Search Results (506)

Background/Objectives: Clomiphene citrate (CC) is widely used off-label for male infertility despite limited evidence and inconsistent guideline recommendations. Although previous studies suggest variability in clinical practice, real-world data on prescribing patterns, patient selection, monitoring, and treatment success definitions remain limited. This study assessed CC prescribing patterns among urologists and identified factors associated with its use. Methods: A national, cross-sectional, web-based survey was conducted among urologists in Türkiye between November and December 2025. Of 1558 invited participants, 421 responded (27.0%), and 402 were included in the final analysis. The questionnaire was based on European Association of Urology and American Urological Association guidelines, refined through expert consensus, and pilot-tested. Multivariable logistic regression identified factors independently associated with CC use. Results: CC was used by 39.3% of respondents and was independently associated with private practice (odds ratio [OR] = 2.90, p < 0.001), greater professional experience (OR = 2.18, p = 0.002), and higher infertility case volume (OR = 2.27, p = 0.001). Substantial heterogeneity was observed in patient selection, dosing, monitoring, and success definitions. Treatment goals and perceived success definitions most frequently focused on laboratory-based endpoints, including semen parameters and testosterone levels, which were more frequently selected than pregnancy-related endpoints. However, spontaneous pregnancy was also commonly reported as a perceived success definition, whereas live birth was not separately assessed. An apparent indication paradox was observed for hypogonadotropic hypogonadism, which may reflect differing interpretations of functional versus irreversible hypogonadotropic states, and 31.6% of clinicians reported not routinely providing risk counseling. Conclusions: CC prescribing for male infertility remains heterogeneous among responding urologists and was associated with clinician experience, practice setting, and infertility case volume rather than standardized protocols. The predominance of laboratory-based endpoints, together with the frequent inclusion of spontaneous pregnancy as a perceived success definition and the absence of separate live-birth assessment, underscores the need for clearer terminology, standardized prescribing frameworks, structured risk counseling, and future studies incorporating clinically meaningful reproductive endpoints. Full article

Background/Objectives: Cervical intraepithelial neoplasia (CIN) exhibits heterogeneous clinical behavior, with some lesions regressing spontaneously, whereas others persist or progress to higher-grade disease. Identifying biomarkers that reflect lesion dynamics remains a major clinical challenge. This study aimed to evaluate the clinical significance of CD86 expression in cervical lesions by examining longitudinal changes and determining whether temporal alterations in CD86 expression are associated with lesion regression and epithelial-associated immune dynamics. Methods: Cervical samples were collected from patients with CIN, and gene expression was analyzed using reverse transcription–quantitative PCR. Longitudinal analyses were performed using paired samples to evaluate the temporal changes in CD86 expression. Regression status and time to regression were assessed, and associations with CD86 changes were evaluated using receiver operating characteristic analysis, logistic regression, and Cox proportional hazards models. Longitudinal patterns were further characterized using a spaghetti plot and slope analyses. Results: Baseline CD86 expression did not associate with regression status or CIN grade. However, longitudinal changes in CD86 expression differed significantly between the regression and non-regression group. CD86 change demonstrated moderate predictive performance for regression and was significantly associated with both regression and shorter time to regression. Longitudinal analyses revealed distinct temporal patterns between the regression and progression groups. Baseline CD86 expression was strongly correlated with FOXP3 expression, whereas CD86 dynamics were not independently associated with lymphocyte-related markers. Conclusions: Longitudinal changes in CD86 expression are significantly associated with lesion regression in CIN and may reflect lesion-associated immune dynamics during follow-up, particularly within epithelial-derived cervical cytology specimens. Full article

