Opioid Rotation vs. Dose Titration in Refractory Cancer Pain: A Meta-Analysis of Efficacy and Adverse Events

Background: The management of refractory cancer pain represents a formidable clinical challenge at the intersection of oncology and palliative medicine. When patients with advanced malignancy fail to achieve adequate analgesia or develop intolerable adverse effects from their opioid regimen, clinicians are faced with a crucial decision: to escalate the dose of the current opioid (dose titration) or to switch to a different opioid agent (opioid rotation). The optimal strategy remains a subject of intense debate and variable practice. This meta-analysis was conducted to rigorously compare the efficacy and safety of these two common interventions. Methods: A systematic and comprehensive search was performed in the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) published between January 2015 and December 2024. We included studies that directly compared opioid rotation with dose titration in adult palliative care patients diagnosed with refractory cancer pain. The primary efficacy outcome was the change in pain intensity, analyzed using the Standardized Mean Difference (SMD) to accommodate pain scales such as the Numerical Rating Scale (NRS) and Visual Analogue Scale (VAS). Primary safety outcomes were the incidence of severe neurotoxicity and severe constipation. Data were pooled using a random-effects model, and results were expressed as SMD for the continuous pain outcome and Risk Ratio (RR) for dichotomous adverse events, with corresponding 95% confidence intervals (CI). Results: Seven RCTs, encompassing a total of 962 patients, met the stringent inclusion criteria. The pooled analysis revealed that the strategy of opioid rotation resulted in a statistically significant and clinically substantial greater reduction in pain intensity compared to continued dose titration (SMD -0.65, 95% CI [-0.88, -0.42], p<0.00001; I²=81%). Furthermore, the risk of developing severe neurotoxicity, including delirium and myoclonus, was significantly lower in the rotation group (RR 0.62, 95% CI [0.45, 0.85], p=0.003; I²=18%). There was no statistically significant difference in the incidence of severe constipation between the two intervention groups (RR 0.90, 95% CI [0.71, 1.14], p=0.38; I²=24%). Conclusion: In patients with refractory cancer pain, the strategy of opioid rotation provided superior analgesia and was associated with a markedly lower risk of severe neurotoxicity when compared to the continued dose titration of the same opioid. These findings provide strong, high-level evidence to support the use of opioid rotation as a primary and proactive strategy for managing uncontrolled pain or dose-limiting side effects in the palliative care population

Enhancing the Early Inflammatory Response: The Role of Ozonated Aloe Vera Oil on IL-6 and TNF-α in Cutaneous Wound Repair

Background: Dysregulation of the initial inflammatory phase is a primary driver of impaired healing and the formation of chronic wounds, creating a critical need for therapies that can optimize this early response. This study tested the hypothesis that a novel formulation of ozonated aloe vera oil functions as a sophisticated bioregulator, promoting a beneficial, pro-regenerative inflammatory phenotype by transiently enhancing the host's innate repair signals. Methods: This was a preclinical, randomized, controlled study using fifty male Sprague-Dawley rats with 1 cm full-thickness excisional wounds. The therapeutic agent, ozonated aloe vera oil, was chemically characterized by its peroxide value (PV). Animals were randomized to receive topical treatment with either a positive control (aloe vera oil), a negative control (gentamicin ointment), or one of three graded doses of ozonated oil (Low PV, Medium PV, High PV). The primary outcomes, systemic (serum) and local (wound tissue homogenate) concentrations of Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were quantified by ELISA on days 3 and 7. Results: On day 3, all ozonated oil formulations induced a profound and significant upregulation of both local and systemic TNF-α and IL-6 compared to controls (p < 0.001). The topical treatment increased systemic TNF-α levels by over 40% and local tissue concentrations by over 60%. Critically, this pro-inflammatory surge was transient; by day 7, both local and systemic cytokine levels in all groups had returned to statistically indistinguishable baseline levels. Conclusion: Ozonated aloe vera oil acts as a potent, transient modulator of the wound microenvironment, enhancing the expression of key initiatory cytokines. This mechanism, likely mediated by the activation of redox-sensitive transcription factors, optimizes the crucial first phase of healing without inducing pathological chronic inflammation. This study supports a novel therapeutic paradigm aimed at enhancing, rather than suppressing, the body's innate capacity for repair

Corticosteroids, Azole Antifungals, and Biologic Agents for the Management of Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Network Meta-Analysis

