Clinical Manifestations Research Articles

Clinical and genetic characteristics of children with Pitt-Hopkins syndrome caused by TCF4 gene variants

The clinical data of children with Pitt-Hopkins syndrome (PTHS) who were treated in the Affiliated Women and Children's Hospital of Ningbo University from September 2022 to January 2024 were retrospectively included. The patients were followed up to June 2024, and their clinical and genetic characteristics were analyzed. A total of 4 children were included, 2 males and 2 females, with a diagnostic age [M (Q1, Q3)] of 22 (10, 32) months. All the patients presented with typical facial and overall developmental delay (developmental, motor and language delay). The 4 patients were found to harbor de novo heterozygous variants of the TCF4 gene, including the c.990G>A(p.S330S), c.1417_1418delinsT (p.Pro473ArgfsTer15), c.1028C>G (p.S343*) and c.500-2delinsTC. After 15 months of follow-up, all 4 patients received early rehabilitation treatment, and their gross motor function improved to varying degrees, while 3 patients had no improvement in language function. TCF4 gene variation in 4 children had phenotypic heterogeneity, and the main clinical manifestations were developmental delay, language development disorder and special facial features. Among the gene variation types, there was 1 case each of synonym variation, frameshift variation, nonsense variation and splicing variation.

Long-Term Efficacy and Safety of Risankizumab for csDMARD-IR Patients With Active Psoriatic Arthritis: 196-Week Results From the KEEPsAKE 1 Trial

Introduction & Objectives: Here, we report the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 196 from the KEEPsAKE 1 trial. Materials & Methods: The ongoing KEEPsAKE 1 clinical trial is a global, phase 3, multicenter study to evaluate the efficacy and safety of RZB versus placebo (PBO) in patients with active PsA. Patients are at least 18 years old and demonstrated an inadequate response, intolerance or contraindication to ≥1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR). Following a 24-week double-blind, PBO-controlled, parallel-group treatment period (period 1), all patients received open-label RZB every 12 weeks thereafter (period 2). Safety assessments were based on monitoring of treatment-emergent adverse events (TEAEs) reported as events per 100 patient-years (PY). Efficacy and safety analyses were conducted in all randomized patients who received ≥1 dose of the study drug. Results: Overall efficacy results were maintained at week 196 of the KEEPsAKE 1 trial, as compared to previously reported timepoints. At week 196, 39.4% of patients receiving continuous RZB and 38.1% of PBO/RZB patients achieved ACR50; 39.6% of RZB and 35.2% of PBO/RZB patients achieved MDA. In patients with psoriasis severity of ≥ 3% of body surface area (BSA) at baseline, 65.2% on RZB and 62.9% on PBO/RZB achieved PASI90 at week 196. mNAPSI and PGA-F scores improved from baseline by 14.99 and 1.5 points, respectively, for RZB, and by 14.73 and 1.5 points for PBO/RZB patients. In patients with enthesitis at baseline, 60.1% on RZB and 63.4% on PBO/RZB achieved resolution. For patients with dactylitis at baseline, 72.3% on RZB and 77.6% on PBO/RZB achieved resolution. HAQ-DI (RZB -0.40, PBO/RZB -0.33), SF-36 PCS (RZB 8.98, PBO/RZB 7.21) and FACIT-Fatigue (RZB 7.7, PBO/RZB 5.6) scores maintained improvement from baseline to week 196. The overall rates of TEAEs (121.4 E/100PY), serious TEAEs (7.7 E/100PY) and AEs leading to discontinuation of study drug (1.8 E/100PY) have remained stable and comparable to those reported in period 1. Conclusion: The 196-week results of the ongoing KEEPsAKE 1 trial demonstrate the durable efficacy of RZB 150 mg in treating the different clinical manifestations and improving health-related quality of life in csDMARD-IR patients with PsA. RZB continued to be well-tolerated, with no new safety signals.

