Accreditation
SINTA 2Nationally Accredited Journal
Vol. 9 No. 11 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Articles
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Beyond the Usual Suspects: Phialophora verrucosa Chromoblastomycosis in a Swimming Pool Attendant and Gardener
Views: 451Downloads: 373Background: Chromoblastomycosis (CBM) is a chronic, debilitating subcutaneous mycosis caused by traumatic inoculation of dematiaceous fungi. As a Neglected Tropical Disease, it poses significant diagnostic and therapeutic challenges, particularly in the endemic tropical and subtropical regions where it is most prevalent. While Fonsecaea pedrosoi is the most common etiologic agent, infections by other species are crucial to document for accurate epidemiological surveillance.
Case presentation: A 26-year-old immunocompetent male presented with a four-year history of a slowly progressive, verrucous plaque on his right hand, initiated by minor trauma. His history was notable for regular gardening without protective gear. A comprehensive diagnostic workup was performed. Dermoscopy revealed features characteristic of CBM, including reddish-black dots and yellowish-orange areas. While direct microscopy of skin scrapings was negative, histopathology of a skin biopsy confirmed a suppurative granulomatous reaction with pathognomonic muriform cells. Fungal culture on Sabouraud's dextrose agar definitively identified the causative agent as Phialophora verrucosa. The patient showed marked clinical improvement after three months of treatment with oral itraconazole (200 mg/day).
Conclusion: This case highlights the successful diagnosis of a rare CBM pathogen in Indonesia through a systematic, multimodal approach. It reinforces the need for a high index of suspicion for this mycosis in patients from endemic areas with chronic verrucous lesions and a history of cutaneous trauma. The essential role of mycology culture for definitive species identification is underscored, a critical step for guiding therapy and informing public health strategies.
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Catamenial Pneumothorax in a Patient with Adenomyosis: A Case Report on a Successful Multidisciplinary Approach with Pleurodesis and Hormonal Therapy
Views: 449Downloads: 335Background: Catamenial pneumothorax, a rare manifestation of thoracic endometriosis syndrome (TES), presents a significant diagnostic and therapeutic challenge. It is characterized by recurrent spontaneous pneumothorax occurring in temporal relation to menstruation in women of reproductive age. The underlying pathophysiology is complex, often involving the ectopic presence of endometrial tissue within the thoracic cavity. Coexisting pelvic pathologies, such as adenomyosis, may be associated, further complicating the clinical picture.
Case presentation: We present the case of a 38-year-old woman with a four-month history of recurrent, right-sided pneumothorax, with symptoms consistently commencing 24 to 48 hours prior to the onset of her menstrual cycle. Initial investigations, including high-resolution computed tomography of the thorax performed between menstrual cycles and microbiological analysis for tuberculosis, were unremarkable. The diagnosis of catamenial pneumothorax was established based on the distinct cyclical pattern of her symptoms. A subsequent gynecological evaluation, prompted by a history of secondary dysmenorrhea and menorrhagia, revealed uterine adenomyosis via transvaginal ultrasonography. The patient was managed through a collaborative, multidisciplinary approach involving pulmonology, thoracic surgery, and gynecology. Treatment consisted of chemical pleurodesis with doxycycline, administered via a chest tube, followed by continuous hormonal suppression therapy with oral progestin (2 mg/day).
Conclusion: This case highlights the critical importance of maintaining a high index of suspicion for catamenial pneumothorax in women of reproductive age presenting with recurrent pneumothorax. A successful outcome was achieved through a coordinated, multidisciplinary strategy combining definitive pleural symphysis via pleurodesis with systemic hormonal therapy to suppress the underlying endometriotic process. This dual approach effectively prevented pneumothorax recurrence over a 12-month follow-up period, underscoring its efficacy in managing this complex condition.
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Diagnostic Performance of Imaging Modalities in Persistent or Recurrent Hyperparathyroidism: A Network Meta-Analysis of 18F-Fluorocholine PET/CT, 4D-CT, and Scintigraphy
Views: 441Downloads: 370Background: The surgical management of persistent or recurrent primary hyperparathyroidism (PHPT) is critically dependent on accurate preoperative localization of ectopic or residual hyperfunctioning glands within a scarred anatomical field. While 18F-Fluorocholine Positron Emission Tomography/Computed Tomography (18F-FCH PET/CT), four-dimensional computed tomography (4D-CT), and 99mTc-Sestamibi scintigraphy are employed, a definitive evidence-based hierarchy to guide their use is absent. This study aimed to establish this hierarchy by comparing their diagnostic performance through a network meta-analysis.
Methods: A systematic search of PubMed, Embase, and Scopus was conducted for comparative studies published between January 2015 and August 2025 evaluating these modalities in persistent/recurrent PHPT. A Bayesian bivariate network meta-analysis was performed to calculate pooled sensitivities and specificities on both a per-patient and per-lesion basis. Modalities were ranked using Surface Under the Cumulative Ranking (SUCRA) scores. Methodological quality, inconsistency, and heterogeneity were formally assessed.
Results: Seven studies involving 687 patients were included. On a per-patient analysis, 18F-FCH PET/CT demonstrated the highest sensitivity at 94.1% (95% Credible Interval [CrI]: 89.8%–97.5%), significantly outperforming 4D-CT (82.5%; 95% CrI: 75.1%–88.9%) and scintigraphy with SPECT/CT (60.3%; 95% CrI: 51.2%–69.1%). Specificities were uniformly high. Per-lesion analysis confirmed this hierarchy. SUCRA rankings identified 18F-FCH PET/CT as the superior modality for both per-patient (98.7%) and per-lesion (99.1%) detection. No significant network inconsistency was detected.
Conclusion: 18F-FCH PET/CT exhibits superior diagnostic accuracy for localizing culprit parathyroid glands in persistent or recurrent PHPT. Its performance, grounded in robust metabolic targeting that overcomes the challenges of a reoperative field, supports its positioning as the primary imaging modality in this setting. These findings advocate for a revision of current diagnostic algorithms to enhance surgical planning and improve patient outcomes.
