Search Results (130)

The transition to a post-antibiotic era necessitates novel interventions to mitigate gastrointestinal inflammation and optimize metabolic efficiency in monogastric animals. This review evaluates the Hermetia illucens (BSF) lipid matrix as an evolutionary signal sensor rather than merely a caloric substrate. The BSF lipid fingerprint—rich in lauric acid and bioactive co-factors—exerts a synergistic “entourage effect,” which is proposed to thermodynamically disrupt pathogenic membranes and engage GPR84/PPARγ crosstalk to silence sterile inflammation. Metabolically, medium-chain fatty acids bypass the CPT-1 bottleneck, enabling rapid mitochondrial ATP rescue that supports intestinal tight junction restoration. This targeted immunomodulation is hypothesized to underpin an “immune-energy sparing” effect—redirecting bioenergetic fluxes from inflammatory antagonism toward muscle protein deposition—a phenomenon that correlates with improved feed conversion ratios in vivo. Full article

Background/Objectives: Postoperative pain remains a significant clinical challenge, often requiring multimodal strategies to mitigate opioid-related adverse events. The fixed-dose combination (FDC) of Diclofenac, a non-steroidal anti-inflammatory drug, and Orphenadrine, a muscle relaxant, targets distinct nociceptive pathways to potentially enhance analgesia and reduce opioid consumption. This systematic review aims to evaluate the analgesic efficacy and safety profile of the fixed-dose combination of Diclofenac and Orphenadrine for postoperative pain management and quantify its opioid-sparing effect compared to standard monotherapies or placebo. Methods: A systematic search of electronic databases (MEDLINE, Scopus) and clinical trial registries (including ClinicalTrials.gov and CTIS) was conducted up to 20 September 2025. Fourteen (14) randomized controlled trials (RCTs) involving 981 adult patients undergoing various surgical procedures were included. Due to high clinical and methodological heterogeneity, a Synthesis Without Meta-analysis (SWiM) approach was utilized. The certainty of evidence was assessed using the GRADE methodology. Results: The synthesis demonstrated that the FDC may improve pain relief (measured by the Visual Analog Scale and Numeric Rating Scale scores) and may reduce opioid consumption compared to active comparators and placebo. The opioid-sparing effect could be correlated with a reduced incidence of dose-dependent adverse events, particularly nausea and vomiting. However, the overall certainty of the evidence was graded as “Very Low” due to the high risk of bias and lack of transparency in the included studies. Conclusions: The FDC of Diclofenac and Orphenadrine is a rational addition to multimodal postoperative analgesic regimens, which may potentially reduce the perioperative opioid burden without compromising pain control. Nevertheless, because almost all included studies suffer from severe methodological flaws, these apparent efficacy findings must be interpreted with caution. Future high-quality, pre-registered, and low-bias randomized controlled trials are required to draw firm clinical conclusions. Full article

Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70% of newly diagnosed bladder cancer cases but exhibits significant clinical heterogeneity in treatment response and progression risk. While intravesical bacillus Calmette–GuérinCa (BCG) therapy remains the gold standard for high-risk disease, approximately 30–50% of patients experience BCG failure, creating a critical decision point between additional bladder-sparing therapy (BST) and early radical cystectomy (RC). Recent clinical data from the CISTO study suggest that, in appropriately selected patients, RC may be associated with higher 12-month recurrence-free survival while maintaining comparable cancer-specific survival and physical functioning. In this narrative review, we synthesize contemporary evidence on NMIBC genomic and transcriptomic subtypes, immune contexture, and clinicopathologic features associated with BCG response and progression risk, with emphasis on clinically oriented classification systems such as BCG Response Subtypes (BRS1–3) and UROMOL21. We highlight how tumor-intrinsic biology (e.g., EMT-associated programs), immune phenotypes (inflamed vs. immune-cold microenvironments), and genomic alterations may help refine risk stratification beyond traditional clinicopathologic models. To facilitate clinical integration, we propose a conceptual decisional framework that combines molecular subtype assignment, immune profiling, key pathologic risk factors, and patient considerations to generate probabilistic risk tiers that support selection among early RC, BST, and clinical trial strategies. Standardized multicenter cohorts and prospective evaluation are needed to validate integrated models and define their clinical utility for the precision timing of cystectomy in BCG-unresponsive NMIBC. Full article

