Maintenance therapy for chronic lymphocytic leukaemia.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in adults and currently remains incurable. As the progression-free period shortens after each successive treatment, strategies such as maintenance therapy are needed to improve the degree and duration of response to previous therapies. Monoclonal antibodies, immunomodulatory agents, and targeted therapies are among the available options for maintenance therapy. People with CLL who achieve remission after previous therapy may choose to undergo medical observation or maintenance therapy to deepen the response. Even though there is widespread use of therapeutic maintenance agents, the benefits and harms of these treatments are still uncertain. OBJECTIVES: To assess the effects and safety of maintenance therapy, including anti-CD20 monoclonal antibody, immunomodulatory drug therapy, anti-CD52 monoclonal antibody, Bruton tyrosine kinase inhibitor, and B-cell lymphoma-2 tyrosine kinase inhibitor, for individuals with CLL. SEARCH METHODS: We conducted a comprehensive literature search for randomised controlled trials (RCTs) with no language or publication status restrictions. We searched CENTRAL, MEDLINE, Embase, and three trials registers in January 2022 together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included RCTs with prospective identification of participants. We excluded cluster-randomised trials, cross-over trial designs, and non-randomised studies. We included studies comparing maintenance therapies with placebo/observation or head-to-head comparisons. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We assessed risk of bias in the included studies using Cochrane's RoB 1 tool for RCTs. We rated the certainty of evidence for the following outcomes using the GRADE approach: overall survival (OS), health-related quality of life (HRQoL), grade 3 and 4 adverse events (AEs), progression-free survival (PFS), treatment-related mortality (TRM), treatment discontinuation (TD), and all adverse events (AEs). MAIN RESULTS: We identified 11 RCTs (2393 participants) that met the inclusion criteria, including seven trials comparing anti-CD20 monoclonal antibodies (mAbs) (rituximab or ofatumumab) with observation in 1679 participants; three trials comparing immunomodulatory drug (lenalidomide) with placebo/observation in 693 participants; and one trial comparing anti-CD 52 mAbs (alemtuzumab) with observation in 21 participants. No comparisons of novel small molecular inhibitors were found. The median age of participants was 54.1 to 71.7 years; 59.5% were males. The type of previous induction treatment, severity of disease, and baseline stage varied among the studies. Five trials included early-stage symptomatic patients, and three trials included advanced-stage patients (Rai stage III/IV or Binet stage B/C). Six trials reported a frequent occurrence of cytogenic aberrations at baseline (69.7% to 80.1%). The median follow-up duration was 12.4 to 73 months. The risk of selection bias in the included studies was unclear. We assessed overall risk of performance bias and detection bias as low risk for objective outcomes and high risk for subjective outcomes. Overall risk of attrition bias, reporting bias, and other bias was low. Anti-CD20 monoclonal antibodies (mAbs): rituximab or ofatumumab maintenance versus observation Anti-CD20 mAbs maintenance likely results in little to no difference in OS (hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.73 to 1.20; 1152 participants; 3 studies; moderate-certainty evidence) and likely increases PFS significantly (HR 0.61, 95% CI 0.50 to 0.73; 1255 participants; 5 studies; moderate-certainty evidence) compared to observation alone. Anti-CD20 mAbs may result in: an increase in grade 3/4 AEs (rate ratio 1.34, 95% CI 1.06 to 1.71; 1284 participants; 5 studies; low-certainty evidence); little to no difference in TRM (risk ratio 0.82, 95% CI 0.39 to 1.71; 1189 participants; 4 studies; low-certainty evidence); a slight reduction to no difference in TD (risk ratio 0.93, 95% CI 0.72 to 1.20; 1321 participants; 6 studies; low-certainty evidence); and an increase in all AEs (rate ratio 1.23, 95% CI 1.03 to 1.47; 1321 participants; 6 studies; low-certainty evidence) compared to the observation group. One RCT reported that there may be no difference in HRQoL between the anti-CD20 mAbs (ofatumumab) maintenance and the observation group (mean difference -1.70, 95% CI -8.59 to 5.19; 480 participants; 1 study; low-certainty evidence). Immunomodulatory drug (IMiD): lenalidomide maintenance versus placebo/observation IMiD maintenance therapy likely results in little to no difference in OS (HR 0.91, 95% CI 0.61 to 1.35; 461 participants; 3 studies; moderate-certainty evidence) and likely results in a large increase in PFS (HR 0.37, 95% CI 0.19 to 0.73; 461 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. Regarding harms, IMiD maintenance therapy may result in an increase in grade 3/4 AEs (rate ratio 1.82, 95% CI 1.38 to 2.38; 400 participants; 2 studies; low-certainty evidence) and may result in a slight increase in TRM (risk ratio 1.22, 95% CI 0.35 to 4.29; 458 participants; 3 studies; low-certainty evidence) compared to placebo/observation. The evidence for the effect on TD compared to placebo is very uncertain (risk ratio 0.71, 95% CI 0.47 to 1.05; 400 participants; 2 studies; very low-certainty evidence). IMiD maintenance therapy probably increases all AEs slightly (rate ratio 1.41, 95% CI 1.28 to 1.54; 458 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. No studies assessed HRQoL. Anti-CD52 monoclonal antibodies (mAbs): alemtuzumab maintenance versus observation Maintenance with alemtuzumab may have little to no effect on PFS, but the evidence is very uncertain (HR 0.55, 95% CI 0.32 to 0.95; 21 participants; 1 study; very low-certainty evidence). We did not identify any study reporting the outcomes OS, HRQoL, grade 3/4 AEs, TRM, TD, or all AEs. AUTHORS' CONCLUSIONS: There is currently moderate- to very low-certainty evidence available regarding the benefits and harms of maintenance therapy in people with CLL. Anti-CD20 mAbs maintenance improved PFS, but also increased grade 3/4 AEs and all AEs. IMiD maintenance had a large effect on PFS, but also increased grade 3/4 AEs. However, none of the above-mentioned maintenance interventions show differences in OS between the maintenance and control groups. The effects of alemtuzumab maintenance are uncertain, coupled with a warning for drug-related infectious toxicity. We found no studies evaluating other novel maintenance interventions, such as B-cell receptor inhibitors, B-cell leukaemia-2/lymphoma-2 inhibitors, or obinutuzumab.

