Search Results (7,617)

Background and Clinical Significance: Dystrophic calcinosis cutis involves calcium deposition in damaged or chronically inflamed tissues despite normal calcium and phosphate metabolism. Although typically associated with systemic sclerosis and dermatomyositis, it is rare in rheumatoid arthritis. Ulceration over calcified deposits may impair healing and function. This case highlights a staged reconstructive strategy to remove calcified tissue and achieve definitive wound closure. Case Presentation: A 73-year-old woman with a 22-year history of rheumatoid arthritis presented with painful, partially confluent pretibial ulcerations, purulent drainage, impaired mobility, and extrusion of chalk-like material. Radiographic and histopathological findings supported dystrophic calcinosis cutis. Deep-tissue culture grew Escherichia coli, treated with intravenous ertapenem. Tangential excision of necrotic tissue and accessible calcific deposits resulted in an irregular full-thickness defect extending to the pretibial fascia. A synthetic polylactic acid matrix was applied with single-use negative pressure wound therapy for 14 days, followed by split-thickness skin grafting on day 21. Graft take exceeded 90%, and residual areas epithelialized without regrafting. At 12 months, the wound remained completely epithelialized without recurrent ulceration, with pain resolution and return to baseline activities. Conclusions: In this patient with ulcerated dystrophic calcinosis cutis associated with rheumatoid arthritis, staged reconstruction using surgical excision, a polylactic acid matrix, single-use negative pressure wound therapy, and split-thickness skin grafting facilitated recipient-bed preparation and definitive cutaneous closure of the post-excisional defect. This case supports the feasibility of this sequence for wound reconstruction in selected complex ulcerated lesions. Further studies are needed to define its comparative role. Full article

Non-cirrhotic portal hypertension (NCPHT) is defined as portal hypertension (PHT) occurring in the absence of cirrhosis. Major etiological causes of NCPHT include immunological disorders, chronic infections, exposure to medications or toxins, prothrombotic conditions, and several genetic syndromes, highlighting that NCPHT is not a single disease but a shared phenotype arising from diverse underlying pathways. NCPHT is frequently misdiagnosed, largely due to inconsistent nomenclature and limited scientific literature. The broader term non-cirrhotic portal fibrosis (NCPF) or porto-sinusoidal vascular disease (PSVD) includes patients in a preclinical stage who demonstrate histological features similar to NCPHT but lack clinical evidence of PHT. Early detection is linked to a favorable prognosis and improved clinical outcomes. Management strategies in pediatrics continue to rely on extrapolations from adult practice, with sparse evidence to guide pediatric care. Liver biopsy remains the cornerstone of diagnosis, demonstrating nodular regenerative hyperplasia, obliterative portal venopathy, or incomplete septal fibrosis. Management focuses on prophylactic and symptomatic care, with endoscopic therapy for controlling variceal bleeding. Porto-systemic shunts and, ultimately, liver transplantation therapies may be needed for advanced stages. A pressing need exists for standardized diagnostic criteria and multicenter studies to define natural history, refine risk stratification, and evaluate therapeutic approaches in the pediatric population. This review provides an overview of the pediatric causes of NCPHT, outlines the current understanding of pathophysiology, and discusses the clinical presentations and management strategies, while highlighting existing research gaps. Full article

Amyotrophic lateral sclerosis (ALS) usually enters diagnostic pathways after motor symptoms emerge, by which time neural injury has been ongoing. Long-term heredi-tary ALS cohorts show that some pathogenic-variant carriers may show elevated neu-rofilament light chain (NfL), mild motor impairment (MMI), electromyographic ab-normalities, or imaging changes before clinical manifestation. Since 2022, research has shifted from detecting presymptomatic abnormalities to identifying observable pro-dromal phenotypes and predicting phenoconversion timing. Operational MMI criteria, longitudinal imaging in chromosome 9 open reading frame 72 (C9orf72) expansion carriers, TAR DNA-binding protein 43 (TDP-43)-related fluid biomarkers, and plasma proteomic models spanning prediction horizons have broadened early identification. The ATLAS study, a trial of tofersen initiated in clinically presymptomatic carriers of superoxide dismutase 1 (SOD1) variants, incorporated specific SOD1 variants and within-person NfL increases into risk monitoring and used these criteria to select par-ticipants for the randomized treatment phase. Evidence remains concentrated in a few genetic subtypes, and no single marker accurately predicts individual phenoconver-sion. Identification requires genotype-specific natural history, serial clinical examina-tions and biomarker testing, with clinical utility validated in independent longitudinal cohorts and prevention trials. Full article