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The Molecular and Epidemiological Atlas of Primary Orbital Lymphoma: A Global Meta-Analysis of 3,832 Cases and Pathophysiological Correlates
Views: 406Downloads: 245Background: Primary orbital lymphoma is the most common orbital malignancy in adults, yet its global distribution and the prevalence of its histopathological subtypes remain poorly defined by large-scale evidence. This study provides a comprehensive quantitative synthesis of the global landscape of orbital lymphoma to inform diagnostic frameworks and guide future research.
Methods: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of studies published between January 2015 and December 2023. We searched PubMed, Scopus, Web of Science, and Embase for observational studies reporting histopathological data on orbital lymphoma. Two independent reviewers performed study selection, data extraction, and quality appraisal using the Joanna Briggs Institute (JBI) checklist. Pooled prevalence for each lymphoma subtype was calculated using a random-effects model. Heterogeneity was explored via subgroup analyses and meta-regression, and the robustness of findings was confirmed with a sensitivity analysis.
Results: Fifteen studies comprising 3,832 patients met the inclusion criteria. Extranodal marginal zone lymphoma (EMZL) was the most prevalent subtype globally, with a pooled prevalence of 57.1% (95% CI: 51.5-62.7%). This was followed by diffuse large B-cell lymphoma (DLBCL) at 16.5% (95% CI: 13.1-20.0%), follicular lymphoma (FL) at 10.2% (95% CI: 8.0-12.4%), mantle cell lymphoma (MCL) at 5.1% (95% CI: 3.6-6.6%), and small lymphocytic lymphoma (SLL) at 3.4% (95% CI: 2.2-4.5%). Subgroup analysis revealed a significantly higher prevalence of EMZL in Asia (61.3%) compared to Europe (54.2%) and North America (55.8%) (p=0.04), while FL was more common in North American (14.1%) and European (12.8%) cohorts versus Asian cohorts (4.5%) (p<0.01). Sensitivity analysis confirmed the stability of these estimates.
Conclusion: This meta-analysis establishes EMZL as the predominant histopathological subtype of orbital lymphoma worldwide, while highlighting profound geographical disparities in the distribution of EMZL and FL. These findings provide a robust global benchmark critical for clinical practice and underscore the influence of distinct geographical, genetic, and microenvironmental factors in orbital lymphomagenesis.
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Malignant Transformation of Primary Acquired Melanosis into Conjunctival Melanoma in an Adolescent Male: A Clinico-Pathological Case Report and Management Review
Views: 572Downloads: 630Background: Conjunctival malignant melanoma (CMM) is a rare but potentially lethal ocular surface malignancy, especially uncommon in adolescents. It often arises from a precursor lesion known as primary acquired melanosis (PAM) with atypia. We present a case of CMM developing from long-standing PAM in an 18-year-old male, highlighting the diagnostic and therapeutic challenges in this unusual demographic.
Case presentation: An 18-year-old male presented with a pigmented conjunctival lesion in his right eye, which had been present for over a decade but had recently shown progressive enlargement and darkening. Slit-lamp biomicroscopy revealed a 5x2 mm, variegated, hyperpigmented lesion on the bulbar conjunctiva with a prominent feeding vessel. The patient underwent an excisional biopsy using a "no-touch" technique with 4 mm margins and adjunctive double freeze-thaw cryotherapy. Histopathological analysis confirmed an invasive malignant melanoma, Breslow thickness of 1.8 mm, arising from PAM with severe atypia. Surgical margins were clear of the tumor.
Conclusion: This case underscores that malignant transformation of conjunctival melanocytic lesions can occur even in young patients. The presence of a changing pigmented lesion, regardless of patient age, necessitates a high index of suspicion and a low threshold for excisional biopsy. Meticulous surgical technique combined with adjuvant therapy and vigilant long-term surveillance is paramount for optimizing patient outcomes.
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Genetic and Epigenetic Alterations in Exhaled Breath Condensate for Early Detection of Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Views: 348Downloads: 266Background: Early detection of non-small cell lung cancer (NSCLC) is critical for improving patient survival, yet current methods face challenges of invasiveness and limited accuracy. Exhaled breath condensate (EBC) offers a non-invasive window into the deep airways. This study aimed to synthesize and critically evaluate the diagnostic accuracy of genetic and epigenetic alterations in EBC for NSCLC detection.
Methods: We conducted a systematic review and meta-analysis of studies published between January 2015 and August 2025, sourced from PubMed, Scopus, Web of Science, and Embase. We included diagnostic accuracy studies evaluating genetic (KRAS, EGFR, p53) or epigenetic (gene methylation) markers in EBC against a histopathological reference standard. Data were used to construct 2x2 contingency tables. Methodological quality was assessed using the QUADAS-2 tool. A bivariate random-effects model was used to derive pooled accuracy estimates.
Results: Seven case-control studies, comprising 812 NSCLC patients and 995 controls, met the inclusion criteria. The analysis yielded a pooled sensitivity of 0.81 (95% Confidence Interval [CI]: 0.74–0.87) and a pooled specificity of 0.96 (95% CI: 0.93–0.98). The pooled diagnostic odds ratio was 112 (95% CI: 65–194), and the area under the SROC curve was 0.95 (95% CI: 0.93–0.97). However, extreme statistical heterogeneity (I² > 80%) was observed, and all included studies were rated at high risk of bias due to their case-control design, suggesting the pooled estimates must be interpreted with significant caution.
Conclusion: Analysis of DNA alterations in EBC shows promising diagnostic potential for NSCLC, particularly with high specificity. However, the current evidence is limited by significant methodological heterogeneity and study design flaws that likely overestimate performance. The primary contribution of this analysis is not a definitive accuracy value, but a critical appraisal of the monumental challenges in pre-analytical and analytical standardization that must be overcome for this technology to achieve clinical translation.
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Systemic HIV-1 Viremia as an Independent Predictor of Reduced Intraocular Pressure: A Multivariable Regression Analysis in Cohorts with and without Cytomegalovirus Retinitis
Views: 465Downloads: 244Background: The association between human immunodeficiency virus (HIV) and reduced intraocular pressure (IOP) is recognized, yet its independence from confounding opportunistic infections like cytomegalovirus retinitis (CMVR) remains unquantified. This study aimed to determine the independent association between systemic HIV-1 viral load and IOP by employing a robust multivariable analysis in cohorts with and without CMVR.