Background/Objective: Cervical intraepithelial neoplasia grade 2 (CIN2) shows heterogeneous clinical behavior, with substantial rates of spontaneous regression under active surveillance. Reliable molecular biomarkers are needed to distinguish regressive from transforming lesions and reduce overtreatment. We evaluated the prognostic role of host and viral DNA methylation, alone and combined with HPV genotyping, in predicting CIN2 regression. Methods: This subanalysis derives from a prospective, multicenter Italian cohort of women with histologically confirmed CIN2 managed conservatively. Among 319 enrolled women, 134 with single HPV infections and valid host (FAM19A4/miR124-2) and viral (HPV L1 region) methylation results were included. HPV genotyping was performed with partial stratification (HPV16/18 vs. non-16/18). Clinical outcomes at 24 months were classified as regression versus persistence/progression. Logistic regression models assessed associations between biomarkers and regression. Results: At 24 months, 50% of women showed regression. Host and viral methylation positivity rates were more frequent in non-regressive lesions (40.3% vs. 19.4%, p = 0.01, and 52.2% vs. 32.8%, p = 0.02, respectively). Negative host methylation was significantly associated with regression (Odds Ratio OR = 0.37, 95% CI 0.17–0.81, p = 0.02), as was negative viral methylation (OR = 0.47, 95% CI 0.23–0.96, p = 0.04). Conclusions: Both host and viral methylation are inversely associated with CIN2 regression. Combining methylation markers did not substantially improve predictive accuracy; however, methylation negativity emerged as a potential molecular reassurance marker. When integrated with HPV genotyping, the highest probability of regression was observed among women with non-HPV16/18 infections and negative methylation results. These results endorse DNA methylation testing as a molecular tool for the conservative management of CIN2. Full article

Background: The lactate-to-albumin ratio (LAR) and C-reactive protein-to-albumin ratio (CAR) are biomarkers for metabolic stress and inflammation. However, their prognostic significance after return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) remains unclear. Therefore, this study aims to investigate the association between serial LAR/CAR measurements and in-hospital mortality. Methods: This retrospective observational cohort study included adult comatose patients with OHCA treated with targeted temperature management between January 2022 and December 2025. Serum lactate, albumin, and C-reactive protein levels were measured at admission and at 24, 48, and 72 h after ROSC. The primary outcome was in-hospital mortality. Multivariable logistic regression analyses were performed to assess independent associations of LAR and CAR with in-hospital mortality, and discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: Of the 284 eligible patients, 253 were included in the final analysis. Of these, 80 patients died in hospital, corresponding to an in-hospital mortality rate of 31.6%. LAR and CAR were significantly higher in non-survivors than in survivors at admission and at 24, 48, and 72 h after ROSC. After adjustment for potential confounders, LAR was associated with in-hospital mortality at all assessed time points. CAR was independently associated with in-hospital mortality at admission and at 48 and 72 h after ROSC, but not at 24 h. The AUCs of LAR for predicting in-hospital mortality ranged from 0.702 to 0.734, whereas those of CAR ranged from 0.640 to 0.690. Conclusions: In this single-center retrospective cohort of post-ROSC OHCA patients, sequential tracking of LAR and CAR profiles during the first 72 h after ROSC provided meaningful insights into in-hospital mortality. LAR showed a more consistent independent association with mortality and fair discriminatory performance, whereas CAR demonstrated limited prognostic value despite its association with mortality. Full article

Background: As glucagon-like peptide-1 (GLP-1) receptor agonist use expands globally, reports of psychiatric adverse events (AEs) have increased in spontaneous reporting databases. However, which case-level characteristics are associated with these reporting patterns remains insufficiently characterized. This study aimed to characterize case-level features associated with psychiatric AE reporting in GLP-1 receptor agonist users through pharmacovigilance and explainable machine learning methods. Methods: The FDA Adverse Event Reporting System (FAERS) data (2021 Q2–2025 Q3) were analyzed using a comparator-based approach comprising other antidiabetic and anti-obesity agents. Disproportionality analyses (PRR, ROR, and IC) were performed to detect consolidated safety signals at the Preferred Term (PT) level, with additional drug-specific analyses for individual GLP-1 receptor agonists. Three classification models (logistic regression, XGBoost, and LightGBM) were developed, and SHAP values were used to identify case-level features associated with psychiatric AE reporting patterns. Results: A total of 211,195 unique cases were included (111,105 for GLP-1 receptor agonists; 100,090 for comparators). Sixteen PTs met consolidated signal criteria, with suicidal ideation being the most frequently reported (ROR 2.95). Drug-specific analyses indicated that signal magnitudes were consistently higher for semaglutide than tirzepatide. The XGBoost model achieved an AUROC of 0.816. SHAP analysis showed that age ≥65 years had the highest mean |SHAP| value (0.57) with a negative direction, corresponding to a lower predicted probability of psychiatric AE reporting in older adults. Semaglutide use ranked second (0.35) and showed a positive direction. Absence of concomitant medications (0.20) and diabetes indication (0.10) showed negative directions, while younger age (19–44 years, 0.08) showed a positive direction. These patterns remained consistent in sensitivity analysis excluding concomitant psychotropic medication users (AUROC 0.797). Conclusions: Older age status was associated with decreased predicted probability of psychiatric AE reporting, while semaglutide use and younger age showed positive contributions. These case-level patterns, identified through pharmacovigilance analysis using a comparator-based approach and explainable machine learning, suggest that reporting patterns may differ across subgroups and that the observed reporting heterogeneity among younger adults and semaglutide users merits further investigation in prospective studies. Full article

