Medicine and Pharmacology

Abstract: Background/Objectives: Mean arterial pressure (MAP) is an incomplete surrogate of systemic perfusion: cardiac index (CI) and MAP can become dissociated. Recent cardiac surgery studies report that the burden of low CI during normotensive periods is associated with acute kidney injury (AKI). Whether this pressure--flow dissociation occurs in major aortic surgery and is modulated by the choice of arterial-pressure-derived monitoring strategy (FloTrac vs Acumen IQ/Hypotension Prediction Index, HPI) is unknown. Methods: CI-focused secondary analysis of 100 major aortic surgery patients from a prior MAP-based cohort. Continuous CI signals were newly extracted from the original HemoSphere exports. The primary metric was the percentage of monitoring time with CI<2.2L/min/m² during MAP\(\geq\) 65mmHg; the primary outcome was AKI by KDIGO criteria. Multivariable logistic regression adjusted for baseline demographics, comorbidities, preoperative MAP, surgery duration, and monitoring strategy, with Holm–Bonferroni correction within test families. Reported per STROBE. Results: Pressure–flow dissociation was frequent: low CI during normotension occurred in 94% of patients at CI<2.5 (median burden 27%). The HPI group had numerically lower low-CI burden and higher mean MAP (87 vs 84mmHg, \(p_{\mathrm{raw}} = 0.008\)). AKI occurred in 34/99 evaluable patients (FloTrac 19/49, 38.8%; HPI 15/50, 30.0%). AKI patients did not have higher low CI burden than no-AKI patients (median 5.2% vs 7.6%, \(p = 0.73\)). In multivariable regression, neither low CI burden (adjusted OR 0.88 per 10-pp increase, 95% CI 0.67–1.12, \(p = 0.33\)) nor HPI assignment (adjusted OR 0.57, 95% CI 0.20--1.53, \(p = 0.27\)) was associated with AKI. Sensitivity, time-to-event, and heart rate × CI interaction analyses yielded uniformly null findings.Conclusions: Pressure–flow dissociation is frequent in major aortic surgery, and HPI monitoring modifies the haemodynamic pattern. However, neither the low CI burden nor the choice of monitoring strategy was associated with postoperative AKI, suggesting a boundary condition on the generalisability of recent cardiac surgery CI–AKI associations. Definitive evidence requires prospective randomised evaluation (HYPE-AORTA, NCT07510451).

Abstract: Background/Objectives: Total hip arthroplasty (THA) in older patients is commonly performed under general anesthesia (GA) or spinal anesthesia (SA). Although prior studies have emphasized postoperative outcomes, perioperative hemodynamic differences remain insufficiently characterized. This study compared intraoperative and early postanesthesia care unit (PACU) hemodynamic changes and in-hospital clinical outcomes between SA and GA in older patients undergoing elective THA. Methods: This single-center retrospective observational study included patients aged ≥65 years who underwent THA from 2020 to 2025. Exclusion criteria included below-normal left ventricular ejection fraction, moderate-to-severe valvular heart disease, atrial fibrillation, severe dementia, acute kidney injury, end-stage renal disease, wound infection, sepsis, or dexmedetomidine loading/high-dose maintenance exposure. The primary hemodynamic outcomes were the occurrences of SAP < 90 mmHg intraoperatively and in the PACU. Secondary outcomes included the difference between preanesthetic SAP and the lowest SAP recorded in the PACU (ΔSAP), PACU length of stay, vasopressor use, transfusion volume, hospital stay, and in-hospital complications. Results: SAP < 90 mmHg occurred more frequently with SA than GA intraoperatively (35.8% vs. 24.3%, p = 0.024) and in the PACU (39.3% vs. 24.9%, p = 0.005). SA was associated with lower estimated blood loss [400.0 (350.0–450.0) mL vs. 450.0 (400.0–500.0) mL, p < 0.001], greater phenylephrine and ephedrine requirements, longer PACU stay [30 (20–35) min vs. 25 (20–30) min, p < 0.001], and greater ΔSAP (46.98 ± 23.32 mmHg vs. 32.63 ± 23.12 mmHg, p < 0.001). Hospital stay, transfusion requirements, and 12-h visual analog scale scores did not differ significantly between groups, while major in-hospital complications were uncommon in both groups. Conclusions: In older patients undergoing elective THA, SA was associated with more frequent intraoperative and PACU hypotension than GA. These findings support closer blood pressure monitoring and timely hemodynamic intervention throughout surgery and early recovery.

