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Background: There is no definitive evidence of the prognosis impact of histological variants (HVs) in patients who undergo surgical resection of a nonmetastatic renal cell carcinoma (nm-RCC) with venous tumor thrombus (TT)., Objective: To investigate the impact of HVs on the prognosis of patients with nm-RCC with TT after radical surgery., Design Setting and Participants: Patients who underwent radical nephrectomy with the removal of the venous TT for an nm-RCC were included in a retrospective study., Outcome Measurements and Statistical Analysis: Three groups were identified: clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) RCC. The primary outcome measures (disease-free and overall survival [OS]) were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional hazard models were used to study the impact of HVs on survival., Results and Limitations: A total of 873 patients were included. The histological subtypes were distributed as follows: ccRCC in 780 cases, pRCC in 58 cases, and chRCC in 35 cases. At the time of data analysis, 612 patients were recurrence free and 228 had died. A survival analysis revealed significant differences in both OS and recurrence-free survival across histological subtypes, with the poorest outcomes observed in pRCC patients ( p  < 0.05). In a multivariable analysis, pRCC was independently associated with worse disease-free survival and OS (hazard ratio [HR]: 1.71; p  = 0.01 and HR: 1.24; p  = 0.04), while chRCC was associated with more favorable outcomes than ccRCC (HR: 0.05; p  < 0.001 and HR: 0.02; p  < 0.001). A limitation of the study is its retrospective nature., Conclusions: In this multicentric series, HVs appeared to impact the medium-term oncological prognosis of kidney cancer with TT., Patient Summary: This study investigated the differences in oncological outcomes among histological variants (clear cell, papillary, and chromophobe) in a cohort of nonmetastatic renal cell carcinoma patients with venous tumor thrombus extension. We observed that these histological variants within this specific subgroup exhibit distinct outcomes, with papillary renal cell carcinoma being associated with the worst prognosis., (© 2024 The Authors.)

Background: Intrathoracic intercostal cryoanalgesia (Cryo) during minimally invasive repair of pectus excavatum (MIRPE) reports have been related to improved pain management, although its extent differs amongst studies. We aimed to report our experience using a standardized perioperative approach including Cryo during MIRPE, and compare our actual results with those of a previous thoracic epidural analgesia (TE) cohort. Lessons learned are summarized., Methods: Retrospective study including patients undergoing Cryo during MIRPE between October 2018 and May 2023. Results with a standardized perioperative approach were analyzed. We then compared our Cryo cohort with a previous cohort of 62 patients who underwent TE and MIRPE between 2013 and 2018. Continuous variables were reported as mean and standard deviation, and as median (interquartile range) for variables with non-uniform distribution., Results: We performed 176 Cryo during MIRPE (16.8 ± 4.6 years), with a mean postoperative length of stay (LOS) of 1.4 ± 0.8 days and a median total requirement of 7.5 (0.0; 15.0) oral morphine equivalents (OME) (mg). Patients with Cryo had a significantly lower mean LOS (1.4 ± 0.8 vs. 3.6 ± 1.0 days, p < 0.0001), and median total opioid requirement [7.5 (0.0; 15.0) vs. 77.4 (27.0; 115.5 OME (mg), p < 0.0001) compared to TE patients. Lessons learned included ensuring adequate contact of the cryoprobe with the target, proper exposition, and specialized multidisciplinary perioperative patient and family support, including psychology and physical therapy., Conclusions: In this study, we reported lessons learned after performing a standardized protocol of perioperative care in patients undergoing Cryo during MIRPE. This protocol enabled the achievement of a short LOS and low postoperative opioid requirement., Type of Study: Retrospective comparative study., Level of Evidence: III., Competing Interests: Disclosure Marcelo Martinez-Ferro has ownership of Pampamed SRL, a Metrum distributor., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm that occurs in the synovium of joints, bursae, or tendon sheaths and is caused by upregulation of the CSF1 gene. Vimseltinib is an oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit the CSF1 receptor. Here, we describe the rationale and design for the phase III MOTION trial (NCT05059262), which aims to evaluate the efficacy and safety of vimseltinib in participants with TGCT not amenable to surgical resection. In part 1, participants are randomized to receive vimseltinib 30 mg twice weekly or matching placebo for ≤24 weeks. Part 2 is a long-term treatment phase in which participants will receive open-label vimseltinib.

