Search Results (449)

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

Variants in ELAC2, a gene encoding the mitochondrial RNase Z enzyme essential for mitochondrial tRNA processing, have been associated with severe pediatric-onset mitochondrial dysfunction, primarily presenting with developmental delay, hypertrophic cardiomyopathy (HCM), and lactic-acidosis. We hereby report the case of a 25-year-old young woman presenting with dilated cardiomyopathy (DCM) and peripheral sensorimotor polyneuropathy, harboring a homozygous variant in ELAC2. The same variant has been reported only once so far in a case of severe infantile-onset form of HCM and mitochondrial respiratory chain dysfunction, with in vitro data showing a moderate reduction in the RNase Z activity and supporting the current classification as C4 according to the American College of Medical Genetics (ACMG) criteria (PS3, PM2, PM3, PP4). Our extensive clinical, imaging, histological, and genetic investigations support a causal link between the identified variant and the patient’s phenotype, despite the fact that the latter might be considered atypical according to the current state of knowledge. A detailed review of the existing literature on ELAC2-related disease is also provided, highlighting the molecular mechanisms underlying tRNA maturation, mitochondrial dysfunction, and the variable phenotypic expression. Our case further expands the clinical spectrum of ELAC2-related cardiomyopathies to include a relatively late onset in young adulthood and underscores the importance of comprehensive genetic testing in unexplained cardiomyopathies with multisystem involvement. Full article

Predominantly antibody deficiencies (PADs) are the most prevalent types of inherited errors of immunity (IEI) and are characterized by a broad range of clinical manifestations, such as recurrent infections, autoimmunity, lymphoproliferation, atopy and malignancy. The aim of this study was to identify genetic defects associated with PADs in order to improve diagnosis and personalized care. Twenty patients (male/female: 12/8, median age of disease onset: 16.5 years, range: 1–50) were analyzed by next-generation sequencing (NGS) using a custom panel of 30 genes associated with PADs and their possible disease phenotype. The detected variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines and inheritance, and the penetrance patterns were evaluated by PCR–Sanger sequencing. Novel and rare mutations associated with the phenotype of common variable immunodeficiency (CVID) in genes encoding the transcription factors NFKB1, NFKB2 and IKZF1/IKAROS were identified. Alphafold3 protein structure prediction was utilized to perform a comprehensive visualization strategy and further delineate the mutation-bearing domains and elucidate their potential impact on protein function. This study highlights the value of genetic testing in PADs and will guide further research and improvement in diagnosis and treatment. Full article

Background/objectives: In some cases of concomitant use of direct oral anticoagulants (DOAC) and certain anticancer medications, pharmacokinetic interactions are expected; however, clinical data is scarce. This report reviews the recommendations on the use of DOAC concurrently with anticancer drugs according to different clinical decision support systems and sources, with a focus on discrepancies. Methods: We reviewed the recommendations from the American Heart Association (AHA), European Heart Rhythm Association (EHRA), summary of product characteristics (SPC) in FASS (Swedish medicine information portal), the Swedish clinical decision support system Janusmed, and information from the Food and Drug Administration (FDA) on the concomitant use of apixaban, edoxaban, and rivaroxaban (activated factor X (FXa) inhibitors) and 80 anticancer drugs from 11 categories (240 drug pairs). Results: No warnings of expected pharmacokinetic drug interactions between FXa inhibitors and anticancer drugs were found for 155 drug pairs (65%) across all sources. The remaining 35% of drug pairs were flagged as having possible interactions with FXa inhibitors according to at least one source. Discrepancies in the recommendations from the different sources were reported. The reported discrepancies were, for the most part, associated with different assessments of the mechanism and the extent of pharmacokinetic interactions of each anticancer medication. Also, knowledge sources have different approaches to reporting potential interactions, in some cases reporting clinically relevant strictly pharmacokinetic interactions, whereas others include even patient-specific factors. Conclusions: The lack of clinical data and different recommendations can make clinical decisions on the concomitant use of DOAC and anticancer drugs difficult. Our compilation is meant to assist clinicians in making decisions based on the available evidence, even if it is scarce. Full article

