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.     

Evolution of Pulmonary Valve Management During Repair of Tetralogy of Fallot: A 14-year Experience

BackgroundThe optimal repair strategy for tetralogy of Fallot remains controversial. This report presents a 14-year evolution of management of the pulmonary valve (PV) from transannular patch to valve-sparing repair to neovalve creation using living right atrial appendage tissue.MethodsA retrospective review of 172 consecutive patients undergoing complete repair for TOF between January 2007 and June 2021 was performed. Clinical and follow-up data were analyzed by repair group. Neopulmonary valve (NPV) creation using right atrial appendage tissue was introduced in 2019. Failure of valve-sparing repair was defined as needing reintervention for recurrent right ventricular outflow tract obstruction (RVOTO).ResultsMedian age and weight at repair were 4.9 months and 6 kg, respectively. Median preoperative PV size and z-score were 6.4 mm (5.2-8.3 mm) and ?3.2 (?4.1 to ?2.1), respectively. Patients who underwent valve-sparing repair had larger PV size and z-score compared with patients who underwent transannular patch procedures (8 mm vs 5.6 mm; ?2.1 vs ?3.2; both P < .001). There were no hospital mortalities. Overall follow-up was 44 months. At last follow-up, 10% of patients who underwent valve-sparing repair had repeat intervention for recurrent RVOTO. Patients who had failed valve-sparing repair had significantly lower PV z-scores (?2.6 vs ?1.9; P = .01). An NPV was used in 8 patients with a median PV z-score of ?4 (?4.7 to ?3.9). At 6 months, 6 patients (75%) had mild or trivial pulmonary insufficiency after NPV placement.ConclusionsRepair of tetralogy of Fallot is a safe operation with excellent outcomes. Valve-sparing repair avoids right ventricular dilation but may fail for RVOTO at a PV z-score <?2. NPV creation offers an alternative option in patients with a small PV.     

Difference in Survival in Early Kidney after Liver Transplantation Compared with Simultaneous Liver-Kidney Transplantation: Evaluating the Potential of the “Safety Net”

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Albumin-Bilirubin Score vs Model for End-Stage Liver Disease in Predicting Post-Hepatectomy Outcomes

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Population-Based Analysis of Hepatocellular Carcinoma in Children: Identifying Optimal Surgical Treatment

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Deep Sternal Wound Infection and Mortality in Cardiac Surgery: A Meta-analysis

BackgroundDeep sternal wound infection (DSWI) is a rare but severe complication after cardiac surgical procedures and has been associated with increased early morbidity and mortality. Studies reporting long-term outcomes in patients with DSWI have shown contradictory results. We performed a study-level meta-analysis evaluating the impact of DSWI on short- and long-term clinical outcomes.MethodsA systematic literature search was conducted to identify studies comparing short- and long-term outcomes of patients submitted to cardiac surgical procedures who developed DSWI and patients who did not. The primary outcome was overall mortality. Secondary outcomes were in-hospital mortality, follow-up mortality, major adverse cardiovascular events, myocardial infarction, and repeat revascularization. Postoperative outcomes were also investigated.ResultsTwenty-four studies totaling 407 829 patients were included. Overall, 6437 (1.6%) patients developed DSWI. Mean follow-up was 3.5 years. DSWI was associated with higher overall mortality (incidence rate ratio [IRR], 1.99; 95% CI, 1.66-2.38; P < .001), in-hospital mortality (odds ratio, 3.30; 95% CI, 1.88-5.81; P < .001), follow-up mortality (IRR, 2.02; 95% CI, 1.39-2.94; P = .001), and major adverse cardiovascular events (IRR, 2.04; 95% CI, 1.60-2.59; P < .001). No differences in myocardial infarction and repeat revascularization were found, but limited studies reported those outcomes. DSWI was associated with longer postoperative hospitalization, stroke, myocardial infarction, and respiratory and renal failure. Sensitivity analyses on isolated coronary artery bypass grafting studies and by adjustment method were consistent with the main analysis.ConclusionsCompared with patients who did not develop DSWI, patients with DSWI after cardiac surgical procedures had increased risk of death as well as short- and long-term adverse clinical outcomes.     