Purpose: Partial nephrectomy (PN) for large or complex renal tumors can be difficult and associated with a higher risk of recurrence than radical nephrectomy. We aim to evaluate the clinical useful of nephrometry scores for predicting oncological outcomes in a large cohort of patients who underwent PN for renal cell carcinomas., Methods: Our analysis included patients who underwent PN for renal cell carcinoma in 21 French academic centers (2010-2020). RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Uni- and multivariate cox models were performed to identify predictors of recurrence-free survival and overall survival. The area under the curve (AUC) was used to identify models with the highest discrimination. Decision curve analyses (DCAs) determined the net benefit associated with their use., Results: A total of 1927 patients were analyzed with a median follow-up of 32 months (14-45). RENAL score (p = 0.01), age (p = 0.002), histological type (p = 0.001), high nuclear grade (p = 0.001), necrotic component (p < 0.001), and positive margins (p = 0.005) were significantly related to recurrence in multivariate analyses. The discriminative performance of the 3 radiological scores was modest (65, 63, and 63%, respectively). All 3 scores showed good calibration, which, however, deteriorated with time. Decision curve analysis of the three models for the prediction of overall and recurrence-free survival was similar for all three scores and of limited clinical relevance., Conclusion: The association between nephrometry scores and oncological outcomes after NP is very weak. The use of these scores for predicting oncological outcomes in routine practice is therefore of limited clinical value., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Cut-off time to avoid orchiectomy relies on small series of patients. The objective was to determine the cut-off time to avoid orchiectomy in torsion of the spermatic cord in a large cohort., Methods: We performed a retrospective multicenter study (TORSAFUF cohort) of patients with suspected spermatic cord torsion between 2005 and 2019. All patients aged > 12 years who were suspected of having a torsion of the spermatic cord in 14 University Hospitals in France were included (n = 2986). Patients for whom data on pain duration were not available (n = 923) or for whom the final diagnosis was not torsion of the spermatic cord (n = 807) were excluded. The primary outcome was orchiectomy. The secondary outcomes were testicular survival time and the prediction of orchiectomy with the duration of pain., Results: 1266 patients were included with an orchiectomy rate of 12% (150 patients). The mean age was 21.5 years old in the salvage group and 23.7 years old in the orchiectomy group (p = 0.01), respectively. The median time from the onset of pain to surgery was 5.5 (IQR = 5) hours in the salvage group and 51.1 (IQR = 70) hours in the orchiectomy group (p < 0.0001). The risk of orchiectomy increased after a time cut-off of 6 h 30. A delay of 15 h 30 in pain duration was found to predict orchiectomy (sensitivity: 0.81; specificity: 0.87)., Conclusions: Pain duration can predict the probability of salvaging the testicles and performing orchiectomy. Rapid intervention should be recommended, regardless of the time elapsed from the onset of pain., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The SPARE Nephrometry Score (NS) is described as easier to implement than the RENAL and PADUA NSs, currently more widely used. Our objective was to compare the accuracy of SPARE NS in predicting renal function outcomes following RAPN., Methods: A multicentric retrospective study was conducted using French kidney cancer network (UroCCR, NCT03293563) database. All patients included had RAPN for cT1 renal tumors between May 2010 and March 2021. SPARE was compared to RENAL, PADUA and Tumor Size to predict postoperative acute kidney injury (AKI), chronic kidney disease (CKD) upstaging, de novo CKD at 3-6 months follow-up and Trifecta failure. The ability of the different NSs and tumor size to predict renal function outcomes was evaluated using uni- and multivariate logistic regression models., Results: According to our study criteria, 1171 patients were included. Mean preoperative tumor size and estimated glomerular filtration rate (eGFR) were 3.4±1.4 cm and 85.8 mL/min/1.73 m 2 . In total, 266 (22.7%), 87 (7.4%), 94 (8%), and 624 (53.3%) patients had AKI, de novo CKD, CKD upstaging, and Trifecta failure, respectively. In multivariate analysis, all three NSs and tumor size were independent predictors of AKI, CKD de novo, CKD upgrade and Trifecta failure. There was no significant difference between all three NS and tumor sizes in predicting renal function outcomes., Conclusions: SPARE Score seems to be a valid alternative to predict renal function outcomes after RAPN. Nevertheless, in our study, tumor size was as accurate as NSs in predicting postoperative outcomes and, therefore, seems to be the logical choice for surgical decisions.

Background: The hypertension specialist often receives referrals of patients with young-onset, severe, difficult-to-control hypertension, patients with hypertensive emergencies, and patients with secondary causes of hypertension. Specialist hypertension care compliments primary care for these complex patients and contributes to an overall hypertension control strategy. The objective of this study was to characterize hypertension centres and the practice patterns of Canadian hypertension specialists., Methods: Adult hypertension specialists across Canada were surveyed to describe hypertension centres and specialist practice in Canada, including the following: the patient population managed by hypertension specialists; details on how care is provided; practice pattern variations; and differences in access to specialized hypertension resources across the country., Results: The survey response rate was 73.5% from 25 hypertension centres. Most respondents were nephrologists and general internal medicine specialists. Hypertension centres saw between 50 and 2500 patients yearly. A mean of 17% (± 15%) of patients were referred from the emergency department and a mean of 52% (± 24%) were referred from primary care. Most centres had access to specialized testing (adrenal vein sampling, level 1 sleep studies, autonomic testing) and advanced therapies for resistant hypertension (renal denervation). Considerable heterogeneity was present in the target blood pressure in young people with low cardiovascular risk and in the diagnostic algorithms for investigating secondary causes of hypertension., Conclusions: These results summarize the current state of hypertension specialist care and highlight opportunities for further collaboration among hypertension specialists, including standardization of the approach to specialist care for patients with hypertension., (© 2023 The Authors.)

