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Effectiveness of Erector Spinae Plane Block as Perioperative Analgesia in Midline Sternotomies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
No full textWith the advancements in regional anesthesia and ultrasound techniques, the use of non-neuraxial blocks like the erector spinae plane block (ESPB) has been increasing in cardiac surgeries with promising outcomes. A total of 3,264 articles were identified through a literature search. Intervention was defined as ESPB. Comparators were no regional technique performed or sham blocks. Four studies with a total of 226 patients were included. Postoperative opioid consumption was lower in the group that received ESPB than the group that did not (weighted mean difference [WMD]: -204.08; 95% CI: -239.98 to -168.19; P \u3c 0.00001). Intraoperative opioid consumption did not differ between the two groups (WMD: -398.14; 95% CI: -812.17 to 15.98; P = 0.06). Pain scores at 0 hours were lower in the group that received ESPB than the group that did not (WMD: -1.27; 95% CI: -1.99 to -0.56; P = 0.0005). Pain scores did not differ between the two groups at 4-6 hours (WMD: -0.79; 95% CI: -1.70 to 0.13; P = 0.09) and 12 hours (WMD: -0.83; 95% CI: -1.82 to 0.16; P = 0.10). Duration of mechanical ventilation in minutes was lower in the group that received ESPB than the group that did not (WMD: -45.12; 95% CI: -68.82 to -21.43; P = 0.0002). Given the limited number of studies and the substantial heterogeneity of measured outcomes and interventions, further studies are required to assess the benefit of ESPB in midline sternotomies
Obesity Paradox in Transcatheter Aortic Valve Replacement
No full textBACKGROUND: Obesity paradox in cardiovascular risk prediction has gained increasing attention in recent years. We aimed to investigate the impact of BMI on mortality following transcatheter aortic valve replacement (TAVR).
METHODS: We performed a multi-center retrospective analysis of patients with severe aortic stenosis undergoing TAVR. Patients were categorized into: Underweight (BMI \u3c 18.5), normal weight (18.5 ≤ BMI \u3c 25), overweight (25 ≤ BMI \u3c 30) and obese (BMI ≥ 30). Multivariate cox-proportional hazard model was used to compare all-cause mortality.
RESULTS: Total of 6688 patients included (175 underweight, 2252 normal weight, 2368 overweight and 1893 with obesity). Mean age of patients was 81 ± 8 years with 55% males. Patients with obesity had higher prevalence of comorbidities but a lower overall STS score. Mortality at 30-days post-TAVR was lower in the obese population compared to underweight, normal weight, and overweight patients (1.6% vs. 6.9%, 3.6%, and 2.8%, respectively, p \u3c 0.001). Similarly, 3-year mortality was lowest in patients with obesity (17.1% vs. 28.9%, 24.5% and 18.6%, respectively, p \u3c 0.001). On multivariate analysis, long term all-cause mortality at 3-years remained significantly lower in patients with obesity compared to underweight (HR 1.74, 95% CI: 1.30-2.40, p \u3c 0.001) and normal weight (HR: 1.41, 95% CI:1.21-1.63, p \u3c 0.001) but not in overweight patients (HR: 1.10, 95% CI:0.94-1.28, p = 0.240).
CONCLUSION: In conclusion, patients with obesity have improved short and long term mortality following TAVR with an observed progressive increase in mortality with lower BMI ranges
Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials
No full textBACKGROUND: Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials.
METHODS: ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator\u27s Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349).
FINDINGS: Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p\u3c0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred.
INTERPRETATION: Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved.
FUNDING: Galderma
Multi-organ Thromboembolic Crisis: A Case Report of Concomitant Stroke, Myocardial Infarction, and Pulmonary Embolism
No full textManagement of acute coronary syndrome (ACS), cerebrovascular accident (CVA), and pulmonary embolism (PE) necessitates prompt intervention, as delayed treatment may lead to severe consequences. Each of these conditions presents significant challenges and carries a high risk of morbidity and mortality. We present the case of an 86-year-old female with a history of stage 4 urothelial carcinoma metastasized to the lungs, who presented to the emergency department (ED) with acute ischemic stroke (AIS), ST-segment elevation myocardial infarction (STEMI), and bilateral PE. We propose the term multi-organ thromboembolic crisis (MOTEC) to streamline the communication and management approach for patients experiencing critical thromboembolic events affecting multiple organ systems
Alliance A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer
No full textBACKGROUND: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes.
METHODS: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org .
DISCUSSION: Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer.
TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG)
Malnutrition Severity Predicts Clinical Outcomes in Alcoholic Hepatitis: Evidence from National Data
No full textOBJECTIVE: Alcoholic hepatitis (AH) represents a severe manifestation of alcoholic liver disease (ALD) associated with a wide severity spectrum. ALD is linked to nutritional deficiencies, with the gravity of malnutrition escalating as alcohol abuse and ALD progress. This study aims to delve into the impact of malnutrition on the clinical trajectory of AH.
METHODS: We identified adult patients admitted with AH using the National Readmission Database (NRD) 2016-2020. We further classified AH patients based on the severity of malnutrition. We compared the outcomes of AH hospitalizations using a multivariate regression model.
RESULTS: We included 82,367 AH patients, of whom 15,693 (19.00%) had malnutrition. 4,243 (5.15%) patients exhibited mild to moderate malnutrition, 5,862 (7.07%) patients had severe malnutrition, and 5,588 (6.78%) patients had unspecified severity of malnutrition. We found that adjusted in-hospital mortality due to AH was higher in patients with malnutrition, corresponding to the severity of malnutrition (adjusted odds ratio [aOR] 1.62 and 3.14 in mild-moderate malnutrition and severe malnutrition, respectively; p \u3c .01). Additionally, patients with malnutrition had progressively elevated odds of septic shock, vasopressor requirement, mechanical ventilation, and intensive care unit (ICU) admission with escalating intensity of malnutrition. Liver-related complications, such as spontaneous bacterial peritonitis, coagulopathy, hepatorenal syndrome, and hepatic encephalopathy, were also found to have an increased likelihood in the presence of malnutrition. Furthermore, resource utilization showed a progressive increase with increasing severity of malnutrition.
