One of the most common complaints in ENT clinics is dizziness. Although most cases are caused by vestibular neuritis and benign paroxysmal positional vertigo (BPPV), a significant number of patients experience non-vestibular dizziness. One non-vestibular cause is postural orthostatic tachycardia syndrome (POTS), which presents with symptoms similar to vestibular migraine (VM) and persistent postural perceptual dizziness (PPPD). Dizziness from POTS is related to dysautonomia rather than the vestibular system. In otolaryngology, understanding the autonomic nature of non-vestibular dizziness is important for accurate diagnosis. This study aims to review the clinical characteristics and pathophysiology of POTS, vestibular migraine, and PPPD; examine historical, physical, and diagnostic findings that differentiate autonomic and vestibular causes of dizziness; and develop a more specific model for evaluating chronic dizziness in the ENT setting. Literature on dizziness, vestibular and autonomic pathophysiology, and the clinical presentation of POTS, VM, and PPPD is reviewed in this paper. The timing of symptoms, their triggers, and objective assessment are key differentiating factors for these disorders. Various diagnostic tools, including orthostatic vital signs, oculomotor assessment, gait and balance evaluation, vestibular function assessment, tilt table testing, and neuroimaging, are also reviewed. Clear distinctions among POTS, VM, and PPPD are made. The diagnostic criteria for POTS are orthostatic tachycardia and posture-dependent symptoms that improve when the patient is in a recumbent position, effectively ruling out vestibular involvement in these patients. Vestibular migraine presents with vertigo accompanied by migraine features such as photophobia, phonophobia, or headache, typically triggered by sensory or environmental factors rather than changes in posture. PPPD manifests as chronic non-spinning dizziness and imbalance lasting at least three months, exacerbated by motion, upright posture, and complex visual environments. Orthostatic vital signs and autonomic assessment should be included in the evaluation of patients presenting with dizziness to differentiate between these disorders. Both vestibular and autonomic dysfunction can lead to chronic dizziness. By incorporating autonomic assessments into vestibular evaluations, ENT physicians can apply a more precise diagnostic model for their patients. Identifying dysautonomia-related dizziness, including POTS, helps reduce the misdiagnosis of vestibular disorders. This approach enables physicians to provide more effective interventions for patients with complex dizziness.
Early detection of critical congenital heart disease (CCHD) remains a challenge, especially in settings with early postnatal discharge. Pulse oximetry screening is a simple, non-invasive method that can aid in early diagnosis, but optimal timing in resource-limited settings requires evaluation. This study aims to assess the effectiveness of pulse oximetry screening at 15 minutes and six hours of life in identifying persistent hypoxemia and detecting CCHD or other early echocardiographic cardiac findings among term healthy newborns. This prospective observational study was conducted over six months in a tertiary care hospital and included 530 term newborns with birth weight ≥2.5 kilograms (kg). Oxygen saturation (peripheral capillary oxygen saturation (SpO₂)) was measured at 15 minutes and six hours of life. Newborns with SpO₂ <95% were reassessed, and those with persistent abnormal values or limb saturation difference ≥3% underwent echocardiography. Data were analyzed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York). Of 530 newborns, 81 (15.3%) had SpO₂ <95% at 15 minutes. At six hours, 75 were normalized, while six newborns (1.13%) had persistent abnormal screening findings and underwent echocardiography. Among these, two newborns (0.37%) were diagnosed with CCHD, and four had patent ductus arteriosus (PDA) detected on early echocardiography. Because echocardiography was performed during the early neonatal transitional period, PDA findings may have been physiological and were not confirmed as persistent CHD by follow-up echocardiography. Newborns delivered by lower segment cesarean section (LSCS) showed a higher incidence of low SpO₂ compared to normal vaginal delivery (NVD). Early pulse oximetry screening at 15 minutes and six hours is a practical approach for identifying term newborns with persistent hypoxemia who may require further cardiac evaluation before discharge. This approach may be feasible for routine neonatal care, particularly in settings with early discharge practices; however, larger studies with follow-up are needed to define diagnostic accuracy, false-negative rates, and the clinical significance of early PDA findings.