Methods: A comparative, cross-sectional study was conducted on 100 HIV-positive patients (50 with CMVR, 50 without CMVR) at a tertiary referral hospital. Data included demographics, HIV clinical stage (WHO), quantitative HIV-1 viral load, and IOP measured by applanation tonometry. The primary analysis utilized a multivariable linear regression model to assess the association between log-transformed viral load and continuous IOP, adjusting for age, gender, HIV stage, and CMVR status. An interaction term was used to test for effect modification by CMVR.
Results: After adjusting for all covariates, log₁₀ HIV-1 viral load was a powerful and highly significant independent predictor of lower IOP. For every 10-fold increase in viral load, IOP decreased by an average of 0.88 mmHg (β = -0.88; 95% CI: -1.15 to -0.61; p < 0.001). Advanced HIV stage was also independently associated with lower IOP (Stage IV vs. Stage I: β = -1.25; 95% CI: -2.10 to -0.40; p = 0.004). The effect of viral load on IOP did not significantly differ between the CMVR and non-CMVR groups (p for interaction = 0.762), confirming its independent systemic effect.
Conclusion: Systemic HIV-1 viremia is a dominant, independent predictor of reduced intraocular pressure, irrespective of CMVR status. This dose-dependent relationship highlights a direct pathophysiological link between viral replication and aqueous humor dynamics. IOP measurement represents a potential adjunctive clinical indicator for monitoring systemic HIV-1 disease activity.
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Gray Patch Tinea Capitis by Microsporum canis in a Child: A Case Report Highlighting Environmental Risk Factors and Diagnostic Nuances
Views: 675Downloads: 1,009Background: Tinea capitis, a dermatophytosis of the scalp, is a leading cause of hair loss in children. Its successful management hinges on understanding its complex etiology, including host susceptibility and pathogen virulence. Microsporum canis, a zoophilic fungus, is a primary causative agent, yet its transmission pathways and diagnostic markers are not fully elucidated.
Case presentation: A 3-year-old female presented with a two-week history of progressive, pruritic alopecia. Clinical history was notable for the absence of animal contact but revealed significant environmental exposure at a hair salon. Dermatological examination showed multiple, well-demarcated, alopecic patches with fine scaling, characteristic of gray patch tinea capitis. While Wood's lamp examination was negative, trichoscopy revealed comma hairs and Morse code-like hairs, suggesting fungal infection. Microscopic examination of hair shafts confirmed an ectothrix invasion pattern, and fungal culture definitively identified Microsporum canis. The patient achieved complete resolution following a six-week course of oral griseofulvin and adjuvant topical ketoconazole.
Conclusion: This case demonstrates that indirect fomite transmission from environmental reservoirs like hair salons is a critical risk factor for zoophilic tinea capitis, independent of animal contact. It further establishes trichoscopy as an essential tool for accurate, rapid diagnosis when classic signs, such as Wood's lamp fluorescence, are absent, thereby optimizing patient management and public health outcomes.
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The Emerging Role of Integrins in Diabetic Kidney Disease: A Systematic Review and Meta-Analysis of Their Diagnostic and Prognostic Utility for Early Risk Stratification
Views: 463Downloads: 232Background: Current biomarkers for diabetic kidney disease (DKD), notably albuminuria and eGFR, are markers of established renal damage, limiting opportunities for early intervention. Integrins, cell-matrix adhesion receptors integral to podocyte health, are emerging as potential upstream indicators of the initial injury that drives DKD. This systematic review and meta-analysis provide the first quantitative synthesis of the evidence on the diagnostic and prognostic utility of integrins in DKD.
Methods: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Embase, and Web of Science for studies published up to July 2025. We included studies that evaluated integrins in urine, serum, or tissue for the diagnosis of early DKD (microalbuminuria) or for predicting disease progression. Data were pooled using bivariate random-effects models for diagnosis and generic inverse variance models for prognosis.
Results: Eight studies involving 2,874 patients met the inclusion criteria. For diagnosing early DKD, five studies (n=1,880) yielded a pooled sensitivity of 0.88 (95% CI: 0.82-0.92) and specificity of 0.85 (95% CI: 0.79-0.90). The area under the summary receiver operating characteristic curve was 0.91 (95% CI: 0.88-0.94), indicating excellent accuracy. A subgroup analysis of non-invasive samples (urine/serum) demonstrated similarly high performance. For prognosis, three prospective studies (n=1,224) showed that elevated baseline integrins were associated with a significantly increased risk of disease progression (pooled Hazard Ratio: 2.15, 95% CI: 1.65-2.79) over a median 5-year follow-up.
Conclusion: Based on the current, albeit limited, evidence, integrins show significant promise as highly sensitive and specific biomarkers for the early detection and potent predictors for the progression of DKD. While these preliminary findings require validation in larger cohort studies, the measurement of non-invasive integrins may represent a valuable future tool for improving early DKD risk stratification.
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The Lethal Nexus: Sarcopenic Obesity and the Prospective Risk of All-Cause and Cardiovascular Mortality in Older Adults-A Systematic Review and Meta-Analysis of Longitudinal Cohort Studies
Views: 466Downloads: 334Background: The concurrent presence of excess adiposity and low muscle mass, termed sarcopenic obesity (SO), is an emerging geriatric syndrome hypothesized to confer a greater mortality risk than either condition alone. However, the precise magnitude of this risk remains poorly quantified. This systematic review and meta-analysis aimed to synthesize evidence from longitudinal cohort studies to determine the association between SO in older adults and the risk of all-cause and cardiovascular mortality.
Methods: A systematic search was conducted in PubMed, Embase, and Scopus for longitudinal cohort studies published between January 2015 and August 2025 that evaluated mortality risk in older adults (mean age ≥60 years) with SO. The primary outcomes were all-cause and cardiovascular mortality. A random-effects model was used to pool Hazard Ratios (HRs) and 95% Confidence Intervals (CIs). Heterogeneity was assessed using the I2 statistic.
Results: From 2,450 records identified, eight cohort studies met the inclusion criteria, encompassing 45,280 community-dwelling older adults with a mean follow-up of 8.2 years. Compared to a reference group of non-sarcopenic, non-obese individuals, sarcopenic obesity was associated with a significantly increased risk of all-cause mortality (Pooled HR: 1.58, 95% CI: 1.42–1.76, p < 0.0001). The risk for cardiovascular mortality, assessed in six studies, was even more pronounced (Pooled HR: 1.75, 95% CI: 1.55–1.98, p < 0.0001). Moderate heterogeneity was observed for the all-cause mortality analysis (I2 = 55%), which was partially explained by differences in diagnostic criteria.
