Evaluation of efficacy and safety of PARP inhibitors in breast cancer: A systematic review and meta-analysis

BackgroundMany breast cancer clinical trials with PARPi have been completed or are currently carried out, either by monotherapy or combined with chemotherapy. We aim to assess the efficacy and safety of PARPi in breast cancer patients as compared to chemotherapy.MethodsA comprehensive literature search of PubMed, EMBASE, CENTRAL, conference meetings and clinical trial registry was performed. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR). The secondary outcome was safety profile. The comparative effects were measured using hazard ratio (HR) or relative risk (RR) with 95% confidence interval. Subgroup analyses were conducted based on types of intervention and baseline characteristics of patients.ResultsSix RCTs (n = 1953) were included. Two RCTs were recognized as high risk. PARPi was associated with an improved PFS (HR, 0.65; 95% CI, 0.56–0.74), OS (HR, 0.86; 95% CI, 0.73–1.01), and a higher ORR (RR, 1.38; 95% CI, 1.05–1.82). PARPi, however, significantly increased risk of grade 3–4 thrombocytopenia (RR, 1.63; 95% CI, 1.06–2.52). Monotherapy was observed with lower risk of disease progression and higher ORR rate than combination therapy, 0.56 to 0.65 and 2.21 to 1.05, respectively. For patients without prior platinum treatment, PARPi significantly improved PFS (HR, 0.64; 95% CI, 0.52–0.79).ConclusionsPARPi was observed with a significantly improved efficacy in aspects of PFS and ORR, but also higher risk of grade 3–4 thrombocytopenia as compared to chemotherapy. PARPi was a better choice for patients who had not received previous platinum treatment.     

Mortality after tricuspid valve procedures: A 27-year,single-center experience

ObjectiveTo assess mortality after tricuspid valve (TV) surgery in a large single-center patient cohort.MethodsData from 392 TV procedures performed between 1989 and 2015 in 388 adult patients were retrospectively reviewed. The patients were divided into groups according to the type of concomitant procedure, ie, coronary artery bypass grafting (CABG) (TV + CABG group; n = 87), other valve surgery (TV + valve group; n = 240), or an isolated TV procedure with or without another minor procedure (isolated TV group; n = 65), and the era of the operation, ie, 1989-2005 (n = 173) or 2006-2015 (n = 219). Control groups of patients who underwent other valve procedures and/or CABG during the same time periods were used for comparison.ResultsDuring the most recent era, the annual number of TV procedures increased 2.4-fold, mainly for TV + valve procedures (2.8-fold). Within the TV + valve group, a larger proportion of patients had mild-to-moderate tricuspid regurgitation (grade ≤2) compared with the first-time period (P = .001). The TV + CABG group had significantly greater mortality than both the other groups during both time periods, whereas isolated TV procedure had the lowest mortality rates with the exception of the TV + valve group during the most recent era (P = .41). Survival for patients undergoing TV + valve procedures has improved significantly during the last decade (P = .001) and was comparable with that for other valve operations during this period.ConclusionsIn the last decade, TV repair has been performed more frequently and at lower grades of tricuspid regurgitation compared with previously, and mortality after TV procedures has decreased.     

Distribution and Surgical Management of Visceral Ewing Sarcoma Among Children and Adolescents

IntroductionEwing sarcoma (EWS) is a highly malignant tumor of bone and soft tissue that occasionally arises from viscera. Visceral EWS (V-EWS) is challenging to manage given its varied organ distribution and often late-stage presentation. We aimed to characterize our institutional experience with V-EWS, focusing on its surgical management, and to compare V-EWS outcomes against those with osseous (O-EWS) and soft tissue EWS (ST-EWS).MethodsRetrospective review of all EWS patients ≤21 years presenting to a single institution between 2000 and 2022. Patient- and disease-specific characteristics were compared. Overall and relapse-free survival were estimated using Kaplan Meier methods and log-rank test.Results156 EWS patients were identified: 117 O-EWS, 20 ST-EWS, and 19 V-EWS. V-EWS arose in the kidney (n = 5), lung (n = 5), intestine (n = 2), esophagus (n = 1), liver (n = 1), pancreas (n = 1), adrenal gland (n = 1), vagina (n = 1), brain (n = 1), and spinal cord (n = 1). No significant demographic differences were detected between EWS groups. V-EWS was more frequently metastatic at presentation (63.2%; p = 0.005), yet no significant overall or relapse-free survival differences emerged between EWS groups, with similar follow-up intervals. While V-EWS required multiple unique operative strategies to gain primary control, no significant difference in treatment strategies appeared between groups. Surgery-only primary control was associated with improved overall and relapse-free survival in all groups.ConclusionsV-EWS presents unique management challenges in children and adolescents given its variable sites of origin. This large cohort is the first to describe the surgical management and outcomes of V-EWS, demonstrating more frequent metastatic presentation, while achieving similar survival across groups.Level of evidenceLevel 2 – Cohort Study.     

