Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

Distal medium vessel occlusions in acute ischaemic stroke - Stent retriever versus direct aspiration: A systematic review and meta-analysis.

BACKGROUND: Acute ischaemic stroke due to distal medium vessel occlusion (AIS-DMVO) causes significant morbidity. Endovascular thrombectomy advancement has made treating AIS-DMVO with stent retrievers (SR) and aspiration catheters (AC) possible, however the optimal technique remains unknown. We performed a systematic review and meta-analysis to investigate the efficacy and safety of SR use compared to purely AC use in patients with AIS-DMVO. METHODS: We systematically searched PubMed, Cochrane Library and EMBASE, from inception to 2nd September 2022, for studies comparing SR or primary combined (SR/PC) against AC in AIS-DMVO. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (modified Rankin Scale (mRS) 0-2 at 90 days), first pass effect (modified Thrombolysis in Cerebral Infarction scale (mTICI) 2c-3 or expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c-3 at first pass), successful final recanalisation (mTICI or eTICI 2b-3), and excellent final recanalisation (mTICI or eTICI 2c-3). Safety outcomes were symptomatic intracranial haemorrhage (sICH) and 90-day mortality. RESULTS: 12 cohort studies and 1 randomised-controlled trial were included, involving 1881 patients with 1274 receiving SR/PC and 607 receiving AC only. SR/PC achieved higher odds of functional independence (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.06-1.67) and lower odds of mortality (OR 0.69, 95% CI 0.50-0.94) than AC. Odds of successful/excellent recanalisation and sICH were similar between both groups. Stratified to compare only SR and only AC, the use of only SR, achieved significantly higher odds of successful recanalisation as compared to only AC (OR 1.80, 95% CI 1.17-2.78). CONCLUSION: There is potential for efficacy and safety benefits in SR/PC use as compared to AC only in AIS-DMVO. Further trials are necessary to validate the efficacy and safety of SR use in AIS-DMVO.

Limited liver resections in the posterosuperior segments: international multicentre propensity score-matched and coarsened exact-matched analysis comparing the laparoscopic and robotic approaches.

BACKGROUND: Limited liver resections (LLRs) for tumours located in the posterosuperior segments of the liver are technically demanding procedures. This study compared outcomes of robotic (R) and laparoscopic (L) LLR for tumours located in the posterosuperior liver segments (IV, VII, and VIII). METHODS: This was an international multicentre retrospective analysis of patients who underwent R-LLR or L-LLR at 24 centres between 2010 and 2019. Patient demographics, perioperative parameters, and postoperative outcomes were analysed; 1 : 3 propensity score matching (PSM) and 1 : 1 coarsened exact matching (CEM) were performed. RESULTS: Of 1566 patients undergoing R-LLR and L-LLR, 983 met the study inclusion criteria. Before matching, 159 R-LLRs and 824 L-LLRs were included. After 1 : 3 PSM of 127 R-LLRs and 381 L-LLRs, comparison of perioperative outcomes showed that median blood loss (100 (i.q.r. 40-200) versus 200 (100-500) ml; P = 0.003), blood loss of at least 500 ml (9 (7.4 per cent) versus 94 (27.6 per cent); P < 0.001), intraoperative blood transfusion rate (4 (3.1 per cent) versus 38 (10.0 per cent); P = 0.025), rate of conversion to open surgery (1 (0.8 per cent) versus 30 (7.9 per cent); P = 0.022), median duration of Pringle manoeuvre when applied (30 (20-46) versus 40 (25-58) min; P = 0.012), and median duration of operation (175 (130-255) versus 224 (155-300); P < 0.001) were lower in the R-LLR group compared with the L-LLR group. After 1 : 1 CEM of 104 R-LLRs with 104 L-LLRs, R-LLR was similarly associated with significantly reduced blood loss and a lower rate of conversion to open surgery. CONCLUSION: Based on a matched analysis of well selected patients, both robotic and laparoscopic access could be undertaken safely with good outcomes for tumours in the posterosuperior liver segments.

Outcomes of left ventricular thrombosis in post-acute myocardial infarction patients stratified by antithrombotic strategies: A meta-analysis with meta-regression.