Objective: (a) To analyze the extent and nature of research on the impact of childhood acquired brain injury (ABI) on siblings, (b) to synthetize in a descriptive way the results of these studies and propose perspectives of care/support., Method: A literature search of 3 databases was performed up to August 2022. Studies addressing issues around siblings of children with ABI were included in the scoping review., Results: 25 articles were identified and analyzed. Results indicate that there is a paucity of research on this issue. However, interest in the subject has increased over past decades. Despite variable results, the current literature highlights the negative impact of ABI on family functioning and relationships. The trajectory and quality of life of siblings of children with ABI are modified. ABI causes intense and mixed emotions, psychological distress, behavioral difficulties and social stigma. Siblings have varied ways of coping with ABI and express particular needs that must be addressed., Conclusion: There is a significant impact of childhood ABI on siblings' subsequent life. Existing studies on this subject are few, heterogeneous, and sometimes contradictory. Further studies on this theme therefore appear necessary in order to propose appropriate support for patients' siblings according to their age and situation.

Background/purpose: Quantification of the severity of pectus excavatum deformities is currently performed using the Haller index (HI) and the Correction index (CI), amongst others. However, most indexes characterize the severity at the point of maximum excavation. We present a new index, the Titanic index (TI), aimed at the appraisal of the cephalocaudal extent of the excavation and its potential clinical use., Materials and Methods: Retrospective analysis of a cohort of patients who underwent a minimally invasive repair of pectus excavatum (MIRPE) between July 2020 and April 2022 at a single center. We defined TI as the percentage of the sternum that lied behind the anterior costal line observed in the CT. Demographics, HI, CI, and TI calculated based on computed tomography images (CT) were analyzed. Also, we compared the severity indexes of two groups of patients divided by the number of implants introduced per patient (group A: two implants, and group B: more than two)., Results: Seventy-eight patients (92% male) were included, with a mean age of 17.2 ± 4.8 years. The mean TI was 37%. Albeit weak, we identified significant correlations between the TI and the HI and, more closely, to the CI. Two implants were introduced in 37 (47%) patients, and more than two in 41 (53%) patients. Compared to patients with two implants, the group of patients who received more than two implants were older and showed worse thoracic indexes. Using receiver operating characteristic curve analysis, we identified the TI as a better predictor of the need for more than two implants than HI and CI. In this regard, a TI larger than 66.5% had a sensitivity of 93% and a specificity of 92%., Conclusion: We propose a novel index for the categorization of the severity of pectus excavatum. This index might be useful in planning the number of implants required for complete thoracic remodeling during MIRPE., Level of Evidence: Level III., Type of Study: Retrospective Comparative Study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background/purpose: We explored determinants of success in a large cohort of patients with pectus excavatum submitted to vacuum bell treatment and compared groups with satisfactory versus unsatisfactory outcomes., Methods: Retrospective case-control study in a single center between May 2013 and January 2020, including patients with pectus excavatum treated with vacuum bell. We classified patients according to their status at closure of data registry (surveillance; withdrawal; complete correction; failure) and according to Obermeyer's classification of degrees of pectus excavatum correction. Determinants of success were calculated using receiver operating characteristic curves., Results: Overall, 186 patients were included. Complete correction was achieved by 17% of the cases, while 45% remained under surveillance. Failure rates were low (n = 9; 5%), whereas withdrawal rates were 34%. Based on Obermeyer's classification of degree of excavation correction, 35% had excellent/good, 25% fair, and 40% poor/worse results. When comparing patients with good/excellent results with those with unsatisfactory results, patients with good/excellent results had a longer treatment duration [19.0 (13.0; 28) months vs. 13.0 (6.5; 22.5) months, p<0.0001], and lower initial pectus depth [1.6 (1.2; 2.0) cm, vs. 2.0 (1.5; 2.6) cm, p = 0.001]. Using ROC curves, the best determinants of success were an initial pectus depth ≤ 1.8 cm and a length of treatment > 12 months., Conclusion: One-third of patients in treatment with a vacuum bell achieved excellent or good outcomes in our cohort. Determinants of success included an initial pectus depth of 1.8 cm or less and a minimum length of treatment of 12 months., Type of Study: retrospective comparative study LEVEL OF EVIDENCE: III., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background/purpose: To report telemedicine's feasibility and satisfaction rates for treating patients with pectus carinatum using a dynamic compressor system. We analyzed treatment adherence in comparison with the previous, non-pandemic year., Materials and Methods: Retrospective analysis including patients with pectus carinatum under treatment with a dynamic compressor system using telemedicine at the chest wall centers from two hospitals, private and public, between April and July 2020. A free video conference platform for teleconsultations was employed. We evaluated the incidence of pectus cases with telemedicine, the number of dynamic compressor system prescriptions, the number of patients in the correction phase, and the number who ended treatment. To assess adherence, we compared our cohort with an in-person cohort during the same time frame of the previous, non-pandemic year. In addition, we performed a patient satisfaction survey comprising questions related to socioeconomic status, the likeability of telemedicine, simplicity of modification of the system, and desire to continue with telepectus after the pandemic., Results: One hundred and thirty-six telepectus consultations were performed in 76 patients. During this time frame, 15 patients started using the dynamic compressor system. Compared to the previous, non-pandemic year, the number of consultations per patient was similar (2019: 1.92 ± 1 .0 vs. 2020: 1.79 ± 0.8, p = 0.32), and there was a significant reduction in the number of dropouts with the use of telemedicine (9% vs. 1%, p = 0.025). Fifty-nine patients answered the satisfaction survey. All of them solved their doubts through telemedicine. Overall, 95% found telemedicine comfortable. Of note, those with a lower income evidenced the highest intention in continuing with telemedicine., Conclusions: We demonstrated the feasibility of remote care of patients with pectus carinatum using a dynamic compressor system with a similar frequency of consultations compared to in-person medical care. Telepectus patients revealed a high rate of satisfaction irrespective of their socioeconomic status., Level of Evidence: IV., Type of Study: Retrospective study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.