Conclusion: Sarcopenic obesity is a potent predictor of both all-cause and cardiovascular mortality in older adults, conferring a risk substantially greater than a healthy state. These findings underscore the critical need for routine screening and targeted interventions to address this lethal combination of poor body composition in aging populations.
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Diagnostic Laparoscopy Versus Routine Exploratory Laparotomy in Hemodynamically Stable Abdominal Trauma: A Systematic Review and Meta-Analysis of Non-Therapeutic Intervention Rates and Clinical Outcomes
Views: 967Downloads: 620Background: Exploratory laparotomy (EL) has traditionally been the standard for evaluating significant abdominal trauma, but it carries a high rate of non-therapeutic procedures and associated morbidity. Diagnostic laparoscopy (DL) has emerged as a minimally invasive alternative, though its precise benefits remain to be quantified by a comprehensive meta-analysis of recent evidence. This study aims to compare the rates of non-therapeutic laparotomy and key clinical outcomes between DL and EL in the management of hemodynamically stable patients with abdominal trauma.
Methods: Following PRISMA guidelines, a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted for studies published between January 2015 and February 2025. We included comparative studies (randomized controlled trials and observational studies) evaluating DL versus EL in adult, hemodynamically stable patients with blunt or penetrating abdominal trauma. The primary outcome was the rate of non-therapeutic laparotomy. Secondary outcomes included overall postoperative morbidity, surgical site infection (SSI) rates, length of hospital stay (LOS), and mortality. A random-effects model was used for meta-analysis to calculate pooled Odds Ratios (OR) and Mean Differences (MD) with 95% Confidence Intervals (CI).
Results: Eight studies involving 1,550 patients (775 in the DL group, 775 in the EL group) were included. The DL group had a significantly lower rate of non-therapeutic laparotomy compared to the EL group (11.5% vs. 38.8%; pooled OR 0.18, 95% CI [0.10, 0.31], p<0.00001; I2=45%). Furthermore, DL was associated with a significant reduction in overall morbidity (OR 0.45, 95% CI [0.34, 0.60], p<0.00001; I2=22%) and SSI rates (OR 0.38, 95% CI [0.24, 0.61], p<0.0001; I2=0%). The mean LOS was shorter in the DL group by 3.15 days (MD -3.15, 95% CI [-3.88, -2.42], p<0.00001; I2=78%). There was no significant difference in mortality rates between the two groups (OR 0.85, 95% CI [0.45, 1.62], p=0.62; I2=0%).
Conclusion: In hemodynamically stable patients with abdominal trauma, a selective strategy involving diagnostic laparoscopy drastically reduces the likelihood of non-therapeutic surgical intervention. This approach is also associated with significantly lower postoperative morbidity, fewer surgical site infections, and a shorter hospital stay without compromising patient survival. These findings strongly support the integration of diagnostic laparoscopy as a primary diagnostic and therapeutic tool in modern trauma management algorithms.
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Beta-Blocker Therapy in Older (≥75 Years) and Frail Patients with Heart Failure: A Systematic Review and Meta-Analysis
Views: 413Downloads: 546Background: Beta-blockers are a cornerstone of therapy for heart failure with reduced ejection fraction (HFrEF), but their efficacy and safety in the burgeoning population of very elderly and frail patients, particularly those with preserved ejection fraction (HFpEF), remain uncertain. This population is characterized by unique pathophysiological features, including altered pharmacokinetics, heightened inflammation, and autonomic dysregulation, which may modulate the treatment effect.
Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. We searched MEDLINE, Embase, and CENTRAL for randomized controlled trials (RCTs) and observational studies published between 2015-2025 that evaluated beta-blockers versus placebo or standard care in patients aged ≥75 years or defined as frail with heart failure. The primary efficacy outcome was all-cause mortality. The primary safety outcome was treatment discontinuation due to adverse events.
Results: Eight studies (three RCTs, five observational) involving 8,512 patients were included. In the overall population, beta-blocker therapy was associated with a reduction in all-cause mortality (Hazard Ratio: 0.88; 95% CI: 0.79−0.98), but with significant heterogeneity (I2=68%). Subgroup analysis revealed this benefit was confined to patients with HFrEF (HR: 0.72; 95% CI: 0.63−0.83), with no benefit observed in HFpEF (HR: 1.09; 95% CI: 0.95−1.25). In frail patients with HFpEF, a trend towards harm was noted (HR: 1.21; 95% CI: 0.98−1.49). Beta-blockers significantly increased treatment discontinuation (Odds Ratio: 2.15; 95% CI: 1.55−2.98), driven primarily by bradycardia.
Conclusion: Beta-blocker therapy reduces mortality in elderly patients with HFrEF, consistent with findings in younger populations. However, in elderly and frail patients with HFpEF, beta-blockers offer no mortality benefit and may be associated with harm, likely due to a pathophysiological mismatch between the drug's mechanism and the disease state.
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A Masquerading Giant: Unprecedented Sebaceous Gland Carcinoma with Massive Orbito-facial Invasion and the Diagnostic and Therapeutic Challenges of an Extreme Presentation
Views: 390Downloads: 384Background: Sebaceous gland carcinoma (SGC) is a rare, aggressive adnexal malignancy of the eyelid, notorious for masquerading as benign inflammatory conditions. Presentations involving massive, destructive orbito-facial invasion are exceptionally rare and pose profound diagnostic and therapeutic challenges, often reflecting a confluence of biological aggression and systemic delays in care.
Case presentation: A 68-year-old male presented with a one-year history of a progressively enlarging mass on his left upper eyelid, which had evolved into a giant, 15 x 15 x 7 cm fungating tumor, causing complete destruction of the orbital contents and extensive invasion into adjacent facial structures. An initial incisional biopsy was paradoxically interpreted as benign sebaceous hyperplasia. Due to the stark clinico-pathological discordance, a repeat, deeper biopsy was performed. The subsequent histopathological examination revealed a high-grade carcinoma, and the diagnosis was definitively confirmed by a panel of immunohistochemical stains, including strong positivity for Epithelial Membrane Antigen (EMA) and Cytokeratin 7 (CK7). The disease was staged as T4dN1M0 and deemed unresectable.
