Search Results (609)

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

Endometriosis is a benign and often underdiagnosed condition that affects women of reproductive age, typically between 18 and 45 years. It can cause infertility and pain, including radicular pain and low back pain (LBP). The aim of this case report is to emphasize the importance of making a differential diagnosis when facing LBP and radicular symptoms. We report the case of a 17-year-old female patient, R.A., presented with a significant LBP (NPRS 8/10) radiating from her lumbar spine to her right buttock and occasionally to both legs, accompanied by weakness. She revealed exacerbation of pain during menstruation, despite being under hormonal contraceptive treatment. After three physiotherapy sessions that included education, manual therapy and exercise, the patient’s pain persisted so her physiotherapist recommended an evaluation in the emergency department, where standard radiography did not reveal any significant findings. Physiotherapy continued until the fifth session, when the patient agreed to undergo evaluation at a specialized endometriosis centre. Further investigations revealed endometriotic tissue on the uterosacral ligament, leading to hormonal therapy adjustment, with which pain gradually decreased to a manageable level (NPRS 2/10). This case report highlights the importance of an early differential diagnosis in patients with LBP, as endometriosis can present not only in older women but also in younger patients, including those already on oral contraceptives. Therefore, to mitigate the risk of pattern recognition bias, clinicians must maintain a high index of suspicion for endometriosis, even in atypical or unlikely clinical presentations. Full article

Background/Objectives: Anti-p200 pemphigoid is a rare and likely underdiagnosed autoimmune blistering disorder. Laminin γ1 and laminin β4 have been implicated as potential target antigens in its pathogenesis. Recently, a novel indirect immunofluorescence assay targeting anti-laminin β4 antibodies has been developed, demonstrating high sensitivity and specificity, and offering a valuable tool for improved diagnosis. Methods: Of the 451 patients, 21 were selected for further laboratory analysis based on medical records. Sera from 10 patients, which showed a positive direct immunofluorescence (DIF) result and negative results in multiplex enzyme-linked immunosorbent assays (ELISAs) and/or mosaic six-parameter indirect immunofluorescence (IIF) for various autoimmune bullous diseases, were tested for the presence of anti-laminin β4 antibodies. Additionally, sera from 11 patients with positive DIF and positive ELISA for antibodies against BP180 and/or BP230 were analyzed. Results: Among the 10 patients with positive DIF and negative ELISA and/or mosaic six-parameter IIF, 6 sera were positive for anti-laminin β4 antibodies. These patients presented with atypical clinical features. In contrast, all 11 sera from patients with both positive DIF and positive ELISA for BP180 and/or BP230 were negative for anti-laminin β4 antibodies. Conclusions: In patients with a positive DIF result but negative ELISA and/or mosaic six-parameter IIF findings, testing for anti-laminin β4 antibodies should be considered. Furthermore, in cases presenting with atypical clinical features—such as acral distribution of lesions, intense pruritus, or erythematous–edematous plaques—the possibility of anti-p200 pemphigoid should be included in the differential diagnosis. Full article

Background: Type 2 diabetes (T2D) is a growing public health concern, particularly in low- and middle-income countries. Although prediabetes is a major risk factor for T2D, it remains largely underdiagnosed and untreated. Structured lifestyle interventions have proven effective in preventing diabetes, but their feasibility within the Brazilian public health system remains unclear. Methods: This multicenter pilot randomized controlled trial assessed the feasibility of a culturally adapted lifestyle intervention (PROVEN-DIA) across the five regions of Brazil. A total of 220 adults at high risk for T2D were randomized to an intervention group or a control group (usual care) and followed for three months. Both groups received similar educational content on healthy eating and physical activity, but the intervention group participated in a structured and personalized lifestyle program with regular follow-up sessions. The primary outcome was adherence to dietary recommendations, assessed using the BALANCE Index—a validated dietary score (range: 0–40) based on the Brazilian Cardioprotective Diet that classifies foods into color-coded groups according to nutritional quality—along with engagement in moderate-to-vigorous physical activity (MVPA). Secondary outcomes included diet quality (DQIR), anthropometric and metabolic parameters. Results: Feasibility was demonstrated by a 93.2% retention rate (n = 205). There was no significant difference in the primary outcome (simultaneous improvement in diet and MVPA). However, the PROVEN-DIA group exhibited significantly greater improvements in diet quality, with a 2.8-point increase in the BALANCE Index (vs. 0.5 in the control, p = 0.03), and a significant improvement in the DQIR (p < 0.001). No significant differences between groups were observed in MVPA, HbA1C, glycaemia, or body weight. Conclusions: The PROVEN-DIA intervention proved feasible within the Brazilian public health context, resulting in significant improvements in dietary quality among individuals at high risk for T2D. A larger trial with longer follow-up is warranted to evaluate its effectiveness in preventing the progression to diabetes. However, to enhance physical activity outcomes, specific adaptations and targeted strategies may be required to better support participant engagement in exercise. Full article