Effectiveness of Adaptive Support Ventilation in Facilitating Weaning from Mechanical Ventilation in Postoperative Patients.

OBJECTIVE: This meta-analysis aims to evaluate the effectiveness of adaptive support ventilation (ASV) in facilitating postoperative weaning from mechanical ventilation in cardiac surgery patients. DESIGN: A systematic review and meta-analysis to assess ASV in weaning postoperative cardiac surgery patients. Outcomes included early extubation, reintubation rates, time to extubation, and lengths of intensive care units and hospital stays. SETTING: We searched electronic databases from inception to March 2023 and included randomized controlled trials that compared ASV with conventional ventilation methods in this population. PARTICIPANTS: Postoperative cardiac surgery patients. MEASUREMENTS AND MAIN RESULTS: A random effects model was used for meta-analysis, and trial sequential analysis (TSA) was conducted to assess result robustness. The meta-analysis included 11 randomized controlled trials with a total of 1027 randomized patients. ASV was associated with a shorter time to extubation compared to conventional ventilation (random effects, mean difference -68.30 hours; 95% confidence interval, -115.50 to -21.09) with TSA providing a conclusive finding. While ASV indicated improved early extubation rates, no significant differences were found in reintubation rates or lengths of intensive care unit and hospital stays, with these TSA results being inclusive. CONCLUSIONS: ASV appears to facilitate a shorter time to extubation in postoperative cardiac surgery patients compared to conventional ventilation, suggesting benefits in accelerating the weaning process and reducing mechanical ventilation duration.

Negative pressure wound management in perineal wound status post abdominoperineal resection and extralevator abdominoperineal excision: a meta-analysis and trial sequential analysis.

