Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY.

PURPOSE: The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data. METHODS: The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC. RESULTS: Of 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up. CONCLUSION: The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC. CLINICAL TRIAL REGISTRATION: Clinical trials registration number: NCT03286842.

Longitudinal transcriptional immune profiles and persistent wheezing in moderate-to-late preterm infants.

BACKGROUND: Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing. MATERIALS AND METHODS: A convenience sample of a multicenter birth cohort (SAREPREM) of moderate-late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression. RESULTS: Seventy-six children were included in the study; 33 were classified as non-wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non-wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers. CONCLUSIONS: Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late-preterm infants.

Comparative analysis of 5-year efficacy and outcomes of single anastomosis procedures as revisional surgery for weight regain following sleeve gastrectomy.

BACKGROUND: It is imperative to assess the results of revisional procedures following Sleeve Gastrectomy (SG), given the substantially growing population of patients who experience weight regain within a few years after undergoing this procedure. OBJECTIVE: Examine the comparative effectiveness of the Single Anastomosis Duodeno-Ileal Bypass (SADI-S) and the One Anastomosis Gastric Bypass (OAGB-MGB) as revisional procedures, with respect to their impact on weight loss, resolution of comorbidities, incidence of complications, and rates of reoperation in patients who had weight regain after SG with up to or more than 5 years of follow-up. SETTING: Hamad General Hospital, Academic tertiary referral center, Qatar. METHODS: This study retrospectively analyzed a database of patients who underwent the Single Anastomosis Duodeno-Ileal Switch (SADI-S) or the One Anastomosis Gastric Bypass - Mini Gastric Bypass- (OAGB-MGB) as revisional procedures for weight recidivism after a primary Laparoscopic Sleeve Gastrectomy (LSG). The follow-up period was at least 5 years, during which the impact of both procedures on weight loss, comorbidities, nutritional deficiencies, complications, and outcomes were compared. RESULTS: The study comprised 91 patients, with 42 and 49 in the SADI-S and OAGB-MGB groups, respectively. Significant weight loss (measured by total weight loss percentage, TWL%) was observed at the 5-year follow-up for the SADI-S group compared to the OAGB-MGB group (30.0 ± 18.4 vs. 19.4 ± 16.3, p = 0.008). Remission of comorbidities, specifically diabetes mellitus and hypertension, was more prevalent in the SADI-S group. Notably, the OAGB-MGB group had a higher incidence of complications (28.6% vs. 21.42%) and reoperations (5 patients vs. 1 in the SADI-S group). No mortality events were reported in either group. CONCLUSION: While both the OAGB-MGB and SADI-S have demonstrated efficacy as revisional procedures for weight regain following SG, the SADI-S exhibits superior outcomes compared to the OAGB-MGB with regard to weight loss, resolution of comorbidities, complication rates, and reoperation rates.

Side-to-side magnet anastomosis system duodeno-ileostomy with sleeve gastrectomy: early multi-center results.

