Medicine and Pharmacology

Abstract: An increasing number of older adults are undergoing major surgery. Frailty, multimorbidity and sarcopenia, over and above chronological age, are major determinants of postoperative complications, loss of independence and mortality. Comprehensive geriatric assessment (CGA) and multimodal prehabilitation can mitigate this risk, but hospital-based pathways are constrained by workforce, transport and geography, and these barriers often exclude the frailest patients. This narrative review examines how digital technologies can support preoperative assessment, optimisation, and prehabilitation in older surgical patients. We outline the biological rationale for repeated, dynamic assessment of resilience; review electronic frailty indices, digital CGA, remote functional testing and wearable-derived measures; and appraise remotely delivered exercise, nutritional, psychological, cognitive and medical optimisation. Digital tools appear feasible and can stratify risk in older adults; however, there is not yet evidence that they improve clinical outcomes on their own, and the largest trial of home-based prehabilitation in frail older adults found no benefit, with low adherence. We describe two real-world models from the UK: a remotely delivered multidisciplinary service at University College London Hospitals (UCLH) and PreActiv, a rule-based, individualised digital platform. In 274 patients treated at UCLH, sit-to-stand performance and health-related quality of life improved after prehabilitation and remained above baseline after surgery. Finally, we discuss sensor validity, digital inclusion, governance, health economics and the potential role of artificial intelligence.

Abstract: Background/Objectives: Dental injury is an uncommon complication of tracheal intubation. We examined its association with video laryngoscopy (VL) versus direct laryngoscopy (DL). Methods: Published aggregate dental-injury counts from a Cochrane review were compared across Macintosh-style, hyperangulated, and channeled VL categories. Two-sided Fisher exact tests, unadjusted odds ratios (ORs), relative risk (RR), and log-Wald 95% confidence intervals (CIs) were calculated. Aggregation did not retain trial-level stratification. Results: Dental injury occurred in 5/4,233 VL cases (0.118%) and 15/3,936 DL cases (0.381%). The aggregate OR was 0.309 (95% CI 0.112–0.851; p = 0.023), and the RR was 0.310 (95% CI 0.113–0.852). The absolute difference was 0.263 percentage points, or 2.6 fewer observed injuries per 1,000 intubations with VL. No individual VL category differed significantly from DL (p ≥ 0.091). Conclusions: VL was associated with fewer observed dental injuries in this descriptive aggregate comparison. Rare events, possible shared controls, loss of trial-level stratification, and clinical heterogeneity limit interpretation. The findings are hypothesis-generating and do not establish causation or superiority of a particular device design.

Abstract: Background/Objectives: Computed tomography-based sarcopenia is a marker of reduced physiological reserve, but evidence regarding organ-specific postoperative risk, particularly cardiac complications, remains limited in older patients undergoing lobectomy for non-small cell lung cancer (NSCLC). We evaluated postoperative outcomes and correlates of sarcopenia in this population. Methods: This single-center retrospective study included 147 patients aged ≥60 years undergoing lobectomy for primary NSCLC. Sarcopenia was defined from T12 skeletal muscle index using sex-specific cutoffs. The primary outcome was one-year all-cause mortality; secondary outcomes included postoperative complications. Results: Sarcopenia was present in 81 patients (55.1%). One-year mortality (12.3% vs. 10.6%; p = 0.743) and major postoperative complications did not differ by sarcopenia status. Cardiac complications were more frequent with sarcopenia (33.3% vs. 18.2%; p = 0.038; crude OR, 2.25; 95% CI, 1.03–4.90), although the association was attenuated after multivariable adjustment (adjusted OR, 2.05; 95% CI, 0.90–4.68; p = 0.087). Diabetes mellitus and larger tumor size were associated with higher odds of sarcopenia, whereas higher forced expiratory volume in one second (FEV1; % predicted) was associated with lower odds. Conclusions: Sarcopenia was common and identified a distinct preoperative phenotype. Its association with postoperative cardiac complications warrants further investigation; no association with one-year mortality was observed.