Conclusion: This case documents a catastrophic outcome of SGC, resulting from a combination of delayed patient presentation and initial diagnostic error. It highlights that giant SGC, while rare, must be considered in the differential of destructive facial tumors and underscores that immunohistochemistry is mandatory for resolving clinico-pathological paradoxes in ocular adnexal pathology. This case serves as a call to action for improved public health awareness and enhanced diagnostic acumen to prevent such devastatingly advanced presentations.
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Chylous Ascites in Pediatric Lymphangiomatosis: Definitive Localization and Surgical Guidance with 99mTc-Nanocolloid SPECT/CT
Views: 390Downloads: 238Background: Chylous ascites, the peritoneal accumulation of triglyceride-rich lymphatic fluid, is a rare and clinically formidable condition, especially in children. It signifies a severe disruption of the lymphatic system. Systemic lymphangiomatosis, a congenital lymphatic malformation, is an exceptionally rare underlying cause. The cornerstone of effective treatment for refractory cases is the precise localization of the lymphatic leakage, which remains a profound diagnostic challenge.
Case presentation: We present the case of a 13-year-old female with systemic lymphangiomatosis who developed persistent, high-volume chylous ascites, with outputs reaching 1200 cc/day, following the surgical excision of an abdominal mass. Despite aggressive conservative management, the debilitating leakage continued, precipitating severe metabolic and nutritional derangements. To identify the point of extravasation, the patient underwent lymphoscintigraphy with Technetium-99m (99mTc) nanocolloid and hybrid Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT). While planar imaging confirmed a leak in the right lower abdomen, SPECT/CT provided definitive, high-resolution anatomical localization, pinpointing the site to the pre-peritoneal tissue at the level of the right anterior superior iliac spine. This finding directly guided a successful, targeted surgical repair.
Conclusion: This case demonstrates the indispensable role of 99mTc-nanocolloid SPECT/CT in the management of complex, post-surgical chylous ascites. By transforming a two-dimensional area of suspicion into a three-dimensional, surgically-actionable target, this hybrid imaging modality provided the essential roadmap for a curative intervention where all other measures had failed. This report advocates for the integration of SPECT/CT as a standard of care in the diagnostic algorithm for refractory chylous leaks, representing a key technology that facilitates definitive treatment and fundamentally improves patient outcomes.
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Conservative versus Interventional Management of Ingested Straight Pins in Adolescent Females: A Retrospective Case Series Illustrating Guideline-Based Decision-Making
Views: 334Downloads: 330Background: The ingestion of sharp foreign bodies (FBs) in adolescents presents a critical management dilemma, balancing conservative observation against the risk of gastrointestinal perforation. In certain cultural contexts, the accidental ingestion of straight pins used for hijabs creates a unique patient cohort. This study aims to illustrate the practical, guideline-based application of divergent management strategies in these specific clinical scenarios.
Methods: We conducted a retrospective case series of five female adolescents, aged 13 to 15 years, managed at a single tertiary center for accidental straight pin ingestion. Data on clinical presentation, radiological findings, management strategy (conservative versus endoscopic), and outcomes were extracted and analyzed. Management decisions were dictated by established international guidelines.
Results: Three asymptomatic patients (60%) with pins located distal to the duodenum were managed conservatively and experienced spontaneous passage within 2-4 days. Two patients (40%) required therapeutic endoscopy. One underwent emergent removal for a proximally located pin causing respiratory symptoms. The other, despite being asymptomatic, underwent urgent intervention due to the development of a radiological "sentinel loop" and rising inflammatory markers, which revealed an impacted duodenal pin. No complications occurred in any patient.
Conclusion: This series demonstrates that while active surveillance is a safe strategy for asymptomatic patients with distally located sharp FBs, clinical silence does not preclude impending complications. Subtle radiological findings, such as a sentinel loop, are crucial indicators that must prompt timely endoscopic intervention to prevent morbidity. The educational value lies in highlighting these critical decision-making triggers.
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Platelet-Rich Plasma-Derived Exosomes Modulate Follicular Regeneration: A Comparative Mechanistic Analysis with Minoxidil in a Preclinical Model of Androgenetic Alopecia
Views: 595Downloads: 822Background: The therapeutic armamentarium for androgenetic alopecia (AGA) is limited, with variable efficacy and potential side effects associated with standard treatments like minoxidil. Platelet-rich plasma-derived exosomes (PRP-Exo) represent a novel acellular strategy, offering a concentrated payload of regenerative biomolecules. This study aimed to rigorously evaluate the therapeutic efficacy and underlying mechanisms of PRP-Exo, as a monotherapy and in combination with minoxidil, in a validated murine model of AGA.
Methods: A parallel-group, randomized, double-blind, controlled experimental study was conducted. Thirty-two male C57BL/6 mice with testosterone-induced AGA were randomized (n=8/group) to one of four groups: Negative Control (NC), Positive Control (PC; 5% topical minoxidil), Treatment 1 (T1; intradermal PRP-Exo), or Treatment 2 (T2; combination of PRP-Exo and minoxidil). PRP-Exo were characterized by Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and ELISA for marker proteins. After a 14-day treatment period, efficacy was assessed via hair follicle density (HFD), anagen-to-telogen (A/T) ratio, and hair shaft thickness. Mechanistic insight was obtained by quantifying tissue protein levels of Ki-67 and β-catenin by ELISA.
Results: All active treatments significantly improved hair regeneration compared to the NC group. The combination therapy (T2) demonstrated the most profound effects across all metrics, showing statistically superior outcomes compared to both minoxidil (PC) and PRP-Exo (T1) monotherapies in HFD (65.8 ± 12.1 vs. 36.2 ± 8.5 and 47.3 ± 10.4 follicles/mm², respectively; p<0.01). Furthermore, T2 treatment led to the highest A/T ratio and hair shaft thickness. ELISA revealed that T2 treatment also resulted in the highest tissue concentrations of the proliferation marker Ki-67 and the Wnt pathway protein β-catenin, suggesting enhanced mitogenic activity and modulation of key developmental pathways.