Background/Objectives: Early-onset colorectal cancer (EOCRC), diagnosed before age 50 years, is increasing in many populations and usually arises outside routine screening pathways. We synthesized clinical, demographic, familial, and genetic evidence relevant to risk-stratified early detection. Methods: Two core PubMed searches covering publications from 1 January 2010 through 1 June 2026 were supplemented by targeted PubMed searches and reference-list screening. The present review cited 82 journal publications and synthesized the findings qualitatively; no formal risk-of-bias assessment, certainty-of-evidence grading, or de novo quantitative pooling was performed. Results: EOCRC commonly involves the distal colon or rectum and presents with hematochezia, abdominal pain, altered bowel habits, or iron-deficiency anemia, with diagnostic intervals of several months. Screening colonoscopy in average-risk adults aged 45–49 years has a clinically relevant yield, although generally lower than in older adults, and direct evidence of reduced incidence or mortality remains limited. Risk rises with age before 50; sex and race or ethnicity provide limited, context-dependent discrimination. Family history is a consistent marker, although most cases lack documented familial aggregation. Pathogenic germline variants explain a minority, and polygenic risk scores are not established for routine practice. Conclusions: Early detection should combine timely investigation of warning signs, assessment of family history, equitable access to diagnostics, germline testing for patients with EOCRC, cascade testing, and prospective validation of population-specific models. Full article

Assessing balance is crucial in neurological rehabilitation, yet while wearable sensors enable real-world monitoring, identifying reliable digital biomarkers remains challenging. This study utilized a high-fidelity instrumented walkway to determine which gait parameters best predict balance impairment, providing robust targets for future wearable applications. We analyzed 49 steady-state gait metrics from 140 individuals with diverse neurological conditions. Using statistical analysis and machine learning, we evaluated these parameters against objective force plate sway scores and clinical fall-history labels. Group analysis identified 16 parameters significantly distinguishing fallers from non-fallers, and a neural network classified fallers with an area under the curve of 0.75. Across all analytical approaches, overall gait variability, e.g., Stride Width S.D. and the Gait Variability Index, emerged as a universal predictor of balance impairment and fall risk. Furthermore, while traditional linear models emphasized spatial postural control, machine learning classification uniquely identified inter-limb asymmetry as a premier driver of fall prediction. These findings indicate that instrumented gait analysis effectively identifies digital biomarkers for balance deficits. Isolating these specific metrics provides a clear blueprint for meaningful metrics required for continuous objective monitoring and future development of personalized, adaptive rehabilitation strategies. Full article

Chronic kidney disease (CKD) affects more than 10% of the global population and represents one of the leading causes of mortality. This study aimed to assess the pharmacotherapy of hospitalized patients aged ≥ 65 years with CKD, focusing on the prevalence of polypharmacy, potentially inappropriate medications (PIMs), potentially clinically significant drug–drug interactions (DDIs), the use of renal-risk drugs (RRDs). A prospective observational study was conducted at the Department of Nephrology and Dialysis of University Hospital Dubrava, including 100 participants. A clinical pharmacist obtained the Best Possible Medication History (BPMH) within 24 h of hospital admission. A total of 1324 comorbidities were recorded (median 12 per patient), along with 985 prescribed medications. Polypharmacy (5–9 drugs) was observed in 43% of patients, while excessive polypharmacy (≥10 drugs) was present in 48%. A total of 258 PIMs were identified, with 89% of patients having at least one PIM (mean 2.6 per patient). Nearly 94% of patients had significantly impaired renal function (G3–G5), and 82% were exposed to inappropriately prescribed RRDs. Contraindicated medications based on renal function were identified in 62% of patients, while 52% had at least one medication prescribed at an unadjusted dose. A total of 1097 potentially clinically significant DDIs were identified, with a mean of 10.9 interactions per patient. The results indicate a high prevalence of polypharmacy, PIMs, potentially clinically significant DDIs and inappropriately prescribed RRDs among older hospitalized patients with CKD, increasing the risk of adverse events and unfavorable treatment outcomes. The findings highlight the importance of the 24 h period following hospital admission as an early opportunity for identifying medication-related problems and optimizing pharmacotherapy in highly vulnerable patients, such as elderly patients with CKD. The study also emphasizes the importance of early involvement of a clinical pharmacist in the pharmacotherapy review and obtaining the BPMH. Full article

