Analgesic efficacy of PECS vs paravertebral blocks after radical mastectomy: A systematic review,meta-analysis and trial sequential analysis

Study objectiveDue to conflicting results published in the literature regarding the analgesic superiority between the paravertebral block and the PECS block, the study objective is to determine which one should be the first line analgesic treatment after radical mastectomy.DesignSystematic review, meta-analysis and trial sequential analysis.SettingOperating room, postoperative recovery area and ward, up to 24 postoperative hours.PatientsPatients scheduled for radical mastectomy under general anaesthesia.InterventionsWe searched five electronic databases for randomized controlled trials comparing any PECS block with a paravertebral block.MeasurementsThe primary outcome was rest pain score (0−10) at 2 postoperative hours, analyzed according to the combination with axillary dissection or not, to account for heterogeneity. Secondary outcomes included rest pain scores, cumulative intravenous morphine equivalents consumption and rate of postoperative nausea and vomiting at 24 postoperative hours.Main resultsEight trials including 388 patients were identified. Rest pain scores at 2 postoperative hours were decreased in the PECS block group, with a mean difference (95%CI) of −0.4 (−0.7 to −0.1), I² = 68%, p = 0.01, and a significant subgroup difference observed between radical mastectomy with (mean difference [95%CI]: 0.0 [−0.2 to 0.2], I² = 0%, p = 1.00), or without axillary dissection (mean difference [95%CI]: −0.7 [−1.1 to −0.4], I² = 40%, p < 0.001; p for subgroup difference < 0.001). All secondary pain-related outcomes were similar between groups. The overall quality of evidence was low.ConclusionsThere is low quality evidence that a PECS block provides marginal postoperative analgesic benefit after radical mastectomy at 2 postoperative hours only, when compared with a paravertebral block, and not beyond.Clinical trial number: PROSPERO – registration number: CRD42019131555.     

Efficacy of erector spinae plane block for analgesia in breast surgery: a systematic review and meta-analysis

The erector spinae plane block is a new regional anaesthesia technique that provides truncal anaesthesia for breast surgery. This systematic review and meta-analysis was undertaken to determine if the erector spinae plane block is effective at reducing pain scores and opioid consumption after breast surgery. This study also evaluated the outcomes of erector spinae plane blocks compared with other regional blocks. PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched. We included randomised controlled trials reporting the use of the erector spinae plane block in adult breast surgery. Risk of bias was assessed with the revised Cochrane risk-of-bias tool. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used to assess trial quality. Thirteen randomised controlled trials (861 patients; 418 erector spinae plane block, 215 no blocks, 228 other blocks) were included. Erector spinae plane block reduced postoperative pain compared with no block: at 0-2 hours (mean difference (95% CI) −1.63 (−2.97 to −0.29), 6 studies, 329 patients, high-quality evidence, I² = 98%, p = 0.02); at 6 hours (mean difference (95% CI) −0.90 (−1.49 to −0.30), 5 studies, 250 patients, high-quality evidence, I² = 91%, p = 0.003); at 12 hours (mean difference (95% CI) −0.46 (−0.67 to −0.25), 5 studies, 250 patients, high-quality evidence, I² = 58%, p < 0.0001); and at 24 hours (mean difference (95% CI) −0.50 (−0.70 to −0.30), 6 studies, 329 patients, high-quality evidence, I² = 76%, p < 0.00001). Compared with no block, erector spinae plane block also showed significantly lower postoperative oral morphine equivalent requirements (mean difference (95% CI) −21.55mg (−32.57 to −10.52), 7 studies, 429 patients, high-quality evidence, I² = 99%, p = 0.0001). Separate analysis of studies comparing erector spinae plane block with pectoralis nerve block and paravertebral block showed that its analgesic efficacy was inferior to pectoralis nerve block and similar to paravertebral block. The incidence of pneumothorax was 2.6% in the paravertebral block group; there were no reports of complications of the other blocks. This review has shown that the erector spinae plane block is more effective at reducing postoperative opioid consumption and pain scores up to 24 hours compared with general anaesthesia alone. However, it was inferior to the pectoralis nerve block and its efficacy was similar to paravertebral block. Further evidence, preferably from properly blinded trials, is required to confirm these findings.     