Background: Delirium is a common, underdiagnosed neuropsychiatric syndrome in older adults, associated with high mortality and functional decline. Given its multifactorial nature and overlap with frailty, radiological markers may improve risk stratification in the emergency department (ED). Methods: We conducted a retrospective study on a small sample of 30 patients diagnosed with delirium in the emergency department who had recently undergone brain, thoracic, or abdominal CT scans for unrelated clinical indications. Using post-processing software, we analyzed radiological markers, including coronary artery calcifications (to estimate vascular age), cerebral atrophy (via the Global Cortical Atrophy scale), and cachexia (based on abdominal fat and psoas muscle volumetry). Results: Five domains were identified as significant predictors of 12-month mortality in univariate Cox regression: vascular age, delirium etiology, cerebral atrophy, delirium subtype (hyperactive vs. hypoactive), and cachexia. Based on these domains, we developed an exploratory 10-point delirium score. This score demonstrated acceptable diagnostic accuracy for mortality prediction (sensitivity 0.93, specificity 0.73, positive predictive value 0.77, negative predictive value 0.91) in this limited cohort. Conclusions: While preliminary and based on a small, retrospective sample of 30 patients, this multidimensional approach integrating clinical and radiological data may help improve risk stratification in elderly patients with delirium. Radiological phenotyping, particularly in terms of vascular aging and sarcopenia/cachexia, offers objective insights into patient frailty and could inform more personalized treatment pathways from the ED to safe discharge home, pending further validation. Full article

The diversity and distribution of medical and veterinary-relevant fungal diseases in Africa underscore the critical need for a multisectoral One Health strategy to enhance cost-effective preparedness and prevention. This review explores the geographic spread and epidemiology of key medical and veterinary fungi, including Emergomyces, Blastomyces, Coccidioides, Cryptococcus, Dermatophytes, Histoplasma, Sporothrix, Talaromyces, Paracoccidioides, Aspergillus, and Malassezia. Evidence indicates that many of these infections remain underdiagnosed and underreported, especially in vulnerable immunocompromised populations, due to limited surveillance, diagnostic capacity, and awareness. The increasing prevalence of these diseases, often in tandem with rising HIV rates and environmental changes, highlights the urgent need for coordinated efforts across human, animal, and environmental health sectors. Implementing comprehensive, multisectoral interventions—focused on enhancing diagnostic capabilities, public awareness, surveillance, and cross-sector collaboration—is vital for effective prevention and control of these emerging fungal threats in Africa. Full article

Background/Objectives: Traumatic brain injury is one of the leading causes of death and disability. When traumatic brain injury is repeated over time, it can lead to the development of Chronic Traumatic Encephalopathy, a chronic neurodegenerative disease commonly observed in individuals who engage in contact sports or military personnel involved in activities with a high risk of repeated head trauma. At autopsy, the examination of the brain reveals regional atrophy, corresponding to high concentrations of glutamate receptors. Microscopically, the primary findings are the deposition of neurofibrillary tangles and neuropil threads. The aim of this study is to highlight the clinical and histopathological characteristics of Chronic Traumatic Encephalopathy, providing diagnostic support to forensic pathologists. Additionally, it seeks to aid in the differential diagnosis of similar conditions. Methods: A review of literature was conducted following the PRISMA criteria. Of 274 articles, 7 were selected. Results: According to these papers, most patients were male and exhibited neurological symptoms and neuropsychiatric impairments, and a proportion of them committed suicide or had aggressive behavior. Conclusions: Chronic Traumatic Encephalopathy remains largely underdiagnosed during life. The definitive diagnosis of Chronic Traumatic Encephalopathy is established post-mortem through the identification of pathognomonic tauopathy lesions. Early and accurate antemortem recognition, particularly in at-risk individuals, is highly valuable for its differentiation from other neurodegenerative conditions, thereby enabling appropriate clinical management and potential interventions. Full article

Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Pregnancy rhinitis (PR) is a transient, non-infectious nasal condition affecting a significant number of pregnant women, yet often remains underdiagnosed or misclassified. It can substantially impact maternal quality of life, sleep, and even fetal oxygenation. This narrative review explores the current understanding of PR, including hormonal and vascular mechanisms, clinical criteria, and therapeutic approaches considered safe during pregnancy. Despite increasing recognition, the differentiation between PR and other rhinitis forms remains challenging. Limited therapeutic options and the absence of standard diagnostic guidelines further complicate management. Evidence supports a multifactorial etiology involving estrogen, progesterone, and placental growth factors. Non-pharmacologic strategies are first-line, while pharmacological interventions are cautiously employed. PR is a distinct and clinically relevant condition requiring increased awareness among ENT and obstetric professionals. Future research should focus on standardized diagnostic criteria and evidence-based treatment protocols to improve maternal–fetal outcomes. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article

