Bioscientia Medicina - Journal of Biomedicine and Translational Research
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Dynamic Coupling of Systemic and Intratumoral Estradiol in HER2-Positive and Triple-Negative Breast Cancer: A Validation Study of a Non-Invasive Surrogate
Get PDFBackground: The role of estradiol in the tumor microenvironment (TME) of estrogen receptor (ER)-negative breast cancers is increasingly recognized. Direct measurement of intratumoral estradiol is invasive, creating a barrier to clinical research. This study aimed to determine if circulating plasma estradiol can serve as a high-fidelity, non-invasive surrogate for intratumoral concentrations in HER2-positive (HER2+) and triple-negative breast cancer (TNBC).
Methods: This retrospective, cross-sectional study included 60 women with primary operable HER2+ (n=21) and TNBC (n=39) who underwent mastectomy. Paired pre-operative plasma and post-operative tumor tissue samples were analyzed. Estradiol concentrations were quantified using a validated high-performance liquid chromatography-radioimmunoassay (HPLC-RIA) protocol. Clinicopathological data, including Body Mass Index (BMI), were collected. The primary outcome was the correlation between plasma and intratumoral estradiol, assessed by Spearman's rank correlation. Paired concentrations were compared using the Wilcoxon signed-rank test.
Results: Baseline clinicopathological characteristics, including BMI, were well-balanced between the HER2+ and TNBC cohorts. A highly significant, strong positive correlation was found between plasma and intratumoral estradiol concentrations across the entire cohort (Spearman's ρ = 0.78, p < 0.001). This correlation remained robust in subgroup analyses of menopausal status and tumor grade. Interestingly, median intratumoral estradiol levels (30.0 pg/mL; IQR: 10.0-65.0) were significantly lower than paired median plasma levels (132.0 pg/mL; IQR: 40.0-225.0) (p < 0.001).
Conclusion: Plasma estradiol demonstrates a strong and direct correlation with intratumoral estradiol in HER2+ and TNBC, validating its use as a reliable, non-invasive surrogate. This provides a crucial tool to explore the pathophysiology of the TME. The finding that intratumoral levels are lower than systemic circulation, yet tightly coupled, suggests a dynamic equilibrium that warrants further investigation into local estradiol metabolism and signaling in ER-negative disease
Adjunctive Vaginal Probiotic Therapy for Preterm Premature Rupture of Membranes: A Systematic Review and Meta-Analysis of Latency Period, Maternal Infection, and Neonatal Morbidity
Get PDFBackground: Preterm premature rupture of membranes (PPROM) significantly drives preterm birth rates and consequent neonatal morbidity and mortality. While standard antibiotic therapy aims to prolong pregnancy latency, it concurrently disrupts the protective vaginal microbiota. Adjunctive vaginal probiotics have been investigated as a means to restore beneficial flora, potentially mitigating ascending infection and improving perinatal outcomes. This study systematically synthesized the current randomized trial evidence regarding this adjunctive therapeutic strategy.
Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. PubMed, EMBASE, and CENTRAL databases were searched (2014–October 2025) for randomized controlled trials (RCTs) comparing adjunctive vaginal probiotics plus antibiotics versus antibiotics (alone or with placebo) in singleton pregnancies complicated by PPROM between 24+0 and 34+0 weeks’ gestation. Primary outcomes included the latency period (days) and maternal chorioamnionitis or infectious morbidity. Key secondary outcomes were neonatal intensive care unit (NICU) admission, neonatal sepsis, and neonatal mortality. Data were pooled using a random-effects model, calculating Mean Differences (MD) or Risk Ratios (RR) with 95% Confidence Intervals (CI). Risk of bias was assessed using the Cochrane RoB 2 tool.