Background/Objectives: The course of treatment for renal artery stenosis following renal transplantation depends on the severity of the condition. Mild cases are typically managed medically, while more significant stenosis with flow limitation and graft dysfunction requires percutaneous intervention. Surgical treatment is generally reserved as a last resort. This study aimed to evaluate the outcomes of interventional radiology in managing renal artery stenosis at our transplant center. Methods: The electronic medical records of patients who underwent renal transplantation at our center between January 2020 and December 2024 were reviewed to identify cases of renal artery stenosis and their subsequent management through interventional radiology. Sociodemographic and clinical data were collected for both recipients and donors. Data analysis was performed using SPSS version 26. Results: Out of the total 368 patients who received renal allograft at our center from January 2020 to December 2024, 25 patients were confirmed with duplex ultrasound to have renal artery stenosis. The majority of affected patients were African American, had Class I Obesity and presented with cardiovascular co-morbidities. The mean time from transplant to the diagnosis of RAS was 4.25 (SD ± 3.81) months. The mean serum creatinine level at presentation was 2.54 (SD ± 1.21 mg/dL). All 25 patients underwent digital subtraction angiography, and 24 patients were confirmed to have renal artery stenosis requiring further intervention. The creatinine levels at one week, three months and one year post-intervention were 2.12 (SD ± 1.00), 1.83 (SD ± 0.63) and 2.15 (SD ± 1.68) mg/dL, respectively. Conclusions: Percutaneous interventional treatment for renal artery stenosis is associated with improvements in hemodynamic parameters and the stabilization of allograft function. Follow-up is needed to monitor for the potential occurrence of restenosis. Full article

Background/objectives: Social media has significantly enhanced access to medical knowledge by enabling rapid information sharing. With YouTube being the second-most popular website, we intended to evaluate the quality of its content as a source of information for patients and relatives for information about cerebral palsy. Methods: The first 30 videos for search terms “Cerebral palsy”, “Spastic cerebral palsy”, “Dyskinetic cerebral palsy”, “Worster-Drought syndrome”, and “Ataxic cerebral palsy” were selected for inquiry. Out of 150 films, a total of 83 were assessed with a mixed method approach by two independent raters utilizing evidence-based quality scales such as Quality Criteria for Consumer Health Information (DISCERN), the Journal of the American Medical Association instrument (JAMA), and the Global Quality Score (GQS). Furthermore, audience engagement was analyzed, and the Video Power Index (VPI) was calculated for each video. Results: The mean total DISCERN score excluding the final question (subjective assessment of the video) was 30.5 ± 8.7 (out of 75 points), implying that the quality of the videos was poor. The global JAMA score was 2.36 ± 0.57 between the raters. The mean GQS score reached 2.57 ± 0.78. The videos had statistically higher DISCERN scores when they included treatment options, risk factors, anatomy, definition, information for doctors, epidemiology, doctor as a speaker, and patient experience. Conclusions: YouTube seems to be a poor source of information for patients and relatives on cerebral palsy. The analysis can contribute to creating more engaging, holistic, and informative videos regarding this topic. Full article