Conclusion: PRP-Exo is a potent hair regenerative agent, significantly outperforming minoxidil in this preclinical model. The combination of PRP-Exo and minoxidil exhibits a synergistic effect, promoting superior follicular regeneration by concurrently stimulating tissue proliferation and upregulating key components of the anagen-promoting Wnt signaling pathway. These findings underscore the significant clinical potential of PRP-Exo as a next-generation therapy for AGA.
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A Diagnostic Rarity: Apocrine Hidrocystoma Presenting as a Medial Canthal Mass in Adolescence
Views: 492Downloads: 416Background: Apocrine hidrocystomas are benign adnexal tumors of the glands of Moll, typically diagnosed in adults. Their presentation in adolescence is an exceptional clinical finding that challenges standard diagnostic paradigms for periocular masses in this age group, necessitating a broad and meticulous differential diagnosis.
Case presentation: A 15-year-old female presented with a two-month history of a stable, asymptomatic, 7×5×1 mm cystic mass at the inferomedial canthus of the left eye. The patient's primary concern was cosmetic. A comprehensive ophthalmologic examination was unremarkable. Orbital computed tomography confirmed a simple, preseptal subcutaneous cyst. A complete excisional biopsy was performed, and histopathological analysis revealed a unilocular cyst lined by a double layer of epithelium with inner columnar cells demonstrating pathognomonic decapitation secretion, confirming an apocrine hidrocystoma.
Conclusion: This case highlights the necessity of including apocrine hidrocystoma in the differential diagnosis of periocular masses in adolescents. The primary lesson is that a patient's age should broaden, not narrow, the diagnostic possibilities. Definitive diagnosis relies on histopathology, not demographic probability, and complete surgical excision remains the gold standard for both diagnosis and curative therapy, yielding an excellent prognosis.
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Challenging the Paradigm: A Clinicopathological Case Series on the Discordance between Cutaneous Burn Severity and Airway Injury Following a Volcanic Pyroclastic Flow Exposure
Views: 406Downloads: 241Background: Inhalation injury accompanying severe burns is a major driver of morbidity and mortality. The pathophysiology of injury from volcanic eruptions—a unique combination of extreme heat, abrasive particulates, and corrosive gases—is distinct from typical combustion smoke and not well-characterized. Flexible bronchoscopy is the gold standard for diagnosing and grading airway injury, yet its application in this context, particularly in relation to external burn severity, is unclear.
Case presentation: We present a retrospective analysis of two climbers who were the sole survivors admitted to our tertiary center after exposure to the pyroclastic flow from the 2023 Mount Marapi eruption. A 19-year-old female with 40% Total Body Surface Area (TBSA) deep burns and a 20-year-old male with 30% TBSA deep burns both presented with signs concerning for inhalation injury. Despite the devastating extent of their cutaneous injuries, flexible bronchoscopy in both patients revealed only mild, Grade 1 endobronchial injury (mucosal erythema and edema) based on the Abbreviated Injury Score (AIS) classification. The first patient succumbed to septic shock from her burns, while the second patient showed significant respiratory improvement following therapeutic bronchial lavage and made a full recovery.
Conclusion: This case series presents hypothesis-generating evidence suggesting that in victims of open-air volcanic pyroclastic flows, the severity of cutaneous burns may be a poor predictor of the degree of underlying endobronchial damage. These findings underscore the potential necessity of a low threshold for early flexible bronchoscopy to accurately diagnose, stratify, and therapeutically intervene in this unique patient population, irrespective of TBSA.
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The Inflammatory Correlates of Hypothalamic-Pituitary-Gonadal Axis Dysfunction in Antiretroviral-Naïve Men with HIV: A Cross-Sectional Analysis of the TNF-α and Testosterone Relationship
Views: 499Downloads: 236Background: In men with untreated Human Immunodeficiency Virus (HIV), the mechanisms underlying testosterone deficiency remain incompletely defined. Chronic inflammation is hypothesized to be a key factor in disrupting the hypothalamic-pituitary-gonadal (HPG) axis. This study aimed to investigate the association between the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the HPG axis and to assess this relationship while accounting for nutritional status in ART-naïve men.
Methods: We conducted a cross-sectional study of 40 ART-naïve men with HIV in Palembang, Indonesia. We measured serum total testosterone, Luteinizing Hormone (LH), TNF-α, Interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). Hypogonadism was classified as primary (low testosterone, high LH) or secondary (low testosterone, low/normal LH). Spearman’s correlation was used to assess bivariate relationships. A multiple linear regression analysis was performed to determine the independent association of TNF-α and Body Mass Index (BMI) with testosterone levels.
Results: All 40 participants (100%) presented with secondary (hypogonadotropic) hypogonadism, characterized by a median total testosterone of 6.48 pg/mL and an inappropriately normal median LH of 3.86 mIU/mL. Serum TNF-α was significantly elevated (median: 10.32 pg/mL). A moderate negative correlation was found between TNF-α and total testosterone (ρ = -0.411, p = 0.008). In the multivariate regression model, both higher TNF-α levels (β = -0.38, p = 0.011) and lower BMI (β = 0.45, p = 0.003) were significant, independent predictors of lower total testosterone. The model explained 34.6% of the variance in testosterone levels (Adjusted R² = 0.346).
Conclusion: Our findings demonstrate a universal prevalence of secondary hypogonadism in ART-naïve men with HIV. This HPG axis dysfunction is strongly and independently associated with both the magnitude of systemic inflammation, marked by TNF-α, and the severity of malnutrition. These results suggest a complex interplay where inflammation and poor nutritional status act as distinct, synergistic contributors to the profound endocrine disruption seen in untreated HIV infection.
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Evaluating Platelet-Large Cell Ratio (P-LCR) as an Accessible Biomarker for Myocardial Injury in Acute Coronary Syndrome
Views: 451Downloads: 260Background: The accurate and timely diagnosis of acute coronary syndrome (ACS) in resource-limited healthcare settings is critically hampered by the high cost and limited availability of the gold-standard biomarker, Troponin I. This study aimed to conduct a preliminary evaluation of the association between two accessible platelet indices derived from the complete blood count—the platelet-large cell ratio (P-LCR) and the immature platelet fraction (IPF)—and the quantitative degree of myocardial injury in patients with ACS.