Results: Three RCTs, encompassing 330 participants, met the inclusion criteria. Significant methodological limitations, including high risk of bias and critical baseline confounding by gestational age in the largest trial, were identified across the included studies. A sensitivity analysis addressing high heterogeneity (I²=98%) for latency (excluding one retrospective study; n=290) indicated a modest but statistically significant prolongation associated with probiotics (MD 2.98 days; 95% CI 1.80–4.16; p<0.0001; I²=0%). Probiotic use was linked to a significantly lower risk of maternal infection (RR 0.43; 95% CI 0.24–0.77; p=0.005; I²=0%; n=270). Statistically significant reductions were also observed for NICU admission (RR 0.59; 95% CI 0.46–0.75; p<0.0001; I²=55%; n=330) and neonatal mortality (RR 0.38; 95% CI 0.18–0.81; p=0.01; I²=0%; n=270), although these estimates are likely inflated due to baseline confounding.
Conclusion: This meta-analysis suggests adjunctive vaginal probiotics may offer benefits in PPROM management by modestly prolonging latency and significantly reducing maternal infectious morbidity. While substantial reductions in NICU admission and neonatal mortality were observed, these findings must be interpreted with extreme caution due to the limited quantity and low quality of the primary evidence, particularly the high risk of bias and confounding. Definitive conclusions cannot be drawn, and routine clinical adoption is not supported by current evidence. High-quality, large-scale RCTs are imperative
Adaptive Radiotherapy (ART) versus Non-Adaptive IMRT for Locoregionally Advanced Nasopharyngeal Carcinoma: A Meta-Analysis of Dosimetric Advantages, Clinical Outcomes, and Organ-at-Risk Sparing
Get PDFBackground: Intensity-modulated radiotherapy (IMRT) is the cornerstone of treatment for nasopharyngeal carcinoma (NPC), offering high dose conformity. However, anatomical variations during the multi-week therapy course can compromise dosimetric accuracy. Adaptive radiotherapy (ART), which adjusts the treatment plan based on intra-treatment imaging, aims to mitigate these effects. This meta-analysis synthesized contemporary comparative evidence (2014–2025) on the efficacy and safety of ART versus non-adaptive IMRT in locoregionally advanced NPC.
Methods: Following PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library were searched for studies comparing ART with non-adaptive IMRT (cohorts or hybrid/phantom plan comparisons) in locoregionally advanced NPC. Primary outcomes were locoregional recurrence-free survival (LRFS) and overall survival (OS); secondary outcomes included progression-free survival (PFS), distant metastasis-free survival (DMFS), and dosimetric metrics for targets (D98, Conformity Index [CI]) and organs-at-risk (OARs: parotid Dmean, spinal cord Dmax, brainstem Dmax). Hazard Ratios (HR) and Mean Differences (MD) were pooled using random-effects models. Data estimation methods (Tierney, Wan, Cochrane) were employed where necessary. Heterogeneity was assessed using I².
Results: Nine studies (2 cohort, 7 dosimetric/anatomical) involving 362 patients (clinical) and 215 datasets (dosimetric) were included. ART significantly improved LRFS compared to non-adaptive IMRT (pooled HR = 0.53, 95% CI 0.32–0.88; I²=0%). No significant differences were found for OS (HR=0.98, 95% CI 0.64–1.50), PFS (HR=0.70, 95% CI 0.45–1.07), or DMFS (HR=0.88, 95% CI 0.48–1.62). Compared to hybrid/phantom plans, ART significantly enhanced target coverage (pooled PTV D98 MD = 2.15 Gy, 95% CI 1.10–3.20 Gy; I²=78%) and conformity (pooled CI MD = 0.05, 95% CI 0.02–0.08; I²=85%). ART significantly reduced OAR doses: parotid Dmean (pooled MD = -3.50 Gy, 95% CI -4.95 to -2.05 Gy; I²=90%), spinal cord Dmax (pooled MD = -3.95 Gy, 95% CI -5.80 to -2.10 Gy; I²=93%), and brainstem Dmax (pooled MD = -2.75 Gy, 95% CI -4.40 to -1.10 Gy; I²=91%). Dosimetric analyses exhibited high heterogeneity.