Erector spinae plane block for postoperative analgesia in breast and thoracic surgery: A systematic review and meta-analysis

Study objectiveThe erector spinae plane block (ESPB) is a newly defined regional anesthesia technique first introduced in 2016. The aim of this study is to determine its analgesic efficacy compared with non-block care and thoracic paravertebral block (TPVB).DesignWe systematically searched PubMed, Web of Science citation index, Embase, the Cochrane Library, Google Scholar, and ClinicalTrials.gov register searched up to March 2020. We conducted a meta-analysis of randomized controlled trials (RCTs) that compared an ESPB to non-block care or TPVB for postoperative analgesia in breast and thoracic surgery patients. Primary outcome was 24-hour postoperative opioid consumption. Risk of bias was assessed using Cochrane methodology.Results14 RCTs that comprised 1018 patients were included. Seven trials involved thoracic surgery patients and seven included breast surgery patients. Meta-analysis revealed that ESPB significantly reduced 24-hour opioid consumption compared with the non-block groups (−10.5 mg; 95% CI: −16.49 to −3.81; p = 0.002; I² = 99%). Similarly, the finding was consistent in subgroup analysis between the breast surgery (−7.75 mg; 95%CI −13.98 to −1.51; p = 0.01; I² = 97%) and thoracic surgery (−14.81 mg; 95%CI −21.18 to −8.44; p < 0.001; I² = 96%) subgroups. The ESPB significantly reduced pain scores at rest or movement at various time points postoperatively compared with non-block group, and reduced the rate of postoperative nausea and vomiting (OR 0.48; 95%CI 0.27 to 0.86; p = 0.01; I² = 0%). In contrast, there were no significative differences reported in any of the outcomes for ESPB versus TPVB strata.ConclusionsESPB improved analgesic efficacy in breast and thoracic surgery patients compared with non-block care. Furthermore, current literature supported the ESPB offered comparable analgesic efficacy to a TPVB.     

Supplemental peri-operative intravenous crystalloids for postoperative nausea and vomiting: an abridged Cochrane systematic review

We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri-operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51–0.75) (I² = 57%, p < 0.00001, 18 studies; 1766 participants; moderate-certainty evidence). It also probably reduces the risk of postoperative nausea within 6 h of surgery, with a risk ratio (95%CI) of 0.67 (0.58 to 0.78) (I² = 9%, p < 0.00001, 20 studies; 2310 participants; moderate-certainty evidence) and by around 24 h, the risk ratio (95%CI) being 0.47 (0.32–0.69) (I² = 38%, p = 0.0001, 17 studies; 1682 participants; moderate-certainty evidence). Supplemental intravenous crystalloid probably also reduces the overall risk of postoperative vomiting, with a risk ratio (95%CI) of 0.50 (0.40–0.63) (I² = 31%, p < 0.00001, 20 studies; 1970 participants; moderate-certainty evidence). The beneficial effect on vomiting was seen both within 6 h and by around 24 h postoperatively.     

Opioid versus non-opioid analgesia for spine surgery: a systematic review and meta-analysis of randomized controlled trials

Purpose

Opioids are the primary analgesics used in patients undergoing spine surgery. Postoperative pain is common despite their liberal use and so are opioid-associated side effects. Non-opioid analgesics are gaining popularity as alternative to opioids in spine surgery.

Methods

This systematic review evaluated current evidence regarding opioid and non-opioid intraoperative analgesia and their influence on immediate postoperative pain and adverse events in spine surgery.

Results

A total of 10,459 records were obtained by searching Medline, EMBASE and Web of Science databases and six randomized controlled trials were included. Differences in postoperative pain scores between opioid and non-opioid groups were not significant at 1 h: 4 studies, mean difference (MD) = 0.65 units, 95% confidence intervals (CI) [−0.12 to 1.41], p = 0.10, but favored non-opioid at 24 h after surgery: 3 studies, MD = 0.75 units, 95%CI [0.03 to 1.46], p = 0.04. The time for first postoperative analgesic requirement was shorter (MD = −45.06 min, 95%CI [−72.50 to −17.62], p = 0.001), and morphine consumption during first 24 h after surgery was higher in opioid compared to non-opioid group (MD = 4.54 mg, 95%CI [3.26 to 5.82], p < 0.00001). Adverse effects of postoperative nausea and vomiting (Relative risk (RR) = 2.15, 95%CI [1.37 to 3.38], p = 0.0009) and shivering (RR = 2.52, 95%CI [1.08 to 5.89], p = 0.03) were higher and bradycardia was lower (RR = 0.35, 95%CI [0.17 to 0.71], p = 0.004) with opioid analgesia.

Conclusion

The certainty of evidence on GRADE assessment is low for studied outcomes. Available evidence supports intraoperative non-opioid analgesia for overall postoperative pain outcomes in spine surgery. More research is needed to find the best drug combination and dosing regimen.

Prospero Registration: CRD42020209042.