Background: Use of Doppler ultrasonography (DUS) for patients with suspected testicular torsion (TT) is highly controversial and remains debated, as it can delay surgery and its performance may vary., Objective: To assess the role, impact, safety, and performance of DUS in the management of patients with suspected TT before scrotal exploration., Design, Setting, and Participants: The TORSAFUF cohort retrospectively included patients older than 12 yr who underwent surgery for suspected TT in 14 academic hospitals between 2005 and 2019. Perioperative data and surgical and DUS reports were collected., Outcome Measurements and Statistical Analysis: Clinical factors influencing DUS utilisation were analysed using multivariate logistic regression. The orchidectomy rate and delay to surgery were compared by group with and without DUS receipt using one-to-one propensity score (PS) matching to assess imaging safety. For the group with preoperative imaging, DUS performance was evaluated using a contingency table., Results and Limitations: Overall, 2922 patients were included, of whom 956 (32.7%) underwent DUS before surgery. DUS was more likely to be performed in older patients (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.1-1.2), those who experienced progressive onset of pain (OR 1.5, 95% CI 1.1-2), and patients who presented at the emergency department more than 6 h after their first scrotal symptoms (OR 2.3, 95% CI 1.9-2.8). After PS matching, DUS receipt was not significantly associated with orchidectomy but the delay to surgery was 1 h longer. DUS demonstrated strong sensitivity of 85.2% (95% CI 82.1-88.3%) and specificity of 52.7% (95% CI 48.8-56.6%). The performance was better for younger patients and for those with time since onset of pain of >6 h., Conclusions: In this large retrospective study, DUS before surgery was safe, feasible, and useful in selected cases with suspected TT, but it should not delay or replace surgery in cases with a strong clinical suspicion., Patient Summary: We analysed the performance and safety of an ultrasound scan of the scrotum before surgery for patients with a suspected twisted testicle (TT). This scan before surgery was not associated with a higher risk of negative outcomes but was only moderate in accurately diagnosing TT. Surgery to correct TT should not be delayed., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background / Purpose: To report the implementation of a specially designed vacuometer for the ambulatory measurement of the exact negative pressure self-applied by the patient when using the vacuum bell for the treatment of pectus excavatum and to analyze patient satisfaction with the device, by conducting a survey., Methods: Between October 2018 and June 2020, all patients with pectus excavatum who received a vacuum bell at our Pectus Clinic were provided with a specially designed pectus vacuometer for their personal use. We described the vacuometer, the fundamentals of its development, and the utilization protocol. A survey was conducted evaluating comfort, clarity of instructions, usefulness, simplicity of connection, and likeability. The level of satisfaction was assessed using a Likert scale ranging from 1 (very negative experience) to 5 (very positive experience). The occurrence of skin lesions provoked by the application of the vacuum bell was registered., Results: From 72 submitted surveys, 54 patients answered. Patient demographics comprised 44 (81.5%) males and a mean age of 12.6 ± 6.0 years. The mean initial external pectus depth was 2.0 ± 0.7 cm and the mean duration of treatment was 13.2 ± 8.6 months. No skin lesions were detected while using the vacuum bell and the vacuometer. The mean general satisfaction score was 4.4 ± 0.7 and 83.3% of the respondents did not have any inconvenience with the vacuometer. A patient who considered himself cured was the only dropout during the study., Conclusions: In this study, we described the feasibility and fundamentals of the application of a specifically designed vacuometer for ambulatory use as an adjunct to the treatment of pectus excavatum with a vacuum bell, and demonstrated a high satisfaction level with the device. In addition, the vacuometer might help avoid skin lesions secondary to the vacuum bell and foster adhesion to treatment., Type of Study: Treatment study., Level of Evidence: IV., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Despite the emergent application of 3-dimensional technology for thoracic reconstructions, reports regarding its use for the resolution of the heterogeneous subgroup of complex chest wall malformations are lacking. We