Retrospective characterization of seizure semiology and treatment using continuous video‐EEG monitoring in neonatal encephalopathy in Uganda

AbstractObjectiveNeonatal encephalopathy (NE) is a leading cause of childhood death and disability, particularly in sub‐Saharan Africa. Detection of NE‐related seizures is challenging. We explored NE seizure semiology and management in Uganda.MethodsVideo‐EEG was recorded (days 1–5), seizure semiology reviewed according to ILAE classification and administration of antiseizure medication (ASM) evaluated. Clinicians treated seizures based on the clinical presentation alone.ResultsAmong 50 participants, 52% (26) had EEG‐confirmed seizures; 70% (18) combined electroclinical/electrographic; 4% (1) exclusively electroclinical; 22% (6) electrographic. Of those with electroclinical seizures (19), 42% displayed >1 semiology. Distribution of seizure semiology was; clonic 34% (11); autonomic 24% (8, of which 6 had prolonged ictal apnea); automatisms 18% (6); behavioral arrest 12% (4); and sequential 12% (4). ASM was administered to 64% (32/50). Of those with EEG‐confirmed seizures, only 62% (16/26) received ASM. In the non‐seizure group, 38% (9/24) received ASM during monitoring. ASM was administered 42 times, of which 45% (19) were considered appropriate.SignificanceIn this Ugandan NE population, incidence of seizures was high and clinical manifestations frequent. Clonic, autonomic and automatisms were most common. Clinical management was challenging, with both under and overtreatment evident. Respiratory impairment due to autonomic seizures frequently went unrecognized and is a prominent concern, particularly in settings without neonatal intensive care.

Sjögren’s Disease and Gastroesophageal Reflux Disease: What Is Their Evidence-Based Link?

Sjögren’s disease (SjD), or primary Sjögren’s syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin’s lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sjögren’s Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren’s syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sjögren’s disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sjögren’s disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords ‘Sjögren’s syndrome’ OR ‘Sjögren’s disease’ AND ‘gastroesophageal reflux disease’ AND ‘microbiota’ OR microbiota dysbiosis’. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sjögren’s disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sjögren’s disease and the personalized management of the disease.

Placental Abruption: Pathophysiology, Diagnosis, and Management

Placental abruption is a complete or partial separation of the placenta from the uterine decidua. Clinical manifestations include vaginal bleeding, abdominal pain, uterine contractions, and abnormalities in the fetal heart rate tracing. Placental abruption occurs in 0.4% to 1.0% of all pregnancies. However, the pathophysiology remains incompletely understood. We present a review of the pathophysiology, diagnosis, and management of placental abruption, exploring overlapping processes which contribute to premature placental separation. Classic findings and limitations of ultrasound in evaluating placental abruption are explained. Finally, we discuss the management of placental abruption based on gestational age, fetal status, and maternal hemodynamic stability.

Abstract A012: Aging drives TNBC lung metastasis dependency on FGFR-triggered metabolic reprogramming exposing an age-induced liability with therapeutic potential