PURPOSE: Recent evidence-based publications disclosed that negative pressure wound therapy (NPWT) may reduce the incidence rate of surgical site infection (SSI) and length of stay (LOS) compared with conventional drainage in patient status post abdominoperineal resection (APR) and extralevator abdominoperineal excision (ELAPE). METHODS: Data sources: Eligible randomized controlled trials and retrospective and prospective studies published before January 2023 were retrieved from databases (Cochrane Library, PubMed, and Embase). STUDY SELECTION: (a) The study involved patients undergoing ELAPE or APR with postoperative NPWT; (b) the study compared NWPT with conventional drainage and reported at least one outcome of interest (i.e., SSI); and (c) the study provided adequate information to calculate the effect estimated for meta-analysis. INTERVENTIONS: We calculated the odds ratio (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: The measure outcomes included surgical site infection(SSI) and length of stay (LOS). RESULTS: Eight articles, involving 547 patients, met the selection criteria. Compared to conventional drainage, NPWT was associated with a significantly lower SSI rate (fixed effect, OR 0.29; 95% CI 0.18-0.45; I2 = 0%) in eight studies and 547 patients. Besides, NPWT was associated with a shorter LOS (fixed effect, MD - 2.00; CI - 2.60 to - 1.39; I2 = 0%) than conventional drainage in three studies and 305 patients. In a trial sequential analysis, the cumulative number of patients in the analyses of both outcomes exceeded the required information size and surpassed the significance boundary in favor of NPWT, suggesting conclusive results. CONCLUSION: NPWT is superior to conventional drainage in both SSI rate and LOS, and the statistical power of SSI and LOS are confirmed by trial sequential analysis.

Intravitreal injection versus systematic treatment in patients with uveitis undergoing cataract surgery: a systematic review and meta-analysis.

PURPOSE: Cataract surgery in patients with uveitis is challenging, and postoperative inflammation control is crucial for successful outcomes. No consensus exists regarding the optimal method of controlling postoperative inflammation. In this systematic review and meta-analysis, we compared the outcome of intravitreal injection (IVI), including steroid (triamcinolone acetonide) or steroid implant (dexamethasone), with systemic anti-inflammatory therapy (ST), such as systemic steroids with or without immunomodulatory therapy, in patients with uveitis undergoing cataract surgery. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials (RCTs), comparative cohort studies, and case-control studies published through May 2021 that compared intraoperative IVI of triamcinolone acetonide or steroid implant with ST with or without immunomodulatory therapy. The following outcomes were evaluated: preoperative best-corrected visual acuity, intraocular pressure, laser flare photometry, central macular thickness and cystoid macular edema rate. RESULTS: Five studies were selected. Our analysis indicated that compared with ST, IVI treatment may be associated with less anterior chamber inflammation and a lower cystoid macular edema rate, but the difference in best-corrected visual acuity, intraocular pressure, or central macular thickness was not significant. CONCLUSIONS: IVI of steroid or steroid implants might be beneficial in controlling postoperative inflammation for uveitis cataract, especially in patients who cannot tolerate ST. To the best of our knowledge, this is the first meta-analysis to compare the efficacy of intraoperative IVI of steroids with standard-of-care treatment as a prophylaxis for uveitis cataract. However, large-scale RCTs are warranted to compare the IVI of steroid implants and steroids.

Different pedagogies for acquisition of knowledge and skill: a systematic review and network meta-analysis.

BACKGROUND: This network meta-analysis aimed to assess the efficacy of different educational methods for healthcare professionals. METHODS: A systematic literature search was conducted to identify relevant randomised controlled trials. The standardised mean difference (SMD) with 95% CI was estimated using network meta-analysis for knowledge acquisition and skill performance, and ranked the effects of different educational methods using the surface under the cumulative ranking area (SCURA) technique. RESULTS: Fifty-five randomised controlled trials including of 4292 participants were identified. Compared with no intervention, the results demonstrated all education methods achieved significant improvements in knowledge acquisition (SMD 1.73-2.66). Only education methods involving high fidelity virtual patient simulation reported significantly better skill performance (SMD 1.25-1.81). High fidelity virtual patient simulation plus self-directed learning was the most effective educational method both in terms of knowledge acquisition (SMD 2.66, 95% CI 1.4 to 4.12, SCURA 0.78) and skill performance (SMD 1.81, 95% CI 0.42 to 3.2, SCURA 0.89). CONCLUSIONS: Our study demonstrates all educational methods have positive effects on knowledge acquisition, but education methods involving high fidelity virtual patient simulation are better at improving skill performance than other methods.

Combined Ileoileal and Ileocolic Intussusception Secondary to Inflammatory Fibroid Polyp in an Adult: A Case Report.