Impact of body mass index on overall survival in patients with metastatic breast cancer

BackgroundHigh Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC).MethodsThe National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers.ResultsOf 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m² (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect.ConclusionOverweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.     

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

BackgroundChemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.MethodsWe compared three different doses of q3w nab-PTX (Standard: 260 mg/m² [SD260] vs Medium: 220 mg/m² [MD220] vs Low: 180 mg/m² [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.ResultsOne hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.ConclusionsIntravenous administration of low-dose nab-PTX at 180 mg/m² q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.     

Direct and indirect activation of the adenosine triphosphate–sensitive potassium channel to induce spinal cord ischemic metabolic tolerance

ObjectivesThe mitochondrial adenosine triphosphate–sensitive potassium channel is central to pharmacologically induced tolerance to spinal cord injury. We hypothesized that both direct and nitric oxide–dependent indirect activation of the adenosine triphosphate–sensitive potassium channel contribute to the induction of ischemic metabolic tolerance.MethodsSpinal cord injury was induced in adult male C57BL/6 mice through 7 minutes of thoracic aortic crossclamping. Pretreatment consisted of intraperitoneal injection 3 consecutive days before injury. Experimental groups were sham (no pretreatment or ischemia, n = 10), spinal cord injury control (pretreatment with normal saline, n = 27), Nicorandil 1.0 mg/kg (direct and indirect adenosine triphosphate–sensitive potassium channel opener, n = 20), Nicorandil 1 mg/kg + carboxy-PTIO 1 mg/kg (nitric oxide scavenger, n = 21), carboxy-PTIO (n = 12), diazoxide 5 mg/kg (selective direct adenosine triphosphate–sensitive potassium channel opener, n = 25), and DZ 5 mg/kg+ carboxy-PTIO 1 mg/kg, carboxy-PTIO (n = 23). Limb motor function was assessed using the Basso Mouse Score (0-9) at 12-hour intervals for 48 hours after ischemia.ResultsMotor function was significantly preserved at all time points after ischemia in the Nicorandil pretreatment group compared with ischemic control. The addition of carboxy-PTIO partially attenuated Nicorandil's motor-preserving effect. Motor function in the Nicorandil + carboxy-PTIO group was significantly preserved compared with the spinal cord injury control group (P < .001), but worse than in the Nicorandil group (P = .078). Motor preservation in the diazoxide group was similar to the Nicorandil + carboxy-PTIO group. There was no significant difference between the diazoxide and diazoxide + carboxy-PTIO groups.ConclusionsBoth direct and nitric oxide–dependent indirect activation of the mitochondrial adenosine triphosphate–sensitive potassium channel play an important role in pharmacologically induced motor function preservation.     

Establishment and validation of a nomogram for predicting overall survival of node-negative perihilar cholangiocarcinoma

AimThere lacks a predictive model for overall survival (OS) of node-negative perihilar cholangiocarcinoma (PHC). This study aimed at developing and validating a prognostic nomogram to predict OS of node-negative PHC after resection.MethodsWe established a nomogram via multivariate regression analysis by using the design cohort (n = 410, obtained from Surveillance, Epidemiology, and End Results database), and its external verification was done in the validation cohort (n = 100, the First Affiliated Hospital of Sun Yat-sen University). Predictive accuracy of the nomogram was assessed by concordance-index (C-index), calibration curves, and decision curve analysis (DCA). Performance of the nomogram was compared with the American Joint Committee on Cancer (AJCC) staging system.ResultsMultivariate regression analysis revealed that age, tumor grade, and the count of examined lymph nodes were independent prognostic factors for OS of node-negative PHC. The nomogram had a C-index of 0.603 and 0.626 in design cohort and validation cohort, respectively, which was better than that of AJCC staging system (both p < 0.05). The calibration curves showed good consistency between actual and nomogram-predicted OS probabilities. DCA showed that nomogram had better clinical usefulness. Furthermore, the nomogram-predicted scores could stratify the patients into three risk groups, and patients in higher risk group had worse prognosis than those in lower risk group (all p < 0.05).ConclusionThe proposed nomogram had a better prognostic accuracy than the AJCC staging system in predicting postoperative OS of node-negative PHC. It was helpful to guide the adjuvant therapeutic strategies for node-negative PHC.     

