Dnipropetrovsk State Medical Academy

Acute postoperative pain after emergency laparoscopic cholecystectomy for acute cholecystitis is multifactorial and may limit early mobilization and recovery. A promising strategy is to integrate ultrasound-guided fascial plane blocks into standard multimodal analgesia in order to improve early postoperative pain control and optimize early recovery parameters. Objective. To compare the effectiveness of postoperative analgesia and early recovery outcomes with standard multimodal pharmacological analgesia versus its combination with an erector spinae plane (ESP) block in patients with acute cholecystitis undergoing emergency laparoscopic surgery. Materials and Methods. Sixty patients with acute cholecystitis (2024–2025), ASA physical status I–III, aged 44–60 years, were randomized by the sealed-envelope method into two groups (n=30 each). The control group received acetaminophen 1000 mg every 8 hours and dexketoprofen 50 mg every 8 hours. In the ESP group, the standard regimen was supplemented with a right-sided ESP block at Th7–Th9 performed at the end of surgery before emergence (20 mL of 0.25% bupivacaine, with adherence to a maximum local anesthetic dose of up to 2 mg/kg). Outcomes included pain intensity assessed by the visual analog scale (VAS) at rest and on movement, heart rate (HR), mean arterial pressure (MAP), blood glucose level, incidence of postoperative nausea and vomiting (PONV), time to return of bowel peristalsis (ultrasound-confirmed), time to first ambulation, opioid requirement, subjective sleep quality, daytime sleepiness (Epworth Sleepiness Scale), and anxiety assessed by the Beck Anxiety Inventory and the Hospital Anxiety and Depression Scale (HADS; anxiety/depression subscales). Statistical analysis included parametric (ANOVA) and nonparametric methods. Results. Baseline clinical and psycho-emotional parameters were comparable between groups. Compared with standard multimodal pharmacological analgesia, the addition of an ESP block was associated with lower early postoperative pain scores: most notably, VAS at rest at 4 hours was 3.9±0.5 in the control group versus 1.5±0.4 in the ESP group (p<0.001); VAS on movement at 2 hours was 4.4±0.3 versus 3.1±0.4, respectively (p<0.001). Thereafter, between-group differences in pain at rest diminished after 24 hours. Rescue opioid analgesia was required in 2/30 (6.7%) patients in the control group, whereas no opioid requirement was recorded in the ESP group. PONV incidence did not differ significantly between groups over time (all p>0.05). The ESP group demonstrated faster recovery of bowel motility (time to peristalsis: 11.2±3.2 h vs 20.4±4.2 h in the control group; p<0.001) and earlier first ambulation (5.4±1.0 h vs 7.9±1.1 h, respectively; p<0.001). On postoperative day 1, the ESP group showed lower daytime sleepiness on the Epworth scale (5.5±0.8 vs 7.6±0.6 in the control group; p<0.001) and lower anxiety scores on both the Beck scale (3.8±0.6 vs 9.3±0.5, respectively; p<0.001) and the HADS-Anxiety subscale (6.8±0.7 vs 9.3±1.3, respectively; p<0.001), together with a higher subjective sleep-quality rating. By postoperative days 3 and 5, between-group differences across most outcomes gradually attenuated. Conclusions. In patients with acute cholecystitis undergoing emergency laparoscopic cholecystectomy, combining standard multimodal pharmacological analgesia with a right-sided ESP block (Th7–Th9) provides more effective pain control in the first postoperative hours (particularly during mobilization), reduces the need for rescue opioid analgesia, is associated with a lower early sympathetic response (heart rate), accelerates the recovery of bowel motility and early mobilization, and is accompanied by better early sleep- and anxiety-related outcomes without affecting the incidence of PONV.