Intestinal intussusception is relatively rare in adults and accounts for approximately 5% of intestinal obstruction. Intussusception is classified into subtypes according to the location, including ileoileal, ileocolic, ileo-ileocolic, colo-colic, jejuno-ileal, or jejuno-jejunal; the ileocolic type being the most common. However, intussusception of a combination of different subtypes has rarely been reported in the available literature. Abdominal computed tomography (CT) is the most accurate tool to evaluate intestinal intussusception. The pathological lead point in the intestine typically results in adult intussusception. Surgical intervention is usually adopted in cases of adult intussusception due to a high incidence of underlying bowel malignancy. An inflammatory fibroid polyp (IFP) is one of the uncommon benign neoplasms of the gastrointestinal (GI) system, which can result in intestinal intussusception. Herein, we present a case of a 50-year-old female with combined ileoileal and ileocolic intussusception, which was initially diagnosed by abdominal CT. Therefore, laparoscopic right hemicolectomy surgery was performed, confirming the final diagnosis as ileoileal and ileocolic intussusception secondary to IFP.

Benefit of Uracil-Tegafur Used as a Postoperative Adjuvant Chemotherapy for Stage IIA Colon Cancer.

Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted a population-based cohort study in patients with resected stage II colon cancer comparing the outcomes after postoperative adjuvant chemotherapy with UFT with an observation-only group. The data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the study were disease-free survival (DFS) and overall survival (OS). The hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression models. Results: No differences in the DFS and OS were detected between the UFT (1137 patients) and observation (2779 patients) cohorts (DFS: adjusted HR 0.702; 95% confidence interval (CI) 0.489-1.024; p = 0.074) (OS: adjusted HR 0.894; 95% CI 0.542-1.186; p = 0.477). In the subgroup analyses of the different substages, UFT prolonged DFS in patients with stage IIA colon cancer (adjusted HR 0.652; 95% CI 0.352-0.951; p = 0.001) compared with DFS in the observation cohort, but no differences in the OS were detected (adjusted HR 0.734; 95% CI 0.475-1.093; p = 0.503). Conclusions: Our results show that DFS improved significantly in patients with stage IIA colon cancer receiving UFT as a postoperative adjuvant chemotherapy compared with DFS in the observation group.

Proportional assist ventilation versus pressure support ventilation for weaning from mechanical ventilation in adults: a meta-analysis and trial sequential analysis.

BACKGROUND: Pressure support ventilation (PSV) is the prevalent weaning method. Proportional assist ventilation (PAV) is an assisted ventilation mode, which is recently being applied to wean the patients from mechanical ventilation. Whether PAV or PSV is superior for weaning remains unclear. METHODS: Eligible randomized controlled trials published before April 2020 were retrieved from databases. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs). RESULTS: Seven articles, involving 634 patients, met the selection criteria. Compared to PSV, PAV was associated with a significantly higher rate of weaning success (fixed-effect RR 1.16; 95% CI 1.07-1.26; I2 = 0.0%; trial sequential analysis-adjusted CI 1.03-1.30), and the trial sequential monitoring boundary for benefit was crossed. Compared to PSV, PAV was associated with a lower proportion of patients requiring reintubation (RR 0.49; 95% CI 0.28-0.87; I2 = 0%), a shorter ICU length of stay (MD - 1.58 (days), 95% CI - 2.68 to - 0.47; I2 = 0%), and a shorter mechanical ventilation duration (MD - 40.26 (hours); 95% CI - 66.67 to - 13.84; I2 = 0%). There was no significant difference between PAV and PSV with regard to mortality (RR 0.66; 95% CI 0.42-1.06; I2 = 0%) or weaning duration (MD - 0.01 (hours); 95% CI - 1.30-1.28; I2 = 0%). CONCLUSION: The results of the meta-analysis suggest that PAV is superior to PSV in terms of weaning success, and the statistical power is confirmed using trial sequential analysis.

Ascending Aortic Aneurysm After Repair of Aortico-Left Ventricular Tunnel.

Ascending aortic aneurysm following aortico-left ventricular tunnel (ALVT) repair is an uncommon but life-threatening complication. A 27-year-old man had received patch closure for ALVT at infancy. Eighteen years later, aortic valve replacement for severe aortic regurgitation and direct suture for recurrent slit tunnel were performed. Another 9 years later, ascending aortic replacement was performed because of ascending aortic aneurysm. Thus we report an uncommon case of ascending aortic aneurysm 27 years after the repair of an ALVT.