Polycystic ovary syndrome (PCOS) is associated with a higher incidence of pregnancy-related hypertensive disorders (PHD), and an increased cardiometabolic risk. Chemerin, an adipokine involved in metabolic and inflammatory pathways, has been linked to both PCOS and PHD. This study was designed to test the hypothesis that mid-pregnancy maternal serum chemerin levels may predict persistent hypertension one year after delivery in women with PCOS and a history of PHD. Longitudinal cohort study. Ninety-two patients with and without PCOS and previous PHD were studied 12 months after delivery. Serum chemerin concentrations were measured at 20 weeks of gestation. Logistic regression models were used to assess the association between chemerin and persistent hypertension. Receiver operating characteristic curve analysis evaluated predictive performance. Women with persistent hypertension exhibited significantly higher chemerin levels compared with normotensive women (median 31.3 vs. 20.1 ng/mL; P = 0.0003). Chemerin concentrations resulted independently associated with persistent hypertension (adjusted odds ratio 6.66 per 10 ng/mL; 95% CI 2.21-20.07; P = 0.0007). Among women with PCOS, a higher chemerin threshold (∼32.3 ng/mL) provided a positive predictive value of 57.1% and a negative predictive value of 82.9%. Mid-pregnancy chemerin levels independently predict persistent hypertension after delivery in patients with PCOS and prior PHD.
Ceftazidime-avibactam is widely used to treat infections caused by carbapenem-resistant Gram-negative bacteria. Although it is generally considered safe, cases of severe hypokalemia associated with its use have rarely been reported. A 74-year-old man with severe pneumonia and acute cerebral infarction was treated with ceftazidime-avibactam after sputum culture and nucleic acid testing identified multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae. Soon after initiation of therapy, he developed persistent and refractory hypokalemia. Drug-induced severe hypokalemia secondary to ceftazidime-avibactam was diagnosed. Antimicrobial therapy was continued, and the patient received oral spironolactone and nasogastric potassium chloride. Because of persistent hypokalemia and the development of acute kidney injury, the dose of ceftazidime-avibactam was reduced by half. After dose adjustment and continued potassium supplementation, serum potassium levels gradually stabilized. The patient's condition worsened due to multiple organ failure and septic shock. At the request of his family, he was discharged against medical advice. This case suggests that avibactam may promote potassium loss by enhancing renal tubular secretion and increasing luminal electronegativity. Clinicians should be aware of this potential adverse effect, particularly in elderly patients or those with renal dysfunction. Close monitoring of serum and urinary potassium levels, along with early correction of abnormalities, is strongly recommended during treatment.
Invasive mole is one of the most common forms of gestational trophoblastic neoplasia (GTN), characterized by hydropic chorionic villi with trophoblastic proliferation invading the myometrium. Although it usually develops after complete hydatidiform mole, occurrence following partial hydatidiform mole is uncommon. Delayed follow-up and inadequate β-human chorionic gonadotropin (β-hCG) surveillance may contribute to disease progression and severe complications. A 34-year-old woman para 2 abortus 1, presented with massive vaginal bleeding and hypovolemic shock six months after evacuation of a partial hydatidiform mole. Initial pre-evacuation β-hCG level was 1183002 mIU/mL. Due to financial constraints and inactive health insurance, post-evacuation follow-up was delayed. Serial β-hCG levels declined but remained persistently elevated for more than six months. The patient experienced continuous vaginal spotting and was diagnosed with stage I low-risk gestational trophoblastic neoplasia with a FIGO prognostic score of 4. Two weeks prior to the onset of massive bleeding, the patient had received the first cycle of single-agent methotrexate chemotherapy.Doppler ultrasonography demonstrated markedly increased myometrial vascularity suggestive of invasive mole. Despite blood transfusion, antifibrinolytic therapy, and initiation of single-agent methotrexate chemotherapy, severe vaginal bleeding persisted, resulting in profound anemia (hemoglobin 6.7 g/dL). Emergency total hysterectomy with bilateral salpingectomy was performed due to life-threatening hemorrhage. Histopathological examination confirmed invasive mole with trophoblastic invasion extending into the parametrium. No distant metastases were identified. Invasive mole following partial hydatidiform mole is rare but may lead to severe hemorrhagic complications when diagnosis and follow-up are delayed. Persistent elevation of β-hCG and abnormal uterine bleeding after molar evacuation should prompt early evaluation for gestational trophoblastic neoplasia. Multidisciplinary management, including chemotherapy, hemodynamic stabilization, and surgical intervention when indicated, is essential to achieve favorable outcomes.