Abstract: Horner's syndrome is an uncommon but recognised complication of neuroaxial analgesia in obstetrics procedures, with an incidence of 0.4-4%. The incidence is significantly higher than in non-obstetric patients. This case report describes a 28-year-old primigravida who developed unilateral Horner's syndrome approximately one hour after lumbar epidural analgesia placement for labour pain relief. Upon examination the patient presented with left-sided ptosis, anisocoria, and unexpected sensory blockade extending to the T3-T4 lev-el, accompanied by localised numbness in the left breast and transient upper limb paraesthesia. The pathophysiology of Horner's syndrome involves cephalad spread of local anaesthetic toward the superior cervical sympathetic chain, disrupting sympathetic innervation to the ocular and facial areas. Primary and secondary damage to the sympathetic pathways in the central nervous offer a wide differential diagnosis. The management was conservative, including reduction of epidural bolus infusion rates and careful monitoring. The patient experienced complete resolution of all symptoms within five hours and delivered vaginally without complications. This case demonstrates the charac-teristically benign and self-limited nature of this complication, emphasising the importance of clinical awareness, proper reassurance of patients, and avoidance of unnecessary diagnostic testing.

Abstract: Regenerative medicine restores tissue structure and function by regulating the biological processes that are involved in cellular survival, proliferation, differentiation, as well as tissue remodeling. Peptide-based therapeutics have gained popularity as regenerative tools related to their ability to precisely modulate the defined signaling pathways. Peptides provide high target specificity, biological activity, and translational flexibility while also serving as endogenous signaling molecules that can influence the regenerative processes. FGF-18, TB4, GHK-Cu, MOTS-c, and tesamorelin demonstrate diverse regenerative mechanisms which include cartilage repair, wound healing, extracellular matrix remodeling, and tissue remodeling. Current evidence supports strong regenerative effects in preclinical studies, with clinical translation seen as well. Major barriers include limited bioavailability and delivery challenges. Continued advances in peptide engineering, delivery, and clinical evaluation will all be necessary to establish their long-term therapeutic role in regenerative medicine. This review evaluates peptide-based regenerative therapies by examining mechanisms of action, clinical evidence, and current translational status.

Abstract: Background: Continuous epidural analgesia is widely used for postoperative pain management in neonates and small-weight infants. Epidural catheters may be inserted via a caudal-threaded approach or by direct lumbar/thoracic placement; however, comparative data on placement success, clinical use, postoperative analgesic outcomes, and complications remain limited. This study compared these two epidural techniques in neonates and small-weight infants undergoing surgery.Methods: This retrospective observational cohort study included all neonates and infants admitted to the Neonatal Intensive Care Unit at UPMC Children's Hospital of Pittsburgh who underwent attempted epidural catheter placement between January 2018 and December 2024. Demographic and perioperative data were extracted from the electronic medical record. Outcomes included patient, surgical, and epidural characteristics, epidural medications, postoperative pain and sedation scores, opioid consumption, technical success of catheter placement, and epidural catheter complications. Results: A total of 104 patients underwent attempted epidural catheter placement; five procedures were unsuccessful in four patients, resulting in 100 successful epidural catheter placements (70 caudal-threaded and 30 direct lumbar/thoracic). Epidural catheter placement was successful in 96.2% of patients. Patient and surgical characteristics, postoperative pain and sedation scores, and opioid consumption were similar between groups. Direct lumbar/thoracic epidural catheter placement required longer procedure times. Patients in the direct lumbar/thoracic epidural group were more likely than those in the caudal-threaded group to receive a ropivacaine/clonidine infusion (47% vs. 4%; p < 0.001) and a programmed intermittent bolus of epidural infusion (60% vs. 3%; p < 0.001). The direct lumbar/thoracic group experienced more postoperative catheter-related complications than the caudal-threaded group (20% vs. 4%; p = 0.02), primarily catheter leakage requiring premature catheter removal. Conclusions: Caudal-threaded and direct lumbar/thoracic epidural catheters provided comparable postoperative analgesic outcomes in neonates and small-weight infants when placed by a Pediatric Acute Pain Service. Direct lumbar/thoracic epidural catheters were associated with a higher incidence of postoperative catheter leakage and premature catheter removal. These findings may help clinicians select the most appropriate epidural technique for postoperative pain management in this population.