Background: Weaning from mechanical ventilation remains a complex and failure-prone process, with extubation failure rates reaching up to 30%. Conventional indices inadequately capture the multifactorial physiology underlying weaning failure. This study aimed to evaluate whether a multimodal ultrasound approach could improve the identification of mechanisms and prediction of extubation outcomes. Methods: In this prospective pilot observational study, adult mechanically ventilated patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) undergoing spontaneous breathing trials (SBT) were included. Multimodal ultrasound assessment—including transthoracic echocardiography (TTE), lung ultrasound (LUS), diaphragmatic ultrasound (DUS), and venous excess ultrasound (VExUS)—was performed at two predefined time points. Conventional respiratory mechanics parameters were recorded concurrently. The primary outcome was a composite of SBT failure (permanent weaning failure) or reintubation within 48 h. Results: A total of 27 patients were included, of whom 8 (29.6%) experienced extubation failure (5 permanent SBT failure, 3 post-extubation reintubation). Respiratory system compliance showed consistent associations with extubation failure across both ROC and regression analyses (AUC 0.806, 95% CI 0.611–1.000; cutoff ≤ 45 mL/cmH₂O; sensitivity 88%; specificity 74%; NPV 93%). Diaphragm excursion was significantly lower in the failure group (p = 0.042) and showed useful predictive performance (AUC 0.750, 95% CI 0.565–0.935; cutoff ≤ 24 mm; sensitivity 100%; specificity 58%; NPV 100%). Lung ultrasound, VExUS, and echocardiographic parameters did not demonstrate significant predictive value. Given the limited number of outcome events (n = 8) and events-per-variable ratio of 4.0 (EPV = 4.0), all multivariable findings are hypothesis-generating. Conclusions: In this prospective pilot study, respiratory system compliance and diaphragm excursion were associated with extubation failure in patients with preserved left ventricular function, while echocardiographic indices, LUS, and VExUS grading did not demonstrate significant predictive value. These hypothesis-generating findings suggest that impaired diaphragmatic function and reduced compliance may be more closely associated with weaning failure than cardiopulmonary congestion parameters. However, given the small sample size, low EPV, and single-centre design, all findings require validation in larger multicentre studies including patients with impaired systolic function. Full article

Background/Objectives: This study evaluated whether sequential changes in cervical length (CL) can predict spontaneous preterm birth (sPTB) before 34 weeks of gestation in twin pregnancies. Methods: This retrospective study from a single tertiary-care center analyzed 349 twin pregnancies with deliveries between January 2019 and December 2023. Cervical length assessments began at 18–21 weeks, followed by biweekly serial measurements. The primary outcome was sPTB before 34 weeks. CL changes were assessed descriptively using data from patients with and without sPTB before 34 weeks. We defined the high-risk status for sPTB based on our assessment. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence intervals (CIs) to quantify the relationship between these predictors and sPTB. Diagnostic accuracy was assessed from the area under the curve using receiver operating characteristic curve analysis. Results: The sPTB rate before 34 weeks of gestation was 8.5% (18/212). In the group without -sPTB before 34 weeks of gestation, the 5th percentile CL was approximately 20 mm at 25 weeks and 15 mm at 26–27 weeks of gestation. Sequential CL measurements revealed that a rapid shortening of ≥10 mm within 2 weeks significantly predicted sPTB before 34 weeks. A decrease in CL of ≥10 mm in a 2-week interval was associated with increased odds for sPTB before 34 weeks of gestation [adjusted OR (95% CI): 6.66 (2.32–19.14)]. Conclusions: In twin pregnancies, measuring CL every 2 weeks after approximately 20 weeks of gestation may facilitate sPTB detection before 34 weeks. Full article

