Medicine and Pharmacology

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Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Wei-Hsiu Huang

,

Chih-Shung Wong

Abstract: Diabetic peripheral neuropathy (DPN) remains a leading cause of disability in diabetes, yet current care is largely symptomatic. Increasing evidence places early dysfunction of the blood-nerve barrier (BNB)—a core element of the peripheral nerve neurovascular unit (PNVU)—at the intersection of metabolic stress and neuroinflammation. This review synthesizes a redox-centered model of BNB failure in DPN: (i) chronic hyperglycemia and dyslipidemia overwhelm endogenous antioxidant defenses, driving reactive oxygen species (ROS) imbalance; (ii) ROS-associated endothelial activation promotes endothelial-immune crosstalk, leukocyte recruitment, and macrophage polarization; and (iii) progressive loss of tight-junction and barrier homeostasis increases paracellular permeability and exposure of nerves to pro-inflammatory and neurotoxic mediators. We then evaluate incretin-based therapies—GLP-1 receptor agonists, DPP-4 inhibitors, and emerging multi-agonists—as potential modulators of PNVU/BNB stress. Beyond glucose and weight effects, these agents may dampen oxidative and inflammatory signaling, engage antioxidant pathways (e.g., Nrf2), and potentially support molecular determinants of BNB integrity via indirect metabolic unloading and possible GLP-1R-dependent vascular-immune actions. By reframing DPN as a neurovascular-immune disorder driven by redox imbalance, we highlight barrier-focused biomarkers and hypothesis-generating therapeutic opportunities that require clinical validation.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Ayhan Kaydu

,

İbrahim Andan

,

Günay Kozan

,

Fikret Salık

Abstract: Background and Objectives: Myocardial injury after noncardiac surgery (MINS) is a major determinant of perioperative morbidity and mortality. Its largely silent clinical course often makes early diagnosis difficult and challenging. Cardiac Cycle Efficiency (CCE), is a new parameter that reflects the energy efficiency of the cardiovascular system. This study aimed to evaluate the relationship between intraoperative CCE values and postoperative myocardial injury. Materials and Methods: This prospective observational study included 50 adult patients. The CCE parameters, including baseline CCE, minimum CCE, mean CCE, ΔCCE, and the duration and percentage of CCE<0, were continuously recorded. In all patients, high-sensitivity troponin I (hs-TnI) levels were measured on the postoperative days 1, 2, and 3. The primary endpoint was defined as exceeding the 99th percentile upper limit of the hs-TnI values. Results: Postoperative troponin elevation above the 99th percentile upper reference limit was identified in 11 patients (22%); none of these patients had accompanying ischemic symptoms or new ECG changes. Comparison of CCE-derived parameters between the elevated and normal troponin groups yielded no statistically significant differences for any variable (MinCCE p=0.87, MeanCCE p=0.74, DeltaCCE p=0.69, CCE index p=0.50, time with CCE<0 p=0.19, CCE<0 percentage p=0.51). Spearman rank correlation analysis similarly demonstrated no significant association between any CCE parameter and peak troponin levels; the closest trend was observed for MinCCE (r=–0.244, p=0.08), which nonetheless did not reach statistical significance. On ROC curve analysis, none of the CCE parameters exhibited meaningful discriminative ability, with the highest AUC recorded for cumulative time with CCE below zero (AUC=0.63, 95% CI: 0.43–0.83, p=0.19). Conclusions: Intraoperative CCE parameters failed to predict postoperative troponin elevation in patients at low-to-moderate risk undergoing elective noncardiac surgery. These findings indicate that CCE is not a reliable, standalone predictive marker in this patient population. Studies involving higher-risk patient groups and larger sample sizes are required.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Marshall Bedder

Abstract: Peripheral nerve regeneration remains one of the most difficult clinical problems in neuropathy management, and no currently approved treatment reliably restores nerve structure once damage has occurred. Low-frequency pulsed magnetic fields (LFPMFs) have attracted interest primarily as an analgesic modality, culminating in FDA clearance of a magnetic peripheral nerve stimulation (mPNS) device for painful diabetic neuropathy. However, accumulating preclinical data suggest that LFPMFs may act on the biological determinants of nerve repair, not merely on pain transmission. This review organizes those mechanisms chronologically. Early effects center on the endoneurial microvasculature: LFPMF exposure promotes release of FGF-2 and VEGF from endothelial cells, drives arteriolar dilation, and stimulates capillary neogenesis, restoring oxygen delivery to ischemic nerve segments. These vascular changes are especially relevant in diabetic neuropathy and peripheral vascular disease, where endoneurial ischemia drives progressive fiber loss. Later effects involve Schwann cell proliferation, downregulation of neuroinflammatory cytokines, upregulation of BDNF, NGF, and GDNF, and acceleration of axonal sprouting through calcium-dependent intracellular signaling. Notably, the Brown et al. trial of high-intensity mPNS reported a 53% reduction in numbness—a finding that cannot be explained by analgesia alone and raises the possibility that clinical-grade devices may drive structural regeneration. Whether the regenerative mechanisms identified with lower-power devices translate to, or are amplified by, high-intensity mPNS remains an open and important question.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Cesare Biuzzi