Klebsiella pneumoniae liver abscess is characterized by an aggressive clinical course with a high risk of metastatic complications. Early initiation of appropriate antibiotics and timely drainage are essential for successful management. However, large multiloculated Klebsiella pneumoniae liver abscesses are associated with a high risk of percutaneous drainage failure. A 70-year-old man with a history of prediabetes and chronic kidney disease presented with a 2-week history of progressively worsening right upper quadrant abdominal pain. On presentation, he was tachycardic at 107 beats per minute. Physical examination revealed marked right upper quadrant tenderness and hepatic percussion tenderness. Laboratory testing demonstrated neutrophil-predominant leukocytosis and elevated alkaline phosphatase and gamma-glutamyl transferase levels. Contrast-enhanced abdominal computed tomography (CT) revealed an 11-cm multiloculated mass in the right hepatic lobe consistent with a liver abscess. Intravenous ceftriaxone and metronidazole were initiated, and percutaneous drainage was performed. Culture of the aspirated fluid grew Klebsiella pneumoniae. Despite percutaneous drainage, the patient continued to experience severe pain and persistent leukocytosis, and follow-up CT demonstrated a persistent hepatic abscess. He subsequently underwent laparoscopic partial liver resection with fenestration of the abscess cavity. Postoperative imaging showed marked improvement, with resolution of symptoms and leukocytosis. This case underscores the importance of carefully evaluating morphology and causative organism of abscess when selecting a drainage strategy for pyogenic liver abscess. In patients with multiloculated Klebsiella pneumoniae liver abscess, clinicians should maintain a low threshold for considering early surgical drainage.
Gastrointestinal Kaposi sarcoma is an uncommon but clinically relevant manifestation of human herpesvirus 8-associated disease in patients with human immunodeficiency virus (HIV) infection. Its diagnosis may be delayed because symptoms are often nonspecific and may overlap with other anorectal disorders, particularly in patients with condylomatous disease, fissures, proctitis, or anal malignancy. We report the case of a 25-year-old male with HIV infection on antiretroviral therapy and an undetectable viral load who presented with one month of anal pain and rectal bleeding. Initial colonoscopy demonstrated multiple irregular ulcerated lesions in the distal rectum, and biopsy confirmed Kaposi sarcoma associated with human herpesvirus 8. Despite referral to Medical Oncology and initiation of chemotherapy, the patient had persistent rectal bleeding, mucus discharge, anal condyloma, and fissure. Repeat proctologic evaluation and colonoscopy revealed elevated, irregular, ulcerated circumferential lesions extending from the anal canal to 10 cm proximally, with increased submucosal vascular pattern. Persistent gastrointestinal Kaposi sarcoma with suspicious anorectal tumoral involvement was identified, and the patient was referred for multidisciplinary oncologic management. This case highlights the diagnostic challenge of anorectal Kaposi sarcoma in patients with HIV infection, especially when symptoms overlap with benign anorectal disease or synchronous malignancy. Early endoscopic evaluation, biopsy, and immunohistochemistry are essential for timely diagnosis and appropriate multidisciplinary treatment.
Infective endocarditis (IE) remains a life-threatening condition in which early diagnosis is essential to prevent valvular destruction and systemic complications. Persistent Staphylococcus aureus bacteraemia (SAB) is strongly associated with endocardial infection, yet diagnosis may be challenging when initial imaging is inconclusive. We describe a case of a 55-year-old woman who presented with fever, vomiting, and transient loss of consciousness. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Initial transthoracic echocardiography (TTE) and positron emission tomography-computed tomography (PET-CT) imaging failed to identify endocarditis. Despite appropriate antimicrobial therapy, she developed recurrent bacteraemia, ongoing pyrexia, and clinical deterioration. Transoesophageal echocardiography (TOE) subsequently demonstrated severe aortic regurgitation consistent with IE. Because of significant underlying liver disease, surgery was deemed prohibitive, and she was managed with prolonged intravenous antibiotics and cardiology follow-up for potential future valve intervention. This case highlights the importance of maintaining a high clinical suspicion for IE in patients with persistent SAB. It supports guideline recommendations for early TOE when clinical suspicion remains high despite a negative transthoracic study. The final Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) 2023 classification of the case aligned with definite IE. The patient completed six weeks of antibiotic treatment after blood culture clearance, which was achieved at week two following the start of antibiotic therapy.
Adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a rare etiology of Cushing's syndrome (CS), frequently linked to germline mutations in the ARMC5 gene. These variants exhibit autosomal dominant inheritance with incomplete penetrance and are associated with bilateral adrenal nodularity and autonomous cortisol secretion. In this familial case, the proband's father carried the same heterozygous variant but remained asymptomatic, illustrating the incomplete penetrance characteristic of ARMC5-associated disorders. A 51-year-old male presented with clinical manifestations of hypercortisolism. Biochemical and imaging studies confirmed ACTH-independent cortisol excess due to bilateral adrenal macronodular hyperplasia. Genetic testing revealed a heterozygous pathogenic variant in ARMC5 (c.2692C>T, p.Arg898Trp). Following laparoscopic right adrenalectomy, serial follow-up showed a progressive decline in serum cortisol, albeit with levels persistently above normal and sustained ACTH suppression. Surveillance imaging at six months revealed expected postsurgical changes on the right side, while contralateral lesions demonstrated progression to a cystic morphology. Notably, this cystic transformation represents a novel imaging finding in ARMC5 mutation carriers. This report describes a novel ARMC5 missense mutation in a familial case of AIMAH, highlighting the utility of genetic testing in diagnosis and family screening. The findings further emphasize the necessity of long-term monitoring for mutation carriers due to the variable expressivity of the disease, informing both clinical surveillance and therapeutic decision-making.
Oral leukoplakia (OLK), the most common potentially malignant oral disorder, poses a persistent clinical challenge due to high recurrence and malignant transformation rates, with no curative treatment currently available. Conventional interventions, including medications, surgery, laser, and photodynamic therapy, have shown limited success in cancerization prevention, largely because the abnormal events underlying the development and progression of OLK remain poorly defined. Here, through single-cell RNA sequencing profiles, we identified an OLK-specific cell population characterized by YAP/TAZ overactivation, which was strongly associated with disrupted epithelial homeostasis. Transgenic mouse models confirmed the essential role of YAP/TAZ activation in conferring the malignant phenotype of OLK and driving its progression toward transformation. Interestingly, although YAP/TAZ are technically and strategically considered undruggable, we uncovered a ferroptosis vulnerability in OLK malignant cells mediated by the YAP/TAZ-TEAD-TXNRD1 axis. Notably, we demonstrate that combining sulfasalazine and docosahexaenoic acid, 2 clinically available agents, effectively induces ferroptosis and attenuates OLK progression. These findings establish a mechanistic link between YAP/TAZ activation and OLK progression, specifically revealing the dual roles of YAP/TAZ in maintaining malignant properties while conferring ferroptosis vulnerability. This duality highlights ferroptosis induction as a promising therapeutic strategy for indirectly targeting YAP/TAZ. Moreover, the drug-repurposing approach provides a practical and translationally relevant avenue to improve OLK management and reduce the risk of malignant transformation.
Mucormycosis is a rapidly progressive, invasive fungal infection that predominantly affects immunocompromised individuals. Although rhino-orbital-cerebral disease is the most common clinical presentation, gastrointestinal mucormycosis is rare and associated with higher mortality rates. We report the case of a 55-year-old woman with uncontrolled diabetes mellitus and chronic airway disease who presented with septic shock secondary to emphysematous pyelonephritis and diabetic ketoacidosis. She was treated with insulin infusion and intravenous meropenem for 14 days. Despite recovery from acute kidney injury, she continued to experience persistent nausea and poor oral intake. Upper gastrointestinal endoscopy demonstrated gastric ulceration, and histopathological examination confirmed gastric mucormycosis. Liposomal amphotericin B was initiated with subsequent improvement in patient appetite and resolution of nausea. This case highlights the importance of early endoscopic evaluation and tissue diagnosis in high-risk patients with persistent gastrointestinal symptoms during recovery from critical illness.