Background: The management of allergic bronchopulmonary aspergillosis (ABPA) requires control of complex type 2 inflammation and reduction of fungal burden. The comparative efficacy of the primary therapeutic classes—corticosteroids, azole antifungals, and biologics—is not well established through direct evidence. This network meta-analysis was conducted to determine the optimal hierarchical treatment strategy for ABPA. Methods: A systematic review of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was performed for randomized controlled trials (RCTs) published from January 2015 to July 2025. We included RCTs in patients with ABPA comparing oral corticosteroids (OCS) alone to OCS plus itraconazole or OCS plus a biologic agent (omalizumab, mepolizumab, benralizumab). The primary outcome was a composite therapeutic response (≥25% IgE reduction plus clinical stability). A Bayesian random-effects network meta-analysis was performed, with results presented as odds ratios (OR) and 95% credible intervals (CrI). Results: Seven RCTs enrolling 988 patients were included, forming a star-shaped evidence network anchored by a common placebo comparator. All active add-on therapies were superior to OCS alone for the primary outcome. Based on probabilistic rankings (SUCRA), OCS plus mepolizumab was most likely to be the most effective treatment (OR vs. OCS alone: 5.12; 95% CrI, 2.89-9.15; SUCRA: 94.5%), followed by OCS plus benralizumab (OR: 4.65; 95% CrI, 2.15-8.98; SUCRA: 87.2%), OCS plus omalizumab (OR: 3.88; 95% CrI, 2.10-7.15; SUCRA: 75.1%), and OCS plus itraconazole (OR: 2.54; 95% CrI, 1.55-4.17; SUCRA: 43.2%). Biologic agents demonstrated the greatest reduction in exacerbation rates. Conclusion: In patients with ABPA, combination therapy is superior to OCS monotherapy. This analysis provides compelling indirect evidence that biologic agents, particularly IL-5 inhibitors, represent the most effective therapeutic class for achieving disease control. These findings provide a strong evidence base to guide a hierarchical treatment approach and support the early integration of targeted therapies into the ABPA management algorithm

Chylous Ascites in Pediatric Lymphangiomatosis: Definitive Localization and Surgical Guidance with 99mTc-Nanocolloid SPECT/CT

Background: 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

Continuous Positive Airway Pressure (CPAP) versus Non-Invasive Ventilation (NIV) in Obesity Hypoventilation Syndrome: A Meta-Analysis

Background: Obesity hypoventilation syndrome (OHS) is a serious respiratory condition characterized by obesity, sleep-disordered breathing, and daytime hypercapnia. Both continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV) are commonly used to treat OHS, but their comparative effectiveness remains unclear. This meta-analysis aimed to compare the efficacy of CPAP versus NIV in improving gas exchange, sleep quality, and quality of life in patients with OHS. Methods: A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted from 2013 to 2024 to identify randomized controlled trials (RCTs) comparing CPAP and NIV in adults with OHS. The primary outcomes were changes in daytime arterial carbon dioxide (PaCO2) and apnea-hypopnea index (AHI). Secondary outcomes included changes in daytime arterial oxygen (PaO2), sleep efficiency, and quality of life measures. Data were pooled using a random-effects model, and the standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated. Results: Seven RCTs with a total of 584 participants were included in the meta-analysis. Compared to CPAP, NIV was associated with a significantly greater reduction in PaCO2 (SMD -0.45; 95% CI -0.88 to -0.02; p=0.04) and AHI (SMD -0.61; 95% CI -1.17 to -0.05; p=0.03). NIV also showed a trend towards greater improvement in PaO2, although this was not statistically significant (SMD 0.32; 95% CI -0.06 to 0.70; p=0.10). No significant differences were observed between CPAP and NIV in sleep efficiency or quality of life measures. Conclusion: This meta-analysis suggests that NIV is more effective than CPAP in improving gas exchange and reducing apnea-hypopnea events in patients with OHS. While both treatments appear to be well-tolerated, NIV may be the preferred initial treatment option for OHS, especially in patients with significant hypercapnia

Novel Application of a Modified Small T-Plate as an Internal Joint Stabilizer for Chronic Elbow Instability: Technique and Two-Year Results

Background: Chronic elbow instability, particularly following neglected or recurrent dislocations, presents a significant treatment challenge. Restoring stability while preserving functional motion is difficult, especially when standard internal joint stabilizers (IJS) are unavailable. We explored the use of a readily available small T-plate, modified intraoperatively, as a temporary internal hinge stabilizer. Case presentation: A 33-year-old male presented with chronic left elbow instability and functional impairment persisting for 14 years after an initial injury. Previous treatments, including traditional bone setting and K-wire fixation, had failed, resulting in recurrent dislocations. Surgical exploration revealed significant fibrosis and compromised ligamentous structures. Open reduction was performed, followed by stabilization using a modified small T-plate contoured to act as an internal hinge, maintaining the ulnohumeral joint space. The implant was removed after 4 weeks. At the 24-month follow-up, the patient exhibited excellent functional outcomes, with a stable elbow, substantial improvement in range of motion (Flexion-extension: 4.2°-129.2°; Pronation-supination: 80°), and an excellent Broberg-Morrey score, enabling pain-free daily activities. Conclusion: This case demonstrated that a modified small T-plate can serve as an effective, low-cost internal hinge joint stabilizer for managing complex chronic elbow instability, particularly in resource-limited settings. It facilitated early controlled motion, promoted stable fibrous tissue healing, and resulted in excellent long-term functional outcomes. This technique presents a viable alternative when standard IJS devices are not accessible