Advanced preoperative three-dimensional planning decreases the surgical complications of using large-for-size grafts in pediatric living donor liver transplantation

BackgroundUsing “large-for-size” liver graft, graft-to-recipient weight ratio (GRWR) ≥4%, has been debated in pediatric liver transplantation due to possible graft compartment after abdomen closure. Meticulous preoperative evaluation with three-dimensional (3D) techniques may prevent these problems. This study compared the safety of large-for-size grafts in pediatric living donor liver transplantation (PLDLT) during the eras with or without 3D planning.MethodsWe defined the 3D era was after November 2017 due to our first implication of 3D printing for surgical planning and subsequently developing a 3D simulation implanting model. From November 2004 to July 2021, we enrolled 30 PLDLT patients with body weight (BW) < 10 kg and categorized them into conventional group: GRWR ≥4% before the 3D era (n = 9), 3D group: GRWR ≥4% in the 3D era (n = 8), and control group: GRWR <4% (n = 13). We followed and compared their clinical outcomes.ResultsThe 3D group had the lowest BW and the highest graft volume reduction rate, with all receiving modified left lateral segments (LLS), such as reduced LLS (n = 2), hyperreduced LLS (n = 5), and segment 2 monosegment (n = 1). Overall postoperative complications were similar in conventional and control groups but significantly lower in the 3D group (OR 0.06, 95% CI 0.006?0.70, p = 0.025). However, all groups had similar graft and patient survival at 1, 2, and 4 years.ConclusionAdvanced preoperative 3D planning can decrease post-transplant complications and increase the safety of large-for-size grafts in PLDLT.Level of EvidenceType of study: Retrospective comparative study; Evidence level: Level III     

Development and Validation of a Laboratory Risk Score (LabScore) to Predict Outcomes after Resection for Intrahepatic Cholangiocarcinoma

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Improvements in Extracorporeal Membrane Oxygenation for Primary Graft Failure After Heart Transplant

BackgroundSevere primary graft failure is a life-threatening complication of heart transplantation that may require venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Surgical practices and management strategies regarding VA-ECMO vary between and within centers.MethodsWe performed a single-center retrospective cohort study on adult patients who received VA-ECMO for primary graft failure between 2013 and 2020. Clinical data were obtained from chart review and national databases. Patients were stratified by transplantation before or after 2017, when our center adopted additional objective criteria for VA-ECMO, adopted partial-flow support, and changed from central cannulation to chimney graft arterial cannulation of brachiocephalic, axillary, or aorta. The primary outcome was survival to device weaning. Secondary outcomes were survival to discharge, survival to 1 year, complications on support, and time to sedation weaning and extubation.ResultsFrom 276 heart transplant recipients, 39 severe primary graft failure patients requiring VA-ECMO were identified. Incidence of graft failure was 13% (n = 18 of 135) pre-2017 and 15% (n = 21 of 141) post-2017. Survival at all time points improved significantly after 2017, with greatest difference in survival to device weaning (61% pre-2017 vs 100% post-2017). After controlling for other factors in multivariable Cox regression modeling, transplantation after 2017 was a predictor of reduced mortality (hazard ratio, 0.209; 95% CI, 0.06-0.71; P = .01). Significant differences were not observed in other secondary outcomes of recovery.ConclusionsThe new VA-ECMO strategy displayed reasonable survival and a remarkable improvement from the prior system.     