Researchers from low- and middle-income countries (LMICs) remain underrepresented in global academic publishing despite their substantial contributions to science and public health. Evidence indicates that only a small proportion of articles in leading medical journals originate from LMIC regions that account for the majority of the global population, alongside limited representation in editorial leadership, which remains largely concentrated in high-income countries (HICs). Structural factors, including constrained access to mentorship, limited editorial inclusion, and persistent gender and geographic disparities, continue to restrict equitable participation. These challenges may also influence publication outcomes, contributing to lower acceptance rates, higher desk rejections, and reduced visibility of manuscripts from LMIC authors compared with those from HICs. Although mentorship and capacity-building initiatives have been introduced to address these gaps, their impact remains limited, as many programs operate at a small scale, engage relatively few participants, and lack long-term follow-up for sustained improvements in publication outcomes. Achieving equity in scientific publishing will require sustained structural reform. This includes greater investment in manuscript development, diversification of editorial boards, adoption of equitable authorship practices, and inclusive institutional partnerships between the Global North and South. Journals that adopt inclusive models with minimal financial barriers have a unique opportunity to lead this transformation and contribute to a more representative and just global research ecosystem.
Protected areas (PAs) are critical to mitigation of drastic biodiversity decline and habitat loss. Despite considerable global progress in PAs, future efforts need to overcome persistent challenges related to coverage and effectiveness. With limited capacity for expansion of PAs, achieving the targets of the Kunming-Montreal Global Biodiversity Framework (KM-GBF) will depend on other effective area-based conservation measures (OECMs). Such measures deliver effective and sustained biodiversity conservation outside of PAs. Globally important agricultural heritage systems (GIAHS) are institutionally conserved traditional agricultural landscapes (TAL) that support local livelihoods while conserving agrobiodiversity and resident wild biodiversity. Thus, GIAHS represent a promising yet underutilized model for advancing OECMs agenda. To explore this potential, drawing on a synthesis of peer‑reviewed literature, policy documents, and case studies, we examined the foundations of OECMs, considered the distinctive advantages of GIAHS for achieving global conservation targets, and devised policy and practical strategies for leveraging GIAHS as potential OECMs. First, we found that OECMs can enhance ecological representation and connectivity across broader landscapes and that their inclusive and flexible nature creates opportunities for diverse landscapes to contribute to conservation, including TAL, which are inherently sustainable and multifunctional. Second, the conservation contributions of GIAHS, spanning biodiversity maintenance, ecosystem service provision, and landscape connectivity, provide practical criteria for prioritizing future conserved areas. The synergistic management and biocultural approaches inherent to GIAHS offer models for effective conservation strategies. Finally, conservation outcomes of GIAHS closely align with the outcome-based framework of OECMs. To translate this alignment into action, priorities must include strengthening policy and legal strategies and enhancing the evidence base. Hacer que la conservación sea inclusiva y tenga peso mediante sistemas de patrimonio agrícola de importancia mundial, como posibles medidas de conservación territorial eficaces Resumen Las áreas protegidas (AP) son fundamentales para mitigar la drástica disminución de la biodiversidad y la pérdida de hábitats. A pesar de los considerables avances a nivel mundial en materia de AP, los esfuerzos futuros deben superar los retos persistentes relacionados con la cobertura y la eficacia. Dada la capacidad limitada para ampliar las AP, el cumplimiento de los objetivos del Marco Mundial para la Diversidad Biológica de Kunming‐Montreal dependerá de otras medidas de conservación basadas en el territorio (OMCBT). Dichas medidas permiten una conservación eficaz y sostenida de la biodiversidad fuera de las AP. Los sistemas del patrimonio agrícola de importancia mundial (SPAIM) son paisajes agrícolas tradicionales (PAT) conservados institucionalmente que sustentan los medios de vida locales al tiempo que conservan la agrobiodiversidad y la biodiversidad silvestre residente. Por lo tanto, los SPAIM representan un modelo prometedor, aunque infrautilizado, para impulsar la agenda de las OMCBT. Para explorar este potencial, basándonos en una síntesis de la literatura revisada por pares, documentos de políticas y estudios de caso, examinamos los fundamentos de las OECM, consideramos las ventajas distintivas de los SPAIM para alcanzar los objetivos de conservación globales y diseñamos estrategias políticas y prácticas para aprovechar los SPAIM como posibles OMCBT. En primer lugar, constatamos que las OMCBT pueden mejorar la representación ecológica y la conectividad en paisajes más amplios, y que su naturaleza inclusiva y flexible crea oportunidades para que diversos paisajes contribuyan a la conservación, incluidos los paisajes agrícolas tradicionales, que son intrínsecamente sostenibles y multifuncionales. En segundo lugar, las contribuciones a la conservación de los SPAIM, que abarcan el mantenimiento de la biodiversidad, la provisión de servicios ecosistémicos y la conectividad del paisaje, proporcionan criterios prácticos para priorizar futuras áreas de conservación. La gestión sinérgica y los enfoques bioculturales inherentes a los SPAIM ofrecen modelos para estrategias de conservación eficaces. Por último, los resultados de conservación de los SPAIM se ajustan estrechamente al marco basado en resultados de las OMCBT. Para traducir esta alineación en acciones, las prioridades deben incluir el fortalecimiento de las estrategias políticas y legales y la mejora de la base empírica.