INTRODUCTION: Gastrointestinal anastomoses with classical sutures and/or metal staples have resulted in significant bleeding and leak rates. This multi-site study evaluated the feasibility, safety, and preliminary effectiveness of a novel linear magnetic compression anastomosis device, the Magnet System (MS), to form a side-to-side duodeno-ileostomy (DI) diversion for weight loss and type 2 diabetes (T2D) resolution. METHODS: In patients with class II and III obesity (body mass index [BMI, kg/m2] ≥ 35.0- ≤ 50.0 with/without T2D [HbA1C > 6.5%]), two linear MS magnets were delivered endoscopically to the duodenum and ileum with laparoscopic assistance and aligned, initiating DI; sleeve gastrectomy (SG) was added. There were no bowel incisions or retained sutures/staples. Fused magnets were expelled naturally. Adverse events (AEs) were graded by Clavien-Dindo Classification (CDC). RESULTS: Between November 22, 2021 and July 18, 2022, 24 patients (83.3% female, mean ± SEM weight 121.9 ± 3.3 kg, BMI 44.4 ± 0.8) in three centers underwent magnetic DI. Magnets were expelled at a median 48.5 days. Respective mean BMI, total weight loss, and excess weight loss at 6 months (n = 24): 32.0 ± 0.8, 28.1 ± 1.0%, and 66.2 ± 3.4%; at 12 months (n = 5), 29.3 ± 1.5, 34.0 ± 1.4%, and 80.2 ± 6.6%. Group mean respective mean HbA1C and glucose levels dropped to 1.1 ± 0.4% and 24.8 ± 6.6 mg/dL (6 months); 2.0 ± 1.1% and 53.8 ± 6.3 mg/dL (12 months). There were 0 device-related AEs, 3 procedure-related serious AEs. No anastomotic bleeding, leakage, stricture, or mortality. CONCLUSION: In a multi-center study, side-to-side Magnet System duodeno-ileostomy with SG in adults with class III obesity appeared feasible, safe, and effective for weight loss and T2D resolution in the short term.

Best practice approach for redo-surgeries after sleeve gastrectomy, an expert's modified Delphi consensus.

BACKGROUND: Sleeve gastrectomy (SG) is the most common metabolic and bariatric surgical (MBS) procedure worldwide. Despite the desired effect of SG on weight loss and remission of obesity-associated medical problems, there are some concerns regarding the need to do revisional/conversional surgeries after SG. This study aims to make an algorithmic clinical approach based on an expert-modified Delphi consensus regarding redo-surgeries after SG, to give bariatric and metabolic surgeons a guideline that might help for the best clinical decision. METHODS: Forty-six recognized bariatric and metabolic surgeons from 25 different countries participated in this Delphi consensus study in two rounds to develop a consensus on redo-surgeries after SG. An agreement/disagreement ≥ 70.0% on statements was considered to indicate a consensus. RESULTS: Consensus was reached for 62 of 72 statements and experts did not achieve consensus on 10 statements after two rounds of online voting. Most of the experts believed that multi-disciplinary team evaluation should be done in all redo-procedures after SG and there should be at least 12 months of medical and supportive management before performing redo-surgeries after SG for insufficient weight loss, weight regain, and gastroesophageal reflux disease (GERD). Also, experts agreed that in case of symptomatic GERD in the presence of adequate weight loss, medical treatment for at least 1 to 2 years is an acceptable option and agreed that Roux-en Y gastric bypass is an appropriate option in this situation. There was disagreement consensus on efficacy of omentopexy in rotation and efficacy of fundoplication in the presence of a dilated fundus and GERD. CONCLUSION: Redo-surgeries after SG is still an important issue among bariatric and metabolic surgeons. The proper time and procedure selection for redo-surgery need careful considerations. Although multi-disciplinary team evaluation plays a key role to evaluate best options in these situations, an algorithmic clinical approach based on the expert's consensus as a guideline can help for the best clinical decision-making.