Abstract: Background: Non-odontogenic toothache often persists without an identifiable dental cause and may lead to unnecessary pulpectomy or tooth extraction. It may also result in long-term combined use of psychotropic medications, forming an entrenched clinical vicious cycle. Ultrasound-guided fascia hydrorelease (US-FHR) targeting fascia-derived pathology can be used to treat non-odontogenic toothache; however, treatment regions have not been systematically described. Aim: This article presents an eleven-point US-FHR protocol for non-odontogenic toothache and related orofacial pain, and provides a shared practical framework for pain physicians, dentists, physical therapists, and acupuncturists. Methods: The protocol was organized based on a focused literature search and long-term clinical experience at Kimura Pain Clinic. For each POINT, the anatomical rationale, referred-pain pattern, procedural concept, and major safety considerations were summarized. Results: The protocol comprises 11 POINTs distributed across six anatomical regions: (1) three POINTs in the masticatory muscle region, (2) three POINTs in the medial pterygoid and capsular region, (3) one POINT in the parotid region, (4) two POINTs in the cervical region, (5) one POINT in the facial-artery region, and (6) one POINT in the upper posterior cervical region. For each POINT, the anatomical rationale, referred-pain pattern, procedural concept, and safety considerations are integrated and described. Conclusions: The proposed eleven-point protocol represents an expanded and structured development of the earlier four-region approach. It may serve as a practical basis for the standardization, education, and broader dissemination of US-FHR in non-odontogenic toothache and orofacial pain, although prospective observational studies are needed to evaluate its clinical effectiveness.

Abstract: Paclitaxel chemotherapy frequently induces debilitating paclitaxel-induced peripheral neuropathic pain, which lacks effective treatments. This study demonstrates that dorsomorphin alleviates paclitaxel-induced peripheral neuropathic pain in mice by targeting neuroinflammation and pain pathways. Administering dorsomorphin (8 mg/kg, i.p.) alongside paclitaxel signifi-cantly reduced mechanical allodynia (von Frey test), thermal hyperalgesia (hot-plate test), and cold hyperalgesia (acetone test) compared to paclitaxel alone. Mechanistically, dorsomorphin suppressed spinal neuroinflammation by inhibiting microglial activation, reducing NF-κB pathway activity, and lowering pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in serum. Dorsomorphin also modulated key pain mediators, downregulating sodium channel Scn1a and lysophosphatidic acid (LPA) expression in the spinal cord. Crucially, dorsomorphin synergized with paclitaxel in A549 lung cancer cells in vitro, en-hancing the suppression of proliferation (CCK-8 assay), migration, and invasion (Transwell assays) at combined doses (e.g., 5 nM paclitaxel + 5 μM dorsomorphin) without compromising paclitaxel’s antitumor efficacy. These findings reveal dor-somorphin’s dual role: it mitigates paclitaxel-induced peripheral neuropathic pain by inhibiting neuroinflammation (via NF-κB/microglia/cytokines) and pain pathways (LPA/Scn1a), while concurrently enhancing paclitaxel’s anticancer activity. Dorsomorphin thus represents a promising adjunctive therapy for managing chemotherapy-induced neuropathy and im-proving treatment outcomes.