BACKGROUND: Left ventricular thrombus (LVT) formation is a significant complication of acute myocardial infarction (AMI) due to its embolic potential. However, managing LVT requires balancing therapeutic benefits against bleeding risks. Our study provides a risk-benefit analysis of various antithrombotic regimens on long-term outcomes in treating post-AMI LVT patients. METHODS: We conducted a comprehensive literature search in Medline, Embase and SCOPUS up to 1 April 2020. All studies reporting outcomes of post-AMI LVT patients were included. RESULTS: 17 studies were included in total. Anticoagulation (47-100%) and triple therapy use (38-100%) varied largely across studies. On meta-analysis, administration of anticoagulation (OR 0.14, 95% CI 0.05-0.36, p < 0.001) and triple therapy (OR 0.22, 95% CI 0.07-0.66, p < 0.001) resulted in lower odds of mortality. Neither anticoagulation (p = 0.24) nor triple therapy (p = 0.73) was associated with bleeding. Triple therapy was associated with LVT resolution on meta-analysis (OR 2.53, 95% CI 1.53-4.19, p < 0.001) and regression analysis (OR 1.28, 95% CI 1.03-1.58, p = 0.03). Anticoagulation and triple therapy were independent predictors of systemic embolism ([OR 0.67, 95% CI 0.49-0.93, p = 0.02] and [OR 0.82, 95% CI 0.73-0.93, p = 0.001]) and stroke ([OR 0.62, 95% CI 0.41-0.94, p = 0.03] and [OR 0.73, 95% CI 0.55-0.96, p = 0.03]). CONCLUSIONS: While there is clear therapeutic benefit in anticoagulation for post-AMI LVT, the extent of bleeding risk is uncertain. Future trials are necessary to determine the optimal antithrombotic strategy for post-AMI LVT management.

Computer-Navigated versus Conventional Total Knee Arthroplasty: A Meta-Analysis of Functional Outcomes from Level I and II Randomized Controlled Trials.

The main purpose of this article is to provide an up-to-date systematic review and meta-analysis comparing functional outcomes of total knee arthroplasty using either computer navigation (NAV-TKA) or conventional methods (CON-TKA) from the latest assemblage of evidence. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. All Level I and II randomized controlled trials (RCTs) in PubMed, EMBASE, and Cochrane that compared functional outcomes after NAV- and CON-TKA were included in the review. Selected end points for random effects, pairwise meta-analysis included Knee Society Knee Score (KSKS), KS Function Score (KSFS), KS Total Score (KSTS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and range of motion at three arbitrary follow-up times. A total of 24 prospective RCTs comprising 3,778 knees were included from the initial search. At long-term follow-up (>5 years), NAV-TKA exhibited significantly better raw KSKS (p = 0.001) (low-quality evidence), contrary to CON-TKA, which reflected significantly better raw KSTS (p = 0.004) (high-quality evidence). While change scores (KSKS, WOMAC) from preoperative values favor CON-TKA at short-term (<6 months) and medium-term follow-up (6-60 months), long-term follow-up change scores in KSKS suggest the superiority of NAV-TKA over CON-TKA (p = 0.02) (very low-quality evidence). Overall, sizeable dispersion of nonstatistically significant functional outcomes in the medium term was observed to eventually converge in the long term, with less differences in functional outcome scores between the two treatment methods in short- and long-term follow-up. While raw functional outcome scores reflect no differences between NAV and CON-TKA, long-term follow-up change scores in KSKS suggest superiority of NAV-TKA over its conventional counterpart. Prospective studies with larger power are required to support the pattern of diminishing differences in functional outcome scores from medium- to long-term follow-up between the two modalities.

Robot-Assisted versus Conventional Total and Unicompartmental Knee Arthroplasty: A Meta-analysis of Radiological and Functional Outcomes.