Effect of Levetiracetam on Cognition: A Systematic Review and Meta-analysis of Double-Blind Randomized Placebo-Controlled Trials.

BACKGROUND: Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was reported in patients with amnestic mild cognitive impairment, schizophrenia, and Alzheimer's disease. However, the specific cognitive domains affected and the degree of evidence supporting these effects remain unclear. This systematic review and meta-analysis aimed to explore the effects of levetiracetam on different cognitive domains. METHODS: This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We defined our inclusion criteria for the systematic review as: (1) randomized placebo-controlled trials (RCTs) involving human subjects, (2) double-blinded RCTs, and (3) RCTs evaluating the quantitative differences in cognitive function between levetiracetam and placebo. We excluded: (1) non-RCT studies, (2) open-label studies, and (3) RCTs lacking cognitive assessments for either intervention. Two authors independently searched electronic databases, including PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov, from inception until 2 July 2023. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Meta-analytic techniques were applied to examine the impact of levetiracetam on cognitive domain tests, with Hedges' g facilitating the comparison with placebo. The domains analyzed comprised multi-domain, executive function, processing speed, working memory, verbal memory/learning (verbal ML), visuospatial memory/learning (visuospatial ML), and language. We used odds ratios to compare the incidence of treatment-emergent adverse events between the groups, including somnolence, fatigue, dizziness, headache, irritability, and cognitive adverse events. RESULTS: A random-effects model was utilized to perform a meta-analysis of 16 RCTs including 545 participants. Compared with a placebo, levetiracetam was associated with improved executive function [Hedges'g = - 0.390, 95% confidence interval (CI) = - 0.609 to - 0.172, p < 0.001, I2 = 24.0%]. Subgroup analysis showed that levetiracetam outperformed placebo in patients without epilepsy (Hedges' g = - 0.419, 95% CI = - 0.647 to - 0.191, p < 0.001, I2 = 26.2%). Meanwhile, low-dose levetiracetam showed a moderate favorable effect over placebo (Hedges' g = -0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I2 = 65.3%). In patients without epilepsy, low-dose levetiracetam was associated with improved executive function (Hedges'g = - 0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I2 = 65.3%). Concurrently, levetiracetam was associated with more frequent somnolence than a placebo (odds ratio = 4.654, 95% CI = 1.533 to 14.124, p = 0.007, I2 = 32.9%). Potential publication bias was observed in the executive function domain. CONCLUSIONS: This exploratory study suggests that levetiracetam might improve executive function in specific populations. However, the diversity in study populations and potential publication bias warrant caution.

Perioperative Dexmedetomidine Infusion Improves Perioperative Care of Bariatric-Metabolic Surgery: A Single Center Experience with Meta-Analysis.

PURPOSE: This study aims to determine the effects of perioperative dexmedetomidine infusion (PDI) on Asian patients undergoing bariatric-metabolic surgery (BMS), focusing on the need for pain medications and management of postoperative nausea and vomiting (PONV), and to investigate the association with these variables, including patients' characteristics and BMS data. MATERIALS AND METHODS: A retrospective review of prospectively collected data was conducted in an Asian weight management center from August 2016 to October 2021. A total of 147 native patients with severe obesity were enrolled. All patients were informed of the full support of perioperative pain medications for BMS. The pain numeric rating scale scores, events of PONV, needs for pain medications, and the associated patients' characteristics were analyzed. A p-value of < 0.05 was considered statistically significant. Furthermore, to verify the effects of perioperative usage of dexmedetomidine for BMS, a systematic review with meta-analysis of currently available randomized control trials was performed. RESULTS: Among the 147 enrolled patients, 107 underwent laparoscopic sleeve gastrectomy and 40 underwent laparoscopic Roux-en-Y gastric bypass. PDI has been used as an adjunct multimodal analgesia for BMS in our institution since June 2017 (group D; n = 114). In comparison with those not administered with perioperative dexmedetomidine (group C; n = 33), lower pain numeric rating scale scores (2.52 ± 2.46 vs. 4.27 ± 2.95, p = 0.007) in the postanesthesia care unit, fewer PONV (32.46% vs. 51.52%; p = 0.046), and infrequent needs of additional pain medications (19.47% vs. 45.45%; p = 0.003) were observed in group D. Multivariable analysis demonstrated that type II diabetes mellitus was correlated with the decreased need of pain medications other than PDI (p = 0.035). Moreover, dexmedetomidine seemed to have a better analgesic effect for patients with longer surgical time based on our meta-analysis. CONCLUSION: Based on our limited experience, PDI could be a practical solution to alleviate pain and PONV in Asian patients undergoing BMS. Moreover, it might reduce the need for rescue painkillers with better postoperative pain management for patients with type II diabetes mellitus or longer surgical time.