A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

IntroductionPlatinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.Materials and methodsAll studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.ResultsFrom the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17–1.49, p < 0.00001; I² = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08–1.76, P = 0.009; I² = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48–2.47, p < 0.00001; I² = 32%), as well as PFS(HR 1.13, 95% CI 0.81–1.57, P = 0.47; I² = 0%) and OS (HR 1.89, 95% CI 1.22–2.92, P = 0.004; I² = 0%).ConclusionAccording to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.     

Prognosis stratification and postoperative radiation therapy utilization in adenoid cystic carcinoma of the breast

PurposeAdenoid cystic carcinoma of the breast (ACCB) is a rare malignancy with a favorable prognosis. Little information exists regarding the impact of postoperative radiation therapy (RT) on survival outcome in patients with ACCB. This study aimed to evaluate the clinical significance of postoperative RT in ACCB.MethodsData of patients with ACCB were extracted from the Surveillance, Epidemiology, and End Results database (2000–2019). Univariate and multivariable Cox regression analyses were performed to identify prognostic factors. In addition, a nomogram model was constructed and internally validated for discrimination and calibration. The value of postoperative RT was respectively accessed in each risk subgroup according to nomogram-deduced individualized score.ResultsA total of 689 eligible patients were included in the analysis. Partial mastectomy was associated with an increased risk of death compared with partial mastectomy plus postoperative RT (P = 0.020), but total mastectomy with or without postoperative RT was comparable (P = 0.624). Then, in-depth analysis was performed for patients receiving breast-conserving therapy (n = 485, the training set vs. the testing set = 340 vs. 145). Age at diagnosis, histological grade, and T stage were identified as prognostic factors for overall survival (OS) (All P < 0.05). A nomogram was constructed to provide predictive accuracy toward individual OS rates of ACCB and to divide patients into different risk subgroups. Notably, compared with non-RT, postoperative RT significantly improved OS in the high-risk subgroup (P = 0.006 for the training set, and P = 0.013 for the overall population) but not in the low-risk subgroup (P = 0.807 for the training set, and P = 0.293 for the overall population), suggesting that these patients may be able to exempt from postoperative RT.ConclusionA robust and effective nomogram was developed to predict prognosis and assist in treatment decisions in patients with ACCB undergoing partial mastectomy.     

Results of staged repair of aortic disease in patients with Marfan syndrome

ObjectiveWe present our open surgical strategies for staged replacement of the thoracic and thoracoabdominal aorta in patients with Marfan syndrome.MethodsBetween October 1999 and December 2017, 82 patients with Marfan syndrome underwent 118 aortic repairs. We divided the aorta into 4 segments for categorization: (1) the aortic root, (2) aortic arch, (3) descending thoracic, and (4) abdominal aorta. Procedures were categorized according to the types of surgery. Staged repair was defined as a subsequent operation on a different segment of the aorta after initial repair (n = 111, 94.1%), and reoperation was defined as an operation on the same segment (n = 7, 5.9%).ResultsThe mean age at initial operation was 41.7 ± 14.9 years. Staged repairs included aortic root replacement (n = 42, 36%), total arch replacement (n = 11, 9.3%), combined aortic root and total arch replacement (n = 13, 11%), descending aorta replacement (n = 4, 3.4%), thoracoabdominal aortic repair (n = 36, 31%), and extensive arch-descending or thoracoabdominal repair (n = 5, 4.2%). Four patients received 3 staged repairs. Operative mortality was 0.8% (1/118). Stroke occurred in 1.7% (2/118), and spinal cord injury occurred in 1.7% (2/117). Overall survival was 95.8 ± 2.4% at 10-years. Twenty-four patients underwent replacement of the whole aorta after 2.5 ± 3.8 years following initial repair.ConclusionsOur strategies for staged replacement of the thoracic and thoracoabdominal aorta in patients with Marfan syndrome resulted in excellent early- and long-term outcomes.     