CONCLUSION: Our findings indicate that malnutrition is a common comorbidity in AH patients, with varying degrees of severity, which correlates with higher mortality rates, emphasizing the critical role of nutritional status in the prognosis of AH. These findings underscore the importance of addressing and managing malnutrition in patients with AH, not only for its potential contribution to mortality but also because of its association with a spectrum of complications and increased healthcare resource utilization
Endoscopic ultrasound-guided antegrade treatment versus balloon enteroscopy endoscopic retrograde cholangiopancreatography for choledocholithiasis in patients with Roux-en-Y gastric bypass: a systematic review and meta-analysis
No full textBACKGROUND: The safety and technical success of endoscopic ultrasound-guided antegrade treatment (EUS-AG) compared to balloon enteroscopy-assisted endoscopic cholangiopancreatography (BE-ERCP) for choledocholithiasis in Roux-en-Y gastrectomy has not been well documented. We performed a systematic review and meta-analysis to assess the safety and efficacy of the 2 procedures.
METHODS: A systematic search of multiple databases was undertaken through January 25, 2024, to identify relevant studies comparing the 2 procedures. Standard meta-analysis methods were employed using a random-effects model. For each outcome, risk-ratio (RR), 95% confidence interval (CI), and P-values were generated. P\u3c0.05 was considered significant. Heterogeneity was assessed using the I (2) statistic.
RESULTS: Three studies with 795 patients (95 in the EUS-AG group and 700 in the BE-ERCP group) were included. The technical success rate was similar between EUS-AG and BE-ERCP (RR 1.08, 95%CI 0.84-1.38; P=0.57; I (2)=56%). The overall rate of adverse effects was higher in the BE-ERCP group than in the EUS-AG group (RR 1.95, 95%CI 1.21-3.15; P=0.006; I (2)=0 %). Rates of clinical success, pancreatitis, perforation, and bile peritonitis were similar between the 2 procedure techniques.
CONCLUSIONS: Our analysis showed no distinct advantage in using one technique over the other for patients with Roux-en-Y anatomy in achieving technical and clinical success. However, the incidence of adverse effects was greater in the BE-ERCP group than in the EUS-AG group
Population-based approaches for reducing stroke risk: an update on their success and the challenges ahead
No full textINTRODUCTION: Stroke is a significant public health challenge as it is the second most common cause of death and the third leading cause of disability globally. Additionally, stroke incidence and the number of stroke deaths have been rising. Efforts to prevent stroke have been made, including high-risk approaches where patients are screened for cardiovascular risk factors, and population-based approaches which attempt to reduce stroke rates by improving overall population health.
AREAS COVERED: We summarize studies of population-based approaches to stroke prevention involving greater than 1,000 participants identified on a PubMed database search. Based on these programs, challenges of population-based stroke prevention programs are discussed and potential keys to success are highlighted.
EXPERT OPINION: Population-based stroke prevention programs face challenges including cost and interest of the public and certain stakeholders. Additionally, secular trends for improvement in risk factors and catastrophic adverse environmental circumstances add to the complexity of analyzing program success. Factors leading to successful programs include validated digital solutions for self-monitoring of risks, backing by global policy and legislation, flexibility to the needs of the population, intersectoral programs, community engagement, information dissemination back to the populations, and high-risk screening to develop a complementary combination approach to stroke prevention
Odds of Attaining Orthopaedic Leadership Based on Race, Ethnicity, and Sex
No full textBACKGROUND: Despite widespread acceptance of the importance of diversity in leadership, systemic challenges in leadership attainment in orthopaedic surgery still exist for several groups. We hypothesize that women, underrepresented in medicine groups, and Asians have decreased odds of achieving program director and chairperson positions compared with peers.
METHODS: Demographic data were collected from the Association of American Medical Colleges for faculty, program directors, and chairpersons in orthopaedic surgery. Odds ratios were calculated treating race, ethnicity, or sex as the predictor variables and attainment of a leadership position as the outcome, comparing the composition of program directors in 2020 and chairpersons in 2019 with faculty in 2019.
RESULTS: Significantly decreased odds were found for women at 0.37 (0.264 to 0.51 [P \u3c 0.0001]) and the Other category at 0.16 (0.065 to 0.3864 [P = 0.0001]) while significantly increased odds were found for White and Black/African American faculty at 1.32 (1.02 to 1.71 [P = 0.0314]) and 1.95 (1.17 to 3.26 [P = 0.011]), respectively, in holding program director positions. Significantly decreased odds of attaining chairpersonship were found for women at 0.17 (0.07 to 0.41 [P = 0.0075]) and Asian faculty at 0.33 (0.14 to 0.75 [P = 0.0062]) while White faculty demonstrated significantly increased odds at 2.43 (1.41 to 4.19 [P = 0.0013]).
CONCLUSIONS: Women showed markedly decreased odds of leadership attainment while Black/African American faculty had increased likelihood of becoming program directors but were not markedly more likely to become chairs. Asian faculty were less likely to become program directors and markedly less likely to become chairs. While decreased odds for women were expected based on current literature, decreased odds of Asians becoming chairs and an increased likelihood of Black/African American orthopaedic surgeons becoming program directors but not attaining the role of chairs at the same rate were novel findings, revealing concerning trends for these groups
