Background and Objective: Recent literature frequently explores the clinical intersections between localized dental enamel variations and systemic health conditions. While multidisciplinary evaluations offer valuable clinical insights, premature conclusions regarding genetic etiologies can introduce significant clinical bias if acquired, pharmacological, and environmental confounders are overlooked. This commentary aims to critically examine a recent case report by highlighting key methodological and pathophysiological considerations. Main Topics Addressed: The analysis covers phenotypic classification under the Witkop framework, the physiological distinction between hereditary enamel patterns and acquired developmental defects, and the chronological limitations of utilizing adult presentations as markers of pediatric-onset processes. Furthermore, the discussion addresses unacknowledged metabolic and pharmacological confounders—such as proton pump inhibitor therapy and severe vitamin D deficiency—alongside the necessity of genetic validation and compliance with standardized reporting frameworks. Conclusions: Integrating these critical elements helps clinicians and researchers refine diagnostic precision, avoid premature clinical labeling, and enhance the overall quality and reliability of multidisciplinary medical documentation. Keywords: Amelogenesis Imperfecta; Renal Insufficiency, Chronic; Genetics; Vitamin D Deficiency; Case Reports.
Objective: This study aims to analyze the socio-demographic, epidemiological, and mortality dynamics of the drug addiction profile in Türkiye, and to propose a multi-layered alternative treatment model against the institutional and clinical barriers encountered in both civil society and the correctional system. Method: A systematic literature review and secondary data analysis were conducted, utilizing recent datasets (2023–2026) from the WHO, UNODC, the Turkish Ministry of Health, the General Directorate of Security (EGM), TUBIM, and the General Directorate of Prisons and Detention Houses (CTE). Findings: The data reveals a sharp gender asymmetry (88.4% male) in the treatment-seeking population. While the age of onset is heavily concentrated between 15–24 years, the mean age of treatment admission is 31.2, highlighting a "clinical lost decade" of approximately 10 years. Structural unemployment is critically linked to addiction, with 43.2% of patients lacking regular employment. Methamphetamine (29.1%) and synthetic cannabinoids (8.1%) remain highly dominant in clinical settings, triggering a 42.3% aggressive increase in drug-related deaths (DRD), totaling 427 acute fatalities. From a judicial perspective, individuals incarcerated for drug-related offenses constitute approximately one-third (36%) of the total prison population in Türkiye. Conclusion & Policy Suggestion: Traditional medical detoxification and punitive correctional regimes fail to prevent relapse and recidivism. As a macro-political solution, this study proposes an original “Collective Living and Therapeutic Community Village (Sanative Village)” model. Designed for both post-detoxification civil patients and well-behaved inmates, this model merges eco-rehabilitation with the philosophy of work-integrated restorative justice to foster identity reconstruction through spatial production.
Objective: Lung herniation is a rare and potentially underrecognized clinical entity characterized by protrusion of lung parenchyma through defects in the thoracic wall. It may arise in a variety of clinical settings, most commonly in association with chronic obstructive pulmonary disease (COPD), increased intrathoracic pressure, or prior thoracic interventions. In this study, we present three cases of lung herniation with distinct clinical backgrounds and imaging features, all diagnosed using thoracic computed tomography (CT). Case: Three patients diagnosed with lung herniation at our institution were retrospectively evaluated. The first case was a 67-year-old woman with chronic obstructive pulmonary disease (COPD) and prior lung surgery, in whom CT demonstrated intercostal herniation of the right middle lobe. The second case was a 51-year-old man with COPD and active smoking, showing anterolateral herniation of the right lower lobe with associated ground-glass opacities in the herniated parenchyma. The third case was a 48-year-old man with a history of mitral valve surgery, in whom non-contrast CT revealed focal herniation of the right middle lobe through a mild anterior thoracic wall defect, accompanied by adjacent subpleural reticular opacities. In all cases, CT enabled precise identification of the chest wall defect and associated parenchymal findings. None of the patients showed radiological evidence of incarceration. All patients were managed conservatively and remained clinically stable during 12 months of follow-up. Conclusion: Lung herniation is a rare and heterogeneous condition that may occur in various clinical settings, particularly in the presence of COPD, increased intrathoracic pressure, or prior surgery. CT plays a central role in diagnosis and risk assessment. Conservative management may be appropriate in selected asymptomatic patients, while treatment decisions should be individualized based on clinical and radiological findings.