This study investigates the charging behaviors, routines, and perceptions of Swedish electric vehicle (EV) users who lack access to home charging, a group that remains underrepresented in the EV adoption literature. Based on an online survey of 250 EV users—primarily located in Gothenburg—respondents were divided into two groups: those with and those without home charging availability. Nearly half of the sample (47.6%) reported not having access to charging at home. Comparative analyses, including linear regression models, were conducted to examine differences in sociodemographic characteristics, charging patterns, and perceptions of public charging. While the two groups were similar in terms of age, gender, vehicle type, charging frequency, and minimum state of charge preferences, significant differences emerged in perceived convenience, distance, and freedom to charge. Users without home charging availability reported lower access to workplace charging and evaluated public charging as less convenient and less accessible. Charging behavior in both groups was primarily goal-oriented and triggered by minimum state of charge rather than spontaneous opportunities. The findings highlight the structural disadvantages faced by users without home charging and underline the importance of adapting public charging infrastructure and policy strategies to support a broader and more equitable transition to electric mobility. Full article

Background/Objectives: Predictors of left atrial appendage thrombus (LAAT) in adequately anticoagulated patients with atrial fibrillation (AF) referred for direct current cardioversion (DCCV) remain insufficiently defined, particularly in populations with a high prevalence of cardiac implantable electronic devices (CIEDs). The aim of this study was to identify clinical and echocardiographic determinants of LAAT and/or dense spontaneous echocardiographic contrast (SEC) in patients with persistent AF referred for DCCV. Methods: This prospective observational study included 510 consecutive patients with persistent AF who had received at least 3 weeks of effective anticoagulation and underwent transthoracic and transesophageal echocardiography prior to elective DCCV. The primary endpoint was the presence of LAAT and/or dense SEC (Fatkin grade 3–4). Independent predictors were identified using multivariable logistic regression. Results: LAAT and/or dense SEC were detected in 192 patients (37.6%)—of whom 73 had overt LAAT, 19 had borderline LAAT, and the remainder had dense SEC (Fatkin grade 3–4). Independent predictors included lower left ventricular ejection fraction (OR 0.95 per 1% increase, 95% CI 0.94–0.97, p < 0.0001), reduced right ventricular fractional area change (OR 0.93 per 1% increase, 95% CI 0.91–0.94, p < 0.0001), larger left atrial area (OR 1.05 per 1 cm² increase, 95% CI 1.01–1.09, p = 0.011), and female sex (OR 1.78, 95% CI 1.14–2.79, p = 0.012). Moderate or greater mitral regurgitation was associated with a lower risk (OR 0.50, 95% CI 0.30–0.82, p = 0.007). The CHA₂DS₂-VASc score and the presence of right ventricular leads were not independently associated with LAAT/SEC. The model showed good discrimination (AUC 0.81, 95% CI 0.77–0.84). Conclusions: In anticoagulated patients with persistent AF, LAAT and/or dense SEC remain common and are primarily driven by echocardiographic markers of biventricular dysfunction and left atrial remodeling rather than by traditional clinical risk scores or the presence of cardiac devices. Full article

Agricultural water governance faces persistent challenges, including fragmented responsibilities, insufficient motivation, and weak long-term maintenance. Environmental regulation (ER) is regarded as an important policy instrument for addressing market failures and the limitations of spontaneous village-level governance, yet whether ER improves agricultural water governance effectiveness (AWGE) remains insufficiently examined. Based on survey data from 1304 farmers in seven provinces of China, this study employs ordinary least squares regression to investigate the relationship between ER and village-level AWGE, both measured using farmers’ perceptions collected through questionnaire surveys. The results show that ER and its sub-dimensions are positively associated with AWGE. Mechanism analysis reveals that policy implementation capacity (PIC) and farmer participation (FP) mediate the relationship between ER and AWGE. Heterogeneity analysis indicates that this positive association is more pronounced in central China and in areas where the village-level River Chief System was established earlier. These findings provide empirical evidence for constructing a compound ER mechanism integrating guidance, incentives, and constraints, strengthening the dual pathway of grassroots implementation and FP, and adopting differentiated governance strategies according to regional resource endowments and institutional development stages. Full article