The Efficacy and Safety of Tandem Transplant Versus Single Stem Cell Transplant for Multiple Myeloma Patients: A Systematic Review and Meta-Analysis.

While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-elble multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa Scale. Twelve studies involving 5057 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (HR 1.33, 95% CI 1.03-1.71, I2 = 15%), but no significant differences were observed in PFS (HR 0.75, 95% CI 0.42-1.34, I2 = 14%), OS (HR 0.60, 95% CI 0.33-1.10, I2 = 27%), or the ORR (RR 0.80, 95% CI 0.59-1.08, I2 = 33%). However, tandem ASCT was associated with a significantly higher risk of TRM (RR 1.78, 95% CI 1.00-3.18, I2 = 0%). Tandem ASCT improves the CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient's unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.

Endovascular therapy for acute ischemic stroke in patients with active malignancy: a meta-analysis with trial sequential analysis.

BACKGROUND: Active malignancy has a poorer prognosis and more deaths in patients with acute ischemic stroke (AIS). The outcomes of endovascular therapy (EVT) remain controversial in patients with AIS and active malignancy. METHODS: We searched PubMed, Cochrane, and Embase for articles published up to June 1, 2022. The primary outcome was good functional outcome at 3 months and successful reperfusion between patients with cancer and AIS and control patients. The secondary and safety outcomes included mortality at 3 months, in-hospital mortality, symptomatic intracerebral hemorrhage (sICH), any ICH, and subarachnoid hemorrhage (SAH). RESULTS: Twelve studies involving 5944 patients with AIS secondary to EVT were included (389 patients having active malignancy). The OR of good functional outcome at 3 months was 0.53 (95% CI 0.41 to 0.67) between the two groups. The OR of successful reperfusion between the two groups was 0.90 (95% CI 0.63 to 1.30). Compared with patients without cancers, those with cancers had a higher risk of mortality at 3 months (OR 3.64; 95% CI 2.35 to 6.27) and in-hospital mortality (OR 3.46; 95% CI 1.71 to 7.01). Despite a higher point estimate regarding any ICH (OR 1.41; 95% CI 1.01 to 1.96) and SAH (OR 2.53; 95% CI 1.10 to 5.81), sICH (OR 0.85; 95% CI 0.51 to 1.42) was not significant. CONCLUSION: Although a quarter of patients with active malignancy and AIS regained functional independence, physicians and patients should consider whether to apply EVT in patients with active malignancy.

Timing and Dose of Constraint-Induced Movement Therapy after Stroke: A Systematic Review and Meta-Regression.

The aim of this study is to investigate the effects of constraint-induced movement therapy on stroke patients who had intact cognition and some voluntary finger extension and to identify optimal protocols to apply this therapy method. We searched PubMed, Cochrane Library, and Embase for randomized controlled trials conducted prior to January 2022. The outcomes included the Motor Activity Log, Fugl-Meyer Assessment, and Wolf Motor Function Test. The inverse variance method fixed-effect model as well as the DerSimonian and Laird estimator random-effects model were applied, and the mean difference was calculated with 95% confidence interval to measure continuous outcomes. Six randomized controlled trials involving a total of 169 patients with stroke were enrolled. Compared with conventional rehabilitation methods, there was no significant effect of constraint-induced movement therapy when evaluated by the Motor Activity Log, including the amount of use (random-effect, standardized mean difference 0.65; 95%, confidence interval: -0.23-1.52) and quality of movement (random-effect, standardized mean difference 0.60; 95% confidence interval: -0.19-1.39). However, among patients with chronic stroke symptoms, meta-regression analyses showed better performance with a constraint time of at least 6 h per day and 6 h training per week when assessing the amount of use (p = 0.0035) and quality of movement (p = 0.0031). Daily intervention time did not lead to a significant difference in functional upper limb performance. An efficient protocol of constraint-induced movement therapy designed as 6 h of training per week with 6 h constraint per day could bring significant stroke symptom improvement to patients with chronic stroke.