(1) Background: Murine typhus, caused by Rickettsia typhi, is a neglected rickettsial disease and an underdiagnosed cause of acute febrile illness (AFI), particularly in endemic regions such as Indonesia. (2) Case description: We report a case series of four patients presenting with AFI of less than seven days in duration. Three patients were admitted with moderate disease, while one presented with septic shock with the macrophage activation-like syndrome (MALS) phenotype. Common clinical features included myalgia and headache; additional symptoms included cough, sore throat, and abdominal pain. Laboratory findings revealed bicytopenia, elevated transaminases, and raised inflammatory and bacterial infection markers. Common tropical infections—dengue, typhoid fever, and leptospirosis—and other potential sources of infection were excluded early during hospitalization. Diagnosis was confirmed by nucleic acid amplification testing (NAAT), which detected R. typhi in all patients. Doxycycline was initiated following confirmation, leading to defervescence within 36–48 h. (3) Conclusions: Murine typhus remains an underrecognized cause of febrile illness in Indonesia. In the near future, the inclusion of rickettsial testing in the diagnostic protocol of AFI will be crucial, as it enables timely administration of effective, low-cost treatment. Full article

Background: Migraine is a highly prevalent and disabling neurological disorder among university students that has significant impacts on personal and socioeconomic levels. Despite its impact, migraine remains underdiagnosed and undertreated. Objective: This study aimed to estimate the prevalence of probable migraine among university students in Greece and explore its association with sociodemographic data. Methods: A cross-sectional, questionnaire-based study was conducted between September 2023 and January 2024 among university students in Greece using a convenience sampling method. The Headache Screening Questionnaire—English Version (HSQ-EV) was used to screen for probable migraine, along with additional questions assessing demographic characteristics. Descriptive statistics and bivariate analyses were performed. Results: The prevalence of probable migraine was 20%. Female students were more likely to experience migraine compared to males. Migraine was also statistically significantly associated with marital status and employment status. In a multivariate logistic regression model including sex assigned at birth, age, educational level, marital status, and employment status, older age was independently associated with higher odds of migraine. Conclusions: Migraine is a prevalent health issue among university students in Greece, with clear gender and sociodemographic associations. Future studies with larger, more representative sample sizes and the use of validated diagnostic tools are needed to understand its determinants and inform targeted interventions. Full article

Background/Objectives: Obstructive sleep apnea is a prevalent, yet often underdiagnosed, condition characterized by recurrent upper airway obstruction during sleep, leading to significant perioperative risks in surgical patients. This systematic review aims to evaluate the incidence and impact of objectively diagnosed obstructive sleep apnea on postoperative outcomes across various surgical specialties—including bariatric, orthopedic, cardiac, and otorhinolaryngologic surgeries—and to assess the effectiveness of preoperative screening and perioperative management strategies. Methods: A comprehensive literature search of PubMed was conducted for studies published between January 2013 and December 2024, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies involved adult surgical patients with OSA confirmed by polysomnography or respiratory polygraphy. Studies were assessed for methodological quality using the Oxford Centre for Evidence-Based Medicine Levels of Evidence framework. Results: The findings consistently indicated that obstructive sleep apnea significantly increases the risk of postoperative complications, such as respiratory depression, atrial fibrillation, acute kidney injury, delirium, and prolonged hospital stay. Continuous positive airway pressure therapy demonstrated a protective effect in bariatric and cardiac surgeries, though its effectiveness in orthopedic and otorhinolaryngologic contexts was inconsistent, largely due to adherence variability and limited implementation. Preoperative screening tools such as the STOP-BANG questionnaire were widely used, but their utility depended on integration with confirmatory diagnostics. Conclusions: Obstructive sleep apnea represents a significant, modifiable risk factor in surgical populations. Preoperative identification and risk-adapted perioperative management, including CPAP therapy and multimodal analgesia, may substantially reduce postoperative morbidity. However, further randomized trials and cost-effectiveness studies are needed to optimize care pathways and ensure consistent implementation across surgical disciplines. Full article

Rare genetic diseases are often caused by structural variants (SVs), such as insertions, deletions, duplications, inversions, and complex rearrangements. However, due to the technical limitations of short-read sequencing, these variants remain underdiagnosed. Long-read sequencing technologies, including Oxford Nanopore and Pacific Biosciences high-fidelity (HiFi), have recently advanced to the point that they can accurately find SVs throughout the genome, including in previously unreachable areas like repetitive sequences and segmental duplications. This study underscores the transformative role of long-read sequencing in diagnosing rare diseases, emphasizing the bioinformatics tools designed for detecting and interpreting structural variants (SVs). Comprehensive methods are reviewed, including methylation profiling, RNA-seq, phasing analysis, and long-read sequencing. The effectiveness and applications of well-known tools like Sniffles2, SVIM, and cuteSV are also assessed. Case studies illustrate how this technique has revealed new pathogenic pathways and solved cases that were previously undetected. Along with outlining potential future paths like telomere-to-telomere assemblies and pan-genome integration, we also address existing issues, including cost, clinical validation, and computational complexity. For uncommon genetic illnesses, long-read sequencing has the potential to completely change the molecular diagnostic picture as it approaches clinical adoption. Full article