Background: Obstetric anal sphincter injuries (OASIS) are a major cause of long-term maternal morbidity. Identification of risk factors is central to prevention strategies. Methods: A retrospective cohort study was conducted including all singleton, term, cephalic vaginal births over a four-year period (September 2018 to September 2022) at a UK tertiary maternity unit. OASIS was defined as third- or fourth-degree perineal tears according to RCOG criteria. Multivariable logistic regression analysis was used to identify independent predictors. A pre-specified sensitivity analysis restricted to nulliparous women was performed. Secondary outcomes included postpartum haemorrhage (PPH), defined as blood loss >1 L. Reporting follows the STROBE statement for cohort studies. Results: Among 9586 vaginal births, 270 OASIS cases were identified, corresponding to an incidence of 2.82%. Independent predictors included nulliparity (aOR 7.12, 95% CI 5.07–10.01), Asian ethnicity (aOR 3.50, 95% CI 2.55–4.81), shoulder dystocia (aOR 3.45, 95% CI 1.89–6.32), and birthweight ≥4000 g (aOR 1.85, 95% CI 1.16–2.95). Maternal age ≥35 years showed a borderline association (aOR 1.34, 95% CI 0.99–1.80, p = 0.056). Using forceps as the reference, ventouse (aOR 0.28, 95% CI 0.17–0.47) and spontaneous vaginal delivery (aOR 0.23, 95% CI 0.13–0.39) were associated with lower OASIS odds. Episiotomy (recorded as a binary variable) was associated with lower adjusted odds of OASIS (aOR 0.27, 95% CI 0.17–0.44). PPH occurred in 21.5% of women with OASIS versus 6.5% without (p < 0.001). Conclusions: OASIS risk is driven by a combination of maternal, fetal, and intrapartum factors. Selective mediolateral episiotomy was associated with lower adjusted odds of OASIS in this cohort, but this is an observational finding and does not constitute proof of a causal protective effect. It should be interpreted cautiously given the retrospective design, the recording of episiotomy as a binary variable without procedural detail, and the substantial potential for residual confounding by indication. The findings support targeted perineal protection strategies and selective rather than routine episiotomy use. Full article

Abnormalities of the urachus detected in infancy and early childhood are often interpreted as persistent congenital abnormalities requiring surgical correction. However, growing clinical experience suggests that a proportion of these findings may reflect ontogenetic immaturity of the urachus rather than fixed pathological conditions. As a transient embryological structure, the urachus undergoes postnatal remodeling and involution, which may explain the spontaneous regression of urachal anomalies observed during follow-up. This paper proposes ontogenetic immaturity of the urachus as a biological substrate for the natural resolution of selected urachal changes, including cystic dilatation and incomplete obliteration. We discuss the developmental background of urachal maturation and emphasize the importance of distinguishing delayed involution from true structural pathology. The clinical implications of this concept are highlighted, with particular focus on the role of careful observation and longitudinal monitoring as an alternative to early surgical intervention in asymptomatic or mildly symptomatic patients. Recognizing ontogenetic immaturity as a reversible developmental state may help reduce overtreatment and support more individualized, developmentally informed management strategies. Integrating principles of developmental biology into clinical decision-making reinforces the value of conservative approaches in selected urachal conditions and under-scores the broader relevance of ontogeny in kidney and urinary tract disease. Full article