The study aims to provide an up-to-date systematic review and meta-analysis comparing radiological and functional outcomes of total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) using either robotic assistance or conventional methods from the latest assemblage of evidence. This study was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. All studies in PubMed, EMBASE, Medline, and Cochrane that reported radiological and functional outcomes after TKA or UKA with either robotic or conventional methods were included in the review. Selected endpoints for random effects, pairwise meta-analysis included operative details, radiological outcomes (mechanical axis, component angle deviation, and outliers), and functional outcomes (American Knee Society Score, Knee Society Function Score, revision and complication rate, range of motion (ROM), Hospital for Special Surgery score, and Western Ontario and McMaster Universities Osteoarthritis Index). A total of 23 studies comprising 2,765 knees were included from the initial search. Robot-assisted TKA and UKA were associated with significantly better component angle alignment accuracy (low-to-high quality evidence) at the cost of significantly greater operation time. Robot-assisted UKA was found to have significantly better short-term functional outcomes compared with conventional UKA (moderate-to-high quality evidence). Robot-assisted TKA, however, did not exhibit significantly better short- and midterm subjective knee outcome scores compared with its conventional counterpart (high-quality evidence). Robot-assisted TKA and UKA were associated with nonstatistically significant improved ROM and lesser rates of revision. Robot-assisted total and unicompartmental knee arthroplasty leads to better radiological outcomes, with no significant differences in mid- and long-term functional outcomes compared with conventional methods for the former. Larger prospective studies with mid- and long-term outcomes are required to further substantiate findings from the present study.

Enhanced recovery versus conventional care in gastric cancer surgery: a meta-analysis of randomized and non-randomized controlled trials.

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols have been successfully integrated into peri-operative management of different cancer surgeries such as colorectal cancer. Their value for gastric cancer surgery, however, remains uncertain. METHODS: A search for randomized and observational studies comparing ERAS versus conventional care in gastric cancer surgery was performed according to PRISMA guidelines. Random-effects meta-analyses with inverse variance weighting were conducted, and quality of included studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa scale (PROSPERO: CRD42017080888). RESULTS: Twenty-three studies involving 2686 patients were included. ERAS was associated with reduced length of hospital stay (WMD-2.47 days, 95% CI - 3.06 to - 1.89, P < 0.00001), time to flatus (WMD-0.70 days, 95% CI - 1.02 to - 0.37, P < 0.0001), and hospitalization costs (WMD-USD$ 4400, 95% CI - USD$ 5580 to - USD$ 3210, P < 0.00001), with consistent results across open and laparoscopic surgery. Postoperative morbidity and 30-day mortality were similar, although a higher rate of readmission was observed in the ERAS group (RR = 1.95, 95% CI 1.03-3.67, P = 0.04). Patients in the ERAS arm had significantly attenuated C-reactive protein levels on days 3/4 and 7, interleukin-6 levels on days 1, and 3/4, and tumor necrosis factor-α levels on days 3/4 postoperatively. CONCLUSION: Compared to conventional care, ERAS reduces hospital stay, costs, surgical stress response and time to return of gut function, without increasing post-operative morbidity in gastric cancer surgery. However, precaution is necessary to reduce the increased risk of hospital readmission when adopting ERAS.

Arthroscopic Anterior Cruciate Ligament Reconstruction: A Meta-Analysis Comparing Semitendinosus Alone and Semitendinosus with Gracilis Tendon Autografts.

The objective of this study was to provide a comprehensive systematic review and meta-analysis to compare patient-reported outcomes and functional knee parameters of anterior cruciate ligament (ACL) reconstruction surgery with semitendinosus (ST) and ST-gracilis (G) grafts. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. All studies in PubMed and Embase that reported functional knee parameters and patient-reported outcomes after ACL reconstruction with ST and ST-G grafts independently were included in the review. Selected end points for random effects, pairwise meta-analysis included side-to-side deficit (%) in isokinetic peak torque, peak torque ratio (%), side-to-side difference (mm) in anterior laxity, and patient-reported outcome scores at minimum 2-year follow-up. A total of 15 primary references comprising 1,109 participants were identified. The ST group had decreased side-to-side deficit in isokinetic peak torque when compared with the ST-G group for flexion at 60 degrees/s (p = 0.02) and 180 degrees/s (p = 0.01) at 2-year follow-up. There were no significant differences in side-to-side difference in anterior laxity (p = 0.81), hamstring/quadriceps peak torque ratios at 60 degrees/s (p = 0.83) and 180 degrees/s (p = 0.36), and patient-reported outcomes in the International Knee Documentation Committee score (p = 0.06) and Lysholm score (p = 0.67). The addition of the gracilis tendon to the hamstring autograft in ACL reconstruction results in increased side-to-side deficits in isokinetic peak flexion torque. However, patient-reported outcome scores and knee laxity measurements are comparable with those of ST grafts.