Objective: The present study aimed to investigate the histomorphological alterations induced by high-dose acetaminophen administration on the thyroid gland and trachea in rats, and to comparatively examine the protective efficacy of Vaccinium arctostaphylos (VA) fruit extract versus N-acetylcysteine (NAC). Materials and Methods: A total of 40 male Wistar albino rats were randomly assigned to five equal groups (n=8/group): Control, Acetaminophen (PCM; 2 g/kg), PCM + N-acetylcysteine (NAC; 140 mg/kg), PCM + Vaccinium arctostaphylos extract (VA; 250 mg/kg), and PCM + VA (500 mg/kg). Treatments were administered via oral gavage. After 24 hours, the thyroid gland and trachea were excised following euthanasia under high-dose anesthesia. Tissue sections (5 μm) were stained with hematoxylin-eosin and evaluated histomorphologically using a semi-quantitative scoring system. Intergroup variations were analyzed using the Kruskal-Wallis test followed by Dunn's post-hoc test with Bonferroni correction (p < 0.05). Results: High-dose paracetamol (PCM) administration induced severe tissue damage, characterized by widespread disruption of thyroid follicular architecture (2.25 ± 0.43), decreased colloid density, and variable increases in follicular epithelial cell height. Additionally, significant tracheal alterations, including pseudostratified ciliated epithelial desquamation and tracheitis (moderate in 62.5% and severe in 37.5% of rats), were observed. In contrast, the PCM + VA (500 mg/kg) and PCM + NAC groups demonstrated complete preservation of thyroid follicular regular round-oval morphology and tracheal epithelial integrity, showing no significant differences compared to the Control group ( p = 1.000, score: 0.00 ± 0.00). However, the lower dose of VA (250 mg/kg) failed to exhibit a significant protective effect, resulting in persistent follicular disruption and moderate tracheitis comparable to the PCM-only group (p = 1.000). Conclusion: High-dose paracetamol induces concurrent, severe histomorphological damage in both the thyroid gland and trachea, highlighting their vulnerability to systemic toxic stress due to close anatomical proximity. A 500 mg/kg dose of Vaccinium arctostaphylos fruit extract provides histomorphological protection comparable to N-acetylcysteine, whereas the 250 mg/kg dose is insufficient. These findings demonstrate a clear dose-dependent efficacy and suggest that VA extract holds strong therapeutic potential as a natural antioxidant counteracting paracetamol-induced organ toxicity.
Objective: This study is a retrospective investigation of the relationship among vitamin D levels, neutrophil-to-lymphocyte ratio (NLR), and routine inflammatory markers. Material and Methods: A total of 3,859 individuals were included in this retrospective cross-sectional study. Participants were evaluated for age, sex, vitamin D level, C-reactive protein (CRP), erythrocyte sedimentation rate, lymphocyte, neutrophil, white blood cell (WBC), ferritin, and alanine aminotransferase (ALT) levels. Vitamin D levels were categorized as >30 ng/mL (normal), 20–30 ng/mL (insufficient), <20 ng/mL (deficient), and <10 ng/mL (severe deficiency). Differences and correlations between the groups were analyzed using SPSS v26 software. Results: The participants' average age was 46.9±16.0 years, and 73.1% of them were female. The average vitamin D level was 19.7±12.0 ng/mL. CRP and WBC levels were significantly higher in the severe deficiency group (p<0.01). Vitamin D levels showed a negative correlation with CRP (r = –0.52, p = 0.002) and WBC (r = –0.079, p = 0.000). A borderline negative correlation was observed between vitamin D and NLR (r = –0.32, p = 0.051). Ferritin, eGFR, and hemoglobin levels also showed significant differences across vitamin D categories. Inflammatory markers were higher in men, whereas vitamin D levels were significantly lower in women. Conclusion: Vitamin D deficiency is associated with elevated inflammatory markers. These findings indicate that vitamin D levels should be considered in the clinical evaluation of systemic inflammation and related health conditions.
