Medicine and Pharmacology

Abstract: Introduction: Neuromonitoring during general anesthesia (GA) is recommended to reduce the incidence of postoperative delirium and intraoperative awareness, particularly during total intravenous anesthesia. Guidelines emphasize that anesthesiologists should not rely solely on processed depth-of-anesthesia indices such as the Bispectral Index or Patient State Index but should also interpret the raw electroencephalographic (EEG) waveform and the density spectral array (DSA). While EEG patterns associated with individual anesthetic agents or combinations of hypnotics and opioids have been described, limited evidence exists regarding EEG activity during multimodal anesthetic regimens. This review aimed to evaluate DSA patterns as pharmacodynamic markers of the cortical effects of GABAergic anesthetics, opioids, and ketamine. Methods: PubMed, Embase, and the Cochrane Library were searched without temporal limitation up to September 2025. Eligible studies included adult patients undergoing general anesthesia and reporting raw EEG data or specific DSA patterns associated with the investigated drugs. Results: Out of 273 papers screened, two studies met the inclusion criteria, comprising 53 patients. Both studies achieved an appropriate and stable effect-site concentration of propofol-remifentanil GA, demonstrated by a baseline DSA recorded before ketamine administration. Ketamine administration produced a shift from the baseline alpha-delta pattern to a beta-delta DSA pattern. Conclusion: Ketamine administration during stable propofol-remifentanil anesthesia produces a characteristic shift towards a beta-delta DSA pattern which may increase in processed EEG indices, leading to misinterpretation of anesthetic depth. Further studies are needed to characterize DSA signatures associated with multimodal anesthesia and to identify patterns indicative of adequate anesthetic depth when multiple agents are administered.

Abstract: Background: Hemodynamic instability during anesthesia induction and endotracheal intubation remains a clinically important concern. Low-dose ketamine and intravenous lidocaine may provide complementary effects that improve cardiovascular stability and peripheral perfusion. This pilot study evaluated effects of adding ketamine and lidocaine to a propofol-based induction regimen using mean arterial pressure (MAP) and perfusion index (PI) as monitoring parameters. Methods: In this prospective randomized pilot study, 30 adult patients undergoing elective surgery requiring general anesthesia and endotracheal intubation were allocated to either a standard induction regimen (Group 1: propofol 2 mg/kg and fentanyl 2 μg/kg) or an adjunctive regimen (Group 2: propofol 2 mg/kg, ketamine 0.4 mg/kg, lidocaine 1 mg/kg, and fentanyl 1 μg/kg). Hemodynamic variables and PI were recorded at baseline, after induction, and after intubation. Postoperative sore throat and cough-reflex responses were also assessed. Results: No significant differences between-groups were observed in heart rate, systolic blood pressure, diastolic blood pressure, MAP, or oxygen saturation at any time point. However, MAP decreased significantly within Group 1 after induction (94.9 ± 10.1 vs. 76.9 ± 13.8 mmHg, p < 0.001) and remained lower after intubation (p = 0.001), whereas no significant MAP changes occurred within Group 2. PI increased in both groups but was significantly higher in Group 2 after induction (5.35 ± 2.34 vs. 3.46 ± 2.90, p = 0.043) and after intubation (7.02 ± 2.89 vs. 4.71 ± 2.22, p = 0.020). Postoperative sore throat scores were lower in Group 2 (0.53 ± 0.91 vs. 1.67 ± 1.76, p = 0.035), and cough-reflex scores were also reduced (p = 0.024). Conclusions: The addition of low-dose ketamine and intravenous lidocaine to propofol-based induction was associated with greater MAP stability, higher perfusion index values, and reduced airway-related adverse effects. These findings are hypothesis-generating and warrant confirmation in larger randomized trials.