aim to report a novel, standardized process of personalized repair of complex chest wall malformations comprising multidisciplinary, comprehensive surgical planning; surgical simulation on a 3-dimensionally printed scale model of the area of interest; manufacturing of customized prostheses; and surgical repair according to plan. We propose this therapeutic strategy for the resolution of such a wide variety of chest wall deformities to reduce improvisation and enhance outcomes., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The use of chemotherapy (CT) near the end-of-life (EOL) is an important issue in oncology since it could degrade quality of life. CT near EOL is still poorly studied, with no dedicated study in gastrointestinal (GI) cancer patients., Aim: To analyze in GI cancer patients the factors associated with the use of CT within 3- and 1-month before patients' death., Methods and Participants: All consecutive patients who died from a GI cancer in 10 French tertiary care hospitals during 2014 were included in this retrospective study. Clinical, demographical and biological data were collected and compared between patients receiving or not CT within 3- and 1-month before death. Variables associated with overall survival (OS) was also determined using of univariate and multivariate analyses with a Cox model., Results: Four hundred and thirty-seven patients with a metastatic GI cancer were included in this study. Among them, 293 pts (67.0%) received CT within 3-months before death, and 121 pts (27.7%) received CT within 1-month before death. Patients receiving CT within 3-months before death were significantly younger (median age: 65.5 vs 72.8 years, p < 0.0001), with a better PS (PS 0 or 1: 53.9 vs 29.3%, p < 0.0001) and a higher albumin level (median: 32.8 vs 31.0 g/L, p = 0.048). Similar results were found for CT within 1 month before death. Palliative care team intervention was less frequent in patients who received CT in their last month of life (39.7% vs 51.3%, p = 0.02). In multivariate analysis, median OS from diagnosis was shorter in the group receiving CT within 1-month before death (HR = 0.59; 95% CI [0.48-0.74])., Conclusion: In GI-cancer patients, CT is administered within 3- and 1-month before death, in two and one third of patients, respectively. Patients receiving CT within 1-month before death, had more aggressive disease with poor OS. Palliative care team intervention was associated with less administration of CT in the last month of life. These results highlight the need to better anticipate the time to stop CT treatment in the end-of-life and the importance of an active collaboration between oncology and palliative care teams., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Sarcoidosis is a multisystem disease characterized by the development and accumulation of granulomas, the hallmark of an inflammatory process induced by environmental and/or infectious and or genetic factors. This auto-inflammatory disease mainly affects the lungs, the gateway to environmental aggressions and viral infections. We have shown previously that genetic predisposition to sarcoidosis occurring in familial cases is related to a large spectrum of pathogenic variants with, however, a clustering around mTOR (mammalian Target Of Rapamycin)-related pathways and autophagy regulation. The context of the COVID-19 pandemic led us to evaluate whether such genetic defects may increase the risk of a severe course of SARS-CoV2 infection in patients with sarcoidosis. We extended a whole exome screening to 13 families predisposed to sarcoidosis and crossed the genes sharing mutations with the list of genes involved in the SARS-CoV2 host-pathogen protein-protein interactome. A similar analysis protocol was applied to a series of 100 healthy individuals. Using ENRICH.R, a comprehensive gene set enrichment web server, we identified the functional pathways represented in the set of genes carrying deleterious mutations and confirmed the overrepresentation of autophagy- and mitophagy-related functions in familial cases of sarcoidosis. The same protocol was applied to the set of genes common to sarcoidosis and the SARS-CoV2-host interactome and found a significant enrichment of genes related to mitochondrial factors involved in autophagy, mitophagy, and RIG-I-like (Retinoic Acid Inducible Gene 1) Receptor antiviral response signaling. From these results, we discuss the hypothesis according to which sarcoidosis is a model for studying genetic abnormalities associated with host response to viral infections as a consequence of defects in autophagy and mitophagy processes.