Abstract: Background and Objectives: Apnea test criteria differ between countries and have changed within them. The 2010 American Academy of Neurology guideline accepted a PaCO₂ ≥60 mmHg or a rise of ≥20 mmHg above baseline; the 2023 AAN/AAP/CNS/SCCM consensus guideline requires both together with an arterial pH <7.30; and the Turkish national standard, restated in December 2025, requires both carbon dioxide conditions but no pH target. We examined how the same real-world apnea tests are classified under these three criteria, and what accounts for any disagreement between them. Materials and Methods: All three criteria were applied to every apnea test performed during brain death determination in a tertiary intensive care service between 2019 and 2026 (n = 331). The primary endpoint was the 2023 consensus criterion. Determinants were modelled with Firth penalised logistic regression, with the Turkish criterion as a negative control. Results: 237 adults were evaluable under all three criteria. The proportion of tests meeting the criterion fell from 98.3% (AAN 2010) to 87.8% (Türkiye 2025) to 78.1% (2023 consensus); no test gained positivity at any step, and 48/237 (20.3%) were positive under at least one criterion but not all three. All 23 tests that met the Turkish criterion but failed the 2023 criterion had begun with a pre-test pH above 7.45. Among the 118 tests begun within the pH window that guidelines require, the two criteria were met by the same patients (106/118 (89.8) each). Pre-test bicarbonate was associated with meeting the 2023 criterion (OR 0.84 per mmol/L, 95% CI 0.78–0.92) but not with the Turkish criterion (OR 1.09, 95% CI 0.98–1.20). Conclusions: In this cohort, disagreement between contemporary apnea test criteria was determined mainly by whether the pre-test acid–base requirement had been met, rather than by the criteria themselves.

Abstract: Background: Robot-assisted thoracic surgery (RATS) for mediastinal tumors is a minimally invasive approach that offers three-dimensional magnified visualization, tremor filtration, and articulated instruments. Although it is expected to reduce postoperative pain compared with open surgery, pain may still arise from intercostal ports, subxiphoid incisions and chest tubes. Therefore, a consistent multimodal analgesic strategy is needed from the intraoperative to the postoperative period, tailored to the surgical approach and port placement. Objective: This review aims to characterize the mechanisms underlying postoperative pain after RATS for mediastinal tumors and to examine the current evidence and clinical indications for systemic analgesics and regional analgesic techniques, including thoracic epidural analgesia (TEA), peripheral nerve blocks, and local wound infiltration. Conclusions: Routine use of TEA may not be necessary for all patients undergoing RATS for medi-astinal tumors. In most cases, a multimodal analgesic regimen based on acetaminophen, nonsteroidal anti-inflammatory drugs, or cyclooxygenase-2 selective inhibitors, supplemented with a single-shot regional block or local wound infiltration according to the surgical approach and port placement, appears reasonable. However, individualized analgesic strategies incorporating continuous regional analgesia should be considered in patients undergoing extensive thymectomy, those requiring ports across multiple intercostal spaces, those at risk of conversion to open surgery, and those with severe preoperative pain or an increased risk of chronic postoperative pain.

Abstract: Background: First-pass failure during ultrasound-guided internal jugular vein (IJV) catheterisation is common in critically ill adults and is associated with mechanical complications, yet no model has been developed to estimate its probability before the procedure. We therefore set out to develop and internally validate a preliminary prediction model, ROTATE-ICU. Methods: We conducted a prospective, single-centre, observational cohort study and included 120 of 156 assessed procedures, taking one episode per patient. The pre-specified model combined IJV anterior–posterior diameter, the position of the vein relative to the common carotid artery, and operator experience. The model was fitted with first-pass failure as the outcome and internally validated by bootstrap optimism correction with 1000 replications. Results: First-pass failure occurred in 46 of 120 procedures (38.3%). The odds of failure fell with each millimeter of anterior–posterior diameter (adjusted OR 0.83, 95% CI 0.72–0.95) and with each category of operator experience (adjusted OR 0.29, 95% CI 0.14–0.59), whereas the positional category showed no independent association. The optimism-corrected C-statistic was 0.743, with a calibration slope of 0.914 (95% CI 0.572–1.451) and a Brier score of 0.188. Conclusions: The ROTATE-ICU model estimates the probability of first-pass failure from three variables available at the bedside, of which vein diameter and operator experience carried most of the predictive weight. Because operator experience is itself one of the inputs, the model describes the risk of a given procedure performed by a given operator rather than a fixed property of the patient. The shrinkage-adjusted model and an open-access calculator are available; this is a preliminary model and external validation is now needed.