Prospective assessment of reproducibility of three-dimensional ultrasound for fetal biometry

PurposeTo compare fetal ultrasound measurements performed by two observers with different levels of experience and evaluate the potential contribution of the use of three-dimensional (3D) ultrasound on repeatability, reproducibility and agreement of two-dimensional (2D) and 3D-derived measurements.Materials and methodsTwo observers (one senior and one junior) measured head circumference (HC), abdominal circumference (AC) and femur length (FL) in 33 fetuses (20 to 40 weeks of gestation). Each observer performed two series of 2D measurements and two series of 3D measurements (i.e., measurements derived from triplane volume processing). Measurements were converted into Z-scores according to gestational age. Variability between the different series of measurements was studied using Bland–Altmann plots and intra-class correlation coefficients (ICC).ResultsAgreement with the 2D measurements of the senior observer was higher in 3D than in 2D for the junior observer (systematic differences of −0.4, −0.2 and −0.8 Z-score vs. −0.1, −0.1 and −0.6 for HC, AC and FL on 2D and 3D datasets, respectively). The use of 3D ultrasound improved junior observer repeatability (ICC = 0.94, 0.88, 0.90 vs. 0.94, 0.94 and 0.96 for HC, AC and FL in 2D and 3D, respectively). The reproducibility was greater using the junior observer 3D datasets (ICC = 0.75, 0.60 and 0.45 vs. 0.79, 0.89 and 0.63 for HC, AC and FL, respectively).ConclusionThe use of 3D ultrasound improves the consistency of the measurements performed by a junior observer and increases the overall repeatability and reproducibility of measurements performed by observers with different levels of experience.     

Relative motion flexion following zone I-III flexor tendon repair: Concepts,evidence and practice.

Study DesignNarrative review and case series.IntroductionThe relative motion approach has been applied to rehabilitation following flexor tendon repair. Positioning the affected finger(s) in relatively more metacarpophalangeal joint flexion is hypothesized to reduce the tension through the repaired flexor digitorum profundus by the quadriga effect. It is also hypothesized that altered patterns of co-contraction and co-inhibition may further reduce flexor digitorum profundus tension, and confer protection to flexor digitorum superficialis.MethodsWe reviewed the existing literature to explore the rationale for using relative motion flexion orthoses as an early active mobilization strategy for patients after zone I-III flexor tendon repairs. We used this approach within our own clinic for the rehabilitation of a series of patients presenting with zone I-II flexor tendon repair. We collected routine clinical and patient reported outcome data.ResultsWe report published outcomes of the clinical use of relative motion flexion orthoses with early active motion, implemented as the primary rehabilitation approach after zone I-III flexor digitorum repairs. We also report novel outcome data from 18 patients.DiscussionWe discuss our own experience of using relative motion flexion as a rehabilitation strategy following flexor tendon repair. We explore orthosis fabrication, rehabilitation exercises and functional hand use.ConclusionsThere is currently limited evidence informing use of relative motion flexion orthoses following flexor tendon repair. We highlight key areas for future research and describe a current pragmatic randomized controlled trial.     

Clinical impact of the heart team on the outcomes of surgical aortic valve replacement among octogenarians

ObjectivesThe effectiveness of a multidisciplinary heart team in the management of patients with severe symptomatic aortic stenosis is unknown. This study evaluated the impact of a heart team on the outcomes of surgical aortic valve replacement in octogenarians.MethodsBetween May 2007 and January 2016, 528 patients aged 80 years or more were referred to our institutional heart team for a transcatheter aortic valve replacement. Among these, 101 were redirected to surgical aortic valve replacement (heart team group). These patients were compared with a surgical aortic valve replacement cohort (n = 506) without prior heart team screening (non-heart team group), taken from the same time period. Propensity score matching with bootstrap analysis was performed; 76 heart team patients were matched to 76 non-heart team patients. Early and late outcomes including survival and readmission for cardiovascular causes were compared.ResultsMatched subgroups were largely comparable; congestive heart failure and echocardiographic pulmonary hypertension were more prevalent in the heart team group. In-hospital mortality was significantly lower in the matched heart team group (0% vs 6.0%, bootstrap mean difference 6.0%, 95% confidence interval, 2.2-9.8). The risk of stroke, low cardiac output state, reexploration for bleeding, pneumonia, and prolonged ventilation was also significantly lower in the heart team group. There was no significant between-group difference regarding late survival (hazard ratio, 0.86, 95% confidence interval, 0.55-1.33, P = .49) or readmission for cardiovascular reasons (hazard ratio, 0.70, 95% confidence interval, 0.41-1.20, P = .19).ConclusionsPreoperative multidisciplinary assessment of octogenarians by a heart team was associated with lower in-hospital mortality and adverse events after surgical aortic valve replacement.     