Conclusion: ART significantly improves LRFS in locoregionally advanced NPC compared to non-adaptive IMRT. It provides substantial dosimetric advantages, enhancing target coverage and conformity while critically reducing doses to parotid glands, spinal cord, and brainstem. Despite high dosimetric heterogeneity and no demonstrated OS benefit, the improvements in LRFS and dose delivery support the thoughtful implementation of ART
Beyond Glycemia: Independent Hemodynamic and Metabolic Drivers of Incident Diabetic Kidney Disease in a 5-Year Prospective Indonesian Primary Care Cohort
Get PDFBackground: The relative contributions of hyperglycemia, hypertension, and metabolic adiposity to the progression of diabetic kidney disease (DKD) are debated, particularly in Southeast Asian populations and in the context of modern polypharmacy. We aimed to prospectively quantify the independent impact of glycemic burden, hemodynamic stress, and central adiposity on the 5-year incidence of DKD in an Indonesian primary care cohort.
Methods: We conducted a 5-year, multi-center, prospective cohort study at 25 primary care clinics in Indonesia. We randomly sampled and enrolled 1,250 T2DM patients without pre-existing DKD (eGFR > 60 mL/min/1.73m² and normoalbuminuria). The primary composite outcome was incident DKD, defined as persistent albuminuria (ACR ≥ 30 mg/g on 2 of 3 occasions) or a sustained eGFR decline of ≥ 30%. Baseline predictors included HbA1c, Systolic Blood Pressure (SBP), and Waist-to-Height Ratio (WHtR). Multivariable Cox proportional-hazards models were used to estimate Hazard Ratios (HRs), adjusting for demographics, baseline eGFR, and baseline use of RAAS inhibitors (RAASi) and SGLT2 inhibitors.
Results: Of 1,250 participants, 980 (78.4%) completed the 5-year follow-up. Over a median 4.9 years, 215 participants (21.9%) developed the composite DKD outcome. In the fully-adjusted multivariable Cox model, all three pathways were strong, independent predictors of incident DKD. The standardized HR for SBP (per 1-SD increase) was 1.68 (95% CI: 1.40–2.01; p<0.001), for HbA1c (per 1-SD increase) was 1.45 (95% CI: 1.22–1.73; p<0.001), and for WHtR (per 1-SD increase) was 1.39 (95% CI: 1.18–1.65; p<0.001).
Conclusion: In this prospective primary care cohort, hemodynamic stress (SBP), glycemic burden (HbA1c), and metabolic adiposity (WHtR) were all independent, potent drivers of incident DKD, even after controlling for the use of protective cardio-renal medications. These findings confirm that a multi-pillar strategy, aggressively targeting blood pressure, glucose, and weight/metabolic health simultaneously, is essential for DKD prevention
Hydrostatic Pressure versus Passive Diffusion: A Split-Face Comparative Analysis of Intradermal Injection and Microneedling-Assisted Delivery of Botulinum Toxin Type A for Facial Pore Refinement
Get PDFBackground: Enlarged facial pores, medically termed dilated pilosebaceous follicles, represent a prevalent aesthetic concern driven by seborrhea, follicular hypertrophy, and loss of perifollicular elasticity. Microbotox, the intradermal administration of dilute OnabotulinumtoxinA (BoNT-A), targets these mechanisms through sebosuppression and arrector pili inhibition. However, the optimal delivery vehicle—active intradermal injection versus passive microneedling-assisted transport—remains debated regarding clinical delivery efficiency.
Case presentation: A 23-year-old female with Fitzpatrick Skin Type IV, severe pore enlargement (Kim’s Score 5), and seborrhea participated in a split-face comparative study. The right cheek received standard intradermal microdroplet injections of BoNT-A (20 U diluted in 1.0 mL saline). The left cheek underwent automated microneedling at a depth of 2.0 mm immediately followed by topical application of the same BoNT-A solution. Evaluation was performed at baseline, Day 7, and Day 14 using blinded clinical scoring and digital dermoscopic analysis. At Day 14, the intradermal injection side demonstrated superior pore reduction (Kim’s Score 5 to 3) compared to the microneedling side (Score 5 to 4). Digital quantification confirmed a 45% reduction in mean pore diameter on the injected side versus 18% on the microneedling side. While both modalities effectively reduced sebum scores to 1, the microneedling side exhibited delayed pore refinement, likely attributed to post-traumatic edema and the wash-out effect of blood flow antagonizing passive diffusion.