Remote Ischaemic Pre-Conditioning Reduces Intestinal Ischaemia Reperfusion Injury in a Newborn Rat

ObjectiveRemote ischaemic conditioning (RIC) has been shown to reduce ischaemia-reperfusion injury(IRI) in multiple organ systems. IRI is seen in multiple bowel pathologies in the newborn, including NEC. We investigated the potential of RIC as a novel therapy for various intestinal pathologies in the newborn.MethodsWe used an established intestinal IRI model in rat pups which results in similar intestinal injury to necrotising enterocolitis (NEC). Animals were randomly allocated to IRI only(n = 14), IRI + RIC(n = 13) or sham laparotomy(n = 10). The macroscopic extent of intestinal injury is reported as a percentage of total small bowel. Injury severity was measured using Chiu-Park scoring. Neutrophil infiltration/activation was assayed by myeloperoxidase activity. Immunohistochemistry was used to assess the expression of hypoxia-inducible factor alpha (HIF-1α). Data are median (interquartile range).ResultsAnimals that underwent RIC showed a decreased extent of macroscopic injury from 100%(85–100%) in the IRI only group to 58%(15–84%, p = 0.003) in the IRI + RIC group. Microscopic injury score was significantly lower in animals that underwent RIC compared to IRI alone (3.5[1.25–5] vs 5.5[4–6], p = 0.014). Intestinal myeloperoxidase activity in animals exposed to IRI was 3.4 mU/mg of tissue (2.5–3.7) and 2.1 mU/mg(1.5–2.8) in the IRI + RIC group(p = 0.047). HIF-1α expression showed a non-significant trend towards reduced expression in the IRI + RIC group.ConclusionsRIC reduces the extent and severity of bowel injury in this animal model, supporting the hypothesis that RIC has therapeutic potential for intestinal diseases in the newborn.     

Intraoperative Support for Primary Bilateral Lung Transplantation: A Propensity-Matched Analysis

BackgroundSingle-center studies support benefits of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a method of intraoperative support. Propensity-matched data from a large cohort, however, are currently lacking. Therefore, our goal was to compare outcomes of intraoperative VA-ECMO and cardiopulmonary bypass (CPB) during bilateral lung transplantation (LTx) with a propensity analysis.MethodsWe performed a retrospective analysis of 795 consecutive primary adult LTx patients (June 1, 2011-December 26, 2020) using no intraoperative support (n = 210), VA-ECMO (n = 150), or CPB (n = 197). Exclusion criteria included LTx on venovenous-ECMO, single/redo LTx, ex vivo lung perfusion, and concomitant solid-organ transplantation or cardiac procedure. Propensity analysis was performed comparing patients who underwent intraoperative CPB or VA-ECMO.ResultsThe propensity CPB group required more blood products at 72 hours (P = .02) and longer intensive care unit length of stay (P < .001) and ventilator dependence days (P < .001). There were no differences in cerebrovascular accident (P = 1), reintubation (P = .4), dialysis (P = .068), in-hospital mortality (P = .33), and 1-year (P = .67) and 3-year (P = .32) survival. The CPB group had a higher incidence of grade 3 primary graft dysfunction at 72 hours (P < .001). Neither support strategy was a predictor of 1- and 3-year mortality in our multivariable model (VA-ECMO, P = .72 and P = .57; CPB, P = .45 and P = .91, respectively).ConclusionsIntraoperative VA-ECMO during lung transplantation was associated with fewer postoperative blood transfusions, shorter length of mechanical ventilation, and lower incidence of a grade 3 primary graft dysfunction at 72 hours. Although there were some differences in the postoperative course between the VA-ECMO and CPB groups, support type was not associated with differences in survival.     

Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial

ObjectiveTo determine whether a continuous intravenous infusion of standard amino acids could preserve kidney function after on-pump cardiac surgery.MethodsAdult patients scheduled to receive cardiac surgery lasting longer than 1 hour on-pump were randomized to standard care (n = 36) or an infusion of amino acids initiated immediately after induction of anesthesia (n = 33). The study's primary outcome measurements assessed renal function. These assessments included duration of renal dysfunction, duration and severity of acute kidney injury (AKI), estimated glomerular filtration rate (eGFR) over time, urine output, and use of renal-replacement therapy. Complications and other measures of morbidity were also assessed.ResultsSixty-nine patients (mean age 71.5 [standard deviation 9.2] years; 19 of 69 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (37/69), valve surgery (24/69), coronary artery bypass graft and valve surgery (6/69), or other procedures (2/69). Mean on-pump time was 268 [standard deviation 136] minutes. Duration of renal dysfunction did not differ between the groups (relative risk, 0.86; 95% confidence interval [CI], 0.19-3.79, P = .84). However, patients who received the amino acid infusion had a reduced duration of AKI (relative risk, 0.02; 95% CI, 0.005-0.11, P < .0001) and greater eGFR (+10.8%; 95% CI, 1.0%-20.8%, P = .033). Daily mean urine output was also significantly greater in patients who received the amino acid infusion (1.4 ± 0.5 vs 1.7 ± 0.9 L/d; P = .046).ConclusionsCommencing an infusion of standard amino acids immediately after the induction of anesthesia did not alter duration of renal dysfunction; however, other key measures of renal function (duration of AKI, eGFR and urine output) were significantly improved. These results warrant replication in multicenter clinical trials.     

Retroperitoneoscopic Pyeloplasty for Ureteropelvic Junction Obstruction in Children: Value of Robotic Assistance

AimRetroperitoneal pyeloplasty (RP) for pediatric ureteropelvic junction obstruction (UPJO) performed using retroperitoneoscopy (retro-RP) or robotic assistance (robo-RP) were compared.MethodsAll subjects were Japanese, matched for age, weight, and RP diameters. All RP were performed in the lateral decubitus position at a single institute by the same team using identical protocols. Five independent surgeons were asked to score intraoperative video recordings for perceived difficulty of suturing (DOS; 5 = impossible; 4 = difficult; 3 = tedious; 2 = slow; 1 = easy) and rank RP as +1 if robo-RP appeared to be superior, 0 if they appeared to be the same, and −1 if robo-RP appeared to be inferior.ResultsRobo-RP performed 2018-2022 (n = 22) were matched with retro-RP performed 2011-2019 (n = 34). Mean overall operative times were similar (robo-RP: 305.2 ± 57.8 min versus retro-RP: 340.0 ± 117.9 min; p = 0.19), but securing the larger retroperitoneal space required for robo-RP took significantly longer; 50.8 ± 13.9 min versus 24.3 ± 9.6 min; p < 0.0001. Total anastomotic time (TAT) and TAT per suture were both significantly shorter for robo-RP (p < 0.0001). The coefficient of variation for time taken to place one suture was smaller for robo-RP than for retro-RP. DOS was lower for robo-RP with less variance (p < 0.01). Robo-RP had shorter drainage tube insertion, ambulated quicker postoperatively, and shorter hospitalization. Retro-RP had anastomotic complications; leaks (n = 2) and strictures (n = 2, requiring conventional open re-pyeloplasty). Robo-RP had no anastomotic complications and was ranked +1 unanimously.ConclusionsThe RP anastomosis was quicker with less complications and more precise with robotic assistance in matched patients under similar circumstances. Should RP be indicated, robo-RP is recommended.Level of evidenceIII.     

Asymptomatic degenerative mitral regurgitation repair: Validating guidelines for early intervention