Pan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling.

Accumulating evidence has implicated the aberrant regulation of histone deacetylases (HDACs) as a nexus for multiple cancer hallmarks and in mediating tumor adaptation and resistance to genotoxic chemotherapy, suggesting a rational pairing of HDAC inhibitors with DNA damaging chemotherapeutic agents in the treatment of human malignancies. Here we report that panobinostat (LBH589), a potent pan-HDAC inhibitor, effectively curbed the proliferation of non-small cell lung cancer (NSCLC) cell lines A549, Calu-1, H226, H460, H838 and SKMES-1 at IC50 concentrations between 4 and 31 nmol/L via pleiotropic mechanisms, including crosstalk with EGFR signal transduction cascades. Combination therapy with carboplatin elicited rapid tumor cell kill and effectively restrained anchorage-independent clonogenic survival to a considerably greater extent over either monotherapy. The administration of carboplatin and panobinostat at clinically relevant doses to NOD-SCID xenograft mice drastically stalled disease progression by 92% as compared with negative control (P = .0026), which was greater than the 28% and 54% achieved with either carboplatin (P = .220) or panobinostat (P = .017) alone. These data demonstrate that panobinostat has strong anti-NSCLC activity and chemosensitizes tumors to carboplatin, thus justifying further evaluation of this combination approach in clinical trials.

Conversion Surgery Post-Intraperitoneal Paclitaxel and Systemic Chemotherapy for Gastric Cancer Carcinomatosis Peritonei. Are We Ready?

Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a poor prognosis. Intraperitoneal (IP) delivery of chemotherapy can attain a higher drug exposure in the peritoneal cavity but with reduced systemic toxicity. Therefore, we hypothesized that IP paclitaxel with systemic chemotherapy would be clinically beneficial for gastric cancer with peritoneal metastases. Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology were recruited. They underwent eight cycles of IP paclitaxel and systemic XELOX. The primary endpoint was 1-year overall survival rate and secondary endpoints were safety, response rate, and peritoneal cytological response. Patients who subsequently had no distant metastases and two consecutive negative peritoneal cytologies underwent conversion gastrectomy if there was no macroscopic evidence of peritoneal disease at diagnostic laparoscopy. Twenty-two patients were enrolled, receiving at least one cycle of IP paclitaxel at the time of reporting (data cutoff-March 11, 2016). The median number of cycles was 7.5. The median overall survival was 18.8 months, and the 1-year survival rate was 72.2%. One patient died of neutropenic sepsis. Of 19 evaluable patients with measurable disease, 7 (36.8%) achieved PR, 8 (42.1%) achieved SD, and 4 (21.1%) experienced PD. Peritoneal cytology turned negative in 11 of 17 (64.7%) patients. Six patients underwent conversion gastrectomy (4 R0, 2 R1) with a median survival of 21.6 months (range = 8.7-29.9 months). XELOX and IP paclitaxel appears to be an effective regimen in gastric cancer with peritoneal metastases. Conversion gastrectomy may be considered in patients with a favorable response.

Evolving landscape of tumor molecular profiling for personalized cancer therapy: a comprehensive review.