     

Breast cancer screening using synthesized two-dimensional mammography: A systematic review and meta-analysis

PurposeWe conducted a systematic review and meta-analysis to compare the screening performance of synthesized mammography (SM) plus digital breast tomosynthesis (DBT) with digital mammography (DM) plus DBT or DM alone.MethodsMedline, Embase, Web of Science, and the Cochrane Library databases were searched from January 2010 to January 2021. Eligible population-based studies on breast cancer screening comparing SM/DBT with DM/DBT or DM in asymptomatic women were included. A random-effect model was used in this meta-analysis. Data were summarized as risk differences (RDs), with 95 % confidence intervals (CIs).ResultsThirteen studies involving 1,370,670 participants were included. Compared with DM/DBT, screening using SM/DBT had similar breast cancer detection rate (CDR) (RD = −0.1/1000 screens, 95 % CI = −0.4 to 0.2, p = 0.557, I² = 0 %), but lower recall rate (RD = −0.56 %, 95 % CI = −1.03 to −0.08, p = 0.022, I² = 90 %) and lower biopsy rate (RD = −0.33 %, 95 % CI = −0.56 to −0.10, p = 0.005, I² = 78 %). Compared with DM, SM/DBT improved CDR (RD = 2.0/1000 screens, 95 % CI = 1.4 to 2.6, p < 0.001, I² = 63 %) and reduced recall rate (RD = −0.95 %, 95 % CI = −1.91 to −0.002, p = 0.049, I² = 99 %). However, SM/DBT and DM had similar interval cancer rate (ICR) (RD = 0.1/1000 screens, 95 % CI = −0.6 to 0.8, p = 0.836, I² = 71 %) and biopsy rate (RD = −0.05 %, 95 % CI = −0.35 to 0.24, p = 0.727, I² = 93 %).ConclusionsScreening using SM/DBT has similar breast cancer detection but reduces recall and biopsy when compared with DM/DBT. SM/DBT improves CDR when compared with DM, but they have little difference in ICR. SM/DBT could replace DM/DBT in breast cancer screening to reduce radiation dose.     

Lipopolysaccharide-Induced Bone Loss in Rodent Models: A Systematic Review and Meta-Analysis

Osteoporosis has traditionally been characterized by underlying endocrine mechanisms, though evidence indicates a role of inflammation in its pathophysiology. Lipopolysaccharide (LPS), a component of gram-negative bacteria that reside in the intestines, can be released into circulation and stimulate the immune system, upregulating bone resorption. Exogenous LPS is used in rodent models to study the effect of systemic inflammation on bone, and to date a variety of different doses, routes, and durations of LPS administration have been used. The study objective was to determine whether systemic administration of LPS induced inflammatory bone loss in rodent models. A systematic search of Medline and four other databases resulted in a total of 110 studies that met the inclusion criteria. Pooled standardized mean differences (SMDs) and corresponding 95% confidence intervals (CI) with a random-effects meta-analyses were used for bone volume fraction (BV/TV) and volumetric bone mineral density (vBMD). Heterogeneity was quantified using the I² statistic. Shorter-term (<2 weeks) and longer-term (>2 weeks) LPS interventions were analyzed separately because of intractable study design differences. BV/TV was significantly reduced in both shorter-term (SMD = −3.79%, 95% CI [−4.20, −3.38], I² 62%; p < 0.01) and longer-term (SMD = −1.50%, 95% CI [−2.00, −1.00], I² 78%; p < 0.01) studies. vBMD was also reduced in both shorter-term (SMD = −3.11%, 95% CI [−3.78, −2.44]; I² 72%; p < 0.01) and longer-term (SMD = −3.49%, 95% CI [−4.94, −2.04], I² 82%; p < 0.01) studies. In both groups, regardless of duration, LPS negatively impacted trabecular bone structure but not cortical bone structure, and an upregulation in bone resorption demonstrated by bone cell staining and serum biomarkers was reported. This suggests systemically delivered exogenous LPS in rodents is a viable model for studying inflammatory bone loss, particularly in trabecular bone. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Remote transmission monitoring for postoperative perineural analgesia after major orthopedic surgery: A multicenter,randomized, parallel-group,controlled trial