Introduction. Electrical burns are a major cause of high mortality and morbidity rates worldwide. The leading cause of death in such cases is usually refractory myoglobinuric acute kidney injury (AKI). Evidence collection. A retrospective informative search was conducted using a spatial–vector descriptive model supplemented by a manual search for relevant articles. Matherials and methods. The scientific literature was found using the search engines Scopus, CrossRef, Google Scholar and PubMed. Evidence synthesis. Victims of electrical trauma frequently develop significant hypovolemia as a result of massive tissue damage caused by extravascular fluid leakage (sequestration), which leads to a further reduction of intravascular volume. Hypovolemia due to extravascular fluid loss may result in prerenal azotemia and acute tubular necrosis, typically aggravated by untimely or insufficient fluid resuscitation. Progressive ischemia in electrical injury, together with edema and tissue necrosis, induces metabolic acidosis, perpetuating a vicious cycle. The renal form of AKI is caused by acute tubular necrosis resulting from renal hypoperfusion, hemolysis, rhabdomyolysis, and inter-fascial compartment syndrome. Three major mechanisms are involved in the pathogenesis of AKI: intrarenal vasoconstriction, formation of hemoglobin or myoglobin casts in distal renal tubules, and the direct cytotoxic effect of myoglobin on nephron endothelium. Rhabdomyolysis occurs in 14–42 % of electrical burn cases. Because the definitions of rhabdomyolysis vary widely, the exact incidence of AKI in rhabdomyolysis is difficult to establish but is estimated to range from 13 % to 48 %. Free myoglobin enters the systemic circulation because of massive skeletal muscle necrosis (rhabdomyolysis) and may lead to pigment-induced acute kidney injury. A blood pH below 7.2 is an indication for bicarbonate infusion until normalization (but not beyond). The only effective treatment for AKI patients with elevated creatinine and potassium levels is renal replacement therapy. Conclusions. The main etiological factor of AKI in electrical injury is the presence of free hemoglobin or myoglobin in the bloodstream. Timely and adequate fluid resuscitation prevents and limits AKI in electrical trauma. The combined use of intermittent and prolonged veno-venous hemodiafiltration represents the optimal methods of extracorporeal detoxification in myoglobinemia.

INTRODUCTION:In the phase 3 CASPIAN study, first-line durvalumab plus etoposide combined with either carboplatin or cisplatin (EP) significantly improved overall survival (OS) versus EP alone in treatment-naïve extensive-stage small-cell lung cancer (ES-SCLC). We report exploratory subgroup analyses from CASPIAN. METHODS:Patients with untreated ES-SCLC were randomized to durvalumab plus EP or EP alone. We analyzed OS and safety in subgroups defined by age, sex, and planned platinum agent, and patient-reported outcomes (PROs) by age. RESULTS:Of 537 patients (durvalumab plus EP: n = 268; EP alone: n = 269), 80.6% versus 19.4% were aged <70 versus ≥70 years; 69.6% versus 30.4% were male versus female; and planned platinum was cisplatin versus carboplatin in 25.1% versus 74.9%. The OS HRs for durvalumab plus EP versus EP were 0.71 (95% CI, 0.58-0.88) versus 0.74 (95% CI, 0.49-1.11) for patients aged <70 versus ≥70 years; 0.76 (95% CI, 0.62-0.95) versus 0.60 (95% CI, 0.42-0.84) for males versus females; and 0.65 (95% CI, 0.45-0.94) versus 0.74 (95% CI, 0.60-0.91) for planned cisplatin versus carboplatin. With durvalumab plus EP, rates of grade 3/4 adverse events (AEs) were similar across subgroups; serious AEs were more frequent in patients aged ≥70 versus <70 years; and immune-mediated AEs were more common in females versus males. Adding durvalumab to EP had no detrimental effect on PROs in either age subgroup. CONCLUSIONS:These findings support the use of durvalumab plus EP as first-line standard of care for ES-SCLC. Additional trials focused on elderly populations would be informative.