Background: Vestibular tests are critical for an early detection of balance disorders, thereby reducing the risk of falls, particularly in older adults. The present is an ecologic study where the units of observation are the Italian Regions. Regional scores of access to essential levels of care (LEAs) were employed as predictors to investigate the hypothesis that vestibular examinations supplied by the Italian National Health Service (NHS) were insufficient to meet the needs of the Italian population. Methods: The number of first-level (clinical evaluations of vestibular function) and second-level (recorded spontaneous nystagmus, induced nystagmus, or rotary stimulation) vestibular tests per 100 K population was estimated by Italian region and calendar year during the 2021–2023 period. The odds (i.e., number of any second-level vestibular tests divided by difference between number of first- and second-level tests) by region and calendar year were investigated as a proxy for regional propensity to refer patients to a second-level test following a first-level vestibular assessment. A logistic regression investigated the odds by region and calendar year. Lastly, the regional number × 100 K population (prevalence) of vestibular examinations underwent linear regression analysis, using LEAs as predictors. Results: Descriptive analysis showed that first-level assessments were the most common vestibular tests in Italy during the 2021–2023 period. Prevalence of first-level vestibular examinations was not associated with any indicator of access to healthcare in linear regression. By contrast, the prevalence of second-level vestibular tests decreased with social inequality yet increased with the indicator of higher access to hospital care. In logistic regression, referral propensity to second-level vestibular tests progressively decreased from 2021 to 2023 and exhibited considerable regional variability, being lower than in Lombardy (reference) in all other Italian regions but Veneto (aOR = 4.826; 95%CI: 4.445; 5.329) and Trento autonomous province (aOR = 1.488; 1.363; 1.624). Conclusions: The number of vestibular function tests supplied by the National Health Service in Italy during the 2021–2023 period was probably insufficient to meet the care needs of the general population, forcing more than 66.8% of patients to forgo vestibular evaluation or turn to private audiological services with out-of-pocket payments. The shortfall was greater for more costly instrumental (second-level) vestibular tests, whose supply was influenced by social inequalities and barriers to accessing audiology care at the regional level. The National Recovery and Resiliency Plan has allocated EUR 20.23 billion for healthcare services in Italy, with the aim of addressing patient care requirements in every area of the country. Full article

Background: Staphylococcus aureus acquires methicillin resistance genes through the SCCmec element. Although spontaneous SCCmec excision has been observed, its frequency, type-specific variation, and responsiveness to environmental conditions remain undefined. Here, we systematically quantified SCCmec excision across diverse prototypic types/subtypes and evaluated the factors that contribute to excision variability. Methods: Twenty five prototypic MRSA strains (SCCmec types I–VIII, XI–XIII and defined subtypes) were examined under standard growth temperature (37 °C), elevated temperature (42 °C), desiccation, prolonged continuous culture (30 days), and sub-lethal oxacillin pressure. Excision frequencies were quantified using qPCR, normalized to the gyrB housekeeping gene using the formula: 10^{−((Ct,orfX−Ct,gyrB)/3.32)}. Statistical analyses included one-way ANOVA, t-tests, and OLS regression for time-dependent trends. Results: At 37 °C, excision frequencies ranged from 2.40 × 10⁻⁶ to 1.32 × 10⁻³ and varied among representative SCCmec types/subtypes but were unrelated to SCCmec size (R² = 0.027, p = 0.44). Type I showed no detectable excision due to a truncated ccrB gene. At 42 °C, excision increased in 14 of 24 types (median +11.2%; eight significant) and decreased in 10 (median −7.4%; four significant). Desiccation produced similar effects, with nine types increasing (median +7.1%; four significant), 14 decreasing (median −8.2%; five significant), and one unchanged. Continuous culture exhibited progressive increases in excision across multiple types (R² = 0.3–0.94), whereas sub-lethal oxacillin uniformly maintained low detectable excision frequencies across all SCCmec types. Conclusions: Excision varied among representative SCCmec types and was influenced heterogeneously by distinct stress conditions. Continuous culture promoted excision, whereas oxacillin exposure maintained low detectable excision. This work quantitatively confirms spontaneous SCCmec excision and provides new insights into MRSA genome plasticity. Full article

Background: An infantile hemangioma (IH) is a benign lesion that develops as a result of pathologically dysregulated proliferation of the endothelial cells of the capillaries, typically appearing within the first three years of life. The disease is found mostly on the skin and—less often—in the internal organs. Although IH generally has a good prognosis and may sometimes undergo spontaneous regression, certain types of IH with a specific form, localization, and size may lead to life-threatening conditions including impairment of vital functions. This determines the need for precise diagnostics and treatment. Case presentation: The paper presents a clinical observation of an infant in the first months of life with IH presenting as diffuse hepatic hemangiomatosis and a hemangioma of the left eyebrow area. The IH was associated with life-threatening conditions. However, effective treatment with the non-selective β-adrenoblocker propranolol led to a positive outcome and the resolution of complications. Conclusions: This case demonstrates the critical importance of timely diagnosis and treatment for lesions that, while benign, can lead to fatal complications if not addressed promptly. Full article