Background: The effective management of psychotic and bipolar disorders in tertiary care can improve patient outcomes, yet the role of clinical pharmacists in optimising psychotropic medication use remains underexplored in South Africa. This study aims to investigate the role and interventions of clinical pharmacists in managing psychotic and bipolar disorders within a tertiary hospital in South Africa. Methods: A quantitative, descriptive study was conducted among 60 adult patients admitted to the psychiatric and internal medicine wards diagnosed with psychotic and/or bipolar disorder. A previously validated, standardised pharmaceutical care form was utilised for a purposive sample of inpatient files. Medication-related problems were identified, and appropriate interventions were suggested. Prescriptions were also assessed for adherence to treatment guidelines, including the South African Standard Treatment Guidelines, the American Psychiatric Association guidelines, and the National Institute for Health and Care Excellence guidelines. Results: The study included 60 patients (37 females) with a mean age of 37 years. Diagnoses included schizophrenia (28.8%), bipolar disorder (27.5%), and stimulant-induced psychosis (19.3%). Sixty-two medication-related problems were identified, leading to 77 proposed interventions, of which 65 were implemented. Among the prescriptions, 75% (n = 45) adhered to the South African Standard Treatment guidelines, 76% (n = 46) adhered to the NICE guidelines, and 71% (n = 43) adhered to the APA guidelines. Conclusions: Clinical pharmacists identified a number of medication-related problems in patients with psychotic and bipolar disorders, and their proposed interventions were largely accepted. The findings highlight the pharmacist’s role in optimising medication therapy and adherence to guidelines, suggesting that improved treatment monitoring is necessary in this setting. Full article

Background: Gene variants of unknown significance (VUSs) present a challenge in genetic counselling. The primary aim of this study was to describe the spectrum of genetic findings in a cohort of 5923 Danish patients with suspected predisposition to hereditary breast and/or ovarian cancer, with a focus on classifying gene variants and investigating their distribution. Methods: The gene variants were classified using the American College of Medical Genetics (ACMG) guidelines as well as gene-specific guidelines where applicable. The identified VUSs were further examined through association analysis, comparison of the frequencies in this Danish population to those in the Swedish population using gnomAD 2.1, and splice analysis using RNA sequencing. Results: Of 167 variants that were clinically classified as VUSs prior to this research study, 38 (22.8%) were either up- or downgraded based on the guidelines that were used. We found that 630 patients (10.6%) carried a likely pathogenic or pathogenic variant, mainly in BRCA1 (31.9%) and BRCA2 (26.0%). VUSs were carried by 1606 (27.1%) patients, mainly in BARD1 (27.6%) and ATM (19.3%). Our association study assigned criteria for 10 gene variants, while our splice analysis assigned criteria for 3 gene variants but did not reclassify the variants. Conclusions: A total of 22.8% of the 167 variants that were observed in this study and which were previously classified as VUSs in a clinical setting were reclassified in this study. In total, 10.6% of the patients with a suspected predisposition to hereditary breast and/or ovarian cancer carried a likely pathogenic or pathogenic variant. The high incidence of VUSs observed in this study reflects the challenges faced in the daily clinical setting. Full article

Diabetes is a growing chronic disease with complications that impose a significant burden on healthcare systems worldwide. Pharmacists are readily accessible for diabetes management beyond simply dispensing medications. Consequently, they are involved in disease prevention and detection, therapy management, and patient monitoring. However, with the current escalating impact of diabetes, pharmacists must upgrade their strategies by integrating guidelines from sources like the American Diabetes Association (ADA) 2024 with pharmacy expertise. This perspective serves as a guide for pharmacists, identifying key foundations involved in diabetes management, highlighting five crucial steps for optimal disease control, ranging from prevention strategies to pharmacist-led counseling interventions. We employed PubMed, CDC, WHO guidelines, and key reference texts. Searches were performed using combinations of terms such as “pharmacist”, “type 2 diabetes”, “diabetes prevention”, “pharmacist intervention”, and “diabetes management”, covering publications from January 2010 to March 2025. Studies were included if they focused on pharmacist-led prevention, intervention, or management strategies related to type 2 diabetes (T2D) and were published in English. Studies focusing exclusively on type 1 diabetes were excluded. Generative artificial intelligence was employed to order and structure information as described in the acknowledgments. Conflicting evidence was resolved by giving relevance to recent systematic reviews, randomized trials, and major guidelines. Additional insights were gained through consultations with PharmD professionals experienced in diabetes care. Evidence from selected studies suggests that pharmacist-led care models may enhance and promote the early detection of T2D, improve therapy adherence, enhance glycemic control, and increase overall treatment efficiency. This work suggests that pharmacists must play a key role in diagnosing, preventing, managing, and mitigating the consequences associated with T2D. They must contribute to early treatments with appropriate training and involvement to improve therapeutic outcomes and reduce diabetes-related complications. Full article