Ravulizumab, a long-acting complement C5 inhibitor engineered from eculizumab, allows extending maintenance dosing from every 2-3 weeks to every 4-8 weeks depending on bodyweight. Here, we evaluated the efficacy and safety of ravulizumab in complement inhibitor-naïve children (under 18 years) with atypical hemolytic uremic syndrome. In this phase III, single-arm trial, ravulizumab was administered every eight weeks in patients 20 kg and over, and four weeks in patients under 20 kg. The primary endpoint was a complete thrombotic microangiopathy response (normalization of platelet count and lactate dehydrogenase, and a 25% or more improvement in serum creatinine) through 26 weeks. Secondary endpoints included change in hematologic parameters and kidney function. 18 patients with a median age of 5.2 years were evaluated. At baseline, symptoms of atypical hemolytic uremic syndrome outside the kidney were present in 72.2% of patients and 38.9% had been in intensive care. Baseline estimated glomerular filtration rate was 22 mL/min/1.73 m 2 . By week 26, 77.8% of patients achieved a complete thrombotic microangiopathy response; 94.4%, 88.9% and 83.3% of patients achieved platelet normalization, lactate dehydrogenase normalization and a 25% or more improvement in serum creatinine, respectively. By week 50, 94.4% patients had achieved a complete thrombotic microangiopathy response. Median improvement in platelet count was 246 and 213 x10 9 /L through week 26 and week 50, respectively. The median increase above baseline in estimated glomerular filtration rate was 80 and 94 mL/min/1.73m 2 through week 26 and week 50, respectively. No unexpected adverse events, deaths, or meningococcal infections occurred. Thus, ravulizumab rapidly improved hematologic and kidney parameters with no unexpected safety concerns in complement inhibitor-naïve children with atypical hemolytic uremic syndrome., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Prostate biopsy is sometimes complicated by infection which can lead to death. The risk factors remain controversial, notably the urine bacterial culture carried out before a prostate biopsy. The increase in resistance induces an increase in the number of complications and the need to define new antibiotic prophylaxis strategies. The urine bacterial culture remains widely discussed in cases with post-prostate biopsy infections and urologists or experts await clear recommendations on this subject. The Infectiology Committee of the French Association of Urology has therefore set up a literature analysis work in order to reach a consensus within the committee., Method: A literature search was performed on Pubmed and Medline. We selected randomized studies or meta-analyzes using the keywords "prostate biopsy" and "infection" or "infectious complications". All abstracts and articles have been analyzed. The summary of the analysis was reviewed by all the members of the committee proposing the most consensual recommendation possible., Results: The literature on the subject remains poor, but no evidence of a link between prebiopsy bacteriuria and post-biopsy infection has been demonstrated., Conclusions: Apart from a clinical situation which could evoke a male urinary tract infection, and moreover having to prefer the postponement of biopsies, it is not recommended to perform a routine urine culture before endo-rectal prostate biopsies (expert opinion)., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disease associated with poor outcomes if untreated. Ravulizumab, a long-acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for the treatment of aHUS. Here, we report outcomes from a pediatric patient cohort from the ravulizumab clinical trial (NCT03131219) who were switched from chronic eculizumab to ravulizumab treatment., Methods: Ten patients received a loading dose of ravulizumab on Day 1, followed by maintenance doses administered initially on Day 15, and then, every 4-8 weeks thereafter, depending on body weight. All patients completed the initial evaluation period of 26 weeks and entered the extension period., Results: No patients required dialysis at any point throughout the study. The median estimated glomerular filtration rate values remained stable during the trial: 99.8 mL/min/1.73m 2 at baseline, 93.5 mL/min/1.73m 2 at 26 weeks, and 104 mL/min/1.73m 2 at 52 weeks. At last available follow-up, all patients were in the same chronic kidney disease stage as recorded at baseline. Hematologic variables (platelets, lactate dehydrogenase, and hemoglobin) also remained stable throughout the initial evaluation period and up to the last available follow-up. All patients experienced adverse events; the most common were upper respiratory tract infection (40%) and oropharyngeal pain (30%). There were no meningococcal infections reported, no deaths occurred, and no patients discontinued during the study., Conclusions: Overall, treatment with ravulizumab in pediatric patients with aHUS who were previously treated with eculizumab resulted in stable kidney and hematologic parameters, with no unexpected safety concerns when administered every 4-8 weeks., Trial Registration: Trial identifiers: Trial ID: ALXN1210-aHUS-312 Clinical trials.gov : NCT03131219 EudraCT number: 2016-002499-29 Graphical abstract.