Tiragolumab (tira) + atezolizumab (atezo) has shown encouraging survival outcomes in pts with metastatic NSCLC, primarily in pts with PD-L1-high tumors (tumor proportion score [TPS] ≥50%). SKYSCRAPER-01 (NCT04294810) is a phase III, double-blind, placebo-controlled, randomized trial investigating the efficacy and safety of first-line tira + atezo in pts with PD-L1-high NSCLC. Eligible pts (previously untreated; PD-L1-high, locally advanced unresectable/metastatic NSCLC; EGFR/ALK wildtype) were randomized 1:1 to receive tira 600 mg IV + atezo 1200 mg IV or pbo + atezo 1200 mg IV every 3 weeks until disease progression, loss of clinical benefit, or unacceptable toxicity. Primary endpoints: investigator-assessed progression-free survival (INV-PFS) and overall survival (OS) in the primary analysis set (PAS; TPS ≥50%; 22C3 assay). Secondary endpoints: INV-objective response rate (INV-ORR) and INV-duration of response (INV-DOR) in the PAS; OS in the secondary analysis set (SAS; tumor cell [TC] ≥50%; SP263 assay). A total of 534 pts were randomized (tira + atezo, n=266; pbo + atezo, n=268). Pt characteristics were balanced between treatment arms. At the final PFS analysis (data cut-off 12 Mar 2022; median follow-up 9.9 months), median INV-PFS was 7.0 months with tira + atezo and 5.6 months with pbo + atezo (HR 0.78; 95% CI 0.63, 0.97; p=0.02; PAS). At the final OS analysis (data cut-off 24 Sep 2024; median follow-up 17.9 months), median OS was 23.1 months with tira + atezo and 16.9 months with pbo + atezo (HR 0.87; 95% CI 0.71, 1.08; p=0.22; PAS; Table). Tira + atezo demonstrated an acceptable safety profile, consistent with previous observations. Table PAS (TPS ≥50% per 22C3 assay) Tira + atezo Pbo + atezo (n=262) (n=259) Median PFS, months (95% CI)*† 7.0 (5.6, 9.8) 5.6 (4.4, 7.0) HR (95% CI); p-value 0.78 (0.63, 0.97); p=0.02 Median OS, months (95% CI)*† 23.1 (17.7, 28.8) 16.9 (14.6, 23.1) HR (95% CI); p-value 0.87 (0.71, 1.08); p=0.22 ORR, %* 45.8 35.1 Median DOR, months (95% CI)* 18.0 (13.6, 24.4) 14.6 (9.7, 18.6) SAS (TC ≥50% per SP263 assay) Tira + atezo Pbo + atezo (n=211) (n=209) Median OS, months (95% CI)* 24.6 (17.9, 32.0) 20.6 (16.6, 29.3) HR (95% CI) 0.93 (0.73, 1.18) Safety evaluable set ‡ Tira + atezo Pbo + atezo (n=267) (n=263) Any grade AEs, % 95.9 91.3 Grade 3-4 AEs, % 41.2 33.8 Grade 5 AEs, % 10.9 9.9 Treatment-related grade 5 AEs, % 1.5 0.8 AEs leading to treatment withdrawal, % 16.1 6.5 Any grade AESIs, % 70.0 50.6 * PFS analysis: data cut-off 12 Mar 2022 (PFS final analysis/first OS interim analysis); OS ORR, and DOR analysis: data cut-off 24 Sep 2024 (OS final analysis). PFS, ORR and DOR were assessed by the investigator. † Primary endpoints. ‡ All randomized patients who received ≥1 dose of study treatment. AE, adverse event; atezo, atezolizumab; AESIs, adverse events of special interest; CI, confidence interval; DOR, duration of response; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PAS, primary analysis set; pbo, placebo; PFS, progression-free survival; SAS, secondary analysis set; TC, tumor cell; tira, tiragolumab; TPS, tumor proportion score. The primary endpoints of INV-PFS and OS were not met in the SKYSCRAPER-01 study. Numerical improvements in both PFS and OS with tira + atezo versus pbo + atezo suggest potential antitumor activity of TIGIT targeting in NSCLC. Solange Peters, Roy Herbst, Hidehito Horinouchi, Luis Paz-Ares, Melissa Johnson, Benjamin Solomon, Mahmut Gumus, Mustafa Erman, Igor Bondarenko, Dong-Wan Kim, Enriqueta Felip, Alessandro Morabito, Maciej Bryl, Raymond Meng, Chipman Stroud, Palak Kundu, Xiaohui Wen, Namrata Patil, Meilin Huang, Byoung Chul Cho. SKYSCRAPER-01: A phase III, randomized trial of tiragolumab (tira) + atezolizumab (atezo) versus placebo (pbo) + atezo in patients (pts) with previously-untreated PD-L1-high, locally advanced unresectable/metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT051.