Study objectiveAfter surgery, patients reported the delay in receiving help as the primary factor for poorly controlled pain. This study aimed to compare the effectiveness of patient management through two communication modalities: remote transmission (RT) versus bedside control (BC). We hypothesized that using remote technology for pump programming may provide the best postoperative infusion regimen for the patient's self-assessment of pain and adverse events.DesignA multicenter, randomized, parallel-group, controlled trial.SettingAnesthesiology department and orthopedic surgery ward at three university hospitals.PatientsEighty patients undergoing orthopedic surgery with postoperative perineural patient-controlled analgesia were included.InterventionsTwo groups (n = 40 for each group) were formed by randomization. In the postoperative period, perineural analgesia was followed up via an RT system or BC for 72 h.MeasurementsA nurse assessed daily pain, sensory and motor blocks and adverse events. Patients completed a questionnaire three times a day and alerted for any problem according to the group (RT system or nurses' follow-up). On the third postoperative day, the nurse removed the catheter, completed the final assessment, and collected the historical data from the pump. A physician's shorter response time to change the patient control analgesia (PCA) program was the primary endpoint.ResultsOf the 80 patients, 71 were analyzed (34 were randomized to the RT group and 37 to the BC group). Fifty-eight pump setting changes were noted. Analysis of repeated evaluations shows that mean time (SD) to change the PCA pump settings was significantly lower in the RT group (20 min (22.3 min)) than in the BC group (55.9 min (71.1 min)); mean difference [95% CI], −35.9 min [−74.3 to 2.4]); β estimation [95% CI], −34 [−63 to −6], p = 0.011). Pain relief, sensory and motor blocks did not differ between the groups: β estimation [95% CI], 0.1 [−0.4 to 0.6], p = 0.753; 0.5 [−0.4 to 1.4], p = 0.255; 0.9 [−0.04 to 1.8], p = 0.687, respectively. β = −34 [−63 to −6], p = 0.011). The consumption of ropivacaine, nurse workload and the cost of the analgesia regimen decreased in the RT group. No differences were noted in satisfaction scores or complication rates.ConclusionsThe response time for the physician to change the PCA program when necessary was shorter for patients using RT and alerts to the physician were more frequent compared with spot checks by nurses. RT helps to decrease nurses' workload, ropivacaine consumption, and costs but did not affect postoperative pain relief, complication rate, or patient-reported satisfaction score.IRB contact informationComité de Protection des Personnes, Sud Méditerranée III, Montpellier-Nîmes, France, registration number EudraCT A01698-35.Clinical trial numberClinicalTrials.gov ID:NCT02018068ProtocolThe full trial protocol can be accessed at Department of Anesthesiology and Critical Care Medicine, Medical Research and Statistics Unit, Lapeyronie University Hospital, Avenue Doten G Giraud, Montpellier, France. s-bringuierbranchereau@chu-montpellier.fr     

Perioperative dexmedetomidine administration to prevent delirium in adults after non-cardiac surgery: A systematic review and meta-analysis

Study objectiveTo evaluate the efficacy of perioperative dexmedetomidine (DEX) administration for preventing delirium in adults after non-cardiac surgery.DesignSystematic review and meta-analysis of randomized controlled trials (RCTs).InterventionsPerioperative administration of DEX to prevent delirium in adults following non-cardiac surgery.MeasurementsThe incidence of postoperative delirium (POD).MethodsThe databases of PubMed, Embase and Cochrane Central Register were searched from inception to Mar 4, 2021 for all available RCTs that assessed DEX for POD in adults after non-cardiac surgery. Risk ratio (RR) with a 95% confidence interval (CI) was calculated for dichotomous data. Standardized mean difference (SMD) was calculated for continuous data. Risk of bias was assessed using the second version of the Cochrane risk-of-bias tool for RCTs (RoB 2.0), and the level of certainty for main outcomes were assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.Main resultsThirteen studies, including the meta-analysis with a total of 4015 patients (DEX group: 2050 patients; placebo group: 1965 patients), showed that DEX significantly reduced the incidence of POD in adults after non-cardiac surgery compared with control group (RR: 0.60; 95%CI: 0.46 to 0.77, P = 0.0001, I² = 55%, GRADE = moderate). Meanwhile, there was a statistical difference by the subgroup analysis between the mean age ≥ 65 years group and the mean age<65 years group. There were no statistical differences in length of hospital stay following surgery (SMD: -0.36; 95%CI: −0.80 to 0.07, P = 0.1, I² = 97%, GRADE = low) and all-cause mortality rate (RR:0.57; 95%CI: 0.25 to 1.28, P < 0.17, I² = 0%, GRADE = moderate) compared with placebo group. However, Meta-analysis showed that DEX administration significantly resulted in intraoperative bradycardia when compared with placebo group (RR: 1.39; 95%CI: 1.14 to 1.69, P = 0.0009, I² = 0%, GRADE = high), and as well as intraoperative hypotension (RR: 1.25; 95%CI: 1.11 to 1.42, P = 0.0004, I² = 0%, GRADE = high).ConclusionThis systematic review and meta-analysis suggests that perioperative administration of DEX could significantly reduce the incidence of POD in patients elder than 65 years following non-cardiac surgery. However, there was no definite evidence that perioperative DEX could reduce the incidence of POD in patients younger than 65 years of age after non-cardiac surgery. In addition, perioperative DEX administration was associated with an elevated risk of bradycardia and hypotension.     