Background and Clinical Significance: Radiation-induced lumbosacral plexopathy (RILP) is a rare but potentially debilitating complication of radiotherapy, typically affecting patients treated for pelvic malignancies. We report the first documented case of asymmetric RILP following radiotherapy for breast cancer. Case Presentation: A 64-year-old woman developed progressive left lower limb weakness, foot drop, and sensory disturbances four years after receiving locoregional radiotherapy extending to the left thoracoabdominal and lumbar areas. Electrophysiological studies revealed an asymmetric sensorimotor axonal neuropathy predominantly involving the left lower limb, without conduction block and sparing the upper limbs, whereas needle electromyography of the lower limbs showed fibrillation potentials, positive sharp waves, and fasciculations in the vastus lateralis, tibialis anterior, and medial gastrocnemius muscles on the left. Magnetic resonance imaging demonstrated edema and contrast enhancement of bilateral L2–L4 nerve roots with paraspinal muscle atrophy. Cerebrospinal fluid analysis showed albuminocytologic dissociation and elevated neurofilament levels. After exclusion of alternative diagnoses, including amyotrophic lateral sclerosis and inflammatory neuropathies, a diagnosis of radiation-induced peripheral neuropathy and RILP was made. The patient’s condition stabilized with physiotherapy and symptomatic treatment. Conclusions: This case highlights the need for heightened awareness of RILP as a late complication of breast cancer radiotherapy, underscoring the importance of accurate diagnosis to avoid misclassification and unnecessary treatments. Clinicians should carefully integrate all clinical elements—including a thorough remote medical history—since radiation-related neurological damage may manifest many years after the initial insult. Full article

Juvenile dermatomyositis (JDM) is a rare, idiopathic autoimmune disorder characterized by inflammation of both muscle and skin, with a significant contribution from the interferon (IFN) pathway in its pathogenesis. Here, we present the case of a 4-year-old boy with JDM who tested positive for Mi2-α and MDA5 antibodies and showed combined muscle and skin involvement. In view of his markedly elevated IFN signature, the Janus kinase (JAK) inhibitor baricitinib was introduced very early as a targeted steroid-sparing agent in addition to standard immunosuppressive therapy. The patient experienced marked clinical improvement, with resolution of skin lesions, normalization of MDA5 antibodies, and a pronounced reduction in the IFN signature. This case highlights the potential efficacy of JAK inhibition in managing JDM with a high IFN signature and supports a mechanism-based, interferon-targeted treatment approach, in line with emerging evidence in refractory JDM. Further studies are warranted to define the role of JAK inhibitors in the treatment of JDM. Full article

Background/Objectives: Non-muscle invasive bladder cancer (NMIBC) management is increasingly complex due to conflicting guideline-based risk classifications, ongoing Bacillus Calmette–Guérin (BCG) shortages, and emerging alternative therapies. Computational Histology Artificial Intelligence (CHAI) tests are clinically available, providing insights from tumor specimens including predicting BCG responsiveness and individualized recurrence and progression risks, which may support precision medicine. This technology features biomarkers purpose-built for clinically unmet needs and has practical advantages including a fast turnaround time and no need for consumption of tissue or other specimens. We assessed the impact of such tests on physicians’ decision-making in routine, real-world NMIBC management. Methods: Physicians at six centers ordered CHAI tests (Vesta Bladder) at their discretion during routine NMIBC care. Tumor specimens were processed by a CLIA/CAP-accredited laboratory (Valar Labs, Houston, TX, USA) where H&E-stained slides were analyzed with the CHAI assay to extract histomorphic features of the tumor and microenvironment, which were algorithmically assessed to generate biomarker test results. For each case from 24 June 2024 to 18 July 2025, ordering physicians were surveyed to assess pre- and post-test management plans and post-test result usefulness. Results: Among 105 high-grade NMIBC cases with complete survey results available, primary management changed in 67% (70/105). Changes included modality shifts (n = 7; three to radical cystectomy with high prognostic risk scores; four avoiding cystectomy with low scores) and intravesical agent change (n = 63). Surveillance was intensified in 7%, predominantly among those with ≥90th percentile risk scores. The therapeutic agent changed in 80% (40/50) of predictive biomarker-present (indicative of poor response to BCG) tumors vs. 48% (23/48) of biomarker-absent tumors. Conclusions: In two thirds of cases, CHAI biomarker results influenced clinical decision-making during routine care. BCG predictive biomarker results frequently guided intravesical agent selection. These results have implications for optimizing clinical outcomes, especially in the setting of ongoing BCG shortages. Prognostic risk stratification results guided treatment escalation vs. de-escalation, including surveillance intensification and surgical vs. bladder-sparing decisions. CHAI biomarkers are currently utilized in routine clinical care and informing precision NMIBC management. Full article