Abstract: Airways’ patency and protection, and the feasibility of ventilation, are necessary pre-requisites to have for oxygenation during the induction of a general anesthesia or before intubation in other contexts. The text presents a bulleted and holistic approach to the interwoven dynamics of the two fundamental variables for a safe airway management i.e. oxygenation and ventilation, which is intuitive, easy to grasp and rapid to apply on the scene. The ‘cannot ventilate, cannot intubate’ (CVCI) situation is analysed in its crucial variables and patterns. The concept of anticipated and unanticipated difficult airway is an useful theoretical leverage for the right mind gear. The recently emphasized term of ‘physiologically difficult airway’ is instead a misnomer as it rather refers to special patients at risk of desaturation, hypotension or cardiac arrest on preoxygenation and induction. Emphasis is in an approach on the airways, which is independent on the specialistic background. Control of the airways outdoors follows the same patterns of approach and decision making of indoors, but in difficult or unfriendly contexts.

Abstract: Background/Objectives: Fibromyalgia is a chronic, symptom-defined condition whose recognition and management depend on sustained access to care. Recorded utilization during crises may therefore reflect disrupted access, diagnostic recognition, and longitudinal engagement rather than disease burden. Since 2019, Lebanon has experienced overlapping financial deterioration, the COVID-19 pandemic, the Beirut port explosion, and armed conflict. We characterized recorded fibromyalgia utilization and continuity across these six years. Methods: This retrospective cohort study analyzed all outpatient encounters with fibromyalgia as the primary diagnosis in electronic health records of the American University of Beirut Medical Center, January 2019–December 2024. Monthly encounter volume was the primary utilization outcome. Recorded continuity was evaluated as time from each patient’s index encounter to a subsequent fibromyalgia-coded encounter, with 180-day return as the principal measure. Results: We identified 4,969 encounters from 3,237 patients (87.5% female; mean age, 46.7 years). Monthly encounter volume fell around the 2019 financial and banking disruption and remained below the preceding nine-month level (84.3 vs. 66.8 encounters/month; rate ratio, 0.76; 95% CI, 0.61–0.94), with a further exploratory reduction in mid-2024. The 180-day probability of a subsequent encounter declined from 22.8% in the 2019 cohort to 15.6% in 2024 (hazard ratio, 0.59; 95% CI, 0.45–0.76); lower return rates emerged from the 2022 cohort onward. Conclusions: Recorded fibromyalgia utilization and longitudinal engagement changed at different times during Lebanon’s compounding crises. These findings describe recorded care, not disease occurrence: recovering patient numbers may coexist with persistently impaired longitudinal engagement, so aggregate utilization alone incompletely measures recovery for continuity-dependent chronic conditions.