From Tradition to Translation: A Systematic Review on the Pharmacological Actions of Eugenol Extracted from Ocimum Plants in Oxidative Stress, Inflammation, and Diabetes Mellitus

Background: Ocimum species, commonly known as basil, have a rich history in traditional medicine for various ailments. Eugenol, a primary bioactive compound found in several Ocimum species, has garnered significant scientific attention for its potential therapeutic properties. This systematic review aimed to comprehensively evaluate the pharmacological actions of eugenol extracted from Ocimum plants in the context of oxidative stress, inflammation, and diabetes mellitus. Methods: A systematic literature search was conducted across major scientific databases for studies published between 2013 and 2024 that investigated the effects of eugenol derived from Ocimum plants on oxidative stress, inflammation, and diabetes mellitus. The search strategy included keywords such as "eugenol," "Ocimum," "antioxidant," "anti-inflammatory," and "antidiabetic." Inclusion criteria for studies involving in vitro, in vivo, and clinical studies that specifically examined the pharmacological actions of eugenol extracted from Ocimum species in the aforementioned conditions. Data on study design, intervention, outcomes, and key findings were extracted and synthesized narratively. Results: The review identified ten key studies that met the inclusion criteria. These studies collectively suggested that eugenol extracted from Ocimum plants exhibited significant antioxidant activity by scavenging free radicals and enhancing endogenous antioxidant enzymes. Furthermore, eugenol demonstrated anti-inflammatory effects by modulating pro-inflammatory cytokines and inhibiting key inflammatory pathways such as NF-κB and COX. In the context of diabetes mellitus, studies indicated that eugenol could improve glucose metabolism by enhancing insulin sensitivity, protecting pancreatic beta cells, and inhibiting carbohydrate metabolizing enzymes. Conclusion: This systematic review provided a comprehensive overview of the pharmacological actions of eugenol extracted from Ocimum plants in mitigating oxidative stress, inflammation, and diabetes mellitus. The findings from the included studies supported the traditional uses of Ocimum species and highlighted the therapeutic potential of eugenol as a natural agent in managing these conditions. Further well-designed clinical trials are warranted to validate these preclinical findings and translate them into clinical applications

Phytochemical Screening and In Vitro Antibacterial Activity of Swietenia mahagoni Leaf Extract against Streptococcus mutans: A Promising Natural Approach for Caries Prevention

Background: Dental caries, primarily caused by Streptococcus mutans, is a prevalent oral health issue. The rise of antibiotic resistance and side effects of synthetic antimicrobials have fueled the search for plant-derived alternatives. Swietenia mahagoni (mahogany) leaves, traditionally used for medicinal purposes, exhibit potential antibacterial properties. This study investigated the phytochemical composition and in vitro antibacterial activity of S. mahagoni leaf extracts against S. mutans. Methods: S. mahagoni leaves were collected, processed, and extracted using ethanol. Phytochemical screening identified alkaloids, tannins, flavonoids, and saponins. Antibacterial activity was assessed through the agar well diffusion method against S. mutans, using various extract concentrations (25%, 50%, 75%) and chlorhexidine as a positive control. Inhibition zone diameters were measured to determine antibacterial efficacy. Results: Phytochemical analysis confirmed the presence of alkaloids, tannins, flavonoids, and saponins in the S. mahagoni leaf extract. The extract demonstrated significant antibacterial activity against S. mutans at all concentrations. The highest concentration (75%) showed the largest inhibition zone (18.07 ± 0.37 mm), significantly larger than those of lower concentrations and the positive control (chlorhexidine, 13.87 ± 0.21 mm). Conclusion: S. mahagoni leaf extract exhibits substantial antibacterial activity against S. mutans, likely due to its diverse phytochemical content. These findings suggest its potential as a natural anti-caries agent. Further research is needed to explore its use in developing novel oral health products

A Diagnostic Rarity: Apocrine Hidrocystoma Presenting as a Medial Canthal Mass in Adolescence

Background: 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

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

Background: 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