Laparoscopic adrenalectomy vs. radiofrequency ablation for the treatment of primary aldosteronism. A single center retrospective cohort analysis adjusted with propensity score.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard treatment for unilateral primary aldosteronism. However, satisfactory results have also been published with radiofrequency ablation (RFA). The aim of this study was to compare LA and RFA for the treatment of primary aldosteronism. METHODS: A retrospective cohort study of the patients who underwent LA or RFA in a single center was performed. Morbidity and long-term effectiveness (cure rate and blood pressure control) were analyzed. A multivariate analysis with a propensity score was also performed. RESULTS: Thirty-four patients were included in the study, 24 in the LA group and 10 in the RFA group. Hypertension had been diagnosed a median of 12 years before the intervention. Hypertension was properly controlled before the intervention in 55.9% of the patients. Hypertensive crisis was more common during RFA (4.2% vs. 70.0%, p < 0.001), although no patient suffered any complication because of these crises. LA was longer (174.6 vs. 105.5 min, p = 0.001) and had a longer length of stay (median 2 vs 1 days, p < 0.001). No severe complications were observed in any of the patients. After a median follow-up of 46.2 months, more patients had hypertension cured and blood pressure controlled in the LA group (29.2% vs. 0%, p = 0.078 and 95.5% vs. 50.0%, p = 0.006, respectively). Also, patients in the LA group were taking less antihypertensive drugs (1.8 vs. 3.0, p = 0.054) or mineralocorticoid receptor antagonists (41.7% vs. 90.0%, p = 0.020). Multivariate analysis adjusted by propensity score showed that LA had an OR = 11.3 (p = 0.138) for hypertension cure and an OR = 55.1 (p = 0.040) for blood pressure control. CONCLUSIONS: Although RFA was a less invasive procedure than LA, hypertension was cured and blood pressure was properly controlled in more patients from the LA group. Patients who underwent LA were taking less antihypertensive drugs than patients who had undergone RFA.

Is prophylactic mesh closure effective to decrease the incidence of incisional hernia after laparotomy in colorectal surgery?

BACKGROUND: few studies have studied prophylactic mesh closure after laparotomy for colorectal surgery. METHODS: a retrospective cohort study was performed to compare patients with and without prophylactic mesh closure after open colorectal surgery. RESULTS: 309 patients were included from January 2014 to December 2016. Prophylactic mesh closure was performed in 98 patients (31.7%). After a mean follow-up of 21.7 months, incisional hernia was developed in 9 and 54 patients in the group with and without mesh respectively (9.2% vs. 25.7%, OR = 0.3, p = 0.001). In the multivariate Cox model prophylactic mesh closure was associated with a protective effect on incisional hernia development with a Hazard Ratio of 0.46 (p = 0.033). Surgical site infection was more frequent in the mesh group (19.4% vs. 9.5%, OR = 2.3, p = 0.015). CONCLUSIONS: prophylactic mesh closure is effective to decrease the incidence of incisional hernia after colorectal surgery.

Defining Global Benchmarks in Elective Secondary Bariatric Surgery Comprising Conversional, Revisional, and Reversal Procedures.

OBJECTIVE: To define "best possible" outcomes for secondary bariatric surgery (BS). BACKGROUND: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. METHODS: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. RESULTS: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ±â€Š10 years, 8.4 ±â€Š5.3 years after primary BS, with a BMI 35.2 ±â€Š7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. CONCLUSION: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Trocar-site incisional hernia after laparoscopic colorectal surgery: a significant problem? Incidence and risk factors from a single-center cohort.

BACKGROUND: Trocar-site incisional hernia (TSIH) after laparoscopic surgery has been scarcely studied. TSIH incidence and risk factors have never been properly studied for laparoscopic colorectal surgery. METHODS: A retrospective analytic study in a tertiary hospital was performed including patients who underwent elective laparoscopic colorectal surgery between 2014 and 2016. Clinical and radiological TSIH were analyzed. RESULTS: 272 patients with a mean age of 70.7 years were included. 205 (75.4%) underwent surgery for a malignant disease. The most common procedure was right colectomy (108 patients, 39.7%). After a mean follow-up of 30.8 months 64 (23.5%) patients developed a TSIH. However, only 7 out of 64 (10.9%) patients with a TSIH underwent incisional hernia repair. That means that 2.6% of all the patients underwent TSIH repair. 44 (68.8%) patients had TSIH in the umbilical Hasson trocar. In the multivariate analysis, the existence of an umbilical Hasson trocar orifice was the only statistically significant risk factor for TSIH development. CONCLUSIONS: Incidence of TSIH was high, although few patients underwent incisional hernia repair. Most TSIH were observed in the umbilical Hasson trocar, which was the only risk factor for TSIH development in the multivariate analysis. Efforts should be addressed to avoid TSIH in the umbilical Hasson trocar.