,

Elena Modica

,

Lucrezia Pondrelli

,

Alexander Raimondi

,

Margherita Cavenago

,

Daniele Marianello

,

Filippo Annoni

,

Fabio Silvio Taccone

,

Federico Franchi

,

Sabino Scolletta

Abstract: Central venous pressure (CVP) has long been a cornerstone of hemodynamic monitoring, traditionally interpreted as a surrogate of intravascular volume and cardiac preload. However, current physiological and clinical evidence clearly demonstrates that CVP does not assess volume status and does not reliably predict fluid responsiveness (FR). Ac-cordingly, its role as a target for guiding fluid therapy has been progressively aban-doned. This narrative review retraces the evolution of CVP interpretation, from its physiological foundations to its role in contemporary clinical practice. While early re-suscitation strategies relied on predefined CVP thresholds, this approach has been abandoned. Despite these limitations, CVP remains widely used due to its simplicity and historical familiarity. Importantly, modern perspectives redefine CVP not as a static in-dicator of volume status, but as a valuable marker of systemic venous congestion and right ventricular load. In this context, CVP retains clinical utility when used for waveform interpretation, assessment of venous congestion, and, most importantly, as part of an integrated, multimodal hemodynamic monitoring strategy.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Luciano Frassanito

,

Nicoletta Filetici

,

Francesco Vassalli

,

Alessandra Piersanti

,

Bruno Antonio Zanfini

,

Stefano Catarci

,

Marco Scorzoni

,

Gian Luigi Gonnella

,

Cristina Olivieri

,

Donatella Settanni

+6 authors

Abstract: Background/Objectives: Spinal anesthesia (SA) for elective cesarean delivery (CD) is frequently complicated by maternal hypotension, predominantly attributed to arterial vasodilation and venous pooling. The precise hemodynamic derangements are complex and poorly characterized. We aimed to describe continuous, non-invasively measured maternal hemodynamics changes during CD under SA, focusing on myocardial cardiac contractility (dP/dtmax) and stroke volume index (SVI), and their association with hypotensive episodes. Methods: 95 healthy pregnant women were included. Continuous non-invasive hemodynamic monitoring was performed using a finger-cuff system. We analyzed the incidence, duration, and time-weighted averages (TWA) area under the threshold of hypotension (Mean Arterial Pressure - MAP - &lt;65 mmHg for ≥1 minute), reduced cardiac contractility (dP/dtmax &lt;400 mmHg/sec), and low flow states (SVI &lt;35 mL/b/m2). Results: The median TWA-MAP &lt; 65 mmHg was 0.55 (0.21, 1.13) mmHg, with 2 (1, 5) hypotensive events per patient. Median duration of hypotensive events per patient was 4 (2, 17) min, corresponding to a 5 (2, 15) % of the total monitoring time. Sixty patients (63%) showed a reduced cardiac contractility that averaged 346 (326, 366) mmHg/sec. In 30 patients (31%) at least 1 episode of hypotension (MAP &lt;65 mmHg for &gt;1 minute) was associated with reduced cardiac contractility and a low flow state. In 11 parturients (11%) hypotension was associated to reduced myocardial contractility, while in 8 patients (8%) to low flow alone. Only 9 patients (9%) maintained normal values across all three hemodynamic parameters assessed. No significant correlation emerged between age, body mass index, TWA-MAP, TWA-SVI and TWA-dP/dtmax. Conclusions: Reduced cardiac contractility and low flow states during CD under SA are frequent, but individual expression and the consequent blood pressure decline vary widely. Continuous non-invasive monitoring provides critical, real-time physiological insights that could facilitate individualized, hemodynamically targeted therapies in obstetric anesthesia.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Hwang-Ju You