Abstract: Classical Chinese Medicine conceptualizes the human organism as a dynamic system of relationships in which structure, function, environment, and transformation are inseparable. Although derived from a fundamentally different epistemological framework, contemporary systems biology increasingly describes health and disease through interacting networks involving the nervous system, extracellular matrix and connective tissues, immune and endocrine signaling, metabolism, and the gut microbiome. This conceptual convergence provides an opportunity for dialogue, but not for direct equivalence between traditional constructs and modern biological structures. Acupuncture offers a particularly relevant model through which to examine this interface. Experimental studies have demonstrated that needle insertion and manipulation can generate measurable biomechanical effects within connective tissue, including tissue winding, fibroblast cytoskeletal remodeling, and mechanotransduction. Acupuncture and electroacupuncture can also activate somatosensory pathways and, under defined experimental conditions, engage somato-autonomic reflexes and central neural networks. Evidence for acupuncture-related neuroplasticity has been reported predominantly in preclinical studies and neuroimaging investigations, although its causal relationship with clinical outcomes remains incompletely established. The microbiota–gut–brain axis provides an additional level of biological integration through neural, immune, endocrine, metabolic, and barrier-mediated signaling. Emerging evidence suggests that acupuncture may modify gut microbial composition and microbiota-associated pathways in selected experimental and clinical contexts. However, this literature remains dominated by preclinical studies, substantial methodological heterogeneity, and associative rather than mediation-based evidence. This Perspective therefore proposes a multilayered framework in which connective-tissue mechanotransduction, somatosensory signaling, autonomic regulation, neuroplasticity, immune-metabolic pathways, and the microbiome are considered potentially interacting dimensions of the biological response to acupuncture. Importantly, these mechanisms should not be regarded as anatomical demonstrations of Qi, meridians, or other constructs of Classical Chinese Medicine. Scientific progress is more likely to emerge from rigorous comparison between distinct explanatory systems than from attempts to reduce one to the terminology of the other.

Abstract: Background: Fibromyalgia (FM) is a chronic nociplastic pain condition characterized by widespread pain and non-nociceptive symptoms. The reserpine-induced model is widely used to investigate FM-like phenotypes in rodents, but methodological heterogeneity may affect phenotype expression and reproducibility. Objective: This scoping review intended to identify published research that involved behavioral and neurobiological outcomes of reserpine-induced FM-like conditions and identify factors underlying phenotypic varia-bility. Design: Four databases (PubMed, Embase, Web of Science, and Scopus) were as-sessed. The search strategy was not restricted by publication date. Eligible studies were experimental studies in rats or mice using reserpine-based protocols and reporting affec-tive, cognitive, or neurobiological outcomes. Study selection and data extraction were in-dependently performed by two reviewers, and methodological quality was assessed using SYRCLE. Results: This review shows that a study heterogeneity is further increased by species, strain, sex, reserpine dose and administration regimen, vehicle composition, out-come assessment timing, and experimental settings. Thus, these aspects should be ad-dressed while interpreting and comparing test data. In rodent research, the most consist-ently observed characteristic is the emergence of long-term mechanical and deep-tissue hypersensitivity, accompanied by converging alterations in monoaminergic modulation, neuroimmune and inflammatory signaling, spinal and supraspinal excitability, and pe-ripheral metabolic and oxidative functions. This alignment of behavioral, neurochemical, electrophysiological, histological, and peripheral results offers biological validity to the paradigm, expanding outside simply inducing nociceptive hypersensitivity. Conclusions: Using reserpine to evaluate fibromyalgia-associated pain biology is useful and mechanis-tically relevant. Behavioral, neurochemical, electrophysiological, histological, and periph-eral data support the paradigm beyond nociceptive hypersensitivity.

Abstract: Abstract Background/Objectives Severe traumatic injuries of the upper extremity present a major therapeutic challenge because of extensive tissue damage, severe pain, loss of function, and substantial psychosocial consequences. Continuous multidisciplinary re-habilitation that adapts to the patient's evolving clinical condition may optimize functional outcomes across the entire continuum of care. Methods A 42-year-old man with no prior comorbidities sustained a severe work-related traumatic injury to his left hand. Despite reconstructive surgery and prolonged multidisciplinary treatment, he developed CRPS with persistent neuropathic pain, progressive functional deterioration, and psychological distress. Fourteen months after injury, the affected limb became completely nonfunctional, and elective transradial amputation was recommended after multidisciplinary evaluation. Results Rehabilitation was delivered as a continuous, phase-adapted multidisciplinary program. Before amputation, treatment focused on pain control, reduction of edema and inflam-mation, preservation of joint mobility and muscle function, and management of CRPS using multimodal physical therapy combined with pharmacological treatment and psychological support. As amputation became inevitable, rehabilitation goals shifted toward pre-amputation preparation, promotion of adaptive neuroplasticity, and preven-tion of phantom limb pain. After transradial amputation, pain intensity markedly decreased, functional adaptation improved, and the patient successfully completed prosthetic rehabilitation. Conclusions This case highlights the importance of a continuous, individualized multidisciplinary rehabilitation strategy extending from limb salvage through post-amputation recovery. Integrating multimodal physical therapy, neuroplasticity based interventions, psycho-logical support, and prosthetic rehabilitation may improve pain control, facilitate func-tional recovery, and enhance long-term adaptation after severe traumatic upper extremity injury.