IntroductionMitral repair for asymptomatic (New York Heart Association [NYHA] class I) degenerative mitral regurgitation (MR) is supported by the guidelines, but is not performed often. We sought to determine outcomes for asymptomatic patients when compared with those with symptoms.MethodsBetween 2004 and 2018, 1027 patients underwent mitral replacement (22) or repair with or without other cardiac surgery (1005), the latter being grouped by NYHA class: I (n = 470; 47%), II (n = 408; 40%), or III/IV (n = 127; 13%). Statistical analyses included propensity score matching and weighting, and multistate models.ResultsThe proportion of patients designated as NYHA class I undergoing surgery increased steadily during this period (P < .001). Overall, 30-day mortality was 0.4%, and zero for patients designated NYHA class I. Unadjusted 10-year survival was significantly greater in patients designated NYHA class I compared with II and III/IV (P < .001). Freedom from reoperation at 10 years was 99.8% overall, and 100% for patients designated NYHA class I. In patients designated as NYHA class I, predischarge and 10-year moderate MR were 0.7% and 20.1%, whereas more than moderate was zero and 0.6%. Preoperative ejection fraction less than 60% was associated with late mortality (P = .025). After covariate-adjustments, freedom from MR and tricuspid regurgitation were not statistically significantly different by NYHA class. However, overall survival was significantly worse in patients with NYHA class III/IV, compared with class II.ConclusionsMitral repair in asymptomatic patients is safe and durable. Careful monitoring until class II symptoms is appropriate. However, repair before ejection fraction decreases below 60% is important for late overall survival.     

Successful Treatment of Fibro-Adipose Vascular Anomaly with Sirolimus

BackgroundThe purpose of this study was to present our initial experience in using sirolimus therapy to treat fibro-adipose vascular anomaly (FAVA).MethodsWe retrospectively reviewed the medical records of eight patients with FAVA who were treated with sirolimus at our hospital between July 2017 and October 2020.ResultsSix girls (75%) and two boys (25%) were included in the cohort; the average age was 8 years (range, 1–13 years). Vascular tumors developed mainly on the extremities, including the forearm (n = 2; 25.0%), calf (n = 4; 50.0%), and thigh (n = 2; 25.0%). The predominant symptoms included swelling of the lesion (n = 8; 100%), pain (n = 7; 87.5%), contracture (n = 3; 37.5%), and phlebectasia (n = 3; 37.5%). Magnetic resonance imaging was the primary method used for FAVA diagnosis, and all patients underwent enhanced MRI. All lesions were heterogeneous with hyperintense T1 signals. The fat-suppressed T2-weighted images also revealed heterogeneous hyperintense masses, thus indicating fibrofatty infiltration. All eight patients received a sirolimus treatment regimen after FAVA diagnosis. One patient underwent tumor resection but experienced recurrence, whereas the other six patients underwent biopsy. Histological examination revealed that the lesions consisted of fibrofatty tissue with abnormal venous channels and anomalous lymphatic vascular components. Sirolimus softened the masses and caused tumor shrinkage within 5.25 ± 2.6 weeks (range, 2–10 weeks) after treatment initiation. The tumors also involuted rapidly and became stable within 7.75 ± 2.25 months after treatment initiation (range, 6–12 months). All seven patients experiencing pain reported relief within 3.8 ± 1.8 weeks (range, 2–7 weeks) after initiation of sirolimus therapy. Sirolimus alleviated but did not fully resolve the contracture in three patients. Remarkably, five patients exhibited a complete response, and three patients exhibited a partial response. At the time of the last follow-up, three patients had begun to gradually taper off sirolimus after 24 months of treatment and maintained a low blood sirolimus concentration. No serious adverse effects were observed during treatment.ConclusionFAVA is a complex vascular malformation that appears to respond well to sirolimus treatment. Thus, sirolimus may be an effective and safe treatment for FAVA.Level of evidenceLEVEL IV.     

Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

Derivation and Validation of a Machine Learning Algorithm for Predicting Venous Thromboembolism in Injured Children

BackgroundVenous thromboembolism (VTE) causes significant morbidity in pediatric trauma patients. We applied machine learning algorithms to the Trauma Quality Improvement Program (TQIP) database to develop and validate a risk prediction model for VTE in injured children.MethodsPatients ≤18 years were identified from TQIP (2017–2019, n = 383,814). Those administered VTE prophylaxis ≤24 h and missing the outcome (VTE) were removed (n = 347,576). Feature selection identified 15 predictors: intubation, need for supplemental oxygen, spinal injury, pelvic fractures, multiple long bone fractures, major surgery (neurosurgery, thoracic, orthopedic, vascular), age, transfusion requirement, intracranial pressure monitor or external ventricular drain placement, and low Glasgow Coma Scale score. Data was split into training (n = 251,409) and testing (n = 118,175) subsets. Machine learning algorithms were trained, tested, and compared.ResultsLow-risk prediction: For the testing subset, all models outperformed the baseline rate of VTE (0.15%) with a predicted rate of 0.01–0.02% (p < 2.2e⁻¹⁶). 88.4–89.4% of patients were classified as low risk by the models.High-risk predictionAll models outperformed baseline with a predicted rate of VTE ranging from 1.13 to 1.32% (p < 2.2e⁻¹⁶). The performance of the 3 models was not significantly different.ConclusionWe developed a predictive model that differentiates injured children for development of VTE with high discrimination and can guide prophylaxis use.Level of EvidencePrognostic, Level II.Type of StudyRetrospective, Cross-sectional.     