,

Ji-Yoon Jung

,

Woojin Kwon

,

Sung-Ae Cho

,

Tae-Yun Sung

Abstract: Background and Objectives: Catheter-related bladder discomfort (CRBD) commonly arises as a direct consequence of perioperative urinary catheterization. A fixed dose combination of 1000mg acetaminophen and 300mg ibuprofen provides multimodal analgesia. Accordingly, we assessed the impact of this fixed dose combination on mitigating CRBD in patients undergoing urological procedures. Materials and Methods: In this prospective pilot study, 23 patients undergoing urological surgery requiring urinary catheterization were randomized into 2 groups; approximately 20 minutes before the anticipated end of surgery, patients were administered a combination of 1000 mg acetaminophen and 300 mg ibuprofen (maxigesic group, n = 11) or saline (control group, n = 12). The primary endpoint was the incidence of CRBD immediately after the patient arrived at the post-anesthetic care unit (PACU). The incidence of CRBD at 1,2,6 hours postoperatively, the severity of CRBD at each time point were also assessed. Results: The incidence of CRBD immediately after arrival at the PACU was significantly lower in the maxigesic group (54.5% vs. 100%, p = 0.014), whereas no significant differences were observed at later time points. The incidence of moderate PONV was significantly lower in the maxigesic group at 0 hour and 1hour (p = 0.036, 0.037, respectively). Conclusions: This pilot study indicates that intravenous acetaminophen and ibuprofen could be an effective, well-tolerated strategy for mitigating early postoperative CRBD in urological surgery. While these preliminary results are promising, larger randomized trials are warranted to validate the clinical efficacy of this multimodal regimen.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Dmitrii Balakhnin

,

Artem Ivkin

,

Polina Strelets

,

Anna Sinitskaya

,

Evgeny Grigoryev

Abstract: Cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant complication following cardiopulmonary bypass in pediatric cardiac surgery, often leading to adverse long-term outcomes despite its transient nature in many cases. This single-center cohort study aimed to identify preoperative and intraoperative risk factors for CSA-AKI and evaluate the prognostic value of specific biomarkers. We included 67 children (6–36 months) undergoing elective septal heart defect repair, assessing NGAL, KIM-1, L-FABP, and IL-18 at three perioperative time points. Postoperative AKI, defined by pKDIGO criteria, occurred in 29.85% of patients. Significant preoperative risk factors included younger age, lower weight, anemia, and ventricular septal defects. Key intraoperative predictors were cardiopulmonary bypass, aortic cross-clamp durations and weight-adjusted transfusion volume. A transfusion volume threshold of 13.763 ml/kg (AUC 0.719, Se 0.75, Sp 0.698, p = 0.006) was established as a critical predictor, highlighting the potential for a restrictive transfusion strategy to mitigate AKI risk. These findings allow for early risk stratification and the optimization of intensive care strategies immediately post-surgery. However, the small sample size and focus on septal defects necessitate further multicenter research to validate these diagnostic thresholds across broader congenital heart defect populations.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Y. Van Tran

,

Phong Van Pham

,

Miguel Narvaez Encinas

,

Piercarlo Sarzi- Puttini

,

Dariusz Myrcik

,

Pierfrancesco Dauri

,

Giacomo Farì

,

Christopher Gharibo

,

Matteo Luigi Giuseppe Leoni

,

Giustino Varrassi

Abstract: Regenerative medicine has emerged as a transformative paradigm in contemporary healthcare, shifting the therapeutic focus from symptomatic management toward the restoration of tissue structure and function through biologically active interventions. Within this framework, adipose-derived products have attracted substantial interest owing to their relative abundance, ease of harvesting, and rich cellular and paracrine composition, including mesenchymal stromal cells, pericytes, and bioactive mediators with immunomodulatory potential. Among these technologies, Lipogems® represents an innovative approach based on minimally manipulated microfragmented adipose tissue, because it preserves the native stromal vascular niche and extracellular matrix architecture while avoiding enzymatic processing. This characteristic not only maintains biological integrity but also facilitates regulatory compliance in multiple jurisdictions. This narrative review provides a comprehensive synthesis of the current evidence on Lipogems®, integrating biological rationale, mechanistic insights, and clinical applications across musculoskeletal disorders and chronic pain conditions. Particular attention is devoted to its capacity to modulate inflammatory pathways, promote angiogenesis, and support tissue regeneration within complex pathological environments. In addition, the review critically appraises the methodological limitations of existing clinical studies, including heterogeneity of design and limited high-quality randomized evidence. Finally, future perspectives are explored, emphasizing the integration of precision medicine approaches, biomarker-driven patient stratification, and combinatorial regenerative strategies aimed at optimizing therapeutic outcomes.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Sotiria Rizopoulou