Abstract: Background/Objectives: Bladder cancer is a disease of the elderly population, who often undergo transurethral bladder tumor resections (TURBT). Data on whether cognitive decline occurs after TURBT are limited. This study examined changes in cognitive status after TURBT, as measured by the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), and whether these changes were associated with frailty status, handgrip strength (HGS), and biomarkers. Methods: Biomarkers IL-4, IL-6, S100b, and NSE were measured preoperatively, at 2 hours, and at 24 hours after TURBT. MoCA, MMSE, and HGS were assessed preoperatively and at 24 and 48 hours postoperatively in 60 patients (51 male, 9 female; median age 70 (50-80 years); trial registration number: NCT07165236. Results: Both MMSE and MoCA declined significantly from preoperative 26 (26-27) to 24 (23-25) and 22 (21-23) at 24 and 48 h postoperatively (P<0.001). HGS decreased from 31.8 (27.2 – 32.9) to 27.2 (20.4 – 24.4) and 22.7 (20.4 – 24.4) kilograms at 24 and 48 h postoperatively (P<0.001). The biomarker change was statistically significant, but only IL-6 showed an association with MoCA 24 h after surgery (ρ=-0.419, P<0.001). Clinical frailty at admission showed the strongest correlation with MoCA (ρ=0.495, P<0.001) and MMSE (ρ=-0.520, P<0.001). Conclusion: Early cognitive decline occurs after TURBT in elderly patients with bladder cancer. Clinical frailty is the strongest predictor of postoperative cognitive impairment, while biomarker alterations provide limited prognostic information. Routine preoperative frailty assessment may improve risk stratification and perioperative care.

Abstract: Introduction: Large language models (LLMs) have demonstrated substantial performance on medical licensing and board examinations, but their application to anesthesiology remains less well studied. Prior evaluations have not compared current-generation models from different developers or assessed performance on figure-dependent questions that earlier models lacked the capability to interpret. This study evaluates the performance of two current-generation LLMs on a comprehensive anesthesiology in-training examination (ITE) review question bank, including figure-dependent items. Methods: A total of 1,001 single-best-answer questions from an anesthesiology ITE review text, spanning 11 content chapters, were administered to Claude Opus 5 and GPT-5.6. No questions were excluded. Each item was presented once in a fresh, stateless context with no tool access, retrieval, answer key, or explanation provided in the prompt. Performance was analyzed by question format, and all 27 figure-dependent items were administered with their published figures supplied. Accuracy between models was compared using McNemar’s test. Results: Claude Opus 5 answered 947/1,001 items correctly (94.6%; 95% CI, 93.0–95.8), and GPT-5.6 answered 946/1,001 correctly (94.5%; 95% CI, 92.9–95.8); the difference was not significant (McNemar p = 1.00). Accuracy was similar across most question formats. On standard questions, accuracy was 94.3% and 94.6% for Claude Opus 5 and GPT-5.6, respectively; on the 18 figure-based questions with figures supplied, accuracy was 94.4% and 83.3%, respectively; and both models achieved 100% accuracy on image-option items. Withholding figures from the same 18 figure-based questions reduced pooled accuracy from 88.9% to 52.8% (exact McNemar p = 0.03 and p = 0.04 for Claude Opus 5 and GPT-5.6, respectively). The models agreed on 957/1,001 items (95.6%). Of the 33 items both models answered incorrectly, they selected the same incorrect option on 32 (97%). Discussion: Current-generation LLMs achieved approximately 95% accuracy, substantially improving on our prior results with earlier-generation models and placing both models within the highest band of the ITE normative framework, corresponding approximately to the 99th percentile across training levels. By comparison, our prior work with previous models placed ChatGPT-3.5 at the 52nd, 3rd, and 1st percentiles and ChatGPT-4.0 at the 99th, 95th, and 84th percentiles across increasing levels of training. Multimodal capability now permits successful interpretation of many figure-dependent questions, although performance declines markedly when required visual information is unavailable, and highly concordant errors remain. These findings support an increasingly promising role for LLMs as accessible, on-demand educational adjuncts for anesthesiology trainees, provided complete source material is supplied and outputs are critically reviewed.