Methods: An exploratory, cross-sectional study was conducted on 51 consecutive patients diagnosed with ACS at a tertiary referral hospital in Medan, Indonesia. The relationship between admission P-LCR, IPF, and Troponin I was assessed using a multi-faceted statistical approach, including Spearman's rank correlation, an exploratory multivariable linear regression model, and a Receiver Operating Characteristic (ROC) curve analysis. A post-hoc power analysis was performed to contextualize the findings.
Results: The study was found to be statistically underpowered (power ≈ 60%) to reliably detect weak correlations. A statistically significant but weak positive correlation was observed between P-LCR and Troponin I levels (Spearman's ρ = 0.31, p = 0.026). This association remained significant after adjusting for age, gender, and ACS subtype, but the overall model demonstrated minimal explanatory power (Adjusted R² = 0.18). The ROC analysis for P-LCR in discriminating between normal and elevated Troponin I was poor (Area Under the Curve = 0.65; 95% CI: 0.50 - 0.79). No significant correlation was found between IPF and Troponin I (p = 0.093).
Conclusion: P-LCR exhibits a weak, independent statistical association with the degree of myocardial injury in ACS patients. However, its poor discriminatory performance, coupled with the profound methodological limitations of this preliminary study, demonstrates that P-LCR is not a clinically useful biomarker for the identification or stratification of myocardial injury. These findings underscore the significant translational gap between a plausible biological hypothesis and a clinically viable diagnostic tool, highlighting the immense complexities that must be addressed in future, more robustly designed research.
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UVB-Induced Oxidative Collapse and Melanogenic Activation in a Rat Model of Cutaneous Hyperpigmentation: A Multi-Parametric Analysis
Views: 494Downloads: 361Background: Ultraviolet B (UVB) radiation is a primary driver of cutaneous hyperpigmentation disorders, with oxidative stress recognized as a key pathogenic mechanism. However, a comprehensive, multi-level characterization of the causal link between chronic UVB exposure and the resulting oxidative, histological, and melanogenic responses is needed. This study aimed to quantitatively validate a preclinical model of UVB-induced hyperpigmentation by characterizing the reciprocal regulation of key oxidative stress biomarkers and correlating these changes with objective histological evidence of hyperpigmentation.
Methods: This controlled in vivo experimental study used 14 male Sprague Dawley rats, divided into a control group (KN; n=7) and a UVB-exposed group (KP; n=7). The KP group received chronic UVB radiation (300 mJ/cm² daily, 5 days/week for 4 weeks). Dorsal skin tissue was harvested for analysis. Oxidative stress was assessed by quantifying malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels via ELISA. Hyperpigmentation was objectively validated and quantified using Fontana-Masson staining for melanin deposition and immunohistochemistry for microphthalmia-associated transcription factor (MITF).
Results: Chronic UVB exposure induced significant hyperpigmentation, confirmed by a 5.8-fold increase in epidermal melanin content (p < 0.001) and a 4.1-fold increase in the number of MITF-positive melanocytes (p < 0.001) in the KP group. This was accompanied by a profound oxidative imbalance: MDA levels increased by 7.5-fold (p < 0.001), while the activities of SOD, CAT, and GPx decreased by 80.5%, 65.2%, and 71.4%, respectively (all p < 0.001). A strong negative correlation was observed between MDA and all antioxidant enzymes, particularly SOD (r = -0.985, p < 0.001).
Conclusion: Chronic UVB exposure directly triggers a collapse of the cutaneous antioxidant network, leading to severe lipid peroxidation. This state of profound oxidative stress is causally linked to melanocyte activation and excessive melanin synthesis, driving the hyperpigmentation phenotype. This robustly validated preclinical model provides a powerful platform for investigating the molecular pathophysiology of UVB-induced pigmentary disorders and for evaluating novel therapeutic interventions.
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Beyond 'Blunt': A Pathophysiology-Guided Framework for Managing High-Risk Pediatric Foreign Body Ingestion
Views: 362Downloads: 274Background: Foreign body ingestion is a significant cause of pediatric morbidity. The traditional "blunt" classification is insufficient for risk stratification, as objects like magnets and impacted items pose distinct threats based on their intrinsic properties. This study analyzes how a pathophysiology-based approach, distinguishing active (magnetic) from passive (mechanical) injury mechanisms, guides clinical decision-making.
Methods: We conducted a retrospective, descriptive case series at a tertiary pediatric surgical center, reviewing cases from January 2022 to December 2024. Five illustrative cases of high-risk blunt foreign body ingestion were selected to demonstrate the spectrum of management based on the object's potential for harm.
Results: The series included five children (aged 3-7 years). A 7-year-old with a single gastric magnet retained for five days developed mucosal injury and required urgent endoscopic removal. A 5-year-old with a recently ingested solitary gastric magnet and a 3-year-old with an impacted pyloric pendant also underwent urgent endoscopic removal. A 6-year-old with a gastric coin had elective endoscopy due to socioeconomic factors. In contrast, a 5-year-old with a coin that passed the pylorus was managed conservatively with spontaneous passage. All patients had successful outcomes.
Conclusion: The management of pediatric foreign body ingestion should be dictated by the object's pathophysiological potential for injury, not its shape. Understanding the difference between active magnet-induced pressure necrosis and passive mechanical impaction is paramount for applying guidelines effectively and preventing severe complications. This framework supports a necessary shift from shape-based to mechanism-based risk assessment.
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The Vesicovaginal Fistula Repair Dilemma: A Systematic Review and Meta-Analysis of Transabdominal versus Transvaginal Surgical Approaches
Views: 447Downloads: 521Background: The optimal surgical approach for repairing a vesicovaginal fistula (VVF) remains a subject of significant clinical debate. Both transabdominal and transvaginal techniques have distinct advantages and disadvantages, leading to a dilemma in surgical decision-making. This systematic review and meta-analysis aims to provide a comprehensive, evidence-based comparison of the two approaches, focusing on surgical success, complications, and perioperative outcomes.
Methods: This review was conducted and reported in accordance with the PRISMA 2020 guidelines. A systematic search of PubMed, Scopus, and Web of Science was performed for comparative studies published between January 2015 and August 2025. We included studies directly comparing transabdominal and transvaginal VVF repair. The primary outcome was surgical success (fistula closure). Secondary outcomes included overall complications, mean operative time, and length of hospital stay. A random-effects model was used for meta-analysis to calculate pooled Odds Ratios (OR) and Mean Differences (MD) with 95% Confidence Intervals (CI).