Heterozygous pathogenic variants in GLI1 are a common finding in isolated postaxial polydactyly A/B.

Postaxial polydactyly (PAP) is a frequent limb malformation consisting in the duplication of the fifth digit of the hand or foot. Morphologically, this condition is divided into type A and B, with PAP-B corresponding to a more rudimentary extra-digit. Recently, biallelic truncating variants in the transcription factor GLI1 were reported to be associated with a recessive disorder, which in addition to PAP-A, may include syndromic features. Moreover, two heterozygous subjects carrying only one inactive copy of GLI1 were also identified with PAP. Herein, we aimed to determine the level of involvement of GLI1 in isolated PAP, a condition previously established to be autosomal dominantly inherited with incomplete penetrance. We analyzed the coding region of GLI1 in 95 independent probands with nonsyndromic PAP and found 11.57% of these subjects with single heterozygous pathogenic variants in this gene. The detected variants lead to premature termination codons or result in amino acid changes in the DNA-binding domain of GLI1 that diminish its transactivation activity. Family segregation analysis of these variants was consistent with dominant inheritance with incomplete penetrance. We conclude that heterozygous changes in GLI1 underlie a significant proportion of sporadic or familial cases of isolated PAP-A/B.

Recurrent wheezing during the first 3 years of life in a birth cohort of moderate-to-late preterm infants.

BACKGROUND: Data addressing short- and long-term respiratory morbidity in moderate-late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3 years of life. METHODS: Prospective, multicenter birth cohort study of infants born at 32+0 to 35+0  weeks' gestation and followed for 3 years to assess the incidence of physician-diagnosed recurrent wheezing. Allergen sensitization and pulmonary function were also studied. We used multivariate mixed-effects models to identify risk factors associated with recurrent wheezing. RESULTS: A total of 977 preterm infants were enrolled. Rates of recurrent wheezing during year (Y)1 and Y2 were similar (19%) but decreased to 13.3% in Y3. Related hospitalizations significantly declined from 6.3% in Y1 to 0.75% in Y3. Independent risk factors for recurrent wheezing during Y2 and Y3 included the following: day care attendance, acetaminophen use during pregnancy, and need for mechanical ventilation. Atopic dermatitis on Y2 and male sex on Y3 were also independently associated with recurrent wheezing. Palivizumab prophylaxis for RSV during the first year of life decreased the risk or recurrent wheezing on Y3. While there were no differences in rates of allergen sensitization, pulmonary function tests (FEV0.5 ) were significantly lower in children who developed recurrent wheezing. CONCLUSIONS: In moderate-to-late premature infants, respiratory symptoms were associated with lung morbidity persisted during the first 3 years of life and were associated with abnormal pulmonary function tests. Only anti-RSV prophylaxis exerted a protective effect in the development of recurrent wheezing.

Extraction-site incisional hernia after laparoscopic colorectal surgery: should we carry out a study about prophylactic mesh closure?

BACKGROUND: Prophylactic mesh closure has only scarcely been studied to avoid extraction-site incisional hernia after laparoscopic colorectal surgery. The aim was to analyze extraction-site incisional hernia incidence after laparoscopic colorectal surgery to assess if prophylactic mesh closure should be studied. METHODS: A retrospective analytic cohort study was conducted in patients who had undergone laparoscopic colorectal surgery with an extraction-site incision. Extraction-site incisional hernia was diagnosed during clinical examination or imaging. Risk factors for extraction-site incisional hernia were analyzed. RESULTS: Two hundred and twenty-five patients were included. More than 80% of the patients had a malignant disease. Ninety-two patients (40.9%) underwent right colectomy. Midline extraction-site incision was used in 86 (38.2%) patients. After a mean follow-up of 2.4 years, 39 (17.3%) patients developed an extraction-site incisional hernia. Midline extraction-site incision was associated with incisional hernia when compared to transverse and Pfannenstiel incision (39.5% vs. 3.6%, OR 17.5, p < 0.001). Surgery to repair an extraction-site incisional hernia was also more frequent in the group of patients with a midline incision (10.5% vs. 1.4%, OR 8.0, p = 0.002). In the multivariate analysis, incisional hernia was associated with body mass index, high blood pressure, and midline incision. CONCLUSIONS: Extraction-site incisional hernia was mainly related to midline incisions; therefore, midline incision should be avoided whenever possible. Studying prophylactic mesh closure for Pfannesnstiel or transverse incisions is needless, as these incisions have a low incisional hernia risk.