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare benign disorder characterized by submucosal cartilaginous and osseous nodules of the tracheobronchial tree, typically sparing the posterior membranous wall. Involvement of the vocal cords is exceedingly rare and may result in critical airway obstruction. The underlying genetic and molecular mechanisms of TO remain largely unexplored. Case presentation: We report a rare case of TO extending from the vocal cords to the bronchi in a 76-year-old man who initially presented with pneumonia and later developed acute respiratory failure due to severe airway narrowing, necessitating emergency tracheostomy. Bronchoscopy and computed tomography revealed diffuse calcified nodules involving the anterior and lateral airway walls, including the subglottic region. Histopathology demonstrated chronic inflammatory cell infiltration with squamous metaplasia. To explore the molecular basis of this condition, whole-genome sequencing (WGS) was performed using peripheral blood samples—the first such application in TO. WGS identified 766 germline mutations (including 27 high-impact variants) and 66 structural variations. Candidate genes were implicated in coagulation and inflammation (KNG1), arachidonic acid metabolism and extracellular matrix remodeling (PLA2G4D), ciliary dysfunction and mineralization (TMEM67), vascular calcification (CDKN2B-AS1), smooth muscle function (MYLK4), abnormal calcification (TRPV2, SPRY2, BAZ1B), fibrotic signaling (AHNAK2), and mucosal barrier integrity (MUC12/MUC19). Notably, despite systemic germline mutations, calcification was restricted to the airway. Conclusions: This case highlights that TO with vocal cord involvement can progress beyond a benign course to cause life-threatening airway obstruction. Integrating clinical, histological, and genomic findings, we propose a novel pathophysiological model in which systemic genetic susceptibility interacts with local immune cell infiltration and fibroblast-driven extracellular matrix remodeling, resulting in airway-restricted dystrophic calcification. This first genomic characterization of TO provides new insights into its pathogenesis and suggests that multi-omics approaches may enable future precision medicine strategies for this rare airway disease. Full article

Bladder cancer is the 5th most common cancer in Canada and a quarter of diagnosed patients have muscle-invasive bladder cancer (MIBC). Standard treatment options, systemic therapy and radical cystectomy (RC) are associated with high rates of adverse outcomes. Recently, trimodal treatment (TMT), a bladder preservation strategy defined as maximal transurethral resection of bladder tumor (TURBT) and chemoradiation, has been considered an alternative per guidelines for select patients who prefer bladder preservation or those with comorbidities. Nevertheless, the uptake of bladder preservation strategies in Canada remains low. We conducted a retrospective evaluation in British Columbia (BC) to assess the real-world outcomes of bladder-sparing radiotherapy. Cohort treated with combined chemoradiotherapy (concurrent and/or adjuvant, neoadjuvant chemotherapy) showed numerical improvements across all evaluated endpoints, including disease-specific survival and progression-free survival, compared with radiation therapy alone, which is generally considered an inferior strategy. However, these differences did not reach statistical significance, contrasting with the literature. Despite the limitations posed by the small sample size and the study’s retrospective design, the findings highlight the pivotal role of appropriate patient selection in achieving meaningful therapeutic outcomes. Future studies integrating biomarker-driven strategies are needed to enhance outcomes through individualized treatment selection, particularly for older patients with multiple comorbidities. Full article

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to refine diagnosis and management. We surveyed the literature from 2000 to 2025, prioritizing randomized trials, large cohorts, and translational studies that spanned classic and juvenile DM, amyopathic/hypomyopathic variants, and overlap phenotypes. Key insights include the diagnostic weight of pathognomonic cutaneous lesions with nailfold microangiopathy; the utility of myositis-specific autoantibodies for endotyping and risk (e.g., anti-TIF1-γ/anti-NXP2 and cancer, anti-MDA5 and rapidly progressive ILD); and the value of myxovirus-resistance protein A (MxA) immunohistochemistry and muscle MRI patterning (including distinctions from immune-mediated necrotizing myopathy) when enzymes are normal, or biopsies are treatment-modified. Management is anchored in early steroid-sparing immunosuppression tailored to phenotype, with evidence for IVIG in active DM and growing support for JAK inhibition, particularly in interferon-high or anti-MDA5 ILD, alongside selective use of calcineurin inhibitors and rituximab, with plasma exchange considered for refractory, rapidly progressive ILD. We highlight risk-stratified malignancy screening (IMACS 2023) and complications, including calcinosis, lipodystrophy, and chronic cutaneous damage. Skin-led recognition coupled with antibody-guided, phenotype-directed therapy and interdisciplinary care offers a pragmatic precision framework to improve outcomes and reduce long-term disability. Full article