The effect of tranexamic acid on the values of activated clotting time in patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis

Study objectiveActivated clotting time (ACT) is a non-specific test to evaluate the adequacy of systemic heparinization whose value could be influenced by many factors. Tranexamic acid (TXA) is a widely used antifibrinolytic agent worldwide and whether TXA influences ACT value in cardiac surgical patients remains unknown. Current study was performed to address this question.DesignSystematic review and meta-analysis. PUBMED, Cochrane Library, EMBASE, OVID and Chinese BioMedical Literature & Retrieval System were searched using search terms “tranexamic acid”, “activated clotting time”, “cardiac surgery”, “randomized controlled trial” till May 7th, 2020, to identify all relevant randomized controlled trials (RCTs).SettingOperating room.PatientsCardiac surgical patients.InterventionsTXA or placebo.MeasurementsPrimary outcomes of interest included peri-operative ACT values. Secondary outcomes of interest include heparin dosage, protamine dosage, postoperative bleeding and blood transfusion.Main resultsSearch yielded 13 studies including 1168 patients, and 619 patients were allocated into Group TXA and 549 into Group Control (placebo). Meta-analysis suggested that, ACT values after heparinization [(WMD = −1.45; 95%CI: −12.52 to 15.43; P = 0.84)] and after protamine [(WMD = −1.18; 95%CI: −2.81 to 0.46; P = 0.16)] were comparable between Group TXA and Group Control, and that TXA did not influence heparin dose in adult patients [(WMD = 0.38; 95%CI: 0.30 to 0.46; P<0.00001) with no heterogeneity (I² = 4%, P = 0.35)] and protamine dose for heparin reversal [(WMD = 5.23; 95%CI: −0.33 to 10.80; P = 0.07) with no heterogeneity (I² = 0, P = 0.58)]. Meta-analysis also demonstrated that, TXA administration significantly reduced post-operative bleeding volume [(WMD = −126.33; 95%CI: −177.46 to −75.19; P < 0.0001), post-operative red blood cell (RBC) transfusion volume [(WMD = −71.86; 95% CI: −88.22 to −55.50; P < 0.00001), fresh frozen plasma (FFP) transfusion volume [(WMD = −13.83; 95% CI: −23.67 to −4.00; P = 0.006) and platelet concentrate (PC) transfusion volume [(WMD = −0.20; 95% CI: −0.29 to −0.10; P < 0.0001).ConclusionThis meta-analysis suggested that, TXA administration did not influence ACT value, heparin and protamine doses, but significantly reduced post-operative blood loss and transfusion requirement in cardiac surgical patients.     

Smoking and survival of breast cancer patients: A meta-analysis of cohort studies

ObjectivesPublished articles reported controversial results about the association of breast cancer survival with smoking. Hence, a meta-analysis was performed to investigate this association.MethodsA comprehensive search was performed to identify relevant cohort studies (up to May 31st, 2016). In the current smoking and former smoking v. never smoking analyses, the fixed- or random-effect model was selected based on the heterogeneity test among studies. And the heterogeneity was measured using Q test and I² statistic. Publication bias was estimated using Egger's regression asymmetry test.ResultsThirteen articles with 44 studies were included. Compared with never smokers, current smokers have a higher breast cancer-specific mortality and all-cause mortality, with pooled hazard ratio (HR) (HR = 1.30 95%CI: 1.16–1.45; I² = 52.4%) and (HR = 1.59, 95%CI: 1.41–1.78; I² = 87.1%), respectively. While former smokers tend to have a moderately increased all-cause mortality (HR = 1.10, 95%CI: 1.07–1.12; I² = 0.0%), but there was no significant association between former smoking and breast cancer-specific mortality (HR = 0.95, 95%CI: 0.90–1.02; I² = 0.0%).ConclusionThe present evidence indicates that current smoking leads to higher breast cancer-specific mortality and all-cause mortality than never smoking in breast cancer patients. However former smoking just causes a mild increase in all-cause morality, but not breast cancer-specific mortality.     

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis

ImportanceCarboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial.MethodsThe study was prospectively registered at PROSPERO (CRD42021228386).We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes.ResultsEight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I² 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I² 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44–3.08; I² 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm.Conclusionand relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.     

Postoperative outcomes in older surgical patients with preoperative cognitive impairment: A systematic review and meta-analysis