Abstract: Postoperative pain remains a common and clinically important problem, with inadequate control contributing to delayed recovery, prolonged opioid exposure, and risk of chronic postsurgical pain. Machine learning has been suggested as a strategy to improve postoperative pain management by predicting pain trajectories, estimating opioid requirements, identifying patients at risk for poor outcomes and improving the clinical management. This critical review examines current applications of machine learning in postoperative pain, including preoperative risk stratification, intraoperative and postoperative prediction, objective assessment, wearable monitoring, discharge opioid prescribing, and use in specialized populations.We found that although many models demonstrate moderate to strong predictive performance, their clinical utility remains uncertain. Most studies are retrospective, single-center, or procedure-specific, with limited external validation and heterogeneous outcome definitions. While many models incorporate postoperative variables, this influences the stage of care at which they can be applied, making them more useful for guiding postoperative management than for informing preoperative or intraoperative interventions. As a result, future work should move beyond prediction accuracy toward prospective validation, actionable hypothesis driven multi-modal models, and large-scale trials that determine whether machine learning–guided care improves pain control while reducing unnecessary opioid exposure.

Abstract: High-flow nasal cannula (HFNC) oxygen therapy is widely used in emergency, inten-sive care, perioperative, and procedural settings, but it is often conceptually assimilated to non-invasive positive pressure ventilation (NIPPV). This interpretation is physio-logically misleading. HFNC is an open high-flow oxygen system whose main effects derive from dead-space washout, improved stability of inspired oxygen fraction (FiO₂), heated humidification, patient comfort, and only modest flow-dependent positive airway pressure. Its open interface also facilitates eating, drinking, speaking, and se-cretion clearance. Clinical evidence supports HFNC mainly in selected patients with acute hypoxemic respiratory failure, where it may reduce intubation compared with conventional oxygen therapy. However, evidence is more heterogeneous in hypercap-nic respiratory failure, cardiogenic pulmonary edema, immunocompromised patients, obesity, and settings requiring substantial pressure support or ventilatory unloading. NIPPV or continuous positive airway pressure remain preferable when controlled positive pressure, alveolar recruitment, or ventilatory assistance are central to treat-ment. HFNC should therefore be regarded as optimized high-flow oxygen therapy rather than as “non-invasive ventilation through nasal prongs.” Recognizing this dis-tinction may improve patient selection, guide escalation, and avoid overinterpretation of its clinical effects.

Abstract: Background: Off-pump coronary artery bypass grafting (OPCAB) avoids cardiopulmonary bypass (CPB) and may reduce selected perioperative complications, but its technical and hemodynamic demands remain important limitations. Methods: We narratively reviewed literature indexed in PubMed/MEDLINE and Scopus, supplemented by Google Scholar and reference-list screening, covering January 2000 to September 2025. Priority was given to systematic reviews, meta-analyses, randomized trials, prospective studies, guidelines, and relevant landmark reports. Results: OPCAB may be particularly useful in selected patients at increased risk from CPB or aortic manipulation. Cardiac displacement and coronary stabilization can cause rapid changes in preload, ventricular function, myocardial perfusion, and cardiac output, making invasive monitoring, transesophageal echocardiography, and coordinated hemodynamic management central to anesthetic care. Current evidence does not establish superiority of volatile anesthesia or total intravenous anesthesia. Comparative studies suggest potential reductions in perioperative stroke, transfusion, renal complications, and hospital stay, but concerns remain regarding completeness of revascularization, graft durability, repeat revascularization, and long-term survival. Conclusions: OPCAB should be considered an individualized strategy rather than a universal alternative to on-pump CABG. Optimal outcomes depend on patient selection, surgical expertise, vigilant monitoring, and timely correction of hemodynamic compromise.