Surgical outcomes of acute type A aortic dissection in patients undergoing cardiopulmonary resuscitation

ObjectivesThe surgical indications for acute type A aortic dissection (AAAD) in patients in cardiopulmonary arrest remain controversial. Outcomes of AAAD for patients who underwent cardiopulmonary resuscitation (CPR) were evaluated.MethodsBetween 2004 and 2018, of the 519 patients who underwent AAAD repair, 34 (6.6%) required CPR before or on starting AAAD repair. The patients were divided into 2 groups, survivors (n = 13) and nonsurvivors (n = 21), to compare the early operative outcomes, including mortality and neurological events.ResultsThe major cause of cardiovascular collapse requiring CPR was aortic rupture/cardiac tamponade (n = 21 [61.8%]), followed by coronary malperfusion (n = 12 [35.3%]) and acute aortic valve regurgitation (n = 3 [8.8%]). There were 3 (23.1%) patients in the survivors group and 11 (52.4%) in the nonsurvivors group who required ongoing CPR at the beginning of AAAD repair (P = .039). Of these patients, 1 survivor and 6 nonsurvivors could not achieve return of spontaneous circulation after pericardiotomy (P = .045). Although the duration from onset or arrival to the operating room was similar (P = .35 and P = .49, respectively), overall duration of CPR was shorter in survivors (10 minutes [range, 7.5-16 minutes] vs 16.5 minutes [range, 15-20 minutes]; P = .044). All survivors without any neurological deficits showed return of spontaneous circulation after pericardiotomy. Multivariate regression modeling showed that CPR duration >15 minutes was a significant risk factor for in-hospital mortality (P = .0040).ConclusionsCPR duration beyond 15 minutes may be a contraindication for AAAD repair. Moreover, we should reconsider surgery for patients who cannot achieve return of spontaneous circulation after pericardiotomy.     

Are racial differences in hospital mortality after coronary artery bypass graft surgery real? A risk-adjusted meta-analysis

BackgroundDespite several reports, there are still conflicting data on the influence of ethnicity on mortality rates associated with coronary artery bypass grafting (CABG). We aimed to get further insights into the effect of race on mortality following CABG by performing a risk adjusted meta-analysis.MethodsRelevant studies were searched on PubMed, Embase, BioMed Central, and the Cochrane Central register. Pairwise meta-analysis was used to estimate the relative risk of hospital death of black, Hispanic, and Asian patients using white patients as reference. Risk adjusted meta-analytic estimates were obtained using generic inverse variance methods with random effect model.ResultsA total of 28 studies were selected for analysis. A total of 21 studies reported on hospital mortality in black (n = 222,892) versus white (n = 3,884,043) patients, 7 studies reported on Hispanic (n = 91,256) versus white (n = 1,458,524) and 9 studies reported on Asian (n = 27,820) versus white (n = 1,081,642). When compared with white patients, adjusted risk of hospital death was significantly greater for black patients (adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 1.13-1.39; P < .001), and not statistically different for Asian (OR, 1.33; 95% CI, 0.99-1.77; P = .05) and Hispanic patients (adjusted OR, 1.08; 95% CI, 0.94-1.23; P = .26). Meta-regression showed a significant trend toward lower mortality rates in most recent series in both black (P = .02) and white (P = .0007) and Asian (P = .01) but not for Hispanic (P = .41). However, as mortality rates were lower across the different races, the relative disadvantage between the study groups persisted, which may explain the lack of interaction between study period and race effect on mortality for black (adjusted P = .09), Asian (adjusted P = .63), and Hispanic (adjusted P = .97) patients.ConclusionsThe present meta-analysis showed that despite progress is being made in lowering in-hospital mortality rates among the major racial/ethnic groups, ethnical disparities in hospital mortality after CABG remain.