Study objectiveTo determine the effect of cognitive impairment (CI) and dementia on adverse outcomes in older surgical patients.DesignA systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs). Various databases were searched from their inception dates to March 8, 2021.SettingPreoperative assessment.PatientsOlder patients (≥ 60 years) undergoing non-cardiac surgery.MeasurementsOutcomes included postoperative delirium, mortality, discharge to assisted care, 30-day readmissions, postoperative complications, and length of hospital stay. Effect sizes were calculated as Odds Ratio (OR) and Mean Difference (MD) based on random effect model analysis. The quality of included studies was assessed using the Cochrane Risk Bias Tool for RCTs and Newcastle-Ottawa Scale for observational cohort studies.ResultsFifty-three studies (196,491 patients) were included. Preoperative CI was associated with a significant risk of delirium in older patients after non-cardiac surgery (25.1% vs. 10.3%; OR: 3.84; 95%CI: 2.35, 6.26; I²: 76%; p < 0.00001). Cognitive impairment (26.2% vs. 13.2%; OR: 2.28; 95%CI: 1.39, 3.74; I²: 73%; p = 0.001) and dementia (41.6% vs. 25.5%; OR: 1.96; 95%CI: 1.34, 2.88; I²: 99%; p = 0.0006) significantly increased risk for 1-year mortality. In patients with CI, there was an increased risk of discharge to assisted care (44.7% vs. 38.3%; OR 1.74; 95%CI: 1.05, 2.89, p = 0.03), 30-day readmissions (14.3% vs. 10.8%; OR: 1.36; 95%CI: 1.00, 1.84, p = 0.05), and postoperative complications (40.7% vs. 18.8%; OR: 1.85; 95%CI: 1.37, 2.49; p < 0.0001).ConclusionsPreoperative CI in older surgical patients significantly increases risk of delirium, 1-year mortality, discharge to assisted care, 30-day readmission, and postoperative complications. Dementia increases the risk of 1-year mortality. Cognitive screening in the preoperative assessment for older surgical patients may be helpful for risk stratification so that appropriate management can be implemented to mitigate adverse postoperative outcomes.     

Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – A systematic review and meta-analysis

BackgroundThe non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers.AimsTo evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis.MethodsA systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method.ResultsTwenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I²) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I² = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I² = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I² = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I² = 38%) were equivalent for combined BCT and mastectomy.ConclusionsSurvival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.     

Application of controlled low central venous pressure during hepatectomy: A systematic review and meta-analysis

Study objectivePrevious studies reported that controlled low central venous pressure (CVP) can reduce blood loss during liver resection. This systematic review and meta-analysis sought to explore the efficacy and safety of low CVP in patients undergoing hepatectomy.DesignA systematic review and meta-analysis of randomized controlled trials (RCTs).Review methodsRCTs were searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical database, Chinese Scientific Journals Database, and Wanfang database from inception to April 30, 2021. Subgroup analyses were performed based on different surgical methods (open hepatectomy vs laparoscopic hepatectomy) and published countries (China vs other countries). The quality of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation.Main resultsEighteen RCTs containing 1285 participants (626 patients in the low CVP group and 659 patients in the control group) were included in this study. The forest plot showed that low CVP effectively reduced blood loss during liver resection compared with the control group (MD = −311.92 mL, 95% CI [−429.03, −194.81]; P < 0.001, I² = 96%). Furthermore, blood transfusion volume (MD = −158.85 mL, 95% CI [−218.30, −99.40]; P < 0.001, I² = 55%) and the number of patients requiring transfusion (RR 0.41, 95% CI 0.27–0.65, P < 0.001, I² = 0%) were decreased in the low CVP group. Subgroup analyses showed similar results. Notably, the alanine transaminase level was significantly lower in the low CVP group during the first five postoperative days. However, no significant differences were observed for other postoperative liver function indicators (aspartate aminotransferase, total bilirubin, serum albumin, and prothrombin time), renal function indicators (blood urea nitrogen and serum creatinine) and perfusion parameters (heart rate, mean arterial pressure, and urine volume). The incidence of complications was similar between the two groups.ConclusionThe findings of this study showed that low CVP is effective and safe during hepatectomy. Therefore, this technique is recommended to reduce blood loss during hepatectomy.PROSPERO registration number: CRD42021232829.     

Perioperative intravenous S-ketamine for acute postoperative pain in adults: A systematic review and meta-analysis