,

Spyridon Lygeros

,

Anne-Lise de Lastic

,

Dimitra Georgakopoulou

,

Gerasimos Daniilidis

,

Athanasia Voulgary

,

Diamanto Aretha

Abstract: Background and Objectives: Controlled hypotension during functional endoscopic sinus surgery (FESS) improves surgical field visibility but may pose a risk of subclinical cerebral hypoperfusion. Serum S100Β and neuron‑specific enolase (NSE) are established biomarkers of glial and neuronal injury and may reflect perioperative neuroprotection associated with different anesthetic regimens. This study evaluated the effect of four anesthetic protocols on perioperative brain biomarker release during FESS. Materials and Methods: In this single‑center, randomized, controlled trial, 88 adult patients (ASA I–III) undergoing FESS under moderately controlled hypotension (mean arterial pressure <55 mmHg) were allocated to one of four groups: propofol–remifentanil, propofol–remifentanil with ketamine–magnesium, sevoflurane–remifentanil, or sevoflurane–remifentanil with ketamine–magnesium. Serum S100Β and NSE concentrations were measured at three timepoints: early intraoperatively, during hypotension, and at the end of surgery. Biomarker data were analyzed using nested ANOVA and linear mixed‑effects models adjusted for relevant covariates. Secondary outcomes included recovery characteristics, surgical field quality, bleeding scores, and perioperative hemodynamics. Results: Baseline demographic and perioperative characteristics were comparable across groups. The group receiving sevoflurane–remifentanil combined with ketamine–magnesium showed the lowest S100B levels (p=0.01 compared to the propofol-remifentanil group; p=0.04 compared to the sevoflurane-remifentanil group). Additionally, NSE concentrations were markedly lower in both sevoflurane groups (sevoflurane-remifentanil and sevoflurane-remifentanil plus ketamine–magnesium) compared to the propofol–remifentanil group (p=0.003 and p=0.007, respectively). No intergroup differences were observed at baseline. Recovery and extubation times were shortest with propofol–remifentanil, whereas ketamine–magnesium prolonged emergence. Surgical field quality, bleeding, and hemodynamic parameters did not differ significantly among groups. Conclusions: Anesthetic technique significantly influences perioperative brain biomarker release during FESS. Sevoflurane‑based regimens, with or without ketamine–magnesium, demonstrate more favorable neurobiological profiles under controlled hypotension, although propofol‑based anesthesia offers faster recovery.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Qing Zhao Ruan

,

Woojin Lee

,

Jung Mi Haisman

,

Vahid Grami

,

Kasra Amirdelfan

,

Dawood Sayed

,

Christopher M. Lam

,

Cyrus Yazdi

,

Ronald J. Kulich

,

Claire Yuan

+3 authors

Abstract: Platelet-rich plasma (PRP) is a commonly used intra-articular therapy for knee osteoarthritis (OA), yet substantial heterogeneity in PRP preparation and delivery limits comparability across trials and complicates clinical translation. We conducted a scoping review in accordance with PRISMA and PRISMA-ScR guidance. MEDLINE and Embase were searched from inception to 15 November 2025 for English-language randomized controlled trials comparing PRP with non-regenerative comparators (e.g., hyaluronic acid, corticosteroids, radiofrequency ablation, or saline placebo) in adults with knee OA. Data were charted on study characteristics, OA severity, injection guidance, centrifugation protocols, injected PRP volume and platelet concentration, dosing regimens, follow-up, adverse events, and overall conclusions (superior/non-inferior/inferior). Twenty-one studies (2012–2025) were included, spanning multiple regions and enrolling 21–288 participants per study with follow-up from 12 weeks to 60 months. PRP protocols varied widely, including single- versus double-spin centrifugation, spin rates and durations, injected volumes (approximately 1.4–8 mL), and platelet enrichment (approximately 1.15x to 9.85x baseline when reported). The most common regimen was three injections, typically weekly. Across studies, major adverse events were not reported, and post-injection pain or transient synovitis/effusion were the most frequent events. PRP for knee OA is generally safe and frequently demonstrates comparable or improved outcomes versus standard injectables, but marked protocol heterogeneity persists. Standardized reporting and consensus parameters for PRP preparation and administration are needed to improve reproducibility and guide evidence-based practice.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Daniele Salvatore Paternò