Background/Objectives: Early risk stratification is essential in pulmonary embolism (PE), but a simple tool integrating routinely available clinical and laboratory variables is lacking. We aimed to develop a simple score for predicting 30-day mortality in patients presenting to the emergency department (ED) with PE. Methods: We conducted a multicenter study in three hospitals in Korea. The score was derived at the largest hospital using least absolute shrinkage and selection operator logistic regression with bootstrap stability selection, and validated in the pooled cohort from the remaining two hospitals. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and compared with PESI and sPESI. Calibration was assessed using the Brier score and calibration parameters. Results: Among 2446 patients, 1753 were included in the derivation cohort and 693 in the validation cohort. The final score (3C score) assigned one point each for history of cancer, international normalized ratio ≥1.15, and C-reactive protein ≥50 mg/L. In the validation cohort, the AUROC was 0.767 (95% CI, 0.703–0.822) for 30-day mortality, compared with 0.748 for PESI and 0.725 for sPESI. 30-day mortality increased from 2.4% (score 0) to 34.4% (score 3). A score of 0 identified 42.7% of patients as low risk, with a negative predictive value of 97.6%. Calibration was acceptable (Brier score, 0.077; calibration slope, 1.098). Conclusions: The 3C score showed discrimination comparable to PESI and sPESI and identified a substantial subgroup with low risk. Its simplicity may facilitate ED risk assessment, although further validation is required before clinical implementation. Full article

Background: Congenital heart block (CHB) is a severe disorder, with an estimated incidence of 1 in 20,000 live births. In most cases, the underlying pathophysiology involves transplacental transfer of maternal anti-Ro/SSA and/or anti-La/SSB antibodies, which are thought to bind to L-type calcium channels on fetal cardiac conduction cells, triggering apoptosis and initiating an inflammatory response that ultimately leads to destruction of the conduction system. Case presentation: We report a case of a dichorionic diamniotic twin pregnancy in which one fetus exhibited complete heart block in the 21st week of gestation, whereas the co-twin showed no abnormalities. The maternal history was notable for multiple autoimmune disorders among first- and second-degree relatives. Serological testing revealed markedly elevated titers of anti-SSA autoantibodies. Following parental decision, the pregnancy was terminated. Macroscopic evaluation of the affected fetal heart showed ventricular dilation, while histopathological examination demonstrated fibrotic and degenerative changes as well as focal calcification in the atrioventricular junctional region. In contrast, the cardiac conduction system of the unaffected fetus was preserved. Discussion: Fetuses of seropositive mothers have a 2–5% first-event risk of developing CHB during gestation. The available literature suggests that the underlying pathophysiology in discordant twin pregnancies likely reflects unequal placental transfer of antibodies in combination with subtle differences in fetal susceptibility and local immune responses. Conclusions: This case illustrates the unpredictable course of anti-SSA-associated CHB in twin pregnancies and highlights the importance of careful fetal cardiac surveillance in seropositive women, even in the absence of a clinically apparent autoimmune disease. Furthermore, the comprehensive histopathological documentation provides additional insight into the pathological basis of CHB. Full article

Objectives: The objective of this study was to compare outcomes of universal versus female-inclusive selective ultrasonography screening for developmental dysplasia of the hip (DDH) in a neonatal population. Methods: This prospective cohort study evaluated two consecutive screening strategies at a single institution: a universal ultrasonography program (2019–2020; n = 354) and a selective program (2024–2025; n = 290). The selective protocol included all female neonates, breech presentation, positive family history, or abnormal clinical findings. All examinations were performed by the same operator using the Graf method. The primary outcome was detection of dysplastic hips; secondary outcomes included immature hip distribution, subgroup differences, and screening efficiency. Results: DDH detection rates were identical between cohorts (1.7%). In the universal cohort, six infants had dysplastic hips; in the selective cohort, five infants were affected, all females. Among these, 40% had no major risk factors. The proportions of mature and immature hips were comparable between cohorts. Screening efficiency was similar (number needed to screen: 59 vs. 58), despite a substantially reduced number of scans in the selective program. Conclusions: A selective screening program that includes all female neonates achieved DDH detection rates comparable to universal screening while significantly reducing imaging volume. As all dysplastic cases occurred in girls, this female-inclusive approach captured the highest-risk demographic without relying solely on traditional risk factors. Incorporating sex-based eligibility into selective screening may provide a safe and efficient framework for DDH screening programs in diverse clinical settings. Full article