Conclusion: Direct intradermal injection provides superior clinical delivery efficiency for BoNT-A, resulting in more rapid and significant pore contraction. Microneedling-assisted delivery, particularly at depths inducing vascular injury, acts as a secondary adjunct for textural remodeling but is inferior for immediate pharmacological delivery of large-molecule toxins
Successful Anesthetic Management of Pheochromocytoma in a Patient with Preoperative Hypertension: A Case Report
Get PDFBackground: Pheochromocytoma, a rare tumor arising from chromaffin cells in the adrenal medulla, poses significant anesthetic challenges due to its propensity to release catecholamines, potentially leading to life-threatening hypertensive crises. This case report describes the successful anesthetic management of a patient with pheochromocytoma presenting with preoperative hypertension.
Case presentation: A 37-year-old female with a 12x5 cm right adrenal tumor diagnosed as pheochromocytoma was scheduled for adrenalectomy. She presented with a history of uncontrolled hypertension, episodic headaches, diaphoresis, and palpitations. Preoperative management focuses on blood pressure control using alpha and beta-adrenergic blockers. Anesthesia was induced with propofol, fentanyl, and atracurium, while nitroglycerin and sevoflurane were used to maintain hemodynamic stability. The patient's blood pressure was closely monitored throughout the procedure, with interventions made to manage fluctuations during tumor manipulation.
Conclusion: Successful anesthetic management of pheochromocytoma requires meticulous preoperative preparation, vigilant intraoperative monitoring, and prompt pharmacological interventions. This case highlights the importance of a multidisciplinary approach, including endocrinologists, anesthesiologists, and surgeons, to optimize patient outcomes
Atypical Pneumonia in the Elderly: A Meta-Analysis of Risk Factors, Treatment Outcomes, and Mortality
Get PDFBackground: Atypical pneumonia poses a significant threat to elderly individuals, often leading to severe complications and increased mortality. This meta-analysis aimed to evaluate risk factors, treatment outcomes, and mortality associated with atypical pneumonia in elderly patients.
Methods: A systematic search of PubMed, Embase, and Cochrane Library databases was conducted from January 2013 to December 2024. Studies reporting on atypical pneumonia in patients aged 65 years or older were included. Data on risk factors, treatment outcomes (clinical cure rate, radiological improvement, length of hospital stay), and mortality were extracted and pooled using random-effects models.
Results: Six studies involving 1,875 elderly patients with atypical pneumonia were included. Advanced age (≥80 years), comorbidities (chronic obstructive pulmonary disease, heart failure, diabetes mellitus), and delayed initiation of antibiotic therapy were identified as significant risk factors for severe disease and mortality. Treatment with macrolides was associated with a higher clinical cure rate (OR 2.15, 95% CI 1.52-3.04, p<0.001) and shorter hospital stay (mean difference -2.8 days, 95% CI -4.1 to -1.5, p<0.001) compared to fluoroquinolones. The pooled mortality rate was 12.8% (95% CI 9.5-16.1%).
Conclusion: Atypical pneumonia in the elderly is associated with significant morbidity and mortality. Early recognition of risk factors and prompt initiation of appropriate antibiotic therapy, particularly with macrolides, are crucial for improving outcomes in this vulnerable population
Successful Anesthetic Management of a Cesarean Section in a Patient with Cardiomyopathy and Cardiogenic Shock: A Case Report
Get PDFBackground: Cardiomyopathy in pregnancy is a rare but serious condition that can lead to significant maternal and fetal morbidity and mortality. Anesthetic management of these patients is challenging due to the complex interplay of physiological changes and the potential for hemodynamic instability. This case report describes the successful anesthetic management of a cesarean section in a patient with cardiomyopathy and cardiogenic shock.
Case presentation: A 29-year-old woman with cardiomyopathy and cardiogenic shock presented for emergency cesarean section at 36-37 weeks gestation. She had a history of global hypokinetic, left ventricular and atrial dilatation, and an ejection fraction (EF) of 32%. She was also in atrial fibrillation. Epidural anesthesia was selected due to its lower risk of complications compared to general anesthesia. The patient was carefully monitored throughout the procedure, and her hemodynamics were maintained with a combination of fluids and inotropes. The surgery was successful, and the patient delivered a healthy baby boy.