Objectives: This study aimed to describe the prevalence of malnutrition and its impact on postoperative outcomes in infants and children with congenital heart diseases (CHDs) undergoing cardiac surgeries. Methods: We conducted a single-center, retrospective review of medical records of children aged 1 month to 5 years with CHDs who underwent cardiac surgery at the American University of Beirut Medical Center (AUBMC) between January 2015 and January 2017. Anthropometric data were collected and z-scores for weight-for-age (WAZ), height-for-age (HAZ), weight-for-height (WHZ), and BMI-for-age were calculated. Malnutrition was classified based on the World Health Organization (WHO) definitions and the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. The postoperative outcomes were analyzed using bivariate and multivariable models. Results: The prevalence of malnutrition was 33.8%, with children younger than 24 months having significantly higher odds of malnutrition. The most common CHDs were ventricular septal defect (VSD) and tetralogy of Fallot (TOF), with malnutrition being significantly more prevalent in the children with VSD. Malnutrition was significantly associated with a prolonged pediatric intensive care unit (PICU) stay, with underweight being the strongest predictor. Malnourished children also had a significantly longer mechanical ventilation time (median 9.0 vs. 5.0 h, p = 0.017). Lower weight-for-age (WAZ) and BMI-for-age z-scores were associated with longer hospital stay, PICU stay, and mechanical ventilation durations. Conclusions: Malnutrition is prevalent among children with CHDs and is independently associated with longer hospital and PICU stays, as well as extended mechanical ventilation. Early nutritional assessment and intervention may improve postoperative outcomes in this vulnerable population. Full article

Objectives: The objective of this study was to examine the relationship between multimorbidity and root caries among older American adults. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020, a cross-sectional nationally representative survey of civilian noninstitutionalised Americans was used. The analysis included dentate adults aged 50 years and older. The presence of root caries or root restoration was assessed through clinical dental examinations. Multimorbidity was identified by the existence of five common and serious chronic diseases, namely, diabetes, cancer, coronary heart disease, chronic pulmonary disease and stroke. An aggregate variable of these five conditions was created. Logistic regression models were used to assess the association between multimorbidity and root caries (outcome), adjusting for sociodemographic factors and health behaviours. Results: The analysis included 3274 dentate participants (mean age: 63.6 years), 18.2% had root caries, while 14%. had multimorbidity (two or more conditions). The mean number of multimorbidities was 0.65. The count of multimorbidity was significantly associated with root caries, with odds ratios (OR) of 1.26 (95% Confidence Interval (CI): 1.03, 1.52) in a model adjusting for age, gender, ethnicity, income, and education. After additionally adjusting for dental visits and smoking, the association between multimorbidity and root caries lost statistical significance (OR 1.20, 95% CI: 0.97, 1.48). Conclusions: Individuals with greater numbers of chronic conditions appeared to have higher probabilities of having root caries. However, the significant association was eliminated after accounting for strong behavioural predictors of root caries. The higher level of root caries among those with multimorbidity could be attributed to xerostomia caused by being on multiple medications. The findings highlight the need for interventions to prevent root caries among those with multimorbidity. Full article

Background: Navify^® Mutation Profiler (Navify MP) is a cloud-based, tertiary analysis software that provides curation, annotation, and reporting of somatic genomic alterations and biomarker signatures identified by next-generation sequencing. The Navify MP software leverages Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists (AMP/ASCO/CAP) Somatic Variant Classification Guidelines to provide information on detected somatic genomic variants and associated therapies according to region-specific approvals. Methods: This validation study assessed the accuracy of the Navify MP software and curation process for hematologic malignancies as compared to expert opinion. A total of 86 variants derived from hematologic malignancies (including myeloid and lymphoid leukemias, B cell lymphomas, and multiple myeloma) were used to contrive 12 VCF files. The VCFs were made up of the following classes of genomic alterations: single nucleotide variants, small insertions and deletions, fusions, and copy number alterations. Of the 86 variants, 42 were Tier IA, and 44 were non-Tier IA, based on AMP/ASCO/CAP classification. The study was performed at four sites with seven software users (molecular genetics experts). Results: Tier classification agreement between Navify MP and expert user assignment was 91.34% for Tier IA and 95.02% across all hematologic variants. The agreement on associated therapies for the Navify MP-classified Tier IA hematologic variants was 99.08%. Conclusions: Navify MP is a robust automated solution for genomic variant reporting of hematologic malignancies and remains up to date with evolving regional approvals and medical guidelines. Full article