Incarcerated women face elevated suicide risk at the intersection of chronic loss, cumulative trauma, and constrained environments. In prison, the death of a child constitutes a profound and overlooked traumatic bereavement. This conceptual manuscript examines how carceral environments restrict privacy, autonomy, family contact, mourning rituals, and social and clinical support, thereby adversely reshaping grief. The Dual Process Model of Coping and meaning-making frameworks are integrated to explain how incarceration may constrain oscillation between loss-oriented and restoration-oriented coping. Institutional functioning may resemble restoration-oriented behavior while lacking critical adaptive factors that define restorative coping. Restricted information, exclusion from rituals and relational validation, and punishment for grief-related behavior may obstruct narrative reconstruction, continuing bonds, and maternal identity reorganization. The model further considers how acute grief interacts with chronic stress, sustained threat responsivity, sleep disruption, and cumulative allostatic burden to intensify psychological and somatic distress without assuming a uniform neurobiological pathway. Social determinants of health, histories of victimization, substance use, and facility-level conditions are important sources of variation. Protective pathways are also specified, including family connection, peer support, cultural and spiritual practices, and clinical care. The paper concludes with testable propositions, a research agenda, and a framework for notification, stabilization, and continuing bereavement support. Full article

Atopic dermatitis is a chronic inflammatory skin disease increasingly recognized as part of a broader atopic and type 2 inflammatory spectrum rather than a condition confined to the skin alone. Although its dermatologic burden is well established, its relevance to otorhinolaryngology remains relatively underrecognized. This narrative review examines atopic dermatitis from an otorhinolaryngology-centered perspective, focusing on ear, nose and throat (ENT) associations, clinical overlaps, shared inflammatory pathways, and practical implications for clinical care. Particular emphasis is placed on allergic rhinitis, chronic rhinosinusitis, ear-related eczematous manifestations, and the head and neck phenotype of atopic dermatitis. Shared pathophysiologic mechanisms, including epithelial barrier dysfunction, allergen sensitization, immune dysregulation, type 2 inflammation, microbiome alterations, and allergic multimorbidity, provide a framework for understanding these overlaps. Upper airway and ear-related conditions should not be interpreted as direct manifestations of atopic dermatitis in all patients, but as disorders that may coexist within a shared atopic or type 2 inflammatory background. The review further considers the implications of this perspective for targeted history-taking, differential diagnosis, referral decisions, therapeutic awareness, and multidisciplinary care. Overall, atopic dermatitis may serve as a clinically useful marker of broader allergic and inflammatory multimorbidity, with relevant implications for selected patients encountered in otorhinolaryngology practice. Full article

Background and Objectives: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer, and its global incidence rate constantly rises. However, there are no current epidemiological data for many regions, including Małopolska in southern Poland. This study aimed to characterize the clinical and histological profile of patients with BCC and to identify factors associated with local recurrence and the presence of multiple tumors. Materials and Methods: We performed a single-center, retrospective observational study consistent with STROBE guidelines at the Department of Dermatology and Allergology, University Hospital in Cracow. The included patients were adults with at least one histologically confirmed BCC treated between 2015 and 2025. Demographic, clinical, histopathological, and follow-up data were collected at patient and lesion levels. The results were evaluated using univariable tests, multivariable logistic regression, Kaplan–Meier survival analysis, and generalized estimating equations. Results: We included 108 patients (median age at first diagnosis, 73 years; 52% male) with 418 BCCs; the median follow-up duration was 84 months. Superficial BCC was the most common subtype among lesions with available histological subtype information (56%). The head and neck region was the most frequent anatomical site in this group (51%). Multiple BCCs were present in 62% of patients. Longer follow-up was independently associated with the presence of multiple BCCs. A history of actinic keratoses showed a positive but statistically nonsignificant association with multiple BCCs. Recurrence was observed in 15 lesions (3.6%). Female sex and H-zone involvement showed higher odds of recurrence. Conclusions: In this elderly cohort, multiple BCC tumors may reflect longer follow-up and cumulative actinic damage. Recurrence was relatively infrequent but associated with clinically relevant features, including H-zone involvement and female sex. These findings support an individualized, multifactorial approach to treatment and follow-up, taking into account age, sex, lesion burden, anatomical location, and histological subtype. Full article