Abstract: Background/Objectives: Infectious complications are frequent in neurological intensive care unit (ICU) patients and may contribute to in-hospital mortality. However, their independent prognostic value in full neurological ICU cohorts remains insufficiently defined. This study evaluated documented infectious complications as predictors of in-hospital mortality in a six-year neurological ICU cohort. Methods: We performed a retrospective, single-center cohort study including all available neurological ICU admission episodes recorded between 1 January 2020 and 31 December 2025. The primary outcome was in-hospital mortality. Infectious variables included pneumonia, COVID-related pneumonia, urinary tract infection, pressure sore or pressure sore-related infection, sepsis-related coding, and any infectious complication. Multivariable logistic regression was used to assess independent associations with mortality. The primary model included individual infectious complications without Glasgow Coma Scale (GCS), while a GCS-adjusted model was used as a sensitivity analysis. Incremental model analysis, model validation/calibration, and COVID-related sensitivity analyses were also performed. Results: The cohort included 5,509 neurological ICU admission episodes; 999 ended in in-hospital death, corresponding to a mortality rate of 18.1%. Any infectious complication was documented in 1,911 episodes (34.7%). Pneumonia was the most frequent infectious complication (22.2%) and remained independently associated with mortality in the primary model (adjusted OR 6.82, 95% CI 5.70–8.18; p &lt; 0.001) and in the GCS-adjusted model (adjusted OR 5.25, 95% CI 4.05–6.80; p &lt; 0.001). Sepsis-related coding, interpreted as a documentation-based marker of severe systemic infectious deterioration rather than formally adjudicated sepsis, showed the strongest adjusted association with death (adjusted OR 12.40, 95% CI 6.53–23.54; p &lt; 0.001). Urinary tract infection and pressure sore-related infection were associated with mortality in unadjusted analyses but not after adjustment. Conclusions: Pneumonia and sepsis-related coding were robust independent predictors of in-hospital mortality. Infectious complications added prognostic information beyond baseline clinical variables and should be integrated into neurological ICU risk assessment and infection-surveillance strategies.

Abstract: Cardiac arrhythmias complicate 20–50% of surgical procedures and contribute substantially to perioperative morbidity, mortality, and healthcare costs, with postoperative atrial fibrillation (POAF) being the most frequent form. Their genesis reflects the convergence of surgical stress, anaesthetic agents, autonomic imbalance, systemic inflammation, and electrolyte disturbances, explaining the limited efficacy of single-mechanism interventions. This narrative review synthesises contemporary evidence on pathophysiology, risk stratification, prevention, acute management, and emerging technologies, emphasising individualised, patient-tailored approaches. MEDLINE, Embase, and Cochrane CENTRAL were searched (January 2010–January 2026), prioritising randomised trials, meta-analyses, and guidelines. Contemporary risk stratification integrates clinical scores, biomarkers, and electrocardiographic parameters; machine-learning models show moderate discrimination (pooled AUC 0.84) and may enable more personalised prediction pending external validation. Evidence-based prophylaxis—beta-blockade, magnesium, selective amiodarone, and emerging anti-inflammatory strategies such as colchicine—reduces POAF in high-risk populations, while acute management is guided by haemodynamic status and individual risk. Anticoagulation follows CHA₂DS₂-VASc stratification, although optimal timing and duration remain undefined. Wearable monitoring, AI-based detection, and atrial-selective agents show clinical promise. Systematic, personalised integration of risk assessment, prophylaxis, monitoring, and management offers the clearest path to reducing arrhythmia-associated morbidity.

Abstract: Background: Interindividual variability in response to anti-inflammatory therapies remains a major challenge in clinical practice. Nonsteroidal anti-inflammatory drugs, corticosteroids, and biologic agents are widely used in adult and pediatric inflammatory diseases, but their efficacy and safety are influenced by pharmacokinetic, pharmacodynamic, developmental, and genetic factors. Methods: A structured literature review was conducted in PubMed and Embase for English-language publica-tions from January 2000 to January 2026. Clinical studies, trials, observational studies, systematic reviews, meta-analyses, guidelines, and relevant reviews were analyzed, with emphasis on phar-macogenomic determinants of response and toxicity. Results: The strongest actionable evidence concerns CYP2C9 variants affecting the metabolism of several nonsteroidal anti-inflammatory drugs, including ibuprofen, celecoxib, meloxicam, and related agents. Reduced-function alleles are associated with decreased clearance, increased drug exposure, and higher risk of dose-related ad-verse events. For corticosteroids, variants in NR3C1, FKBP5, STIP1, GLCCI1, and pharmacokinetic genes may contribute to variability in responsiveness and toxicity, although clinical implementation remains limited. For biologics, HLA-DQA1*05 is a reproducible predictor of anti-drug antibody formation and secondary non-response to anti-TNF therapy. Conclusion: Pharmacogenomics offers a promising strategy to personalize anti-inflammatory therapy. While CYP2C9-guided nonsteroidal anti-inflammatory drug prescribing is currently the most clinically actionable application, further prospective and pediatric-specific studies are needed to support broader implementation.