Abstract: Transcatheter tricuspid valve-in-valve replacement offers an alternative to high-risk redo surgery for failed tricuspid bioprostheses. We report a 36-year-old woman with severe right-heart failure, hepatic dysfunction, thrombocytopenia, and a mechanical mitral prosthesis after a previously abandoned transcatheter attempt. Redo implantation was performed under dexmedetomidine-ketamine sedation with spontaneous ventilation and a femoral nerve block. Transoesophageal echocardiography was avoided because of bleeding risk. Fluoroscopy and transthoracic echocardiography provided procedural guidance. Valve deployment was successful, the transvalvular gradient decreased and she was discharged on postoperative day 3, highlighting individualized management of competing haemorrhagic and thrombotic risks.

Abstract: Body Protection Compound-157 (BPC-157) is an unapproved synthetic peptide marketed directly to consumers despite limited human evidence on benefits and risks. We characterized the use of BPC-157 and patient-reported outcomes from 2020 through 2026 using Large Language Model (LLM) curation of de-identified clinical notes from a U.S. federated network with physician validation of each LLM-curation exercise. Of 1,536 patients with a note mentioning BPC-157, 1,039 (67.6%) had documented use, and quarterly newly confirmed users increased 33-fold between 2020 and 2026. Among 972 BPC-157 users with recorded race, 95.9% were White, compared with 78% of the background care population, representing a 1.23-fold enrichment (chi-square test across racial categories, P < 0.001). Among patients with newly documented BPC-157 use, the male proportion increased from 57% in 2020 to 70% in 2026 (Cochran–Armitage trend test across years, P < 0.001), while mean age decreased from 55 years in 2020 to 49 years in 2026. Among 205 patients with a documented consumer source (19.7% of confirmed users), BPC-157 was most commonly obtained from compounding pharmacies (36%) or gray-market peptide vendors (35%). Other therapeutic agents were co-used with BPC-157 by 525 of 1,039 users (50.5%), most commonly testosterone (17.0%), NSAIDs (14.7%), TB-500 (12.9%), and corticosteroids (11.7%), while physical therapy (15.3%), surgery (12.6%), exercise counseling (8.3%), and diet counseling (6.3%) were the documented non-drug co-interventions. Physician-adjudicated extraction accuracy was 96.0% for BPC-157 co-therapies and 74.4% for non-drug interventions, which were treated as exploratory. Reasons for use were documented for 644 patients and included pain (33% of all 1,039 users), gastrointestinal conditions including reflux, inflammatory bowel disease or gastritis (14%), prior injury (11%), and post-surgical healing (10%), physician adjudicated LLM accuracy of 83.9%. Among 80 users with ascertainable start timing, BPC-157 use preceded first clinician documentation by a mean of 60 days. Reported use averaged 2.2 months among 130 patients (12.5%) with an explicitly documented BPC-157 use duration, with 96.7% extraction accuracy. The specialties most often first documenting use were family medicine, internal medicine, gastroenterology, and orthopaedic surgery. Symptomatic improvement of pain, wound or tissue healing and functional return was documented in 79% of 354 BPC-157 users with a directional response, and symptomatic worsening in 5% of the users (LLM-extraction accuracy 78.4%). Response direction was unavailable for 685 of 1,039 users (65.9%). These reports cannot establish efficacy or distinguish BPC-157 effects from peptide stacking, other co-treatments, non-drug interventions, placebo effects or selection, reporting and confirmation biases. LLM-curated adverse events during BPC-157 use were infrequently noted and likely subject to under-reporting, with documented evidence of neuropsychiatric (1.4%), injection-site hypersensitivity (1.4%), and gastrointestinal (1.3%) events, with physician-adjudicated accuracy of 93.9% for drug-attributed adverse-events. With BPC-157 use rising rapidly despite minimal prospective studies and limited evidence-backed consumer awareness of its risk–benefit profile, this study highlights the need for facilitating structured EHR capture of broader gray-market peptide use and a continuous assessment of guidelines to better support healthcare practitioners.