Study objectiveTo evaluate the effectiveness and safety of S-ketamine for pain relief and analgesic consumption in surgical patients.DesignSystematic review and meta-analysis of randomized controlled trials (RCTs).SettingPerioperative setting.PatientsA total of 905 adult patients undergoing surgery using general anesthesia: 504 patients in the S-ketamine group and 401 patients in the placebo group.InterventionIntravenous S-ketamine as an adjuvant to general anesthesia compared with placebo.MeasurementsThe primary outcomes were resting and movement pain scores (VAS/NRS 0–10) and morphine consumption within 4, 12, 24 and 48 h after surgery. The secondary outcomes included postoperative complications such as nausea, vomiting, and psychotomimetic adverse events. We used the guidelines of the Recommendation Assessment, Development, and Evaluation (GRADE) system to evaluate the level of certainty for the main results.Main resultsA total of 12 studies were included. The types of surgery included abdominal surgery, thoracotomy, gynecologic surgery, arthroscopic anterior cruciate ligament repair, cardiac surgery, laparoscopic cholecystectomy, lumbar spinal fusion surgery, radical prostatectomy, and hemorrhoidectomy. There were significant improvements in resting pain scores at 4, 12 and 24 h with S-ketamine versus placebo [4 h: standardized mean difference (SMD) -1.11; 95% confidence interval (CI): −1.53, −0.68, p < 0.00001; GRADE = moderate; 12 h: SMD −0.88; 95%CI: −1.42, −0.34, p = 0.001; GRADE = moderate; 24 h: SMD -0.39; 95%CI: −0.73, −0.06, p = 0.02; GRADE = moderate]. The incidence of pain scores at 48 h showed no statistical difference between the two groups (SMD -0.27; 95%CI: −1.12, 0.58, p = 0.53, GRADE = moderate). The movement pain scores were not significantly different between the two groups at each time point (4 h: SMD −0.34; 95%CI: −0.73, 0.05, p = 0.09, GRADE = moderate; 12 h: SMD −0.42; 95%CI: −1.46, 0.63, p = 0.44, GRADE = low; 24 h: SMD −0.58; 95%CI: −1.25, 0.09, p = 0.09, GRADE = moderate; 48 h: SMD −0.49; 95%CI: −1.11, 0.14, p = 0.13, GRADE = low). At 4 and 12 h after surgery, the consumption of morphine was significantly reduced in the S-ketamine group (4 h: SMD −0.98; 95%CI: −1.37, −0.06, p < 0.00001, GRADE = moderate; 12 h: SMD −1.36; 95%CI: −2.26, −0.46, p = 0.003, GRADE = low). There were no significant differences in morphine use at 24 and 48 h between the two groups (24 h: SMD −0.70; 95%CI: −1.42, 0.02, p = 0.06, GRADE = low; 48 h: SMD −0.79; 95%CI: −2.26, 1.03, p = 0.39, GRADE = low). The risk for nausea [relative risk (RR) = 1.04; 95%CI: 0.83, 1.30, p = 0.73], vomiting (RR = 1.07; 95%CI: 0.84, 1.38, p = 0.57), and psychotomimetic adverse events (RR = 1.57; 95%CI: 0.82, 2.99, p = 0.17) showed no significant increase in the S-ketamine group.ConclusionsIntravenous S-ketamine as an adjunct to general anesthesia is effective for assisting analgesia and decreases the intensity of pain and opioid requirements in a short period of time after surgery, but it may increase the psychotomimetic adverse event rate. Overall, the level of certainty is moderate to low.     

Trends in endocrine therapy prescription and survival in patients with non-metastatic hormone receptor positive breast cancer treated with endocrine therapy: A population based-study

PurposeTo identify prognostic factors of invasive–disease free survival (iDFS) in women with non-metastatic hormone receptor positive (HR+) breast cancer (BC) in daily routine practice.MethodsWe performed a retrospective study using data from the Côte d’Or breast and gynecological cancer registry in France. All women diagnosed with primary invasive non-metastatic HR + BC from 1998 to 2015 and treated by endocrine therapy (ET) were included. Women with bilateral tumors or who received ET for either metastasis or relapse were excluded. We performed adjusted survival analysis and Cox regression to identify prognostic factors of iDFS.ResultsA total of 3976 women were included. Age at diagnosis, ET class, SBR grade, treatment, stage and comorbidity were independently associated with iDFS. Women who had neither surgery nor radiotherapy had the highest risk of recurrence (HR = 3.75, 95%CI [2.65–5.32], p < 0.0001). Receiving aromatase inhibitors (AI) was associated with a lower risk of recurrence (HR = 0.70, 95%CI [0.54–0.90], p = 0.055) compared to tamoxifen. Compared to women with no comorbidities, women with 1 or 2 comorbidities were more likely to receive AI (OR = 1.63, 95%CI [1.22–2.17], p = 0.0009).ConclusionsComorbidities, age at diagnosis and previous treatment were associated with iDFS in non-metastatic HR + BC patients. This study also showed that women who received tamoxifen for their cancer experienced worse iDFS compared to women treated with AI.     

Analgesic efficacy of the Pecs II block: a systematic review and meta-analysis

Surgery is the primary therapeutic intervention for breast cancer and can result in significant postoperative pain. We searched the current literature and performed a meta-analysis in order to compare the analgesic efficacy of the pectoral type-2 (Pecs II) block with systemic analgesia alone and with a thoracic paravertebral block for breast cancer surgery. Primary outcome was postoperative opioid consumption in the first 24 h after surgery. Secondary outcomes were pain scores at 0, 3, 6, 9 and 24 h after surgery, intra-operative opioid consumption, time to first analgesic request and incidence of postoperative nausea and vomiting. We identified 13 randomised controlled trials that included 815 patients. The Pecs II block significantly reduced postoperative opioid consumption (standardised difference in means: −13.64 mg oral morphine equivalents; 95%CI: −21.22 to −6.05; p < 0.01) and acute postoperative pain at all intervals in the first 24 h after surgery compared with systemic analgesia alone. Compared with the thoracic paravertebral block, the Pecs II block resulted in similar postoperative opioid consumption (standardised difference in means: −8.73 mg oral morphine equivalents; 95%CI: −18.16 to 0.69; p = 0.07) and postoperative pain scores after first measurement. In conclusion, the Pecs II block offers improved analgesic efficacy compared with systemic analgesia alone and comparable analgesic efficacy to a thoracic paravertebral block for breast cancer surgery.     