Background: Myasthenia gravis is an autoimmune disorder of the neuromuscular junction characterized by fluctuating skeletal muscle weakness. Late-onset MG (onset ≥ 50 and <65 years) and very late-onset MG (VLOMG; onset ≥ 65 years) are increasingly recognized subgroups, and diagnosis in very elderly patients remains challenging because symptoms frequently overlap with age-related conditions and comorbidities. Case Presentation: An 88-year-old man with very late-onset myasthenia gravis (symptom onset at approximately age 85) was urgently referred because of a several-day history of rapidly worsening dysphagia and dysarthria, superimposed on fluctuating diplopia, dysphagia, dysarthria, and fatigable bulbar symptoms that had progressively worsened over the preceding three years. Initial diagnostic evaluation was challenging because of advanced age, previous lacunar infarctions, and multiple comorbidities, including pulmonary thromboembolism, chronic kidney disease, and permanent pacemaker implantation (which precluded brain MRI). Neurological examination and the characteristic fluctuation of symptoms raised suspicion of myasthenia gravis. Serological testing confirmed markedly elevated acetylcholine receptor antibodies, whereas MuSK antibodies were negative. Repetitive nerve stimulation was not performed given the high antibody titer and unambiguous clinical presentation. Thoracic computed tomography excluded thymoma. Treatment with pyridostigmine, azathioprine (maintenance dose kept lower than standard due to chronic kidney disease stage IIIB), and low-dose prednisone (selected due to age and comorbidity profile) resulted in early, patient-reported clinical improvement (approximately 60% in speech and swallowing) over eight weeks of follow-up; a validated severity scale (MG-ADL) showed a score of six (scoring range 0–24). Conclusions: Myasthenia gravis should remain an important differential diagnosis in very elderly patients presenting with fluctuating ocular and bulbar symptoms, even in the presence of multiple comorbidities that may obscure the diagnosis. In this patient, early recognition, antibody testing, and individualised initiation of therapy were followed by meaningful short-term improvement; a single case with eight weeks of follow-up cannot establish that such therapy prevents disease progression or myasthenic crisis, and longer follow-up and additional cases are needed. Full article

Human Papillomavirus (HPV) is a highly prevalent sexually transmitted infection associated with malignancies of the cervix, vulva, and vagina. While prophylactic vaccination with Gardasil^®9 is FDA-approved through age 45, no clinical trials have evaluated its use in older adults who remain sexually active and at risk for HPV-related cancers. We describe the case of a woman who presented with recurrent high-risk HPV and received the three-dose Gardasil^®9 series off-label at the age of 67. Following vaccination, her cervical cytology was negative for HPV and subsequent colposcopy did not demonstrate any evidence of intraepithelial lesion or malignancy. As this is a single case report, this temporal association cannot establish that vaccination caused viral clearance. Nonetheless, this case raises important questions regarding age-based HPV vaccination limits. Immunosenescence in older populations may impair viral clearance and could increase cumulative risk of progression from dysplasia to malignancy. Vaccination may therefore serve both prophylactic and potentially therapeutic roles; however, this must be evaluated in further controlled studies. This case highlights the need for further research into HPV vaccination in patients over the age of 45 years with or without history of HPV infection. Full article

Background/Objectives: Paediatric pulmonary embolism (PE) is rare but potentially lethal, and its diagnosis is complicated by non-specific presentations and multiple predisposing risk factors. We describe a 15-year-old girl who presented with features of pulmonary hypertension and was found to have extensive pulmonary embolism with right heart strain. Methods: The diagnosis was established with echocardiography, computed tomography pulmonary angiography (CTPA), and Doppler ultrasonography. Results: Her predisposing risk factors comprised obesity (BMI 33 kg/m²), a family history of thrombosis, and heterozygous Factor V Leiden. In retrospect, a six-week illness treated as bronchitis, with haemoptysis and exertional syncope, was the probable index embolic event; the markedly elevated right-sided pressures tolerated without haemodynamic collapse indicate a right ventricle that had adapted over that interval. Anticoagulation with low-molecular-weight heparin, titrated to anti-factor Xa activity, was followed by a vitamin K antagonist while antiphospholipid syndrome was excluded and then by rivaroxaban, with clinical, biochemical, and radiographic improvement. Conclusions: This report underscores the need for greater awareness of PE in children, the value of Full article