Squamous cell carcinoma (SCC) of the anal canal is an uncommon malignancy with increasing incidence, particularly among people living with human immunodeficiency virus (HIV). In rural populations, limited access to specialized screening and fragmented care contribute to delayed diagnosis and advanced-stage presentation. A 58-year-old male patient with a 25-year history of HIV presented with one month of persistent rectal pain, intermittent bleeding, and mass sensation. Physical examination revealed a 5 × 6 cm ulcerated lesion near the anal margin. The patient reported inconsistent adherence to antiretroviral therapy due to transportation barriers and had no prior anorectal screening. Colonoscopy was performed, during which rectal retroflexion revealed an irregular, ulcerated, exophytic lesion with friability and infiltrative features. Biopsies and subsequent examination under anesthesia confirmed anal SCC. Staging demonstrated regional lymph node involvement without distant metastases, consistent with stage IIIA (T3N1M0). The patient was referred to colorectal surgery, radiation oncology, and medical oncology for further treatment. Ultimately, this case highlights how transportation barriers, inconsistent care access, and reliance on multiple geographically separated providers contributed to delayed diagnosis. In resource-limited settings, the lack of high-resolution anoscopy restricts early detection. Although not a primary screening tool, colonoscopy with careful anorectal evaluation may allow for opportunistic detection of malignancy in high-risk individuals. This case underscores the need for improved care integration and expanded access to screening resources among rural communities.
Rosai-Dorfman disease (RDD) is a rare histiocytic disorder that classically presents with massive cervical lymphadenopathy. We report the case of a 38-year-old Indian man referred to the ear, nose, and throat (ENT) clinic via the urgent cancer pathway with a persistent sore throat and unilateral tonsillar hypertrophy, without cervical lymphadenopathy. Clinical examination demonstrated an isolated, firm, non-ulcerative swelling of the right tonsil. Cross-sectional imaging confirmed tonsillar asymmetry without evidence of local invasion or metastatic disease, although increased uptake was noted on positron emission tomography (PET). The patient underwent bilateral tonsillectomy, and histopathological analysis demonstrated large histiocytic cells with immunohistochemistry positive for S100 and CD68 and negative for CD1a, confirming RDD. Subsequent multidisciplinary follow-up identified additional manifestations of the disease, including lung nodules and cutaneous lesions, and the patient remained under the care of the haematology histiocytosis clinic. This case highlights the importance of considering RDD in the differential diagnosis of tonsillar asymmetry and its implications for optimising multidisciplinary patient care.
To evaluate the 10-year economic burden experienced by mothers of children with major congenital anomalies in Denmark. Population-based matched retrospective cohort study. Denmark, 1 January 2007 to 31 December 2017. All women who gave birth to a singleton child with a major congenital anomaly during the study period (n=12 513). A comparison cohort of mothers with singleton births of children without major congenital anomalies was included, matched 1:10 by maternal age, parity and delivery year (n=125 008). Societal costs associated with mothers of children with major congenital anomalies. Costs were quantified as direct healthcare costs (primary care, outpatient, inpatient, psychiatric services and prescriptions) and indirect costs (productivity losses estimated using the human capital approach, including income, labour market contributions, supplementary pensions and fringe benefits). Direct costs peaked in the delivery year with a mean attributable cost of more than €1731 (95% CI €1634 to €1824). Indirect costs increased over time, reaching a peak of €2251 (95% CI €978 to €3442) at 9 years after delivery. Over a median follow-up of 6.3 years, attributable indirect costs were two and a half times higher than direct costs. Total societal costs associated with the 12 513 mothers of children with major congenital anomalies in our cohort were estimated at €152 million (95% CI €92 million to €219 million). Mothers of children with major congenital anomalies experienced substantial and persistent economic burdens, with indirect costs increasing over time and exceeding direct healthcare costs. These findings highlight the need for targeted public health and policy initiatives to support affected families and address long-term societal costs.