The objective was to evaluate the growth in pharmacy student performance in entrustable professional activity (EPA) assessments across the experiential curriculum based on preceptor assessments on an entrustment–supervision (ES) scale. This retrospective cohort study used assessments based on the 2016 American Association of Colleges of Pharmacy Core EPAs and an expanded ES scale during introductory and advanced pharmacy practice experiences (IPPEs/APPEs) in the third and fourth professional years from fall 2020 to fall 2023. The primary outcome was the change in ES level, assessed by preceptors over time. The secondary outcomes were growth rates across types of experiences, training environments, and experience order. A conditional growth curve model and ordinal mixed effects model were used to demonstrate discrete entrustment decisions. A total of 509 students received 12,426 assessments by 557 preceptors. Raw ES levels and unconditional growth curves for EPA show increases in entrustability from years P3 to P4. Comparing care settings, there was lower entrustment in inpatient than outpatient settings and at academic medical centers than other settings. There were no significant differences in ES levels regardless of which IPPE was taken first. However, when the first APPE was an inpatient medicine experience, ES levels across APPEs for EPA 3 were higher when compared to ambulatory care as the first APPE, and they were higher for EPA 5 when compared to community pharmacy as the first APPE. Paired with ES scales, EPAs can be integrated into pharmacy experiential curricula to demonstrate longitudinal growth in student entrustment. Full article

This study investigated the prevalence of cystic fibrosis-related diabetes (CFRD) in the Croatian cystic fibrosis (CF) population, the age at diagnosis, insulin requirements, and the relationship between age at diagnosis and other clinical parameters. Medical records from 152 patients with genetically and laboratory-confirmed CF were reviewed through to 2025. The American Diabetes Association criteria were used to diagnose CFRD. Anthropometric and clinical data were collected from the latest medical records. A total of 17 out of 152 patients had CFRD, with a prevalence of 4.8% in the paediatric population (4/84) and 19.1% in adults (13/68). The median age of CFRD diagnosis was 14 years (range 9–22 years, SD = 3.95). Thirteen patients used insulin: one used bolus only, seven used basal-bolus multiple daily injections, and five used insulin pumps. The average total daily insulin (TDI) per kilogram (kg) body weight was 0.447 U/kg (SD = 0.429). The age at CFRD diagnosis was positively correlated with the body mass index (BMI) (p = 0.029). Patients requiring insulin by age 15 had higher TDI and were more likely to have CF liver disease (p = 0.027, p = 0.037, respectively). The prevalence of CFRD and age at diagnosis aligned with previous studies. Patients diagnosed at a younger age and requiring insulin earlier had lower BMIs, likely due to a faster decline in beta cell function and earlier onset of insulinopenia. Full article

In late 2023, the U.S. Food and Drug Administration (FDA) approved two renal denervation (RDN) systems for the treatment of hypertension. Several professional societies, including the Society of Cardiovascular Angiography and Intervention (SCAI), the American Heart Association (AHA), and numerous European associations, have recognized the potential role of RDN in managing hypertension. Despite widespread enthusiasm from clinicians, patients, and the industry, the American Medical Association’s Current Procedural Terminology (CPT) panel rejected the introduction of new codes for renal denervation at its September 2024 meeting. This article analyzes the latest evidence from clinical trials and registries, reviews current challenges in clinical practice, and explores the role of contemporary hypertension treatment from the perspective of interventional cardiologists. Full article