Abstract The clinical manifestation of metastasis in a vital organ is the final stage of breast cancer progression and the main culprit of breast cancer related mortality. This remain especially problematic in the case of triple negative breast cancer (TNBC), the most aggressive type of breast cancer, often diagnosed in its metastatic form and for which chemotherapies are still the major therapeutic option. Typically, TNBC is seen as a disease of younger women, however, 20% of TNBCs occur in patients aged 65 and older, whose prognosis is equally staggering. Unfortunately, due to co-morbidities, tolerability of chemotherapies, as well as severe reduction in quality of life, majority of women above age 65 can’t or decide not to receive chemotherapy ultimately cutting their lives short. Metastatic outgrowth is largely dictated by the ability of TNBC disseminated cancer cells (DCCs) to thrive distal organs and is largely dependent on the physiology of the specific organs. However, how the aging process, a major driver of changes in organismal physiology, affects the interaction between the host organ and TNBC DCCs remains unknown. Here, we adapted several traditional syngeneic models of TNBC metastasis to old mice of different strains and coupled with RNA-seq to unveil molecular adaptations of TNBC DCCs to the aging lung. We show that the changes that occur in the lung with aging drives an increase in mitochondrial fitness in TNBC DCCs, an adaptation that is necessary for metastasis to thrive in the old lung environment. Mechanistically, our data show that the expression of FGF19, a gut hormone not normally expressed in TNBC DCCs, drives this increase in mitochondrial fitness in the old lung through an autocrine signaling axis impinging on activation of FGF-19 cognate receptor family, FGFRs. Inhibition of FGF19-FGFR signaling using an FDA- approved FGFR inhibitor not only blocks the age-induced increase in mitochondrial fitness but also effectively abolishes lung metastasis in old, but not in young, immune competent and immune compromised mice. We traced this to age-specific metastatic adaptation of TNBC lung metastasis to the increase in bile acids, the canonical regulators of FGF19 expression, in the old lung environment. Together, our work demonstrates an important contribution of age-driven metabolic reprogramming of the host to the traits that enable metastasis to thrive in the lung and provides rationale for the use of FDA-approved FGFR inhibitors for the treatment of breast cancer lung metastasis in the most vulnerable of stage IV metastatic TNBC patients, the elderly. Citation Format: Stanislav Drapela, Shiun Chang, Rojan Chimeh Rad, Vanessa Rubio, Didem Ilter, Paulo Rodriguez, Ana P. Gomes. Aging drives TNBC lung metastasis dependency on FGFR-triggered metabolic reprogramming exposing an age-induced liability with therapeutic potential [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A012.

MPOX (Monkeypox): Current Epidemiology, Clinical Manifestations, and Advances in Treatment and Prevention Strategies

MPOX (formerly known as monkeypox) has emerged as a significant public health concern in recent years, necessitating a comprehensive understanding of its epidemiology, clinical manifestations, treatment options, prevention strategies, and global health impact. This literature review synthesizes the latest data on the spread and incidence of MPOX, with a focus on geographic distribution, affected populations, and emerging trends in transmission. The clinical presentation of MPOX, including symptoms, disease progression, and complications, is explored, with particular attention to variations across different demographics. Recent advances in the treatment of MPOX are analyzed, covering current antiviral therapies, the role of supportive care, and the potential of new treatments under investigation. Prevention strategies are also examined, highlighting the effectiveness of vaccination efforts, public health measures, and containment and control strategies. The review further considers the broader impact of MPOX on global health, discussing its implications for public health policy and pandemic preparedness. Through this comprehensive analysis, the review aims to provide a robust foundation for understanding MPOX and inform future research, clinical practice, and public health initiatives.

Performance Assessment of ELISA Using the Trypanosoma cruzi-Specific Antigen Tc323 for the Diagnosis of Chronic Chagas Disease.

In the chronic phase of Chagas disease (CCD), diagnosis relies on detecting specific IgG antibodies due to the low or absent presence of the parasiteTrypanosoma cruzi in human blood. However, the performance of current serological tests is highly variable, lacking a "gold standard" assay with 100% sensitivity and specificity, which challenges the exploration of new biomarkers. In the present study, we evaluated the diagnostic accuracy of an optimized ELISA using the predicted immunogenic domains (called TcD3 and TcD6) of Tc323, a protein highly conserved among T.cruzi strains but absent in other clinically significant parasites such as Leishmania spp. This study was conducted using plasma or serum samples from CCD individuals with different clinical manifestations and living in endemic regions in Latin America, subjects with unrelated infectious diseases, and noninfected donors. The sensitivity and specificity of recombinant TcD3 were 90.8% and 92.6%, respectively, while rTcD6 displayed values of 93.1% and 93.6% for the same parameters. Area under curve (AUC) values were 0.949 for rTcD3 and 0.954 for rTcD6. The receiver operative characteristic (ROC) curve showed a highly significant difference between CCD individuals and noninfected donors. Cross-reactivity was 10.2% for rTcD3 and 8.2% for rTcD6 in subjects infected with leishmaniasis or with toxoplasmosis. In addition, the reactivity against rTcD3 differed among some geographical areas while no significant difference was found using both domains for the detection of T.cruzi-infected individuals with or without cardiac symptoms. Our findings show that the recombinant antigens rTcD3 and rTcD6 could be used as highly potential biomarkers for the serological diagnosis of CCD.