Abstract: Background Airway contamination during regurgitation, emesis, or aspiration represents a time-critical emergency in pediatric airway management. Although larger suction devices have demonstrated superior performance in open-container and adult simulation models, it remains uncertain whether these findings translate to anatomically constrained pediatric airways. We sought to determine how airway anatomy and fluid viscosity influence suction performance by comparing a Yankauer suction tip and a 14 French suction catheter in both an infant airway mannequin and an unconstrained open-container model. Methods This pilot simulation study used two complementary experimental models: an anatomically constrained infant airway mannequin and an unconstrained open-container model. Three fluids of progressively increasing viscosity (water, whole milk, and plain yogurt) were evaluated using a Yankauer suction tip and a 14 Fr flexible suction catheter under standardized suction pressure. In the mannequin model, suction time, pharyngeal volume evacuated, residual pharyngeal/esophageal volume, and recovered lung volume were measured. In the open-container model, time required for complete evacuation was recorded. Results In the infant airway mannequin, suction times differed minimally between devices, with the Yankauer demonstrating faster evacuation only for water. However, the Yankauer consistently evacuated larger pharyngeal volumes than the 14 Fr catheter across all fluids, with the greatest difference observed for yogurt. Residual pharyngeal/esophageal volume was similar for water and milk but differed for yogurt, suggesting that the flexible catheter may have improved access to anatomically restricted regions despite lower intrinsic suction capacity. Recovered lung volumes did not differ significantly between devices. In contrast, the unconstrained open-container model demonstrated substantially superior intrinsic suction performance of the Yankauer, particularly for high-viscosity material; the 14 Fr catheter was unable to completely evacuate yogurt within five minutes in any trial. Conclusions Airway anatomy and fluid viscosity substantially influence suction performance during simulated pediatric airway contamination. Although the Yankauer demonstrated superior intrinsic suction capability, anatomical constraints reduced the magnitude of these differences within the infant airway model. These findings suggest that data derived from unconstrained bench-top studies should not be directly extrapolated to pediatric airway management and support a complementary suction strategy using rigid suction for rapid bulk decontamination followed by flexible catheter suction for anatomically inaccessible regions.

Abstract: Tracheal intubation in patients at risk of acute hypoxemic respiratory failure (AHRF) carries a high risk of life-threatening desaturation, and the choice of peri-intubation oxygenation strategy critically influences patient safety. This narrative review synthesizes current evidence on non-invasive oxygenation techniques—high-flow nasal oxygen (HFNO), non-invasive ventilation (NIV), and their combination—across the pre-oxygenation, apneic, and awake-intubation phases of airway management. We examine the physiological mechanisms underlying each modality, appraise landmark randomized trials and meta-analyses (including PREOXI, OPTINIV, and OPTIMASK), and address disease-specific considerations in chronic obstructive pulmonary disease, heart failure, interstitial lung disease, severe obesity, obstructive sleep apnea, and obstetric, pediatric, and trauma populations. The evidence supports a phenotype-driven hierarchy rather than a single dominant technique: NIV—optionally combined with HFNO for apneic oxygenation—is preferred in severely hypoxemic critically ill patients, whereas HFNO alone is adequate for many moderately hypoxemic or non-hypoxemic patients. Progressive hypercapnia limits apneic oxygenation, particularly in chronic CO₂ retainers, underscoring the value of continuous CO₂ monitoring. Persistent under-implementation of NIV-based pre-oxygenation reveals a gap between evidence and practice. Individualized, physiology-guided oxygenation—aligned with the goals of personalized peri-procedural medicine—offers the greatest potential to reduce peri-intubation morbidity.