Complications of percutaneous image-guided screw fixation: An analysis of 94 consecutive patients

PurposeThe purpose of this study was to retrospectively assess the safety profile of percutaneous image-guided screw fixation (PIGSF) for insufficiency, impending or pathological fractures.Materials and methodsFrom July 2012 to April 2020, all consecutive patients who underwent PIGSF were retrospectively included in the study. Patient characteristics, fracture type, procedural data and complications were analyzed. Complications were divided into per-procedural, early (< 24 hours) and delayed (> 24 hours) and classified into minor (grade 1-2) and major complications (grade 3-5) according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsA total of 110 fractures (40 insufficiency [36%], 53 pathological [48.5%] and 17 impending [15.5%] fractures) in 94 patients (48 women, 46 men; mean age, 62.7 ± 12.7 [SD] years; age range: 32–88 years) were treated with PIGSF during 95 procedures. Twenty-four-hours follow-up was available for all patients, and > 24-hours follow-up was available for 79 (79/110; 71.8%) fractures in 69 (69/94; 73.4%) patients. Per-procedural complications occurred in 3/110 fractures (2.7%, all minor). Early complications were reported in 4/110 fractures (3.6%, 1 major and 3 minor) and delayed ones in 14/79 fractures (17.7%, 5 major and 9 minor). The most frequent major delayed complication was infection (3/79; 3.8%).ConclusionThe rate of per-procedural and early (within 24 hours) complications following PIGSF is extremely low with most complications being minor, with major complications being delayed ones (> 24 hours).     

Impact of ultra-low dose CT acquisition on semi-automated RECIST tool in the evaluation of malignant focal liver lesions

PurposeTo compare the evaluation of malignant focal liver lesions (FLLs) using a semi-automated RECIST tool with a standard and an ultra-low dose (ULD) computed tomography (CT) protocol.Materials and methodsThirty-four patients with malignant FLLs underwent two abdominal-pelvic CT examinations one using a standard protocol and one using an ULD protocol. There were 23 men and 11 women with a mean age 64.3 ± 14.4 (SD) years (range: 22–91 years). Dosimetric indicators were recorded, and effective dose was calculated for both examinations. Mean malignant FLL attenuation, image noise and contrast-to-noise-ratio (CNR) were compared. The largest malignant FLL per patient was evaluated using the semi-automated RECIST tool to determine longest axis length, longest orthogonal axis length, volume and World Health Organisation area.ResultsDosimetric values were significantly reduced by −56% with ULD compared to standard protocol. No differences in mean malignant FLL attenuation values were found between the two protocols. Image noise was significantly increased for all locations (P < 0.05) with ULD compared to standard protocol, and CNR was significantly reduced (P < 0.05). On the 34 malignant FLLs analyzed, six semi-automated shapes non-concordant with radiologist's visual impression were highlighted with the software, including one FLL (1/34; 3%) with standard CT acquisition only, three FLLs (3/34; 9%) with ULD CT acquisition only and two FLLs (2/34; 6%) with both CT acquisitions. After manual editing, the concordance of the values of the studied criteria between both acquisitions was good and no significant difference was reported.ConclusionSemi-automated RECIST tool demonstrates good performances using ULD CT protocol. It could be used in routine clinical practice with a ULD protocol for follow-up studies in patients with known malignant FLL.     