Gender and role differences of lecturer and student perspectives on sex- and gender-based medicine in the medical curriculum - a cross-sectional survey.

Sex- and gender-based medicine (SGBM) addresses differences between males/men and females/women with regard to clinical manifestation, diagnostics, treatment and outcomes of diseases. The implementation of SGBM in the medical curriculum varies, and data on the knowledge of lecturers and students about SGBM is scarce. This study aims to evaluate the perceived importance and knowledge of SGBM among lecturers and students. This cross-sectional observational survey was conducted using a questionnaire,including ranked with a Likert Scale. Statistical analysis was performed with the Chi-squared test. All lecturers and students at the Bern University Medical School in Switzerland were invited to voluntarily participate. 114 (34.1%) lecturers and 903 (41.4%) students participated in the survey. Women perceived education of SGBM to be of greater importance than men in lecturer and student subgroups respectively (lecturers women vs. men median 6.0 vs. 5.0, P = 0.011; students 6.0 vs. 5.0, P < 0.001). No significant differences between genders of self-reported knowledge of SGBM were found (lecturers women vs. men median 4.0 vs. 4.0, P = 0.624; students 3.0 vs. 4.0, P = 0.562). There were significant differences in the perception of the SGBM being actively addressed in lectures between lecturers and students (59.4% vs. 28.8%, P < 0.001) and whether the curriculum should include SGBM (strongly agree 28.9% vs. 51.3%, P < 0.001). Women lecturers and students consider teaching of SGBM during medical studies to be more important than men. Lecturers perceived the amount of SGBM already included in the lectures to be greater compared to students.

Apraxia: From Neuroanatomical Pathways to Clinical Manifestations.

Apraxia typically involves impairments in gesture production and tool use, affecting daily life activities. This article reviews current conceptualizations and developments in diagnostic and therapy. Apraxia has been studied in various neurological conditions, particularly stroke and dementia, but recent studies show gesturing deficits in psychiatric populations as well. Promising results have emerged from integrative treatment approaches involving intensive practice of gestures or daily activities. However, several reviews have noted the only marginal progress in apraxia therapy research despite new technologies, like virtual reality and brain stimulation, offering fresh opportunities for assessment and therapy. Advances in lesion-symptom mapping and connectivity analyses led to more detailed neuroanatomical models emphasizing parallel and gradual processing. These models facilitate the understanding of underlying mechanisms of motor cognitive performance and its decline. Finally, the digital era prompts the need to study digital tool use in apraxia, with initial efforts underway.

Analysis of the clinical manifestations and diagnostic process of the pleural effusion associated with constrictive pericarditis

ObjectivesThe primary objective of this study is to analyze the clinical manifestations, diagnostic procedures, and outcomes of patients with pathologically confirmed constrictive pericarditis who presented with bilateral pleural effusions. We aim to outline a stepwise diagnostic approach that could assist clinicians in identifying CP in similar cases.MethodsIn this study, we conducted a retrospective analysis of 19 cases of pathologically confirmed constrictive pericarditis. These patients were admitted to our hospital between January 2019 and December 2022 after pericardial stripping. The collected data included imaging findings, clinical manifestations, pleural effusion characteristics, postoperative pathology, and the diagnostic process.ResultsIn this study, the age of the 19 patients ranged from 25 to 74 years, with a median age of 59 years. All patients presented with bilateral pleural effusions, with or without pericardial lesions such as pericardial effusion or thickening. Pleural effusion biochemistry did not exhibit specific characteristics, and both etiology and pleural pathology were negative. Radiographic examinations, including cardiac ultrasound and chest CT, revealed signs of pericardial thickening and/or pericardial effusion or no abnormalities. Pericardial stripping was performed in all patients, and the postoperative pathology confirmed various degrees of thickened pericarditis, consistent with constrictive pericarditis. During a follow-up period of 6–18 months, most patients (17 out of 19) showed favorable recovery with no recurrence of bilateral pleural effusions.ConclusionThis study emphasizes the importance of pleural effusion as a clinical sign of constrictive pericarditis and highlights that a stepwise diagnostic approach, guided by clinical presentation and imaging, can enhance its recognition, particularly in cases with bilateral pleural effusions.