Objective: Microplastics (MPs) and nanoplastics (NPs) are increasingly detected in water, food, air and, importantly, within human tissues. Because the liver receives both intestinal and systemic inputs, it becomes a likely site where these particles may accumulate or exert secondary effects. Experimental work suggests hepatotoxicity mediated through oxidative, inflammatory and metabolic pathways, but the strength, direction and clinical relevance of these changes remain uncertain. To perform a PRISMA-compliant systematic review of in vivo and translational studies examining how MPs influence hepatic structure and function, with emphasis on mechanisms related to oxidative stress, inflammation, gut–liver axis disturbance, metabolic dysregulation, fibrotic signaling and carcinogenesis. A specific goal was to determine whether MPs can initiate hepatocellular carcinoma (HCC). Methods: A structured search of PubMed/MEDLINE, Scopus, and Web of Science (2016–2026) identified experimental in vivo, ex vivo, and translational human biomonitoring studies reporting hepatic outcomes after MP or NP exposure, using Boolean combinations of microplastic/nanoplastic and hepatic/hepatotoxicity terms. Two independent reviewers screened titles, abstracts, and full texts against predefined eligibility criteria. Studies lacking liver-related biological endpoints were excluded. Risk of bias was assessed using an adapted SYRCLE tool (animal studies) and a qualitative methodological evaluation (in vitro studies). Data were extracted for polymer type, exposure route, and mechanistic endpoints, then synthesised narratively across seven mechanistic domains. 22 studies met predefined criteria and are summarised in three analytic tables. Results: Across mammalian models and aquatic vertebrates, MPs consistently induced hepatic oxidative stress, mitochondrial injury, Kupffer-cell activation, inflammatory signaling, barrier disruption along the gut–liver axis, and metabolic changes resembling early MASLD. Some studies reported fibrotic signaling and stellate-cell activation, though these findings were less frequent. No study showed de novo tumor initiation by MPs; however, a limited number of studies suggest mechanistic plausibility for a tumor-promoting role under conditions of combined hepatic stress rather than independent carcinogenic activity. Conclusions: Current evidence suggests that MPs disturb hepatic metabolic and immune homeostasis through interconnected oxidative, mitochondrial and gut-derived pathways. These effects echo mechanisms that drive MASLD progression and could potentially worsen underlying liver disease. However, there is no evidence that MPs independently initiate HCC, highlighting a major gap in the field. Studies using long-term, low-dose and environmentally relevant exposures are needed to define the true clinical impact of MPs on liver health. In addition, current animal models primarily focus on healthy livers, but mechanistic parallels between MP-induced injury and established pathways in viral hepatitis (HBV/HCV), autoimmune hepatitis, alcohol-associated liver disease, and MASLD suggest that microplastic exposure could potentially worsen pre-existing hepatic susceptibility. No studies have directly evaluated these interactions. However, the overlap in oxidative stress, immune activation, mitochondrial dysfunction, and gut-derived endotoxemia increases concern that MPs may quicken decompensation or progression in chronic liver diseases.
Objective: Reset osmostat (RO) is an under-recognized disorder of osmoregulation characterized by a downward resetting of the plasma osmolality threshold for arginine vasopressin release. Affected individuals develop chronic, typically mild and stable hypotonic hyponatremia while preserving the ability to dilute urine and excrete a water load. Because RO is frequently misclassified as the syndrome of inappropriate antidiuresis (SIAD), patients may undergo unnecessary investigations and receive potentially harmful therapies aimed at normalizing serum sodium. To summarize the physiology of the osmostat, identify clinical contexts associated with RO—including congenital midline brain malformations—and highlight practical diagnostic features that distinguish RO from SIAD and other causes of euvolemic hyponatremia. Material and Methods: This narrative review is based on targeted literature searches of PubMed and manual review of reference lists, with emphasis on osmoregulatory physiology, diagnostic strategies, and reported associations with congenital midline brain abnormalities. An illustrative case of chronic asymptomatic hyponatremia is also presented. Conclusions: RO represents a regulated but abnormally set osmoregulatory state in which vasopressin secretion occurs at a lower plasma osmolality threshold. Key diagnostic features include chronic, stable hyponatremia, preserved urinary dilution, normal fractional excretion of urate, and limited response to SIAD-directed therapies. RO has been reported in association with central nervous system disorders, particularly congenital midline malformations such as agenesis of the corpus callosum. Recognition of RO is essential to avoid misdiagnosis and inappropriate treatment. Management is typically conservative, with emphasis on avoiding unnecessary correction of serum sodium and preventing overly rapid correction when superimposed acute processes occur