RNA sequencing holds great promise to improve the diagnostic of hematological malignancies, because this technique enables to detect fusion transcripts, to look for somatic mutations in oncogenes, and to capture transcriptomic signatures of nosological entities. However, the analytical performances of targeted RNA sequencing have not been extensively described in diagnostic samples. Using a targeted panel of 1385 cancer-related genes in a series of 100 diagnosis samples and 8 controls, we detected all the already known fusion transcripts and also discovered unknown and/or unsuspected fusion transcripts in 12 samples. Regarding the analysis of transcriptomic profiles, we show that targeted RNA sequencing is performant to discriminate acute lymphoblastic leukemia entities driven by different oncogenic translocations. Additionally, we show that 86% of the mutations identified at the DNA level are also detectable at the messenger RNA (mRNA) level, except for nonsense mutations that are subjected to mRNA decay. We conclude that targeted RNA sequencing might improve the diagnosis of hematological malignancies. Standardization of the preanalytical steps and further refinements of the panel design and of the bioinformatical pipelines will be an important step towards its use in standard diagnostic procedures., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background/purpose: The development of computer-aided design/manufacturing and digital image technology shows promise to revolutionize several medical and surgical fields. In this context, we propose a different approach for minimally invasive repair of pectus excavatum (MIRPE) including preoperative planning, ambulatory template fitting, and implant customization., Methods: We prospectively collected data on 130 consecutive patients who underwent a novel process of implant customization for MIRPE between November 2015 and September 2019 at our institution. This process consisted of: 1) preoperative planning using 3D computed tomography scan reconstruction and 3D printing of the implant template, 2) an ambulatory fitting session with the template, and 3) manufacture of a custom made, prebent, metallic implant based on the 3D printed templates. We described the process in detail and analyzed the "implant-deformity" match, need for rebending, modification of the curvature or shape of the pectus implant intraoperatively, and accuracy of the number of bars planned preoperatively., Results: Preoperative planning including 3D reconstruction and printing resulted in a 92.3% optimal "implant-deformity" anatomic match. Minimal rebending without flipping of the implants was required in 5.4% of the patients. In two cases (1.5%), the implants were too short, and they tended to sink into the intercostal space, and in one case (0.8%), the patient's chest was extremely asymmetric, and the implant had to be removed and rebent intraoperatively. The number of implants planned preoperatively was precise in 100%., Conclusions: In this study, we demonstrated that minimally invasive repair of pectus excavatum assisted by preoperative planning, ambulatory template fitting, and implant customization enables an excellent anatomic match, leading to minimal rebending, and avoiding implant flipping or removal after retrosternal passage as well as accuracy in the number of bars programmed preoperatively., Type of Study: Prospective registry., Level of Evidence: III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The pectus bar removal procedure is often considered a simple, straightforward surgery with a low incidence of complications. However, life-threatening bleeding complications have been reported requiring major measures for hemostatic control. Our objective is to share a simple maneuver that our group has systematically included in the bar removal procedure to facilitate bleeding control in case hemorrhage occurs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval from two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults with atypical hemolytic uremic syndrome presenting with thrombotic microangiopathy. In this global, phase 3, single arm study in complement inhibitor-naïve adults (18 years and older) who fulfilled diagnostic criteria for atypical hemolytic uremic syndrome, enrolled patients received ravulizumab through a 26-week initial evaluation period. The primary endpoint was complete thrombotic microangiopathy response defined as normalization of platelet count and lactate dehydrogenase and 25% or more improvement in serum creatinine. Secondary endpoints included changes in hematologic variables and renal function. Safety was also evaluated. Ravulizumab treatment resulted in an immediate, complete, and sustained C5 inhibition in all patients. Complete thrombotic microangiopathy response was achieved in 53.6% of patients. Normalization of platelet count, lactate dehydrogenase and 25% or more improvement in serum creatinine was achieved in 83.9%, 76.8% and 58.9% of patients, respectively. Improvement in estimated glomerular filtration rate by one or more stage was achieved in 68.1% of patients by day 183. No unexpected adverse events were reported across a safety analysis set of 58 patients. Four deaths occurred (three within one month of study initiation, including one in a patient excluded based on eligibility criteria after the first dose) with none considered treatment-related by the study investigator. Thus, treatment with ravulizumab once every eight weeks resulted in rapidly improved hematologic and renal endpoints with no unexpected adverse events in adults with atypical hemolytic uremic syndrome., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Purpose: Urinary tract infections are amongst the most frequent nosocomial infections followed by surgical site infections (SSI). Antibiotic prophylaxis is only one way to reduce the risk of post-operative infection. Our aim was to establish a review of the literature on measures to reduce post-operative infections outside antibiotic prophylaxis., Methods: We performed a review of the literature in February 2019 using Medline database to identify relevant studies published in the last 10 years. We arbitrarily decided to fix our limit to the 10 last years considering that the resistance rate of bacteria to antibiotics and the surgical technics evolve over time. This search identified 229 studies. We included 53 studies selected upon the title or the abstract., Results: Forty-four studies were finally included. We evaluated the efficacy to prevent SSI by skin antisepsis, surgical hand hygiene and technique, type of surgeons' caps, preservation of normothermia, hair removal, increased oxygen delivery, wound protectors, bathing, normoglycemia and immunonutrition., Conclusions: Antibiotic prophylaxis represents one way to prevent SSI but various other measures should be known and considered by anesthesiologists and surgeons. Some measures to reduce post-operative infections are not clearly established yet and more studies are needed.

Purpose: To modify the Performance-Oriented Mobility Assessment-Gait (POMA-G) subtest and validate this modified POMA-G (mPOMA-G) in children with hypophosphatasia (HPP), a rare metabolic disorder that can manifest with musculoskeletal symptoms that impair mobility and ambulation., Methods: Based on feedback from an expert panel, the POMA-G was modified by removing gait initiation/path assessments and expanding the rating scale for step length/continuity to capture aspects of observational gait analysis relevant to children with HPP. Three trained physical therapists used the mPOMA-G for video-based assessments of gait in 14 children with childhood HPP who participated in a clinical study of asfotase alfa or in a natural history study. Intraclass correlation coefficients (ICCs) were calculated to determine interrater and intrarater agreement. Concurrent validity was evaluated by correlations with other validated assessment tools., Results: Across 192 observations from available videos, interrater and intrarater agreement of mPOMA-G scores was significant (ICCs: 0.76 for both; P< 0.001). mPOMA-G scores had strong concurrent validity with the Childhood Health Assessment Questionnaire, Pediatric Outcomes Data Collection Instrument Transfer and Mobility Scale, Sports and Physical Function subscale, and 6-Minute Walk Test (all P⩽ 0.0002)., Conclusion: The mPOMA-G is a reliable and valid measure for detecting clinically significant impairments in children with HPP.