Percutaneous ablation of obscure hypovascular liver tumours in challenging locations using arterial CT-portography guidance

PurposeThe purpose of this study was to evaluate the feasibility, safety and efficacy of percutaneous ablation (PA) of obscure hypovascular liver tumors in challenging locations using arterial CT-portography (ACP) guidance.Materials and methodsA total of 26 patients with a total of 28 obscure, hypovascular malignant liver tumors were included. There were 18 men and 6 women with a mean age of 58 ± 14 (SD) years (range: 37–75 years). The tumors had a mean diameter of 14 ± 10 (SD) mm (range: 7–24 mm) and were intrahepatic cholangiocarcinoma (4/28; 14%), liver metastases from colon cancer (18/28; 64%), corticosurrenaloma (3/28; 11%) or liver metastases from breast cancer (3/28; 11%). All tumors were in challenging locations including subcapsular (14/28; 50%), liver dome (9/28; 32%) or perihilar (5/28; 18%) locations. A total of 28 PA (12 radiofrequency ablations, 11 microwave ablations and 5 irreversible electroporations) procedures were performed under ACP guidance.ResultsA total of 67 needles [mean: 2.5 ± 1.5 (SD); range: 1–5] were inserted under ACP guidance, with a 100% technical success rate for PA. Median total effective dose was 26.5 mSv (IQR: 19.1, 32.2 mSv). Two complications were encountered (pneumothorax; one abscess both with full recovery), yielding a complication rate of 7%. No significant change in mean creatinine clearance was observed (80.5 mL/min at baseline and 85.3 mL/min at day 7; P = 0.8). Post-treatment evaluation of the ablation zone was overestimated on ACP compared with conventional CT examination in 3/28 tumors (11%). After a median follow-up of 20 months (range: 12–35 months), local tumor progression was observed in 2/28 tumours (7%).ConclusionACP guidance is feasible and allows safe and effective PA of obscure hypo-attenuating liver tumors in challenging locations without damaging the renal function and with acceptable radiation exposure. Post-treatment assessment should be performed using conventional CT or MRI to avoid size overestimation of the ablation zone.     

Ministernotomy compared with right anterior minithoracotomy for aortic valve surgery

ObjectivesMinisternotomy and right anterior minithoracotomy are the 2 main techniques applied for minimally invasive aortic valve replacement. The goal of this study is to compare early and long-term outcomes of both techniques.MethodsThe data of 2419 patients undergoing isolated minimally invasive aortic valve replacement between 1999 and 2019 were prospectively collected. Retrospectively, patients were divided into the ministernotomy group (n = 1352) and the minithoracotomy group (n = 1067).ResultsAfter propensity score matching, 986 patients remained in each group. Operation time and rate of conversion to full sternotomy were significantly higher in the minithoracotomy group than in the ministernotomy group (184.6 ± 45.2 vs 241.3 ± 68.6, relative risk, 2.54, P = .005 and .09 vs .23, relative risk, 1.45, P = .013, respectively). The 30-day mortality, excluding cardiac death, was lower in the ministernotomy group than in the minithoracotomy group (0.012 vs 0.028, relative risk, 1.41, P = .011, respectively); the intensive care unit length of stay (12.4 vs 16.5, relative risk, 1.62, P = .037, respectively) and hospital length of stay (5.4 vs 8.7, relative risk, 1.74 P = .028, respectively) were significantly longer in the minithoracotomy group. The minithoracotomy surgical approach was the strongest independent predictor of early mortality (odds ratio, 4.24 [1.67-7.35], P = .002). The actuarial survival by Kaplan–Meier analysis at 1, 3, 5, 10, and 20 years was significantly better in the ministernotomy group than in the minithoracotomy group (P = .0001). Actuarial freedom from reoperation at 5 years was 97.3% ± 4.4% in the ministernotomy group versus 95.8% ± 5.2% in the minithoracotomy group (P = .087).ConclusionsMinimally invasive aortic valve replacement using ministernotomy is associated with reduced operative time, intensive care unit stay, hospital length of stay, and postoperative morbidities and incisional pain, and improves early and long-term mortality.