The first consensus statement on revisional bariatric surgery using a modified Delphi approach.

BACKGROUND: Revisional bariatric surgery (RBS) constitutes a possible solution for patients who experience an inadequate response following bariatric surgery or significant weight regain following an initial satisfactory response. This paper reports results from the first modified Delphi consensus-building exercise on RBS. METHODS: We created a committee of 22 recognised opinion-makers with a special interest in RBS. The committee invited 70 RBS experts from 27 countries to vote on 39 statements concerning RBS. An agreement amongst ≥ 70.0% experts was regarded as a consensus. RESULTS: Seventy experts from twenty-seven countries took part. There was a consensus that the decision for RBS should be individualised (100.0%) and multi-disciplinary (92.8%). Experts recommended a preoperative nutritional (95.7%) and psychological evaluation (85.7%), endoscopy (97.1%), and a contrast series (94.3%). Experts agreed that Roux-Y gastric bypass (RYGB) (94.3%), One anastomosis gastric bypass (OAGB) (82.8%), and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) (71.4%) were acceptable RBS options after gastric banding (84.3%). OAGB (84.3%), bilio-pancreatic diversion/duodenal switch (BPD/DS) (81.4%), and SADI-S (88.5%) were agreed as consensus RBS options after sleeve gastrectomy. lengthening of bilio-pancreatic limb was the only consensus RBS option after RYGB (94.3%) and OAGB (72.8%). CONCLUSION: Experts achieved consensus on a number of aspects of RBS. Though expert opinion can only be regarded as low-quality evidence, the findings of this exercise should help improve the outcomes of RBS while we develop robust evidence to inform future practice.

Low-value care practice in headache: a Spanish mixed methods research study.

BACKGROUND: Headache is one of the most prevalent diseases. The Global Burden of Disease Study ranks it as the seventh most common disease overall and the second largest neurological cause of disability in the world. The "Do Not Do" recommendations are a strategy for increasing the quality of care and reducing the cost of care for headache. This study aimed to identify specific low-value practices in headache care, determine their frequency, and estimate the cost overrun that they represent, in order to establish "Do not Do" recommendations specifically for headache by consensus and according to scientific evidence. METHODS: This was a mixed methods research study that combined qualitative consensus-building techniques, involving a multidisciplinary panel of experts to define the "Do Not Do" recommendations in headache care, and a retrospective observational study with review of a randomized set of patient records from the past 6 months in four hospitals, to quantify the frequency of these "Do Not Do" practices. We calculated the sum of direct costs of medical consultations, medicines, and unnecessary diagnostic tests. RESULTS: Seven "Do Not Do" recommendations were established for headache. In total, 3507 medical records were randomly reviewed. Low-value practices had a highly variable occurrence, depending on the hospital and type of headache. Overall, 34.1% of low-value practices were related to treatment, 21% were related to overuse of imaging in consultation, and 19% were related to emergency care. The estimated cost of low-value practices in the four hospitals was 203,520.47 euros per 1000 patients. CONCLUSIONS: This study identified low-value headache practices that need to be eradicated and provided data on their frequency and cost overruns.