Case report: Infection-associated HPS during pregnancy cured by HLH-94 protocol with induction therapy of ruxolitinib

Hemophagocytic syndrome (HPS) is a rapidly progressive and highly fatal disease, and is even more complex when it occurs during pregnancy. Currently, the HLH-94 protocol is commonly used for treatment for HPS, with ruxolitinib being mostly used for salvage therapy. Here, we report a pregnant woman who presented with fever, thrombocytopenia, splenomegaly, and subsequently developed into severe pneumonia and multiple organ dysfunction(MODS). The patient was diagnosed as HPS based on clinical manifestations, laboratory indexes, and hemophagocytosis observed in bone marrow aspirate smear. After receiving ruxolitinib as induction therapy combined with HLH-94 protocol, the patient significantly improved and eventually cured.

ADVANCEMENTS IN UNDERSTANDING AND MANAGING ALCOHOL WITHDRAWAL SYNDROME: A COMPREHENSIVE REVIEW

Alcohol withdrawal syndrome (AWS) is a clinically significant condition that can arise upon abrupt cessation or reduction of alcohol consumption in individuals with alcohol dependence. This review article provides a comprehensive overview of AWS, encompassing its epidemiology, pathophysiology, clinical manifestations, assessment tools, and management strategies. We discuss the neurobiological mechanisms underlying AWS, including the role of neurotransmitter systems such as gamma-aminobutyric acid (GABA) and glutamate, as well as neuroadaptive changes that occur with chronic alcohol use. Furthermore, we explore the spectrum of clinical manifestations associated with AWS, ranging from mild withdrawal symptoms to severe complications such as delirium tremens and seizures. Diagnostic tools and scoring systems commonly used for assessing AWS severity are examined, along with evidence-based approaches for pharmacological and non-pharmacological management of AWS. Additionally, we highlight emerging research areas and future directions in the field of AWS, including novel treatment modalities and potential biomarkers for predicting withdrawal severity and treatment response. This comprehensive review aims to provide clinicians, researchers, and healthcare professionals with a thorough understanding of AWS to facilitate early recognition, appropriate management, and improved outcomes for individuals affected by this condition.

Incidence, clinical manifestations and characterization of Enterovirus in the last decade (2014-2023) in Asturias (Spain). Effect of the SARS-CoV-2 pandemic.

Enteroviruses (EVs) are a large group of genotypes that cause a variety of pathologies, some of them very serious. This study analyzed the last 10 years (2014-2023) of EVs diagnosis and classification. In 166,674 samples collected, EVs were found in 9,535 (5.7%) by rt-RT-PCR, and 332 (3.5%) were classified by Sanger methods. Symptoms were analyzed in 7623 cases. EVs were found in 5718/63,829 (8.9%) before, 1384/42,373 (3.3%) during and 2433/60,472 (4%) after the Covid pandemic (p < 0.0001), and in 7249/69,700 (10.4%) children under 6 years and in 2286/96,974 (2.35%) in oldest (p < 0.0001). The positive rate of EVs was high but decreased during the Covid period. In the youngest children EVs-A (associated with exantematohous disorders as well as respiratory manifestations and febrile syndromes) was most common, while EVs-B (frequent in neurological symptoms) was most common in children aged 6-15 years and EVs-D (associated to respiratory manifestations) in adults.

