly Individuals with Dengue in Guangdong, China.

Guangdong, China, has experienced several dengue epidemics involving thousands of confirmed cases in recent decades, and elderly individuals suffered severe dengue (SD) most seriously. However, the clinical characteristics and risk factors for SD among elderly patients in Guangdong have not been investigated. Patients older than 65 years were recruited and divided into a dengue fever (DF) group and an SD group according to the 2009 Dengue Guidelines of the WHO. We analyzed the clinical manifestations of the elderly patients with dengue and then assessed the risk factors for SD. Of a total of 1,027 patients, 868 patients were diagnosed as having DF and 159 as having SD. Of the 159 elderly patients with SD, 129 (81%) had comorbidities, with hypertension being the most common. Severe organ impairment (SOI) (115, 54%) was the most common presentation in SD patients, followed by severe plasma leakage (52, 24.4%) and severe hemorrhage (46, 21.6%). The most common symptom of SOI was kidney injury, followed by heart injury and central nervous system injury. Furthermore, multivariate regression revealed that the presence of chronic obstructive pulmonary disease (COPD), a lower red blood cell (RBC) count (≤3.5 × 1012/L; odds ratio [OR], 0.35; 95% CI, 0.17-0.55; P <0.001), lower serum albumin (ALB) (≤35 U/L; OR, 0.18; 95% CI, 0.09-0.32; P <0.001), and hyperpyrexia (body temperature ≥39°C; OR, 1.8; 95% CI, 1.2-2.6, P <0.001) were risk factors for SD. Severe organ impairment was the predominant manifestation in elderly individuals with SD characterized by kidney injury. The potential risk factors of SD such as presence of COPD and hyperpyrexia and lower RBC and ALB levels might help clinicians identify patients with SD early.

Human DNA-dependent protein kinase catalytic subunit deficiency: A comprehensive review and update

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has an essential role in the non-homologous end-joining pathway that repairs DNA double-strand breaks in V(D)J recombination involved in the expression of T- and B-cell receptors. Whereas homozygous mutations in Prkdc define the Scid mouse, a model that has been widely used in biology, human mutations in PRKDC are extremely rare and the disease spectrum has not been described so far. To provide an update on the genetics, clinical spectrum, immunological profile, and therapy of DNA-PKcs deficiency in human. The clinical, biological, and treatment data from the 6 cases published to date and from 1 new patient were obtained and analyzed. Rubella PCR was performed on available granuloma material. We report on 7 patients; 6 patients displayed the autosomal recessive p.L3062R mutation in PRKDC-encoding DNA-PKcs. Atypical severe combined immunodeficiency with inflammatory lesions, granulomas, and autoimmunity was the predominant clinical manifestation (n= 5 of 7). Rubella viral strain was detected in the granuloma of 1 patient over the 2 tested. T-cell counts, including naive CD4+CD45RA+ T cells and T-cell function were low at diagnosis for 6 patients. For most patients with available values, naive CD4+CD45RA+ T cells decreased over time (n= 5 of 6). Hematopoietic stem cell transplantation was performed in 5 patients, of whom 4 are still alive without transplant-related morbidity. Sustained T- and B-cell reconstitution was observed, respectively, for 4 and 3 patients, after a median follow-up of 8 years (range 3-16 years). DNA-PKcs deficiency mainly manifests as an inflammatory disease with granuloma and autoimmune features, along with severe infections.

Diagnostic Yield of Same Setting Oesophago-Gastro-Duodenoscopy (OGD)and Colonoscopy for Pediatric Patients with Chronic Diarrhea

Abstract Background In patients with unexplained chronic diarrhea colonoscopy and upper GI endoscopy are helpful in the diagnosis. It is the routine practice in Ain Shams University pediatric endoscopy unit to perform both procedures at same setting for patients with unexplained chronic diarrhea. Aim of the Work To find out whether doing Oesophago-gastro-duodenoscopy (OGD) and colonoscopy in patients with chronic diarrhea in one setting is essential for the diagnosis of all cases. Patients and Methods Fifty patients presenting with chronic unexplained diarrhea (&amp;gt;4 weeks duration) in Paediatric Gastroenterology Unit, Children’s Hospital, Ain-Shams University were enrolled. After full history taking, physical examination, both endoscopies were performed biopsy taken and histopathological recording for each sample. Results Of 50 patients with chronic diarrhea included in our study; 23 (46%) had positive endoscopic findings in the OGD. Most common findings in esophagus and stomach were inflammation and erythema. while most common findings in duodenum were edema and flattened mucosa. Colonoscopy findings were positive in 50% of patients including inflammation, nodularity, and edema mostly in the ileum. 50% of endoscopied patients reached final diagnosis based on endoscopy and histopathology. Definitive diagnosis reached through EGD alone in (12%) of cases, through colonoscopy alone in (28%) and through both techniques in (60%). There was no statistical significant agreement between endoscopy findings and predominant gastrointestinal manifestations including different types of diarrhea, fecal calprotectin with p-value =0.150, and 0.833 respectively. There was no statistical significant agreement between final diagnosis and suspected GIT part involvement on initial clinical evaluation with p- value=0.805. Conclusion Endoscopy for upper gastrointestinal tract and colonoscopy at same day may be helpful in diagnosis of cases with chronic diarrhea as we can't decide which one to perform based on clinical presentation.

Clinical Analysis of Patients Diagnosed with Cutaneous Sporotrichosis in China.

This study aimed to improve the understanding of sporotrichosis by analyzing the epidemiological characteristics, clinical manifestations, mycological features, and pathological characteristics of the disease in eastern China. Clinical data of 49 patients diagnosed with cutaneous sporotrichosis in dermatology clinics over a 20-year period were collected and analyzed retrospectively. The analysis included patient demographics, occupations, clinical types, lesion sites, misdiagnosis rates, laboratory investigations, treatment and outcomes. The study included 22 male and 27 female patients, with a mean age of 52.4 years. Farmers (42.86%) and manual workers (28.57%) had a higher risk of infection. The most common clinical types were lymphocutaneous (30.61%) and fixed (69.39%), predominantly affecting the face and upper limbs. Misdiagnosis as other infectious skin diseases occurred in 35 patients (71.43%). Fungal culture and histopathological examination were important diagnostic tools. Treatment with oral itraconazole for three months led to relief and regression of the skin lesions in most patients, although a few experienced recurrences. Cutaneous sporotrichosis mainly affects individuals working in agriculture and manual labour, with lymphocutaneous and fixed types being the predominant clinical manifestations. The high misdiagnosis rate emphasizes the importance of early recognition, accurate diagnosis and standardized treatment for the prognosis and cure of sporotrichosis. Fungal culture and histopathological examination are essential for diagnosis, and oral itraconazole is an effective treatment option.