Objective: Primary acquired nasolacrimal duct obstruction (PANDO) is a common cause of epiphora in adults. External dacryocystorhinostomy (DCR) is considered the reference surgical treatment; however, the impact of prior dacryocystitis on surgical outcomes remains controversial. This study aimed to evaluate the impact of previous dacryocystitis on anatomical and functional outcomes after external DCR. Material and Methods: This retrospective cohort study included 574 eyes of 524 patients who underwent standardized external DCR between January 2011 and January 2016 at a tertiary referral center. Eyes were categorized into a study group with prior dacryocystitis (99 eyes, 17.2%) and a control group without prior infection (475 eyes, 82.8%). Surgical success was defined as anatomical patency confirmed by irrigation combined with functional success (Munk grades 0-1). Functional outcomes were retrospectively assessed based on clinical records. Univariate and multivariable logistic regression analyses were performed. A reduced model was constructed to minimize overfitting, and a post-hoc power analysis was conducted. Results: The overall surgical success rate was 93.2% (535/574 eyes). Success was achieved in 96 eyes (97.0%) in the study group and 439 eyes (92.4%) in the control group, with no statistically significant difference between the groups (p=0.102). In multivariable analysis, prior dacryocystitis was not identified as an independent predictor of surgical failure (adjusted OR: 2.41; 95% CI: 0.68-8.52; p=0.171). No significant associations were observed for age, sex, diabetes mellitus, hypertension, silicone tube use, or anesthesia type. The majority of anatomically successful cases corresponded to Munk grades 0-1. The model demonstrated limited discriminative ability (AUC: 0.56). Post-hoc power analysis indicated a statistical power of 47.8%. Conclusion: External DCR provides high anatomical and functional success rates in patients with PANDO, regardless of prior dacryocystitis. When inflammation is adequately controlled before surgery, previous infection does not appear to adversely affect outcomes.
Objective: The gut–brain axis has predominantly been investigated through biological mechanisms, whereas behavioral dimensions such as microbiota awareness have received limited attention. This study aimed to examine the relationship between microbiota awareness and cognitive flexibility among health sciences students. Materials and Methods: This cross-sectional study was conducted with 490 undergraduate students enrolled in a Faculty of Health Sciences in Istanbul. Data were collected using a sociodemographic information form, the Microbiota Awareness Scale (MAS), and the Cognitive Flexibility Inventory (CFI). The association between MAS and CFI scores was analyzed using Pearson correlation analysis. Predictors of cognitive flexibility were examined using multiple linear regression. Results: Participants’ MAS scores indicated a moderate-to-high level of microbiota awareness, while CFI scores suggested generally good cognitive flexibility. A statistically significant positive correlation was identified between total MAS and CFI scores (p < 0.05). In the multiple regression analysis, microbiota awareness remained a significant predictor of cognitive flexibility after controlling for demographic and lifestyle variables. The overall model was statistically significant and explained 21.5% of the variance (R² = 0.215, F = 13.124, p < 0.001). Conclusion: Microbiota awareness is positively associated with cognitive flexibility. These findings contribute a behavioral dimension to the gut–brain axis literature. Longitudinal studies incorporating biological measurements are warranted to clarify causal relationships.
Objective: Somatic delusions are common in schizophrenia; however, delusional zoopathy—defined as the conviction that macroscopic animals (e.g., reptiles or mammals) inhabit the body—is rare and phenomenologically distinct from classical delusional infestation (Ekbom syndrome), which typically involves microscopic organisms. We report a 35-year-old married woman from Assam with chronic schizophrenia and comorbid hypothyroidism who, following an 11-year illness course characterized by persecutory delusions toward neighbors and family members, third-person auditory hallucinations, self-talking, and inappropriate smiling, developed a fixed belief that a snake had entered through her mouth and was residing in her stomach. Case: This delusion was accompanied by severe abdominal pain, marked restlessness, and prominent cenesthopathic “writhing” sensations attributed to the snake’s movements, resulting in persistent demands for abdominal ultrasonography to “detect the snake,” despite normal findings and repeated reassurance. The patient showed no response to adequate trials of aripiprazole and olanzapine but demonstrated marked clinical improvement with clozapine 200 mg/day, including reduction in somatic complaints, attenuation of cenesthopathic sensations, and emergence of partial insight. Conclusion: This case illustrates that highly bizarre zoopathic delusions may emerge in chronic, treatment-resistant schizophrenia, highlights the reinforcing role of cenesthopathic hallucinations in somatic delusional conviction, and underscores the importance of addressing both positive psychotic symptoms and aberrant bodily experiences, including timely initiation of clozapine when standard antipsychotics fail.