,

Luigi La Via

,

Rossella Moltisanti

,

Antonio Putaggio

,

Angela Maria Piccolo

,

Giuseppe Scibilia

,

Antoinette Marie Bonaccorso

,

Emilia Concetta Lo Giudice

,

Massimiliano Sorbello

Abstract: Background: Patients with chronic cardio-respiratory diseases face substantially elevated perioperative complication risks. High-flow nasal oxygen (HFNO) therapy has emerged as a promising non-invasive respiratory support modality, yet evidence specific to this high-risk population has not been comprehensively synthesized. Objectives: To systematically evaluate HFNO effectiveness across the perioperative continuum—including pre-oxygenation, apneic oxygenation, and post-extubation support—in patients with chronic obstructive pulmonary disease, heart failure, interstitial lung disease, obesity, and related conditions. We aimed to compare HFNO with alternative modalities and provide evidence-based implementation guidance. Methods: We conducted a comprehensive narrative review with systematic search of major databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials, systematic reviews, and observational studies involving adult patients with chronic cardio-respiratory diseases undergoing surgery with HFNO intervention at any perioperative phase. Quality assessment using established tools was performed with structured narrative synthesis organized by perioperative phase and disease population. Results: The review synthesizes evidence across multiple perioperative applications, comparing HFNO effectiveness with conventional oxygen therapy and non-invasive ventilation. Disease-specific considerations for chronic obstructive pulmonary disease, heart failure, obesity and obstructive sleep apnea, interstitial lung disease, and thoracic surgery populations are delineated. Evidence-based clinical algorithms for patient selection, protocol optimization, and escalation strategies are provided. Cost-effectiveness, implementation barriers, training requirements, and integration into Enhanced Recovery pathways are addressed. Conclusions: HFNO represents a valuable non-pharmacological intervention for perioperative respiratory optimization in chronic cardio-respiratory disease patients. This comprehensive synthesis provides clinicians with evidence-based guidance for implementation while identifying critical research gaps. Proper patient selection and protocol optimization can reduce postoperative pulmonary complications, prevent reintubation, and improve outcomes in this high-risk population. Future research should focus on personalized approaches, long-term outcome assessment, and implementation science. Keywords: High-flow nasal oxygen; HFNO; perioperative care; chronic obstructive pulmonary disease; heart failure; respiratory failure; non-invasive respiratory support; surgical complications; perioxygenation.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Claire Yuan

,

Ashu K. Goyle

,

Maged Guirguis

,

Alan D. Kaye

,

Vahid Grami

,

Karan Dave

,

Ronald J. Kulich

,

Timothy E. Deer

,

David Rosenblum

,

Vwaire Orhurhu

+2 authors

Abstract: Micro-fragmented adipose tissue (mFAT) is a promising autologous biologic in regenerative medicine because it provides a mechanically processed adipose-derived product that preserves native extracellular matrix architecture and a cellular milieu rich in mesenchymal stem cells, pericytes, growth factors, cytokines, and extracellular vesicles. Mechanistically, mFAT is hypothesized to act largely through paracrine signaling that dampens inflammation, supports vascular stabilization, and promotes cartilage and soft-tissue repair; in vitro data suggest modulation of osteoarthritic synovial macrophage signaling, including reductions in chemokines such as CCL2 and CCL3. Preparation involves liposuction harvest followed by closed, sterile mechanical processing without enzymatic digestion or cell expansion, aligning with “minimal manipulation” concepts relevant to regulatory frameworks. Preclinical animal studies generally demonstrate favorable effects on synovial inflammation and cartilage matrix markers (e.g., glycosaminoglycan content) with limited adverse events. Clinically, the strongest body of evidence is in knee osteoarthritis, where multiple prospective and retrospective studies report improvements in pain and function from months to several years after single injections, though response rates vary and study designs are heterogeneous. Evolving data support potential benefit in hip osteoarthritis and select tendon conditions, but cohorts remain small. Overall, mFAT appears safe and potentially effective, yet larger, standardized, long-term randomized controlled trials and comparative studies versus platelet-rich plasma and bone marrow aspirate concentrates are needed to clarify indications, dosing, durability, and mechanisms in vivo.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Daniele Salvatore Paternò