INTRODUCTION: Tumour molecular profiling has been at the crossroads of large-scale integrative genomic studies and major clinical trials over the past 5 years and has provided roadmaps for better disease stratification and therapeutic management. AREAS COVERED: We review the landscape of precision oncology trials in Asia, Europe and the United States, and emerging insights gained from recently reported studies such as the SHIVA and CUSTOM trials. Changes in the molecular portraits of human cancers and the immune contexture of the tumor microenvironment during treatment may predict the course of tumor progression, including the development of treatment resistance. 'Liquid biopsy' approaches that harness circulating tumor cells, cell-free DNA and exosomes may provide a non-invasive means of monitoring the parent tumor in real-time. Several molecular signatures are being evaluated as biomarkers for emerging immunologic approaches, such as the mismatch-repair deficiency status and nonsynonymous mutation burden in anti-PD-1 immune checkpoint blockade. Finally, we review the current actionability and future clinical impact of multigene panel and next-generation sequencing (NGS)-based profiling. EXPERT OPINION: In the future, molecular profiling may help to fulfill unmet needs for predictive biomarkers in novel immunotherapeutic approaches, while ongoing precision trials are laying the foundations for clinical uptake of NGS testing.

Dose modifications in Asian cancer patients with hepatic dysfunction receiving weekly docetaxel: A prospective pharmacokinetic and safety study.

Hepatic dysfunction may modify the safety profile and pharmacokinetics of docetaxel in cancer patients, but no validated guideline exists to guide dose modification necessitated by this uncommon comorbidity. We carried out the first prospective study of a personalized dosage regimen for cancer patients with liver dysfunction treated with docetaxel. Weekly dosages were stratified by hepatic dysfunction classification as such: Category 1, normal; Category 2, mild--alkaline phosphatase, aspartate aminotransferase, and/or alanine aminotransferase ≤5× upper limit of normal (ULN), and total bilirubin within normal range; and Category 3, moderate--any alkaline phosphatase, and aspartate aminotransferase or alanine aminotransferase ≤5-10× ULN, and/or total bilirubin ≤1-1.5× ULN. Category 1, 2 and 3 patients received starting dosages of 40, 30, and 20 mg/m(2) docetaxel, respectively. Pharmacokinetics were evaluated on day 1 and 8 of the first treatment cycle, and entered into a multilevel model to delineate interindividual and interoccasion variability. Adverse event evaluation was carried out weekly for two treatment cycles. We found that docetaxel clearance was significantly different between patient categories (P < 0.001). Median clearance was 22.8, 16.4, and 11.3 L/h/m(2) in Categories 1, 2, and 3, respectively, representing 28% and 50% reduced clearance in mild and moderate liver dysfunction patients, respectively. However, docetaxel exposure (area under the concentration-time curve) and docetaxel-induced neutropenia (nadir and the maximum percentage decrease in neutrophil count) were not significantly different between categories. Median area under the concentration-time curve was 1.74, 1.83, and 1.77 mg·h/L in Categories 1, 2, and 3, respectively. The most common Grade 3/4 toxicity was neutropenia (30.0%). An unplanned comparison with the Child-Pugh and National Cancer Institute Organ Dysfunction Working Group grouping systems suggests that the proposed classification system appears to more effectively discriminate patients by docetaxel clearance and dose requirements. (ClinicalTrials.gov registration no. NCT00703378).

Genetic factors affecting drug disposition in Asian cancer patients.

INTRODUCTION: In the era of genomic medicine, it is increasingly recognized that ethnogeographic differences in drug pharmacology exist between Asian and other populations. This is particularly pertinent to oncology, where drugs forming the backbone of chemotherapy often have narrow therapeutic windows and are frequently dosed close to maximally tolerable levels. AREAS COVERED: At the population level, ancestry is important because historical-biogeographical confluences have shaped population genetics and pharmacoethnicity in the Asian race through allelic differentiation and interethnic differences in inheritance patterns of linkage disequilibrium. At the individual level, cis- and trans-acting germline polymorphisms and somatic mutations in genes encoding drug-metabolizing enzymes and transporters act in a multifactorial manner to determine drug disposition phenotype and clinical response in Asian cancer patients. A growing body of evidence also finds that complex genetic interactions and regulation, including a multiplicity of gene control mechanisms, are increasingly implicated in genotype-phenotype correlates than has hitherto been appreciated--potentially serving as the mechanistic links between hits in non-coding regions of genome-wide association studies and drug toxicity. Together, these genetic factors contribute to the clinical heterogeneity of drug disposition in Asian cancer patients. EXPERT OPINION: This topic has broad relevance for the optimization and individualization of anticancer strategies in Asians.