Objective: Accessory navicular bone is a relatively common anatomical variant; however, symptomatic cases that are refractory to conservative treatment and require surgical intervention remain clinically challenging. This case report aims to highlight the clinical presentation, surgical management, and functional outcome of a patient with symptomatic accessory navicular bone treated using the modified Kidner procedure, emphasizing its relevance in daily orthopedic practice. Case Presentation: A 27-year-old female patient presented with chronic medial foot pain exacerbated by activity and resistant to prolonged conservative treatment, including orthotic support and non-steroidal anti-inflammatory drugs. Physical examination revealed localized tenderness over the navicular region, and imaging confirmed a type II accessory navicular bone. Pain severity was assessed using the visual analog scale (VAS). Given the persistence of symptoms, surgical management with the modified Kidner procedure was performed. Results: Postoperatively, the patient experienced significant pain relief and functional improvement, with marked reduction in VAS scores and successful return to daily activities. No surgical complications were observed during follow-up, and both clinical and radiological outcomes were satisfactory. Conclusion: This case demonstrates that the modified Kidner procedure is an effective and reliable surgical option for patients with symptomatic accessory navicular bone unresponsive to conservative treatment. The report is clinically valuable as it reinforces decision-making criteria for surgery, illustrates favorable mid-term outcomes, and contributes to the limited body of detailed case-based evidence supporting operative management of this condition.
Objective: The present study aimed to examine the effect of training on tissue plasminogen activator (TPA) administration provided to nurses caring for patients diagnosed with stroke on nurses’ anxiety levels. Material and Methods: This study was designed as a quasi-experimental, single-group pretest–posttest study. The study sample consisted of 50 nurses. Nurses received structured training on TPA administration, and their knowledge and anxiety levels were assessed before the training, immediately after the training, and one month after the training. Data were collected through face-to-face interviews and analyzed using SPSS software. Results: A statistically significant difference in nurses’ knowledge scores regarding TPA administration was observed across the three measurement points (p < 0.01). In addition, significant differences were found in State and Trait Anxiety Scale scores before, after, and one month after the training (p < 0.01). Overall, the findings indicate that improvements in knowledge following the training were accompanied by reductions in anxiety levels among nurses. Conclusion: The findings suggest that training on TPA administration may contribute to improved professional and reduced anxiety among nurses involved in stroke care.
Dear Author The incorporation of immune checkpoint inhibitors into neoadjuvant and adjuvant treatment strategies for early-stage solid tumors has prompted a critical reassessment of how treatment response should be interpreted and translated into long-term therapeutic decisions. Data from contemporary neoadjuvant immunotherapy trials across multiple tumor types have revealed a recurring and biologically intriguing pattern: patients achieving deep pathologic responses may experience durable clinical benefit despite limited or even absent adjuvant immune checkpoint inhibition, whereas patients with residual disease appear to derive disproportionate benefit from continued postoperative therapy. This divergence—observed in KEYNOTE-522 in early-stage triple-negative breast cancer, CheckMate 816 in resectable non–small-cell lung cancer, response-adapted melanoma studies such as PRADO and NADINA, and short-course neoadjuvant immunotherapy in mismatch repair–deficient colon cancer (NICHE-2)—suggests that mechanisms beyond treatment intensity alone are operative and challenges the implicit assumption that immunotherapy benefit follows a linear “dose–duration–benefit” paradigm (1–6). The immune system is inherently adaptive; however, immune learning does not progress in a strictly linear or indefinitely amplifiable manner. Once critical thresholds of antigen recognition, effector T-cell activation, and immune memory formation are achieved, additional immune stimulation may yield diminishing marginal returns. This biologic ceiling effect provides a plausible explanation for the limited incremental benefit of continued adjuvant immunotherapy in patients who have already achieved a pathologic complete response (pCR). In such cases, treatment continuation may primarily serve to preserve an already established immune equilibrium rather than generate further clinically meaningful immune education (7). Importantly, the efficiency and durability of this immune learning process likely vary across tumor types and individual patients, influenced by baseline tumor immunogenicity, tumor mutational burden, and immune contexture, including PD-L1 expression. In contrast, patients with residual disease but without clear evidence of immune escape may represent a distinct and potentially modifiable biologic state. In these individuals, neoadjuvant therapy may have successfully primed antitumor immunity without surpassing the threshold required for complete tumor eradication. Following surgical debulking, the persistence of minimal residual disease and continued antigen exposure may allow adjuvant immunotherapy to stabilize this partially trained immune response and suppress micrometastatic progression. Accordingly, the observed benefit in patients with residual disease may reflect not greater therapeutic