Endovascular thrombectomy for basilar-artery occlusion: A meta-analysis with trial sequential analysis.

Background and purpose: Basilar-artery occlusion (BAO) usually accounts for devastating neurologic sequelae, poor prognosis, and even death. While endovascular thrombectomy (EVT) is the most successful treatment for anterior circulation stroke with large vessel occlusion, its effectiveness in treating acute BAO is still debatable. Our aim is to compare the efficacy and safety between EVT and conservative medical treatment (CMT) in BAO. Methods: Up until May 2022, relevant literature was gathered using searches in Embase, PubMed, and the Cochrane Library. The primary outcomes were defined as good functional outcome (modified Rankin Scale 0-2) and favorable functional outcome (modified Rankin Scale 0-3) at 3 months between EVT and CMT groups. The secondary outcomes included mortality at 3 months, symptomatic intracerebral hemorrhage (ICH), and any ICH. Results: Eight studies involving 3733 patients with BAO were enrolled 2573 individuals underwent EVT, and the remaining 1160 patients received CMT. Compared with CMT, EVT achieved more favorable functional outcome (odds ratio (OR) 1.26, 95% CI 1.03-1.55, I2 = 54%, p = 0.05) in BAO. The good functional outcome showed a similar tendency (OR 1.23, 95% CI 0.97-1.57, I2 = 63%, p = 0.02) as well. EVT decreased mortality at 3 months (OR 0.81, 95% CI 0.70-0.93, I2 = 31 %, p = 0.19), although having a tendency to cause symptomatic ICH (OR 2.91, 95% CI 1.38-6.18, I2 = 22 %, p = 0.27). Conclusions: EVT in BAO provides superior functional outcomes and less mortality compared with CMT. Even though EVT has the propensity to cause symptomatic ICH, EVT nevertheless improved posterior circulation stroke.

Effect and Optimal Timing of Extracorporeal Shock-Wave Intervention to Patients With Spasticity After Stroke: A Systematic Review and Meta-analysis.

OBJECTIVE: This study investigated the efficacy of extracorporeal shock wave therapy as well as the optimal intervention timing for extracorporeal shock wave therapy for patients with spasticity after stroke. DESIGN: A search of randomized controlled trials was conducted in different electronic databases. We performed a meta-analysis to measure the effect of extracorporeal shock wave therapy versus sham interventions on spasticity and limb functionality. The meta-regression analysis was performed to determine the adequate intervention timing of extracorporeal shock wave therapy. The follow-up period of the outcomes was divided into the short (<2 wks), mid (>2 wks and ≤4 wks), and long (>4 wks and ≤3 mos) terms. RESULTS: Thirteen studies with 677 participants were evaluated. Spasticity significantly improved throughout the follow-up duration. Limb functionality significantly improved in the short-term follow-up period. The meta-regression analysis showed that patients with stroke duration less than 45 mos may be benefited from extracorporeal shock wave therapy in improving limb function in all follow-up periods. CONCLUSIONS: Extracorporeal shock wave therapy is an effective method for reducing spasticity in patients with stroke, and the effect could be maintained for up to 3 mos. Its effects on limb functionality could persist for at least 2 wks. Patients who had stroke for less than 45 mos may have significant benefit from extracorporeal shock wave therapy in all follow-up periods.

Is Thrombocytopenia an In-Hospital Mortality Risk Factor among Patients with Acute Ischemic Stroke? A Propensity Score-Matched Analysis from the MIMIC-IV Database.