,

Luigi La Via

,

Emilia Concetta Lo Giudice

,

Massimiliano Sorbello

Abstract: The work of anesthesiologists–intensivists, critical care specialists, and medical emergency teams is multifaceted and complex, with airway management representing a cornerstone and a common denominator of many procedures and interventions. Tracheal intubation has represented, and still represents today, the gold standard for airway control. Laryngoscopy evolution has progressed in parallel with technological development and innovation, resulting in the evolution of new skills and in the expansion of possibilities and safety for patient care. The evolution of laryngoscopy essentially took place between the late 1800s and the first half of the 1900s, with the consecration of the MacIntosh laryngoscope. Almost 50 years later, the world witnessed a pivotal turning point around the 2000s with the introduction of videolaryngoscopes. Along this path, the devices that have succeeded one another introduced new problems, driving the search for new solutions. At present day, tracheal intubation with videolaryngoscopy has achieved success and safety standards that are certainly superior, if not unimaginable, when compared with the early days of the technique. In this review we will retrace the historical aspects of the evolution of laryngoscopy, analyzing the problems that have emerged over time with the various devices and the solutions adopted. We will then examine the evolution of videolaryngoscopes, the impact of these devices on both technical skills and non-technical skills, as well as the debate surrounding their routine use (universal videolaryngoscopy) and the choice of the best adjuncts to optimize success during their use, including the application of assistive artificial intelligence to improve both success rates and the learning curve. This journey, after 150 years of evolution, has probably reached today the highest possible level of expression in terms of safety and efficacy.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Isabella Barrios

,

Sara A. Thomas

,

Yesenia Hernandez

,

Ana Pagan

,

Emily Munoz

,

Kamilah Cespedes

,

Saurabh Aggarwal

Abstract: Cancer-related pain remains one of the most prevalent and distressing symptoms across the disease trajectory, significantly impairing function and quality of life. This narrative review examines contemporary approaches to cancer pain management within a palliative care framework, emphasizing the transition from opioid-centric strategies toward multimodal, patient-centered care. Although opioids remain essential for moderate to severe pain, their use is limited by adverse effects, dependence risk, and increasing regulatory and societal concerns. Cancer pain is heterogeneous, arising from tumor progression and treatment-related injury, underscoring the need for mechanism-based assessment to guide therapy. This review highlights the expanding role of adjuvant analgesics, including antidepressants, anticonvulsants, corticosteroids, bisphosphonates, and topical agents, within multimodal regimens designed to optimize analgesia while minimizing opioid exposure. Non-pharmacological and interdisciplinary interventions are emphasized as integral components of supportive and palliative care, addressing both physical and psychosocial suffering. Emerging therapies, including cannabinoids and gene-targeted approaches, are discussed in the context of evolving evidence and personalized medicine. A multidisciplinary, patient-centered framework that integrates pharmacologic and non-pharmacologic strategies is essential for improving symptom control, functional outcomes, and quality of life in patients with cancer.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Patricia Piñeiro

,

Francisco Sanchez

,

Alberto Calvo

,

María Tudela

,

Silvia Ramos

,

Sergio García-Ramos

,

Pilar Benito-Saz

,

Isabel Solchaga

,

Raquel Vela

,

Claudia Menendez

+2 authors

Abstract: Background: Esophagectomy is associated with substantial postoperative morbidity, with infectious complications remaining a leading cause of mortality. Septic shock represents the most severe infectious complication; however, data on its perioperative predictors and long-term impact after esophagectomy are limited. Methods: We conducted a retrospective observational study including consecutive adult patients who underwent esophagectomy with curative intent for esophageal cancer between January 2015 and December 2024 at a tertiary referral center. Postoperative septic shock was defined according to Sepsis-3 criteria. Demographic, clinical, surgical, laboratory, and oncological variables were analyzed. Independent risk factors for septic shock were identified using multivariate logistic regression. Overall survival was assessed using Kaplan–Meier analysis. Results: Among 106 patients, 19 (17.9%) developed postoperative septic shock. These patients had a lower body mass index, reduced preoperative and postoperative albumin levels, and a higher incidence of advanced lymph node involvement. Septic shock was strongly associated with severe postoperative complications, including anastomotic leakage, hemorrhagic shock, acute respiratory distress syndrome, acute kidney failure, and increased rates of PICU readmission. In multivariate analysis, lower albumin levels at PICU admission (OR 0.54; 95% CI 0.29–0.99) and advanced nodal stage (OR 4.98; 95% CI 1.36–18.3) were independently associated with the development of septic shock. Patients who developed septic shock had significantly higher in-hospital mortality (31.6% vs. 1.1%, p < 0.001) and markedly reduced long-term survival, even among those discharged alive. Conclusions: Postoperative septic shock after esophagectomy is a devastating complication with a profound negative impact on both short- and long-term survival. Hypoalbuminemia and advanced lymph node involvement are independent predictors of septic shock. These findings underscore the importance of multidisciplinary perioperative optimization strategies, including nutritional assessment and tailored surgical planning, to mitigate the incidence and consequences of this life-threatening complication.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Paulo Warpechowski