Penile cancer (PeCa) is a rare malignancy with substantial global variation in clinical presentation, staging practices and treatment approaches. This scoping review synthesises current evidence across key domains of PeCa management, including tumour classification, human papillomavirus (HPV) integration, organ preservation, nodal staging, systemic therapy and survivorship care. Despite recent updates in the American Joint Committee on Cancer staging system, limitations persist, particularly the absence of biologically relevant factors such as HPV status. While HPV-associated tumours may exhibit different responses to radiotherapy and systemic treatments, routine HPV testing and serotyping are not yet standardised in clinical practice. Early-stage PeCa remains amenable to organ-sparing approaches-including brachytherapy and reconstructive surgery-yet access to these modalities varies widely. Nodal management remains an area of controversy, with global inconsistencies in surgical templates and staging algorithms. Dynamic sentinel lymph node biopsy is emerging as a minimally invasive alternative but remains underused outside of high-volume centres. For node-positive disease, there is growing support for treatment intensification with chemotherapy and radiotherapy; however, prospective evidence is limited. Survivorship issues, particularly regarding psychosocial support and functional outcomes, remain poorly addressed in both research and routine care. This review identifies persistent gaps in the literature and highlights the need for international consensus-building, longitudinal data collection and equitable access to multidisciplinary care through collaborative efforts.
We assessed the global burden of thyroid cancer caused by high body mass index (BMI) from 1990 to 2021 and evaluated whether obesity is genetically supported as a causal risk factor using bidirectional Mendelian randomization (MR). First, we utilized the Global Burden of Disease (GBD) to estimate the deaths, disability-adjusted life years (DALYs), years lived with disability, and years of life lost (YLLs) attributable to high BMI for thyroid cancer, examining age- and sex-specific patterns from 1990 to 2021. Joinpoint regression analyzed temporal trends, and a decomposition analysis was performed to quantify the contributions of population growth, population aging, and epidemiological changes to the burden change. An autoregressive integrated moving average (ARIMA) model was used to forecast changes in the age-standardized death rate (ASDR). Second, we performed bidirectional MR to test whether genetic predisposition to obesity classes influences thyroid cancer risk and whether reverse causation is supported. The GBD analysis showed that high BMI contributed to 5255 global thyroid cancer deaths and 144,955 DALYs in 2021, with a persistently higher burden in females across all age groups. Death and DALY rates for both sexes increased significantly after age 60, with females exhibiting consistently higher rates across all age groups. While absolute numbers of deaths and DALYs increased substantially from 1990 to 2021, age-standardized rates remained relatively stable, and for all metrics women had higher values than men. Average annual percent changes (AAPCs) were found to be higher among males compared to females by joinpoint analysis. Population growth accounted mainly for increasing deaths and DALYs through decomposition analysis. The ARIMA analysis indicates that the level of ASDR among the male population will continue to rise in the future, and it will accelerate after 2025. In contrast, we did not detect a statistically significant causal effect of obesity on thyroid cancer in this MR analysis (Class 1: odds ratio [OR] = 0.82, P = .41; Class 2: OR = 0.96, P = .84; Class 3: OR = 0.86, P = .39). Key limitations include ancestry constraints of the available GWAS instruments and the use of summary-level data.
In recent years, metal-organic frameworks (MOFs) have emerged as highly promising materials for advanced gas sensing owing to their tunable pore structures, high surface area, and chemical versatility. The urgent need for portable, selective detection of industrial pollutants and chemical warfare agents motivates a comprehensive assessment of MOF-based sensors. This review examines the evolution of MOF films and their integration with field-effect transistors (FETs), particularly organic FETs (OFETs). It connects molecular-level adsorption and diffusion processes, such as grain boundary ingress, stress-driven film recrystallization, and π-π interactions, to device-level charge transport and response. Highlighting key case studies like CPO-27-Ni OFET sensors for mustard simulants, we articulate design principles for MOF selection, thin-film deposition, and device architecture. Persistent challenges, electrical conductivity, film processability, and environmental stability, are discussed alongside advances such as mixed-metal MOFs, hydrophobic modifications, and artificial intelligence-guided MOF discovery. We show why MOF-semiconductor hybrids are poised to enable next-generation toxic gas sensors for environmental, industrial, and defense use.