Abstract: Cridanimod (acridoneacetic acid), the active ingredient of the immunomodulatory drug Cycloferon®, has a well-characterized antiviral profile, but an unexplored analgesic potential. Bornane monoterpenes, notably (+)-camphor and (−)-fenchone, are established scaffolds for analgesic drug design. We therefore synthesized thirteen cridanimod–monoterpene conjugates — seven amides, three acylhydrazones, and three esters — by EDC/DMAP-mediated coupling or CDI/DBU-promoted esterification, and evaluated them in mice at an oral dose of 10.0 mg/kg in the acetic acid writhing and hot plate tests, with diclofenac sodium (10.0 mg/kg) as the reference. Acridoneacetic acid and Cycloferon® were themselves inactive in both assays. By contrast, six of the thirteen conjugates were significantly active (p < 0.05) in at least one test, with distinct leads in each: amide 19 matched diclofenac in the writhing test (−63.7% vs −64.4%), whereas acylhydrazone 23 exceeded diclofenac in the hot plate test (+43.9% vs +25.7%). The divergent profiles suggest that different structural subclasses engage peripheral and central antinociceptive mechanisms. Conjugation thus converts an analgesically inactive immunomodulator into a substance yielding analgesics that match or exceed a standard NSAID at the same oral dose, providing a promising starting point for the development of new pain-relieving agents.

Abstract:

Background: Midazolam is widely used as pediatric premedication, but evidence directly comparing oral and sublingual administration in children with congenital heart disease remains limited, particularly when pharmacokinetic and physiologic data are analyzed together. Methods: We conducted a single-center prospective randomized study comparing oral midazolam 0.5 mg/kg with sublingual midazolam 0.3 mg/kg in children undergoing cardiac surgery or catheterization procedures under general anesthesia. Plasma midazolam and 1-hydroxymidazolam concentrations were measured approximately 30 minutes after administration. Log-transformed concentrations were compared using regression/ANCOVA models adjusted for dose and age. Changes in mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) were analyzed from baseline to 15 and 30 minutes. Behavioral outcomes included sedation score, separation from parents, and mask acceptance. Results: Sixty-eight children were randomized; 65 had evaluable pharmacokinetic samples and formed the complete-case pharmacokinetic cohort. Adjusted plasma midazolam concentrations did not differ significantly between groups, with an adjusted geometric mean ratio for sublingual versus oral administration of 0.98 (95% CI 0.53-1.79; p=0.940). The corresponding ratio for 1-hydroxymidazolam was 1.37 (95% CI 0.55-3.41; p=0.494). HR and SpO2 changes were similar between groups. At 30 minutes, sublingual administration was associated with a lower adjusted change in MAP compared with oral administration (adjusted difference -12.08 mmHg, 95% CI -19.74 to -4.42; p=0.002). Behavioral outcomes were comparable between groups. Conclusions: In this prospective randomized pediatric cardiac cohort, oral midazolam 0.5 mg/kg and sublingual midazolam 0.3 mg/kg produced comparable plasma concentrations and similar behavioral outcomes. Sublingual administration was not associated with worse HR or SpO2 responses, although an isolated lower MAP change at 30 minutes warrants confirmation in larger studies. Sublingual midazolam may represent a feasible lower-dose alternative for premedication in this population.

Abstract: Albumin administration in sepsis and septic shock remains controversial because of uncertain clinical benefits and complex acid–base effects. Unlike crystalloids, albumin influences acid–base equilibrium through effects on chloride balance, strong ion dif-ference (SID), buffering systems, and weak acid concentration. These effects may be in-terpreted differently by the traditional bicarbonate-centered framework and Stewart’s physicochemical approach. In the traditional paradigm, albumin acts mainly as a non-bicarbonate plasma buffer influencing base excess and anion gap interpretation. In the Stewart framework, albumin is a weak non-volatile acid contributing to total weak ac-ids (Atot), thereby influencing hydrogen ion dissociation and pH regulation. This nar-rative review compares these two approaches to albumin-related acid–base physiolo-gy in sepsis, with emphasis on chloride balance, strong ion difference, hypoalbu-minemia, dilutional effects, and cardiorespiratory interactions during mechanical ven-tilation and septic shock. We also contextualize these mechanisms within major ran-domized trials of albumin and resuscitation fluids and provide conceptual simulations illustrating the directional acid–base effects of different fluid compositions. The review focuses on masked acidosis in hypoalbuminemic patients and on the interpretation of pH changes after albumin administration. Finally, we propose an integrated bedside framework combining traditional, physicochemical, respiratory, and hemodynamic variables for acid–base interpretation during fluid resuscitation.

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.