potency, but rather the continued presence of a biologically relevant immune target (8). These considerations raise important questions regarding the adequacy of pCR as a standalone biomarker for predicting immunotherapy benefit. While surgical pathology effectively captures local tumor eradication, the principal contribution of immunotherapy likely lies in the establishment of durable, systemic immune surveillance. Consequently, pCR—although a robust surrogate for chemotherapy sensitivity—may incompletely capture the long-term clinical impact of immune-based therapies (9). The integration of additional biomarkers reflecting systemic immune activation, such as circulating tumor DNA clearance or markers of immune memory, may therefore be necessary to more accurately define the threshold of effective immune learning. In summary, although the efficacy of immunotherapy in early-stage disease is well established, increasing attention should be directed toward defining treatment duration according to biological necessity rather than maximal exposure, as schematically illustrated in Figure 1. Recognizing the nonlinear nature of immune learning supports the development of more refined treatment strategies that integrate pathologic response, residual disease biology, and markers of immune memory. Future clinical trials should be explicitly designed to test response-adapted and biomarker-driven de-escalation strategies, including randomized studies in which patients achieving pCR or deep molecular response are assigned to abbreviated or omitted adjuvant immunotherapy. Such approaches may represent a critical step toward more rational, personalized, and toxicity-conscious treatment paradigms (10).
Objective: Low vision substantially affects individuals’ functional capacity and quality of life and may compromise their ability to perform work-related tasks effectively. Beyond the direct consequences of visual impairment, there is a growing need to understand how psychosocial factors within the workplace influence work ability among individuals with low vision. Objective of this study is to evaluate the impact of psychosocial work environment factors on work ability in individuals with low vision. Material and Methods: A cross-sectional study was conducted involving 600 participants, including 450 individuals with low vision (visual acuity ranging from 0.05 to 0.3 due to conditions such as glaucoma and diabetic retinopathy) and 150 visually healthy controls (visual acuity greater than 0.5). Health-related quality of life was assessed using the EQ-5D and EQ-VAS instruments. Work ability was evaluated using the Work Ability Index (WAI), while psychosocial working conditions were assessed with the Copenhagen Psychosocial Questionnaire (COPSOQ). Data analysis included descriptive statistics and correlation analyses examining associations between psychosocial factors and WAI scores. Results: Mean WAI scores among individuals with low vision indicated a reduction in work ability compared with visually healthy controls. Adverse psychosocial factors—including high quantitative demands, cognitive demands, emotional demands, exhaustion, and work-related stress—demonstrated significant inverse correlations with WAI scores. In contrast, positive psychosocial factors such as influence at work, opportunities for development, meaningfulness of work, quality of leadership, social support, and job satisfaction were significantly and positively associated with work ability. These associations were more pronounced within the low-vision group. Conclusion: Work ability among individuals with low vision is significantly influenced by psychosocial characteristics of the work environment. Targeted improvements in workplace psychosocial conditions may enhance occupational participation and overall work ability in this population.
Objective: Accurate positioning of the umbilical venous catheter (UVC) tip is critical for reducing catheter-related complications in preterm infants. This study aimed to compare the accuracy of the Revised Shukla–Ferrara formula and the Dunn nomogram for UVC insertion depth estimation using echocardiography as the reference standard, and to evaluate the concordance between anteroposterior (AP) chest radiography and echocardiography in confirming UVC tip position. Material and Methods: This retrospective case–control study included 69 preterm infants who underwent UVC placement in two level III neonatal intensive care units. Insertion depth was determined using either the Revised Shukla–Ferrara formula (n = 43) or the Dunn method (n = 26). UVC tip position was initially assessed by AP chest radiography and subsequently verified by echocardiography. Placement accuracy and concordance between imaging modalities were analyzed. Results: On chest radiography, accurate placement rates were 53.5% in the Revised Shukla–Ferrara group and 42.3% in the Dunn group. The Revised Shukla–Ferrara formula was more frequently associated with low placement, whereas the Dunn method showed a higher rate of high placement. Echocardiography demonstrated correct UVC positioning in 61.8% of infants in the Revised Shukla–Ferrara group and 38.2% in the Dunn group. Notably, substantial discordance was observed between radiography and echocardiography, with a significant proportion of malpositioned catheters misclassified as accurately positioned on chest X-ray. Conclusion: Both the Revised Shukla–Ferrara formula and the Dunn method are useful for estimating UVC insertion depth in preterm infants; however, each demonstrates distinct malposition tendencies. Reliance on AP chest radiography alone is insufficient for confirming accurate UVC tip placement. Routine echocardiographic verification should be incorporated into standard NICU practice to enhance procedural safety and reduce catheter-related complications.