Abstract: Background/Objectives: Because affect is challenging to quantify in fibrom-yalgia, previous network analyses have primarily relied on symptom-severity measures, whereas emotion regulation and affective hypersensitivity have rarely been included. We examined where emotional allodynia, the tendency to respond with disproportion-ate distress to neutral or low-intensity interpersonal cues, sits in this network. Methods: Cross-sectional analysis of 149 consecutive outpatients with fibromyalgia (2016 Ameri-can College of Rheumatology criteria; 91.9% women; mean age 57.5 years). A regularized partial correlation network (EBICglasso: extended Bayesian information criterion graphical lasso; γ = 0.5, Spearman) was estimated over twelve nodes: emotional allo-dynia, pain catastrophizing, central sensitization, depression, state and trait anxiety, and six facets of emotion dysregulation. Accuracy was assessed with 5000 bootstrap replica-tions. Results: The correlation of emotional allodynia with depression (ρ = 0.502) was shrunk to exactly zero in the network and under every sensitivity analysis, and was near zero when the penalty was removed (ρ = -0.033). Its two strongest edges were with pain catastrophizing (0.190) and the Impulse facet of emotion dysregulation (0.184), non-zero in 98.9% and 99.6% of replications. It was among the less connected nodes, but, forming a community of one, all its connectivity crossed a domain boundary. Of that, 59.8% went to emotion regulation and 30.2% to pain, the largest share of any node outside either domain (77.0% and 48.1% of replications). Depression and anxiety received 10.0% (24.6% for catastrophizing). Conclusions: In this exploratory analysis, emotional allodynia oc-cupied a bridging position directed at emotion regulation and pain rather than at de-pression and anxiety, and was not reducible to depressive symptom severity once the other measures were held constant. It overlapped substantially with catastrophizing, and these data do not adjudicate their separability. These preliminary single-centre findings are hypothesis-generating and require replication.

Abstract: Background/Objectives Hypoxaemia is the most common adverse event during procedural sedation. High-flow nasal ox-ygen (HFNO) may reduce desaturation through continuous positive airway pressure, elimination of anatomical dead space, and precise FiO₂ delivery. This study aimed to assess the association between HFNO and the incidence of desaturation (SpO₂ < 90% at any time) during deep seda-tion for colonoscopy in a high-risk population. Methods A single-centre retrospective cohort study with propensity score matching was performed. It in-cluded 200 consecutive adult patients at high risk of adverse respiratory events undergoing deep sedation, grouped by oxygen delivery device: HFNO via nasal cannula versus Venturi mask. Results After 1:1 nearest-neighbour propensity score matching, 71 matched pairs were obtained. In the matched cohort, desaturation occurred in 12.7% of patients receiving HFNO versus 22.5% of controls (matched-pairs OR 0.53; 95% CI: 0.23–1.23; p = 0.211; McNemar's test), an absolute risk reduction of 9.8 percentage points. A sensitivity analysis using conditional logistic regression confirmed the direction and magnitude of the effect (adjusted OR 0.52; 95% CI: 0.22–1.21; p = 0.129). Post hoc power analysis indicated 30.8% statistical power in the current sample; 265 matched pairs would be required to achieve 80% power. Conclusions HFNO was associated with a meaningful reduction in the likelihood of desaturation during deep sedation for colonoscopy in a high-risk population (OR 0.53), consistent with available me-ta-analytic evidence for this risk stratum. This study provides a data-derived sample size estimate (265 matched pairs) for a future prospective randomised trial.