,

Bruna Eibel

,

Gustavo Glotz de Lima

,

Tiago Batista Warpechowski

,

Ari Tadeu Santos

,

Tiago Luz Leiria

Abstract: Introduction: Propofol is one of the most commonly used intravenous anesthetics worldwide and is considered safe for all age groups. However, there have been reports that propofol can induce severe atrioventricular block in humans, and several studies have shown that propofol hinders or prevents the inducibility of arrhythmias during electrophysiological studies (EPS) and radiofrequency (RF) ablation. Objectives: Verify whether propofol prevents or hinders the inducibility of arrhythmias during EPS and RF ablation procedures in children with Wolff-Parkinson-White Syndrome. Methods:We conducted a retrospective observational cohort study including 45 pediatric patients aged 0–18 years. Patients were identified through a review and analysis of a database of individuals with Wolff–Parkinson–White syndrome who were referred for electrophysiological study and/or radiofrequency ablation at the Electrophysiology Laboratory of the Institute of Cardiology (IC/FUC) in Porto Alegre over the past five years (2019-2024). Patients with prior ablation, structural heart disease, or ongoing antiarrhythmic therapy were excluded. The patients were divided into two groups and designated as group S (who received sedation) or group G (who received general anesthesia). Sedation (group S) was performed with midazolam (0.08–0.2 mg/kg), fentanyl (0.1–0.2 μcg/kg), and propofol 50–60 µg/kg/min in continuous infusion. General anesthesia (group G), in turn, was performed with sevoflurane at an average dose of 2% (1 MAC according to age). Results: From 4,874 invasive electrophysiology procedures performed during the study period, 45 involved pediatric patients with WPW. The sedation group (n=29) had significantly older patients (14.6±2.5 vs 10.3±2.8 years, p<0.001) with higher weight (65.9±16.3 vs 41.2±7.8 kg, p<0.001) compared to the general anesthesia group (n=16). Arrhythmia was successfully induced in 15/29 (51.7%) patients in the sedation group compared to 13/16 (81.2%) in the general anesthesia group (p=0.062, Fisher's exact test). Although this difference did not reach statistical significance, it represents a clinically relevant 29.5% lower induction rate in the sedation group. Post-hoc power analysis revealed the study was underpowered (49.8%), suggesting a possible Type II error. Analysis of the "procedure room time" revealed a longer duration in the general anesthesia group (97.8±36.7 vs 67.8±24.4 minutes), and this difference was statistically significant (p = 0.002). Conclusions: This study compared propofol-based sedation with sevoflurane-based general anesthesia in pediatric WPW patients. While sedation with propofol did not show a statistically significant reduction in arrhythmia inducibility, there was a concerning trend toward lower induction rates (29.5% difference) that may be clinically relevant. The study's limited statistical power (49.8%) suggests these findings should be interpreted cautiously, and larger prospective studies are needed to definitively establish whether propofol affects arrhythmia inducibility in this population. Propofol remains a viable option for these procedures, but clinicians should be aware of the potential for reduced inducibility, particularly in cases where arrhythmia induction is critical for diagnosis and treatment.

Article
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Wojciech Danysz

,

Paulina Nunez-Badinez

,

Andreas Gravius

,

Klaus Fink

,

Jens Nagel

Abstract:

Background/Objectives: Trigeminal neuralgia (TN) is a debilitating neurological condition characterized by recurrent, severe pain linked to peripheral and central sensitization within trigeminal pathways. Although current pharmacologic treatments are limited by inadequate efficacy or dose-limiting side effects, botulinum neurotoxin type A (BoNT/A) has emerged as a viable option. However, its potential use in the management of TN is hampered by methodological limitations in existing studies and a lack of pivotal clinical trials. This study investigated the efficacy, optimal treatment site, preventive utility, and duration of effect of incobotulinumtoxinA (Inco/A), a BoNT/A, in a model of TN. Methods: An infraorbital nerve chronic constriction injury model was used to induce mechanical allodynia in male Sprague–Dawley rats, reproducing the trigeminal sensitization seen in TN. The effects of subcutaneous Inco/A (1, 2, and 4U) were measured using the mechanical sensitivity (von Frey) test to evaluate the dose response, effect of injection location, potential preventive nature of treatment, and duration of benefit. Results: Inco/A produced a robust, dose-dependent reduction in mechanical allodynia, predominantly via a local mechanism of action. Both preventive and therapeutic administration of Inco/A was efficacious, with significant reduction of allodynia even when administered up to 28 days before nerve injury. The anti-allodynic effect persisted up to 56 days post-injection. Conclusions: Inco/A is highly effective in alleviating mechanical allodynia in a validated rat model of TN. The findings highlight Inco/A as a promising candidate for clinical translation in TN and related neuropathic pain syndromes and support systematic investigation in well-controlled human trials.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Daniel John Doyle