Objective: Trichotillomania, classified under obsessive–compulsive and related disorders, is characterized by recurrent and irresistible urges to pull out hair, resulting in noticeable hair loss, functional impairment, and repeated unsuccessful attempts to stop the behavior. Childhood-onset trichotillomania is relatively uncommon and frequently under-recognized, which may lead to delayed diagnosis and treatment. Case: An 11-year-old male from a low socioeconomic background presented with compulsive hair pulling involving the scalp, eyelashes, and hands, accompanied by distractibility, irritability, and a decline in academic performance. Routine laboratory investigations were within normal limits. A diagnosis of trichotillomania was established based on ICD-10 criteria. Management included pharmacological treatment with selective serotonin reuptake inhibitors, antipsychotics, and benzodiazepines, in combination with psychological interventions such as psychoeducation, coping skills training, habit reversal therapy, and intelligence quotient assessment with appropriate management Conclusion: Significant clinical improvement was observed, with family members reporting a 70–80% reduction in hair-pulling behavior and visible hair regrowth. Habit reversal therapy is ongoing. This case underscores the importance of early identification and comprehensive management of childhood trichotillomania and highlights the need for increased clinical awareness and academic discussion among clinicians and trainees
Objective: Li-Fraumeni syndrome (LFS), an autosomal dominant condition, is defined by germline TP53 gene mutations. This predisposes carriers to a spectrum of early-onset tumours, including breast cancer, sarcomas, and adrenal cortical carcinomas. This report details a case with clinical and familial characteristics that fulfil the established diagnostic criteria for LFS. Case presentation: A 33-year-old Turkish woman presented with multiple primary malignancies, initially diagnosed with invasive breast carcinoma at age 28, followed by a subepidermal fibrohistiocytic tumour in her left leg, and adenocarcinoma at the oesophagogastric junction. Subsequent genetic testing confirmed a germline TP53 mutation. Conclusion: This case underscores the critical importance of maintaining a high index of suspicion for LFS in patients presenting with multiple early-onset malignancies. Genetic confirmation facilitates the implementation of targeted surveillance and family screening protocols.
Dear Editor, We read with great interest the pivotal report on dual immune checkpoint blockade (anti–PD-1/PD-L1 plus anti–CTLA-4) in advanced malignancies, which highlighted the clinical activity of combination immunotherapy in a large cohort (1). While combination regimens can provide meaningful efficacy outcomes, the toxicity burden remains a defining limitation. In the referenced trial, high-grade immune-related adverse events (irAEs), frequent treatment interruptions, and a non-negligible risk of fatal toxicity were notable alongside the efficacy signals (2). Current toxicity management frameworks in major guidelines (including NCCN and ESMO) provide comprehensive algorithms for irAE recognition and treatment; however, these recommendations have largely been shaped by monotherapy experience and selected trial populations (3). In routine practice, clinicians increasingly observe that combination regimens may generate earlier onset, higher severity, and more complex multisystem irAEs than those anticipated from guideline-based expectations derived predominantly from single-agent paradigms (4). Importantly, pharmacovigilance data reinforce this concern. Analyses of spontaneous reporting systems (e.g., FAERS, VigiBase, and JADER/PMDA) consistently demonstrate disproportionately higher reporting of severe irAEs with combination ICI regimens compared with monotherapy, supporting a signal of increased real-world toxicity burden (5-7). These findings should be interpreted as reporting/association signals (disproportionality) rather than incidence estimates; nevertheless, their concordance across databases suggests that the real-world safety profile of combination ICIs warrants heightened attention. Clinical Significance and Current Evidence Recent real-world and pharmacovigilance analyses have reported an increased likelihood of severe irAE reporting with combination regimens relative to single-agent therapy, including signals for organ-specific toxicities such as hepatitis, colitis, pneumonitis, and myocarditis (8-11). Likewise, meta-analytic evidence indicates that combination immunotherapy yields higher overall irAE rates than monotherapy across multiple settings; for example, in metastatic melanoma, overall irAE frequency has been reported as