The mystery of abdominal snow-grip sensation: emphysematous cystitis complicated with bladder gangrene and rupture—case report and literature review

Emphysematous cystitis (EC) refers to a rare form of complicated urinary tract infection (UTI), which is typically observed in elderly females with severe diabetes mellitus. EC was triggered by bacteria, producing gas filled cysts in the bladder wall and lumen, the most common of which are Escherichia coli and Klebsiella pneumoniae. Since EC could be potentially life-threatening, severe form of EC (like septic shock) can cause gangrenous cystitis (GC). This case report describes an 85-year-old female patient with type 2 diabetes mellitus (DM) who presented with EC and bladder gangrene due to the growth of Candida glabrata in urine. Our case describes patient’s progression in detail, ranging from the initial clinical manifestations to specific management actions, which may provide new insights and ideas for the diagnosis and treatment of such disease.

Understanding oral malignancies: 2 case reports

The clinical presentation, diagnosis, and management of several squamous cell carcinoma cases are covered thoroughly. Roughly 94% of all mouth malignancies are squamous cell carcinomas. Race, gender, and age group differences exist in annual incidence and mortality rates. This percentage is 7.7 per 100,000 in the US. Like other carcinomas, intraoral carcinoma is more common in older adults, especially in men. Individuals with oral SCC have often known about an abnormality in that area for four to eight months prior to seeking professional medical attention. Early growth is characterized by little discomfort, which may account for the delay in seeking professional assistance. The clinical manifestations of oral SCC include exophytic, endophytic, leukoplakic, and erythroplakic, all of which exhibit apparent surface alterations.Tobacco usage, excessive alcohol consumption, HPV infection, eating little fruits and vegetables, prolonged sun exposure, and having a compromised immune system are risk factors. Improving outcomes requires early discovery and treatment, which may include chemotherapy, radiation therapy, surgery, or a combination of these. In order to improve the prognosis for oral cancer, early identification and intervention are crucial. Survival risk from squamous cell carcinoma is often low. This article emphasis on the clinical presentation of oral malignancies.

Vascular endothelial growth factor in inflammatory bowel disease: A systematic review and meta-analysis.

Vascular endothelial growth factor (VEGF) is linked to inflammation and angiogenesis, indicating a possible role in inflammatory bowel disease (IBD) and its main clinical manifestations, Crohn's disease (CD) and ulcerative colitis (UC). This systematic review and meta-analysis investigated studies assessing circulating VEGF concentrations in IBD patients and healthy controls, considering the effect of IBD type, sample type and geographical location. A systematic search identified 18 studies (28 group comparators) investigating 1741 IBD patients and 1291 controls. Data were extracted and analysed using standardized mean differences (SMD) with 95% confidence intervals (CI). VEGF concentrations were significantly higher in IBD patients (SMD = .71, 95% CI .38 to 1.04; p < .001). UC patients showed higher VEGF concentrations than CD patients. Serum samples indicated significant VEGF elevations, unlike plasma samples. Significant VEGF increases were observed in studies conducted in Western Europe and Asia, but not in Eastern Europe. No significant differences were found between active and inactive disease. VEGF concentrations are elevated in IBD patients, with variations by disease type, sample type and geography. However, VEGF is not a reliable marker of disease activity. Future research should standardize methods and explore regional influences to enhance VEGF's clinical utility as a biomarker of IBD.

Recent Therapeutic Advancements for Gaucher Disease

AbstractGaucher Disease (GD) is a well‐known lysosomal storage disease resulting from mutations in the GBA1 gene. GD exhibits a range of clinical manifestations, each with unique symptoms and severity levels. This review explores the genetic foundations of GD, highlighting the significance of Glucocerebrosidase (GCase) deficiency, resulting in the skeletal complications associated with GD, such as osteonecrosis, fractures, and bone pain, all of which significantly negatively influence the quality of life for patients. Over 700 mutations in the GBA1 gene are found to cause variations in gene expression in GD, indicating the disease's complexity and the need for continued research. Early diagnosis and prognosis evaluation depend heavily on diagnostic approaches integrating laboratory assessments, genetic testing, and clinical symptoms. Treatment strategies like enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) have advanced, but issues like high costs and invasiveness still exist. This review focuses on novel therapeutic approaches that show promise in treating GD, including gene and cell‐based therapies, pharmacological chaperone therapy (PCT), and drug delivery via nanoparticles. Finally, discussions on current clinical trials, limitations of the advanced therapies, and future scope are summarized.