(1) Background: We aimed to evaluate the aspect of thrombocytopenia in patients with acute ischemic stroke (AIS); (2) Methods: Patients with AIS were recruited in the Medical Information Mart for Intensive Care IV database from 2008 to 2019. The thrombocytopenia was defined as a platelet blood count of less than 150 K/µL. We compared the patient characteristics and clinical outcomes using propensity score matching (PSM); (3) Results: Thrombocytopenia affected 151 out of the 1236 patients (12.2%). Patients with thrombocytopenia were older (70.5 ± 12.8 vs. 68.4 ± 14.4; SMD = 0.154) and had a higher Charlson comorbidity index (7.3 ± 2.5 vs. 6.7 ± 2.7; SMD = 0.228) and acute physiology score III (44.8 ± 21.0 vs. 38.2 ± 19.1; SMD = 0.328) than those without thrombocytopenia. The risk of in-hospital mortality did not increase linearly or nonlinearly with a lower platelet count (overall p value = 0.794; nonlinear p value = 0.646). After PSM, 147 pairs remained. Thrombocytopenia was not linked with in-hospital mortality (HR: 1.06, 95% CIs: 0.60-1.88); (4) Conclusions: We described the clinical characteristics of patients admitted for thrombocytopenia and AIS who did not receive reperfusion therapy; additionally, we found that thrombocytopenia was not an independent short-term risk factor of in-hospital mortality.

Incentive spirometry is an effective strategy to improve the quality of postoperative care in patients.

Postoperative pulmonary complications (PPCs) most commonly occur after thoracic surgery. Not only prolonged hospital stay and increased financial expenses but also morbidity and even mortality may be troublesome for those with PPCs. Herein, we aimed to conduct a comprehensive systematic review and meta-analysis of available data to examine the effectiveness of incentive spirometry (IS) to reduce PPCs and shorten hospital stay. This systematic review and meta-analysis included 5 randomized controlled trials (RCT) and 3 retrospective cohort study (10,322 patients in total) in PubMed, Embase and Cochrane Library until September 31, 2021. We assessed the clinical efficacy of IS using length of hospital stay, PPCs, postoperative pneumonia, and postoperative atelectasis with meta-analysis, meta-regression and trial sequential analysis (TSA). With this meta-analysis, the length of hospital stay in patients undergoing IS was significantly shorter (1.8 days) than that in patients not receiving IS (MD = -1.80, 95% CI = -2.95 to -0.65). Patients undergoing IS also had reduced risk of PPCs (32%) and postoperative pneumonia (17.9%) with statistical significance than patients not undergoing IS (PPC: OR = 0.68, 95% CI = 0.51-0.90) (Pneumonia: OR = 0.821, 95% CI = 0.677-0.995).In meta-regression, the benefits of undergoing IS in patients with preoperative predicted FEV1 of <80% in a linear fashion with decreasing PPCs. IS is an effective modality to improve the quality of postoperative care for patients after pulmonary resection, compared with the control group without using IS; and applying IS has favorable outcomes of shorter length of hospital stay (1.8 days) and lower occurrence of PPCs (32% of risk reduction), which are conclusive and robust based on our validation via TSA. Moreover, the IS device is more beneficial for patients with preoperative predicted FEV1 of <80% than that in others.

Progression-Free Survival Efficacy in Refractory/Relapsed Multiple Myeloma among Elderly Patients: A Systematic Review.

BACKGROUND: Over the last decade, many studies have assessed the efficacy of treatments for refractory/relapsed multiple myeloma (R/R MM). While combination therapies show greater efficacy than traditional methods, limited research has targeted elderly patients who might be less resilient to treatments. Our study aimed to evaluate treatment efficacy for these elderly patients. METHODS: We carried out a comprehensive review of the literature using a systematic approach. Initially, 4966 citations were retrieved and subsequently narrowed down to 13 eligible randomized controlled trials (RCTs) through our systematic review process from databases like Embase, PubMed, and Cochrane Library from 1 January 2000 to 31 December 2022. Evidence was collated through a frequentist network meta-analysis, using the hazard ratio (HR) for evaluation. RESULTS: Combined therapy of daratumumab, lenalidomide, and dexamethasone (DaraLenDex) was the preferred treatment for R/R MM elderly patients. Its strengths included an HR for progression-free survival (0.15; 95% CI: 0.09-0.25) and a 96% P-score. CONCLUSIONS: Our analysis suggests that, pending more comprehensive RCTs, DaraLenDex is the treatment with the highest efficacy for R/R MM in elderly patients.