Defining Global Benchmarks in Bariatric Surgery: A Retrospective Multicenter Analysis of Minimally Invasive Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

OBJECTIVE: To define "best possible" outcomes for bariatric surgery (BS)(Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]). BACKGROUND: Reference values for optimal surgical outcomes in well-defined low-risk bariatric patients have not been established so far. Consequently, outcome comparison across centers and over time is impeded by heterogeneity in case-mix. METHODS: Out of 39,424 elective BS performed in 19 high-volume academic centers from 3 continents between June 2012 and May 2017, we identified 4120 RYGB and 1457 SG low-risk cases defined by absence of previous abdominal surgery, concomitant procedures, diabetes mellitus, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, anticoagulation, BMI>50 kg/m and age>65 years. We chose clinically relevant endpoints covering the intra- and postoperative course. Complications were graded by severity using the comprehensive complication index. Benchmark values were defined as the 75th percentile of the participating centers' median values for respective quality indicators. RESULTS: Patients were mainly females (78%), aged 38±11 years, with a baseline BMI 40.8 ±â€Š5.8 kg/m. Over 90 days, 7.2% of RYGB and 6.2% of SG patients presented at least 1 complication and no patients died (mortality in nonbenchmark cases: 0.06%). The most frequent reasons for readmission after 90-days following both procedures were symptomatic cholelithiasis and abdominal pain of unknown origin. Benchmark values for both RYGB and SG at 90-days postoperatively were 5.5% Clavien-Dindo grade ≥IIIa complication rate, 5.5% readmission rate, and comprehensive complication index ≤33.73 in the subgroup of patients presenting at least 1 grade ≥II complication. CONCLUSION: Benchmark cutoffs targeting perioperative outcomes in BS offer a new tool in surgical quality-metrics and may be implemented in quality-improvement cycle.ClinicalTrials.gov Identifier NCT03440138.

Incidence and outcome of invasive fungal disease after front-line intensive chemotherapy in patients with acute myeloid leukemia: impact of antifungal prophylaxis.

Few reports analyze the incidence and clinical outcome of invasive fungal disease (IFD) in patients with newly diagnosed acute myeloid leukemia (AML) undergoing intensive chemotherapy, and thus the impact of different antifungal prophylactic regimens remains unclear. We analyze the incidence and clinical outcome of IFD in a large series of adult AML patients undergoing front-line intensive induction and consolidation chemotherapy between 2004 and 2015 in a single institution. Three antifungal prophylaxis regimens were given (2004-2005 oral fluconazole, 2006-2012 intravenous itraconazole, and 2013-2015 voriconazole). Overall, 285 patients and 589 intensive chemotherapy episodes were assessed (47%) (induction courses 47% and consolidation 53%). The median age was 51 years (range, 17-65). We observed 56 (10%) episodes of IFD. According to the EORTC 2008 criteria, IFD was classified as possible (29, 52%), probable (17, 30%), and proven (10, 18%). Possible/probable/proven IFD rate was significantly lower during HiDAC consolidation as compared to any anthracycline-containing chemotherapy courses (2% vs. 11%, P = 0.001), and under voriconazole prophylaxis as compared to itraconazole and fluconazole (6% vs. 11% vs. 15%, P = 0.007), and the multivariate analysis showed that they were independent risk factors. Patients under voriconazole prophylaxis had shorter hospitalization duration and less frequent use of empirical or directed antifungal therapy. In conclusion, IFD was a frequent complication during upfront intensive chemotherapy courses for adult AML patients. This retrospective study shows that voriconazole prophylaxis was feasible and associated with a lower risk of IFD compared with intravenous itraconazole or oral fluconazole schedules.