Conclusion: This case report demonstrates that successful anesthetic management of cesarean section is possible in patients with cardiomyopathy and cardiogenic shock. Careful planning, close monitoring, and a multidisciplinary approach are essential for a positive outcome
Guava Leaf Extract: A Promising Alternative to Chlorhexidine for Reducing Streptococcus mutans Colonization on Orthodontic Appliances
Get PDFBackground: Streptococcus mutans is a major contributor to the formation of dental plaque and the initiation of caries. Orthodontic appliances, particularly removable ones, can create favorable conditions for S. mutans colonization, increasing the risk of caries and other oral health issues. Chlorhexidine is a commonly used antimicrobial agent in dentistry, but it can have side effects like tooth staining and altered taste. Guava leaf extract has shown promising antibacterial properties due to its rich content of flavonoids, tannins, and other bioactive compounds. This study aimed to compare the effectiveness of guava leaf extract and chlorhexidine in reducing S. mutans colonization on acrylic-based removable orthodontic appliances.
Methods: This in vitro study used 25 acrylic plates, which were divided into five groups: guava leaf extract at concentrations of 75%, 80%, and 90%, chlorhexidine gluconate 0.2% (positive control), and aquades (negative control). The acrylic plates were first contaminated with S. mutans and then immersed in the respective solutions for 10 minutes. The number of S. mutans colonies was then counted using a colony counter.
Results: The mean number of S. mutans colonies was significantly lower in the chlorhexidine group (27.8 ± 6.6 CFU/ml) and the guava leaf extract groups (9.4 ± 3.3 CFU/ml for 90%, 42 ± 7.8 CFU/ml for 80%, and 381 ± 81.1 CFU/ml for 75%) compared to the aquades group (1461.2 ± 274.5 CFU/ml). There was no significant difference between the chlorhexidine group and the 90% and 80% guava leaf extract groups.
Conclusion: Guava leaf extract, particularly at concentrations of 90% and 80%, is as effective as chlorhexidine in reducing S. mutans colonization on orthodontic appliances. Guava leaf extract may be a promising natural alternative to chlorhexidine for maintaining oral hygiene in orthodontic patients, especially those with concerns about chlorhexidine's side effects
High-Frequency Chest Wall Oscillation versus Conventional Airway Clearance Techniques in Non-Cystic Fibrosis Bronchiectasis: A Meta-Analysis
Get PDFBackground: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic lung disease characterized by irreversible airway dilation and impaired mucociliary clearance, leading to chronic cough, sputum production, and recurrent infections. This meta-analysis aims to compare the efficacy of high-frequency chest wall oscillation (HFCWO) with conventional airway clearance techniques (CACT) in adults with NCFB.
Methods: A systematic search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases was conducted from January 2013 to March 2024. Randomized controlled trials (RCTs) comparing HFCWO with CACT (postural drainage, percussion, active cycle of breathing technique, positive expiratory pressure therapy) in adults with NCFB were included. The primary outcomes were a change in forced expiratory volume in one second (FEV1) and sputum weight. Secondary outcomes included quality of life, exacerbation frequency, and adverse events. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Data were pooled using a random-effects model, and heterogeneity was assessed using the I² statistic.
Results: Nine RCTs involving a total of 485 participants were included. The meta-analysis showed no statistically significant difference in FEV1 change between HFCWO and CACT (mean difference [MD] 0.05 L, 95% confidence interval [CI] -0.02 to 0.12; I² = 45%). HFCWO was associated with a statistically significant increase in sputum weight compared to CACT. SGRQ total score showed a statistically significant improvement in the HFCWO group compared to CACT (MD -4.21, 95% CI -7.88 to -0.54; I² = 58%).
Conclusion: HFCWO may provide a modest benefit in terms of increased sputum clearance and improved quality of life compared to CACT in adults with NCFB. However, there was no significant difference in lung function (FEV1) or exacerbation frequency. The moderate to high heterogeneity in some outcomes suggests that further research is needed to confirm these findings and identify patient subgroups who may benefit most from HFCWO