Despite the advent and growth of endoscopic and nephron-sparing management approaches, the mainstay treatment for upper tract urothelial carcinoma (UTUC) in 2025 remains radical nephroureterectomy (RNU). Classic teaching, largely derived from the benefit seen in the muscle-invasive bladder cancer (MIBC) population, supports the inclusion of retroperitoneal lymph node dissection (LND), particularly for high-risk and high-grade disease. However, no level 1 evidence exists supporting the inclusion of an LND at the time of extirpative surgery for UTUC. Moreover, studies attempting to map lymph node dissection relative to primary UTUC tumor location are plagued by limitations. Herein, we summarize and review available data regarding proposed LND templates for the management of UTUC. Full article

Background: Bladder cancer is the ninth most prevalent cancer globally. Most cases are urothelial carcinoma, classified as non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC); approximately 70% are diagnosed as NMIBC. Current standard of care for high-risk NMIBC includes transurethral tumour resection, followed by intravesical therapy with Bacillus Calmette-Guérin (BCG). However, significant unmet needs persist due to disease recurrence, BCG unresponsiveness, or progression to MIBC. Radical cystectomy is recommended after BCG unresponsiveness but may not be viable due to its invasiveness and morbidity. The paucity of treatment options for BCG-unresponsive NMIBC has driven research into alternatives such as gene therapy. The bladder’s anatomy allows direct vector–tumour contact, while urine and tissue samples allow for easy monitoring of therapeutic effects. Methods: This narrative review integrates findings from recent clinical and preclinical studies identified through comprehensive searches of peer-reviewed literature to provide an overview of the current landscape of gene therapy for BCG-unresponsive NMIBC. Results: Nadofaragene firadenovec, a recombinant adenovirus delivering interferon alpha-2b (IFNα2b), is the first FDA-approved gene therapy for BCG-unresponsive NMIBC with carcinoma in situ (CIS). A phase III nadofaragene firadenovec study (NCT02773849) demonstrated a 53% complete response (CR) rate at 3 months; and 43% of patients with CIS had bladder preservation at 60 months. Cretostimogene grenadenorepvec (CG0070), an oncolytic vector, demonstrated a 47% 6-month CR rate in a phase II study (NCT02365818). Detalimogene voraplasmid (EG-70), a nonviral gene therapy, demonstrated a 47% 6-month CR in a phase I/II study (NCT04752722). Future advances are likely to focus on patient selection, novel vectors, and combination strategies to improve treatment outcomes. Conclusions: Gene therapy represents a significant addition to the bladder cancer treatment landscape by offering bladder-sparing alternatives where conventional therapies are limited. Full article

Bladder cancer (BC), particularly its muscle-invasive subtype (MIBC), remains a clinical challenge due to high recurrence and limited therapeutic options. Emerging evidence suggests that probiotics may offer selective anticancer effects while preserving healthy tissue. In this study, we evaluated the antitumor potential of OxxySlab, a multistrain probiotic formulation, in two BC cell lines (T24 and 5637) and a non-tumorigenic urothelial cell line (SV-HUC1). OxxySlab lysate dose-dependently inhibited BC cell proliferation, clonogenicity, and migration, while sparing normal cells. Mechanistically, the treatment suppressed epithelial–mesenchymal transition (EMT), induced senescence, and disrupted redox homeostasis in malignant cells. These effects were associated with the induction of oxidative stress and impaired antioxidant defenses. Co-treatment with vitamin C attenuated ROS accumulation and senescence, implicating oxidative stress as a key mediator. Notably, SV-HUC1 cells retained viability and phenotype, confirming the formulation’s selectivity. Overall, these findings support OxxySlab as a promising adjunctive strategy in BC therapy, capable of reducing tumor aggressiveness through redox-mediated senescence and EMT inhibition without harming normal urothelial cells. Full article