Results: From 1,284 articles identified, seven comparative studies involving 678 patients (335 transvaginal, 343 transabdominal) were included. The meta-analysis revealed no statistically significant difference in surgical success rates between the transvaginal and transabdominal approaches (OR 1.12, 95% CI 0.68,1.85, p=0.65; I²=21%). However, the transvaginal approach was associated with a significantly lower rate of overall complications (OR 0.45, 95% CI 0.28,0.73, p=0.001; I²=0%). Furthermore, the transvaginal approach demonstrated significantly shorter mean operative times (MD -58.45 minutes, 95% CI−75.60,−41.30, p<0.00001; I²=88%) and a shorter mean length of hospital stay (MD -3.15 days, 95% CI −4.01,−2.29, p<0.00001; I²=92%).
Conclusion: While both surgical approaches yield comparable fistula closure rates, the transvaginal technique offers a superior safety and efficiency profile, with significantly fewer complications, shorter operative times, and reduced hospitalization. These findings suggest that the transvaginal route should be considered the preferred approach for anatomically suitable fistulas, though surgeon expertise and fistula characteristics remain paramount in resolving the VVF repair dilemma.
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Gonococcal and Non-Gonococcal Urethritis in a Global Travel Hub: A Retrospective Analysis of Syndromic Management, Suboptimal Cefixime Monotherapy, and the Public Health Crisis of Patient Retention in Bali, Indonesia
Views: 417Downloads: 451Background: The inexorable rise of antimicrobial resistance (AMR) in Neisseria gonorrhoeae represents a formidable threat to global public health, jeopardizing the efficacy of last-line treatments for gonococcal urethritis (GO). Southeast Asia is a recognized epicenter for the emergence and dissemination of AMR, yet granular surveillance data from many high-risk localities remain critically sparse. This study aimed to provide a comprehensive characterization of the clinical epidemiology, frontline management practices, and patient outcomes of male urethritis at a tertiary referral center in Bali, Indonesia—a major international crossroads for tourism and migration.
Methods: A retrospective, cross-sectional analysis was conducted on the medical records of male patients diagnosed with urethritis at the Dermatology and Venereology Polyclinic of Ngoerah Hospital between January 1st, 2021, and December 31st, 2024. A rigorous screening process of 215 initial records was undertaken to identify eligible cases. Data on sociodemographics, behavioral risk factors, clinical presentation, syndromic diagnosis, prescribed pharmacotherapy, and follow-up adherence were systematically extracted and analyzed using descriptive and comparative statistics.
Results: From the initial cohort, 58 male patients met the final inclusion criteria. The cohort was predominantly diagnosed with GO (n=39, 67.2%) over non-gonococcal urethritis (NGO) (n=19, 32.8%). Patients were primarily of productive age (25–44 years, 58.6%) and reported high-risk behaviors, including multiple sexual partners (65.5%). A critical deviation from international treatment guidelines was identified: 97.4% (38/39) of GO patients received oral cefixime 400 mg monotherapy, a regimen no longer recommended for first-line use due to AMR concerns. Furthermore, a profound fracture in the care cascade was evident, with an overall loss-to-follow-up rate of 58.6% (34/58). This failure was most pronounced in the GO cohort, where 76.9% (30/39) of patients did not return for scheduled follow-up, a rate significantly higher than the 21.1% (4/19) observed in the NGO cohort (p<0.001).
Conclusion: The clinical management of gonorrhoea at this major Indonesian referral center is defined by two systemic failures: the routine prescription of a suboptimal antimicrobial monotherapy and a near-total collapse of patient follow-up. This combination, situated in a high-transience international hub, creates an unmonitored, high-risk environment for the selection, amplification, and global dissemination of antimicrobial-resistant N. gonorrhoeae. These findings signal an urgent imperative to align local therapeutic protocols with evidence-based global standards and to implement robust, innovative strategies to ensure patient retention and verify the cure.
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A Retrospective Analysis of Clinical Characteristics and Neutrophil-to-Lymphocyte Ratio in Hospitalized Indonesian Patients with Pemphigus Vulgaris and Bullous Pemphigoid: A Single-Center Experience
Views: 396Downloads: 231Background: Comprehensive clinical-epidemiological data on severe autoimmune bullous diseases (ABDs) from Southeast Asian populations are notably scarce. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are the most common ABDs, and understanding their presentation in diverse ethnic and geographic contexts is crucial for global health equity. This study’s primary aim was to characterize a cohort of hospitalized ABD patients in Central Java, Indonesia, and to secondarily explore the behavior of the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory marker within this real-world clinical setting.
Methods: A retrospective, cross-sectional study was conducted at a tertiary referral hospital in Surakarta, Indonesia. The study included all patients admitted with a final diagnosis of PV or BP between January 2019 and December 2023. Comprehensive data on demographics, documented comorbidities, duration of hospitalization, and admission hematological parameters were extracted from medical records. Clinical characteristics were compared, and the non-parametric Mann-Whitney U test was used to analyze the difference in NLR. A post-hoc power analysis was performed to contextualize the hematological findings.
Results: This study provides a detailed clinical profile of 30 hospitalized ABD patients. The PV cohort (n=17) was characterized by a younger age of onset (mean age 54.29 ± 14.83 years) and a strong female predominance (70.6%). In contrast, the BP cohort (n=13) was older (mean age 63.08 ± 22.01 years) with a balanced gender distribution. A key finding was that patients with PV had a significantly longer duration of hospitalization than those with BP (13.24 vs. 10.15 days, p < 0.05). The mean NLR was descriptively higher in BP (10.56 ± 7.22) than in PV (9.43 ± 6.14), but this difference was not statistically significant (p = 0.770), a finding consistent with the study’s critically low statistical power of 9.8%.
Conclusion: This study presents a valuable clinical and epidemiological snapshot of hospitalized patients with PV and BP in an underrepresented Indonesian population, highlighting a significantly greater clinical burden for PV as quantified by length of stay. The exploratory analysis of the NLR was inconclusive and should not be interpreted as definitive evidence against its utility. Instead, it serves as a powerful illustration of how the effects of low statistical power and overwhelming, unmeasured confounding from disease severity and corticosteroid treatment present profound challenges to the validation of non-specific biomarkers in complex, real-world clinical scenarios.