Duloxetine for the treatment acute postoperative pain in adult patients: A systematic review with meta-analysis

BackgroundDuloxetine administered during the acute perioperative period has been associated with lesser postoperative pain and analgesic consumption.Study objectivesThe study aimed to quantify the pooled effects of duloxetine on postoperative pain, analgesic consumption, and side-effects in the first 48 postoperative (PO) hours.DesignSystematic review with meta-analysis.SettingPostoperative pain management.PatientsAdult patients undergoing elective surgery.Search strategy and study selection. Medline, Cochrane, EMBASE, CENTRAL, and Web of Science were searched without language restrictions for prospective, parallel randomized controlled trials comparing duloxetine to placebo for the management of postoperative pain in adult patients.MeasurementsPain scores (11-point scales), opioid consumption (i.v. morphine equivalents), and frequency of side-effects were compared between duloxetine and placebo. Effect sizes were summarized as mean differences (MD), standardized mean differences (SMD) or risk ratios (RR) with the respective 95% confidence intervals (95% CI). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were used to classify the quality of evidence.ResultsThirteen studies were included. Duloxetine decreased pain at 24 h (MD = −0.66 points; 95% CI = −1.14 to −0.19 points; SMD = −0.59; 95% CI = −1.06 to −0.12; p = 0.01; I2 = 88%), and at 48 PO hours (MD = −0.90 points; 95% CI = −1.54 to −0.26 points; SMD = −0.66; 95% CI = −0.94 to −0.38; p = 0.01; I2 = 93%); and opioid consumption at 24 PO hours (MD = −8.21 mg; 95% CI = −13.32 mg to −3.10 mg; SMD = −2.17; 95% CI = −3.10 to −1.24; p < 0.001; I2 = 95%), and at 48 PO hours (MD = 7.71 mg; 95% CI = −13.86 mg to −1.56 mg; SMD = −2.13; 95% CI = −3.51 to −0.75; p = 0.02; I2 = 97%). Duloxetine did not affect the prevalence of postoperative nausea and/or vomiting (PONV) pruritus, headache or dizziness. High inter-study heterogeneity and within-study bias resulted in very-low quality of evidence for the primary outcomes.ConclusionsAlthough statistically significant effects of duloxetine were found on postoperative pain and opioid consumption during the first 48 postoperative hours, the effect sizes were below the expected minimal clinically relevant differences. Also, high risk-of-bias and inter-study heterogeneity caused the very-low quality of evidence (GRADE). We conclude that the currently available evidence does not support the clinical use of duloxetine for the management of acute postoperative pain.     

A randomised controlled trial of pectoral nerve-2 (PECS 2) block vs. serratus plane block for chronic pain after mastectomy

Thoracic interfascial plane blocks are effective for post-mastectomy acute analgesia. However, their effects on chronic pain are uncertain. We randomly allocated 80 women equally to pectoral nerve-2 (PECS 2) block or serratus plane block. The pectoral nerve-2 block reduced the rate of moderate or severe chronic pain from 13/40 (33%) with the serratus plane block to 4/40 (10%), p = 0.03, adjusted odds ratio (95%CI) 0.23 (0.07–0.80), p = 0.02. The rates of pain-free women at six postoperative months were indeterminate, 10/40 (25%) after serratus plane block vs. 19/40 (48%) after pectoral nerve-2 block, p = 0.06, adjusted odds ratio (95%CI) 2.9 (1.1–7.5), p = 0.03. Health-related quality of life at six postoperative months was similar after serratus plane and pectoral nerve-2 blocks, mean (SD) EQ-5D-3L scores 0.87 (0.15) vs. 0.91 (0.14), respectively, p = 0.21. The pectoral nerve-2 block reduced median (IQR [range]) morphine consumption in the first 24 postoperative hours from 6 (3–9 [1–25]) mg to 4 (2–7 [0–37]) mg, p = 0.04. However, acute pain scores after serratus plane and pectoral nerve-2 blocks were similar, median (IQR [range]) 23 (11–35 [0–70]) mm vs. 18 (11–27 [0–61]) mm, respectively, p = 0.44. Pectoral nerve-2 block reduced chronic pain 6 months after mastectomy compared with serratus plane block.