Long-term spaceflight induces multisystem stress, including cardiovascular deconditioning, skeletal muscle atrophy, immune suppression, and neuro-ocular syndromes. Current countermeasures reduce symptoms but cannot replicate the synergistic resilience needed for extended missions or critical illness. Hibernating animals, specifically brown bears (Ursus arctos), survive prolonged immobility, starvation, and bradycardia without resultant pathology. This review incorporates adaptations observed in bears and certain torpid species, including reversible insulin resistance, suppression of muscle atrophy genes MuRF1 and Atrogin-1, and maintenance of the heart despite seasonal production decline. The thirteen-lined ground squirrels (Ictidomys tridecemlineatus) maintain retinal structure and synaptic stability throughout torpor, avoiding neuro-ocular complications despite prolonged inactivity. Mechanisms span from RBM3-dependent synaptic maintenance, titin isoform remodeling under the control of RBM20, mTOR and FOXO pathway regulation, remodeled hydrogen sulfide metabolism, and microbiome-mediated nitrogen salvage. These adaptations are different from human adaptation to microgravity and disuse and offer translational candidates for synthetic torpor, probiotic engineering, neuroprotection, and protein-sparing therapy. Hibernators are not passive stress subjects; they perform coordinated anticipatory responses in multiple organs. Comparing these systems in large and small hibernators, we aim to uncover a biologically realistic path to human resilience. These findings guide a shift from reactive, pharmacological measures for preserving human health during space flight, intensive care, and extreme environments towards proactive, biologically initiated measures. Full article

Background: Breast-conserving surgery (BCS) combined with radiotherapy achieves oncologic outcomes comparable to mastectomy while preserving breast integrity. However, resections of more than 20% of breast volume or those in challenging quadrants may compromise cosmetic results. Level II oncoplastic techniques using volume replacement flaps aim to address this. The lateral intercostal artery perforator (LICAP) flap is a reliable, muscle-sparing option for lateral and central–lateral breast defects. This study reports our initial experience with LICAP in Level II oncoplastic breast reconstruction. Methods: A retrospective review was conducted of women undergoing BCS with LICAP reconstruction between March 2024 and March 2025. The primary outcome was flap-related complications within 90 days. Secondary outcomes included operative time, hospital stay, donor-site morbidity, and six-month aesthetic results using the Harvard scale and BREAST-Q^® module. Results: Nine women underwent LICAP reconstruction. All tumours were ≤pT2 with negative margins. Mean operative time was 128 min, and the median hospital stay was 2 days. One minor flap-related complication (seroma, 11%) occurred, which was managed conservatively without re-operation or delay in adjuvant therapy. At six months, all patients achieved good or excellent Harvard scores. The mean BREAST-Q^® satisfaction score was 79 ± 12. Conclusions: LICAP reconstruction is safe, efficient, and provides reliable early aesthetic and patient-reported outcomes. Its low complication rate, high satisfaction, and minimal morbidity support its broader adoption, while larger prospective studies are needed to assess long-term results and refine indications. These findings also underline the role of LICAP reconstruction as part of a personalized surgical strategy, where the choice of technique is tailored to individual anatomy and expectations. Full article

Background/Objectives: Patients with pancreatic neuroendocrine tumors (PanNETs) often have a good prognosis with long overall survival. We evaluated quality of life (QoL) after surgery for PanNETs, using the new EORTC-specific questionnaires. Methods: PanNET patients operated on in our unit (1990–2023) received three EORTC questionnaires (QLQ-C30 and the new P.NET15 and P.NET19). We evaluated the following: (1) QLQ-C30 outcomes; (2) mixed domains from QLQ-C30, P.NET15, and P.NET19; and (3) domains from P.NET19 and P.NET15 only. Functional and symptom scales were investigated in relationship with clinical variables. Gamma regression and multivariable analyses were performed with R software. Results: The 100 patients enrolled (median time 133 months after surgery) showed a good QoL (median 83.3/100). Old age was related to worse QoL and physical functioning (p = 0.007 and p < 0.001, respectively). Diabetes negatively influenced QoL (p < 0.001), physical functioning (p = 0.005), and fatigue (p = 0.03). Patients undergoing parenchyma-sparing surgery showed less fatigue (p = 0.046), while non-insulinoma PanNET diagnosis was related to worse QoL (p = 0.039). Multiple comorbidities were negatively associated with physical functioning (p = 0.010), fatigue (p = 0.001), and pain (p = 0.021). According to the new questionnaires, the most affected outcome was muscle energy, depending on age (p = 0.042), diabetes (p = 0.014), type of surgery (p = 0.018), and non-insulinoma diagnosis (p = 0.007). Conclusions: A good QoL evaluated with EORTC questionnaires is reported in PanNET patients after surgery. Elderly and diabetic patients who underwent standard resection for gastrinoma/non-functioning PanNETs showed worse QoL outcomes. Full article