higher with combination therapy compared with single-agent ICI (12). Collectively, these data suggest that rare but potentially fatal toxicities—particularly myocarditis and severe neurologic syndromes—may occur at clinically meaningful rates and require proactive mitigation strategies (13). From a practical standpoint, irAEs under combination regimens often show earlier presentation, higher-grade severity, and greater need for immunosuppressive escalation, including steroid-refractory cases requiring second-line agents (e.g., infliximab, mycophenolate mofetil, vedolizumab, or other targeted immunosuppression) (14). Recent real-world cohort reports further indicate that hepatotoxicity, colitis, endocrine toxicities, pulmonary toxicity, and cardiotoxicity remain among the most clinically consequential events, frequently driving dose delays, prolonged immunosuppression, and permanent discontinuation (15). The burden is particularly pronounced in older patients and those with poorer performance status or significant comorbidities, where severe toxicity risk appears elevated and outcomes can be compromised by treatment discontinuation and prolonged recovery (16). Conclusions and Recommendations Taken together, contemporary evidence suggests that the toxicity profile of combination ICI regimens may exceed what clinicians expect when extrapolating from monotherapy-based guideline paradigms. We believe several practical steps could improve safety: Early recognition and intensified monitoring during the initial treatment period (when severe irAEs often emerge) (13). Structured, multidisciplinary toxicity pathways (oncology, gastroenterology, pulmonology, cardiology, endocrinology, rheumatology) to shorten time-to-treatment for severe irAEs (3). Risk-adapted patient selection incorporating age, performance status, comorbidity burden, prior autoimmunity, and organ reserve, with explicit counseling on discontinuation risk (17). Guideline refinements that clearly distinguish combination-regimen toxicity phenotypes from monotherapy and integrate high-quality real-world safety signals (pharmacovigilance + prospective observational cohorts). We respectfully suggest that future guideline updates include a dedicated section on combination ICI-specific toxicity patterns, emphasizing early severe irAE recognition, escalation strategies for steroid-refractory events, and risk stratification in vulnerable subgroups. Sincerely
Objective: Polymerase chain reaction (PCR) is a core technology in medical diagnostics and bioscience research. DNA isolation is a critical pre-analytical step; however, despite regulatory requirements, there is a lack of published evidence regarding the long-term stability and shelf life of commercial DNA isolation kits. Material and Methods: Stability experiments were conducted over an eight-year period using the Genekam mini-column DNA isolation kit. DNA was extracted from multiple biological matrices and analysed by conventional PCR and real-time PCR targeting the human beta-globin gene and Epstein–Barr virus (EBV). Results: High-quality DNA suitable for PCR was consistently obtained for at least five years after the manufacturing date. Conventional PCR yielded specific amplicons, and real-time PCR showed stable Ct values for both human internal controls and pathogen targets. Conclusion: This study provides the first published evidence that a commercial mini-column DNA isolation kit maintains functional performance for over five years, supporting an extension of its shelf life beyond the current two-year specification.
Objective: Plants have long been vital sources of medicinal compounds, playing a crucial role in disease treatment. Despite centuries of advancements, their relevance remains undiminished. Not only do plants serve as living testaments to traditional therapeutic approaches, but they also offer invaluable remedies in an increasingly urbanized and technologically advanced society. Their significance stems from the diverse array of bioactive metabolites they produce, which interact with human biological systems to treat complex diseases and severe illnesses. In some cases, plant-based therapies remain the only available treatment options. Among the widely distributed plant genera, Indigofera comprises over a hundred species, many of which have been extensively studied for their phytochemistry and pharmacological properties. One particularly noteworthy species is Indigofera heterantha var. gerardiana, which contains a diverse range of phytochemicals and has been traditionally used for centuries in disease treatment. This review aims to provide a comprehensive understanding of the phytopharmacological properties of Indigofera heterantha var. gerardiana by evaluating current scientific evidence.