Abstract: Ultrasound-guided fascial hydrorelease (FHR) occasionally elicits a brief localized contraction ("local twitch") at the moment the needle tip contacts a fascial layer; the anatomical basis of this reaction has not yet been systematically characterized. To examine local twitch occurrence relative to stacking fascia (yes/no) at the needle tip (primary outcome), as well as the anatomical distribution and per-video capture rate (secondary outcomes), we retrospectively analyzed 11,205 ultrasound videos from a single pain clinic (October 2015–March 2026). Twitches were identified by prospective clinical observation and computational screening (frame-difference-based Profile Match classifier; 417 candidates over 30 review rounds). The stacking fascia status was independently determined by two FHR-experienced clinicians, with discordant cases jointly adjudicated. Inter-rater agreement was 86/90 (95.6%; 95% CI 89.0–98.8%); one case was reassessed, deemed to not be a twitch, and excluded. In the final cohort (n = 89), local twitches occurred at stacking fascia in 89/89 (100%; 95% CI 95.9–100%). Events were concentrated in gluteal/pelvic (51%) and lumbar paraspinal (28%) regions, with a per-video capture rate of 0.98% (110/11,205; 95% CI 0.81–1.18%). Local twitches during ultrasound-guided FHR essentially always coincide with the needle tip lying within stacking fascia, identifying this as the structural locus within this cohort.

Abstract: Objective: To evaluate whether deep neuromuscular blockade (DNMB) improves surgical conditions and facilitates low-pressure pneumoperitoneum compared with moderate neuromuscular blockade (MNMB) during minimally invasive surgery. Data Sources PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, Scopus, Web of Science, and LILACS were searched from inception through May 2026. Study Selection Randomized controlled trials comparing DNMB versus MNMB in adults undergoing laparoscopic or robot-assisted surgery were included. Data Extraction Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias tool (RoB 2). Certainty of evidence was evaluated using the GRADE approach. Primary Outcomes: Primary outcomes were surgical workspace quality and intra-abdominal pressure requirements. Secondary Outcomes: Secondary outcomes included postoperative pain at 24 hours and referred shoulder pain. Data Synthesis: Seventeen randomized controlled trials involving more than 1700 patients were included. DNMB consistently improved surgical workspace conditions and facilitated lower pneumoperitoneum pressures compared with MNMB. Pooled analyses additionally suggested reductions in postoperative pain and referred shoulder pain in selected studies, although postoperative outcomes demonstrated greater heterogeneity across procedures and perioperative protocols. Conclusions: Current evidence suggests that the principal clinical value of DNMB during minimally invasive surgery is optimization of surgical exposure and facilitation of low-pressure pneumoperitoneum strategies. Benefits related to postoperative pain may occur in selected settings but appear less consistent across procedures.

Abstract: Background: Thoracic surgery is associated with severe post-operative pain caused by chest wall manipulation and intercostal nerve injury. Multimodal analgesia with non-opioid agents such as lidocaine, ketamine and magnesium might be beneficial for pain control and reduce opioid consumption. Methods: In this prospective cohort study, we recruited 118 consecutive patients who underwent lung resection via thoracotomy from January 2019 to January 2021 at Hospital Universitari de Girona Doctor Josep Trueta. The primary outcome was total intravenous morphine consumption within the first 24 h post-operatively. Multi-variable linear regression modelling was used to determine the adjusted association between lidocaine, ketamine and magnesium administration and morphine consumption in the first 24 h after surgery. Statistical analysis was performed using Wilcoxon’s rank-sum and Fisher’s exact tests. Results: In total, 71 patients received lidocaine, ketamine and magnesium intraoperatively (LKM) and 47 patients did not receive this regimen (non-LKM group). The LKM group had a higher prevalence of hypertension and higher proportions of patients undergoing lobectomy and pneumonectomy. Morphine consumption within 24 h post-operatively was lower in the LKM group than in the non-LKM group (median [interquartile range], 2 [2–6] mg vs. 5 [3–8] mg; p = 0.001). No drug-related adverse events were observed. After multi-variable risk adjustment, lidocaine, ketamine and magnesium use was associated with significantly decreased total intravenous morphine consumption within 24 h post-operatively (−1.76, 95% confidence interval = −3.40 to −0.12, p = 0.03). Conclusions: Lidocaine, ketamine and magnesium use was associated with lower 24-h morphine consumption in our prospective cohort.

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 and surgical field quality, bleeding, and hemodynamic parameters did not differ significantly among groups. Recovery and extubation times were shortest with propofol–remifentanil, whereas ketamine–magnesium prolonged emergence. 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.