Abstract: Respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis, and acute respiratory distress syndrome (ARDS) remain leading causes of morbidity and mortality worldwide. Traditional respiratory care faces challenges in early diagnosis, personalized treatment, efficient resource allocation, and optimal mechanical ventilation management. Artificial intelligence (AI) has emerged as a transformative tool, offering applications in diagnosis, monitoring, treatment optimization, critical care support, and automated ventilator control. This comprehensive review examines AI's role across the respiratory care continuum, from diagnostic imaging and spirometry interpretation to autonomous multiparameter ventilator adjustment during maintenance and weaning phases. The article highlights quantitative evidence of clinical impact, regulatory status, challenges including algorithmic bias and health equity concerns, implementation strategies, and detailed analysis of AI-driven mechanical ventilation systems. Case studies illustrate real-world outcomes with specific effect sizes. The discussion emphasizes both the promise and limitations of AI, preparing healthcare professionals and students to critically evaluate its role in clinical practice.

Review
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Daniele Salvatore Paternò

,

Luigi La Via

,

Emilia Concetta Lo Giudice

,

Mario Lentini

,

Antonino Maniaci

,

Antoinette Marie Bonaccorso

,

Rossella Moltisanti

,

Antonio Putaggio

,

Federico Pappalardo

,

Massimiliano Sorbello

Abstract:

Background: Unanticipated difficult airways remain a leading cause of anesthesia-related morbidity and mortality, with traditional bedside predictors demonstrating limited sensitivity. Point-of-Care Ultrasound (POCUS) has emerged as a non-invasive adjunct offering real-time visualization and quantitative measurement of airway anatomy. This narrative review, structured according to the Scale for the Assessment of Narrative Review Articles (SANRA), synthesizes current evidence on Point-of-Care Ultrasound (POCUS) as an adjunct for airway evaluation. We explore the sonoanatomy of the upper airway, the utility of ultrasound in predicting difficult laryngoscopy and intubation, its critical role in emergency front-of-neck access (FONA), and the verification of endotracheal tube placement. Furthermore, we discuss the integration of Artificial Intelligence (AI) in image interpretation and the necessity of standardized training curricula. Methods: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science for English-language peer-reviewed studies addressing sonographic airway assessment, including sonoanatomy, prediction of difficult laryngoscopy/intubation, guidance for emergency front-of-neck access (FONA) and endotracheal tube confirmation. Results: POCUS enhances visualization of critical anatomical structures, improves predictive accuracy when combined with clinical assessment, and provides real-time guidance during emergency procedures. Integration of Artificial Intelligence shows promise for automated image interpretation. Conclusions: Airway ultrasound represents a paradigm shift toward personalized, safer airway management. However, standardized training protocols and validation in diverse clinical settings remain essential. Future research should focus on developing evidence-based algorithms integrating POCUS into airway management guidelines.

Case Report
Medicine and Pharmacology
Anesthesiology and Pain Medicine

Jeongsoo Choi

,

Ho Soon Jung

,

Da Hyung Kim

,

Yong Han Seo

,

Hea Rim Chun

,

Hyung Yoon Gong

,

Jae Young Ji

,

Jin Soo Park

,

Sangwoo Im

Abstract: Background and Clinical Significant: Patent ductus arteriosus (PDA) is a common car-diovascular disorder in extremely low birth weight(ELBW) infants, for which surgical ligation is indicated when pharmacologic closure fails. Sudden increases in afterload combined with immature myocardial contractility can lead to post-ligation cardiac syn-drome, which usually occurs within hours after surgery. However, acute intraoperative hemodynamic collapse during PDA ligation has rarely been described. Case Presenta-tion: A preterm infant born at 24 weeks and 3 days of gestation with a birth weight of 890 g underwent emergency PDA ligation for a hemodynamically significant PDA refractory to pharmacological treatment. Fifteen minutes after skin incision, the infant developed severe hypoxemia, bradycardia, and non-measurable noninvasive blood pressure, which required immediate hemodynamic resuscitation with manual ventilation, fluid admin-istration, and dopamine and dobutamine infusions. Hemodynamics gradually recovered after completion of ductal ligation, whereas hypoxemia persisted. Postoperative chest radiography revealed a left-sided pneumothorax, and oxygen saturation stabilized after pleural air aspiration. The subsequent clinical course was uneventful, and typical post-ligation cardiac syndrome did not develop. Conclusions: This case suggests that intraoperative hemodynamic collapse during PDA ligation may share pathophysiologic features with post-ligation cardiac syndrome, and that concomitant pneumothorax can further aggravate hemodynamic instability by worsening hypoxemia and reducing venous return.

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