Validation of a multivariable prediction model for post-engraftment invasive fungal disease in 465 adult allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Recently, we reported a simple prognostic score for post-engraftment invasive fungal disease (IFD) obtained in 404 adult allogeneic hematopoietic stem cell transplant (alloSCT) (training cohort). OBJECTIVES: We aim to validate this score in an external cohort assessing the 1-year cumulative incidence (CI) of post-engraftment IFD. Additionally, we analyse the type of IFD and incidence of IFD according to type of prophylaxis. PATIENTS/METHODS: We included 465 consecutive adult recipients surviving >40 days who engrafted and were discharged without prior IFD (median age 45 years, range, 14-69). RESULTS: Patients classified as low-risk, 139; intermediate-risk, 162; and high-risk, 164 (35% vs 27% in the training cohort, P = 0.03). The CI of probable/proven IFD in the validation cohort was 8% vs 11% in the training cohort (P = 0.006). The only voriconazole prophylaxis used in the training cohort was 100 mg/12 h, 65% vs 27% in the validation cohort, but 38% received 200 mg/12 h. Thus, the validation cohort showed a lower CI of IFD (P = 0.009). The post-engraftment IFD score was validated, showing a CI of IFD for low-, intermediate- and high-risk of 3%, 6% and 14%, respectively (P < 0.001). CONCLUSION: To our knowledge, this is the first prognostic index to predict the occurrence of post-engraftment IFD after alloSCT that has been validated in an external cohort.

Intraluminal mesh erosion after prosthetic hiatoplasty: incidence, management, and outcomes.

The purpose of the present study was to analyze the incidence, presentation, and treatment of mesh erosion into the esophagus or stomach after mesh hiatoplasty for primary or recurrent hiatal hernia. The study is a single-institution, retrospective cohort study. From November 2005 to December 2016, 122 patients consecutively underwent mesh hiatoplasty in our department, 91 during a primary surgery and 31 for a surgical revision. Follow-up was complete for 74%. Six patients of this series were evaluated for mesh erosion. In all cases, the mesh employed was a dual-type circular one. The mean time from surgery to erosion diagnosis was 42 months (median time 46 months, interquartile range 64 months). Three patients were asymptomatic, 1 had dysphagia, 1 had reflux recurrence, and 1 presented with mediastinal perforation. The absolute erosion rate was 4.9%. For patients under surveillance, the erosion rate was 6.6%, or 1 case every 48 patient-years of follow-up. The erosion rate after primary surgery was 3% or 1/86 patient-years of follow-up, and after surgery for recurrent hernia recurrence was 16% or 1/29 patient-years of follow-up. The mesh was left in place in 2 asymptomatic cases and endoscopically removed in 2 cases. Two patients submitted to surgical removal of the mesh, and only one needed a limited gastroesophageal junction resection for a conversion to a Roux-en-Y gastric bypass. The patient with esophageal perforation submitted to mesh removal, drainage, and an anterior partial fundoplication. There was no mortality. Mesh erosion after hiatoplasty presents with a high rate, especially when hiatoplasty is performed during revisional antireflux surgery. Most patients can be managed conservatively, and endoscopic removal should be considered a first-line therapy.

Factorial Validity of the Toronto Alexithymia Scale (TAS-20) in Clinical Samples: A Critical Examination of the Literature and a Psychometric Study in Anorexia Nervosa.

There is extensive use of the 20-item Toronto Alexithymia Scale (TAS-20) in research and clinical practice in anorexia nervosa (AN), though it is not empirically established in this population. This study aims to examine the factorial validity of the TAS-20 in a Portuguese AN sample (N = 125), testing four different models (ranging from 1 to 4 factors) that were identified in critical examination of existing factor analytic studies. Results of confirmatory factor analysis (CFA) suggested that the three-factor solution, measuring difficulty identifying (DIF) and describing feelings (DDF), and externally oriented thinking (EOT), was the best fitting model. The quality of measurement improves if two EOT items (16 and 18) are eliminated. Internal consistency of EOT was low and decreased with age. The results provide support for the factorial validity of the TAS-20 in AN. Nevertheless, the measurement of EOT requires some caution and may be problematic in AN adolescents.