Streptococcus suis infective endocarditis in patients with Streptococcus suis bacteremia: a retrospective study of prevalence and outcomes.

Streptococcus suis (S. suis) is a zoonotic disease that is transmitted to humans via contact or oral route. Although the major clinical presentation of this pathogen is known to be meningitis, S. suis infective endocarditis (IE) has recently emerged as a clinical manifestation of increasing interest. Echocardiography may be an underutilized modality for evaluating patients with S. suis bacteremia. The primary objective was to estimate the prevalence of S. suis IE in patients with S. suis bacteremia. The secondary objective was to investigate the predictors, echocardiographic features, and clinical outcomes of S. suis IE in patients with S. suis bacteremia. This single-center retrospective study was conducted at Siriraj Hospital - Thailand's largest university-based tertiary referral center. Adult patients (aged > 18 years) who were admitted to our center with confirmed diagnosis of S. suis bacteremia during January 2007 to September 2023 were included. Prevalence is reported as percentage and confidence interval. Baseline characteristics and clinical manifestation were compared between the IE and non-IE groups. Factors found to be statistically significant were further analyzed using binary logistic regression analysis to identify univariate predictors of S. suis IE. A total of 71 patients with S. suis bacteremia were included in this study. The prevalence of S. suis IE was 26.8% (95% confidence interval: 17.85-38.05). Perivalvular complications and significant valvular regurgitation were found in 52.6% and 80.0% of patients, respectively. Thirteen of 19 patients (68.4%) required valvular surgery according to standard guidelines. By univariate analysis, dyspnea, new murmur, immunologic phenomenon, and heart failure were predictors of S. suis IE in patients with S. suis bacteremia. The results of this study revealed a sizable prevalence of S. suis IE in patients with S. suis bacteremia, and there were high rates of both valvular damage and perivalvular complications. Our results strongly suggest that echocardiography may be indicated to evaluate for S. suis IE in patients diagnosed with S. suis bacteremia. Reclassification of S. suis from an atypical organism to a typical organism should be considered.

Ultrasonographic characteristics of neonatal appendicitis: a case series.

Neonatal appendicitis is a rare but critical condition that presents diagnostic challenges due to its nonspecific symptoms and clinical manifestations. Early and accurate diagnosis is crucial for reducing the high mortality rates associated with this condition. Abdominal ultrasonography plays a pivotal role in identifying characteristic signs of appendicitis in neonates. This study aimed to investigate whether neonatal appendicitis can be diagnosed with abdominal ultrasonography by identifying its specific signs. This study reviewed 20 consecutive cases of neonatal appendicitis confirmed through surgery at a National Medical Center. Preoperative abdominal ultrasonography was analyzed for direct and indirect signs of appendicitis. Our study included neonates with a mean age of 13.0 ± 7.1 days. The appendix was identifiable in 13 out of 20 cases (65%). The mean outer diameter of the appendix was 4.6 ± 1.8mm. Eight cases had appendix diameter ≥ 4mm. Fluid accumulation within the appendiceal cavity was noted in 6 (30%) patients, and peri-appendiceal fluid accumulation was detected in 5 (25%) patients. Ultrasonography revealed appendiceal perforation in 12 out of 16 cases (75%). The indirect signs of neonatal appendicitis included right lower quadrant (RLQ) abscess, pneumoperitoneum, and thickening of the intestinal wall and mesentery in the RLQ. Most cases of neonatal appendicitis may be diagnosed through abdominal ultrasonography by identifying both direct and indirect signs. Future studies with larger patient cohorts are needed to improve ultrasonographic diagnosis of neonatal appendicitis.