Purpose: The optimal vitamin D 3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D 3 . The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D 3 , to alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients., Methods: We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student's t tests., Results: The mean dose of active vitamin D 3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P < 0001) after the switch from alfacalcidol to calcitriol. PTH significantly decreased from 94.4 to 82.6 pmol/L (-11.8 pmol/L, P = 0.02). The mean corrected calcium increased from 2.17 to 2.25 mmol/L (+0.08 mmol/L, P < 0.001) without any clinically significant hypercalcemia, and phosphorus levels were stable. Results were similar in a subgroup of patients (n = 17) for whom the medication was administrated during the hemodialysis session, ensuring a complete compliance., Conclusions: According to our study, calcitriol in equal dosage is more effective than alfacalcidol in lowering serum PTH level in chronic hemodialysis patients. This suggests that calcitriol may be the optimal active vitamin D 3 for the treatment of SHPT in chronic hemodialysis patients.

Preterm birth (PTB) is a leading cause of neonatal mortality and morbidity worldwide, and surviving infants are at increased risks of lifelong complications. PTB has been firmly linked to inflammation regardless of infection, specific aetiology or timing of birth. Deleterious inflammation is observed in maternal and fetal tissue, and correlates with the severity of perinatal complications. At present, PTB is treated with tocolytics as though it is exclusively a myometrial contractile disorder. These agents do not address underlying inflammatory processes and are thus vastly ineffective at improving neonatal outcomes. Of all inflammatory mediators, IL-1 is central to the pathophysiology of PTB and most adverse neonatal outcomes. We thus present herein a review of the various effects of IL-1 in utero, with a brief overview of its mechanism of action. We then discuss the potential of different IL-1-targeting agents based on pre-clinical testing in relevant models of PTB and neonatal inflammatory injuries., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Purpose: Hyperphosphatemia and metabolic acidosis are frequently encountered in advanced chronic kidney disease (CKD) patients. Correction of metabolic acidosis in patients with advanced CKD leads to a decrease in the progression of renal impairment and improves nutritional outcomes. Lanthanum carbonate is used for control of hyperphosphatemia. This study evaluated the effect of lanthanum carbonate on metabolic acidosis in CKD IV-V patients and in patients on dialysis., Methods: Retrospective data of patients in whom lanthanum carbonate therapy was initiated were collected from 2009 to 2013 in a single dialysis center. Of the 79 patients in whom lanthanum carbonate was introduced, 51 patients were included in the analysis. Of the 51 patients, 39 patients received chronic hemodialysis, two patients received peritoneal dialysis therapy, and 10 patients had stage IV-V CKD not on dialysis. The primary outcome was the serum bicarbonate change after the introduction of lanthanum carbonate., Results: There was a significant increase in mean serum bicarbonate concentration of 2.79 mmol/L (p ≤ 0.001) compared to baseline. The increase remained in the CKD IV-V patients (2.50 mmol/L, p = 0.005) and in the patients on dialysis (2.81 mmol/L, p < 0.001). Serum bicarbonate remained higher (p > 0.05) than baseline up to 6 months after lanthanum carbonate introduction., Conclusion: In this study, lanthanum carbonate introduction increased serum bicarbonate concentration in a small sample of CKD IV-V patients and in patients on dialysis. Further studies are needed to confirm this effect and investigate whether the correction of metabolic acidosis by using lanthanum carbonate in CKD IV-V patients can improve clinical outcomes.

Purpose: Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations., Experimental Design: A total of 107 plasma samples were collected from the BioCAST/IFCT-1002 lung cancer study (never-smokers cohort). Matched tumor DNA (tDNA) was obtained for 68 cases. Multiplex PCR-based assays were designed to target specific coding regions in EGFR, KRAS, BRAF, ERBB2, and PI3KCA genes, and amplicon sequencing was performed at deep coverage on the cfDNA/tDNA pairs using the NGS IonTorrent Personal Genome Machine Platform., Results: CfDNA concentration in plasma was significantly associated with both stage and number of metastatic sites. In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. Sensitivity of the test was 58% (95% confidence interval, 43%-71%) and the estimated specificity was 87% (62%-96%)., Conclusion: These data demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of a range of tumor biomarkers in patients with metastatic lung cancer., (©2014 American Association for Cancer Research.)

Background: Telavancin, a novel lipoglycopeptide, exerts concentration-dependent, rapid bactericidal activity on account of its multiple mechanisms of action. Telavancin is highly active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate, and vancomycin-resistant strains., Methods: We conducted a randomized, double-blind, controlled, phase-2 clinical trial. Patients > or = 18 years of age with a diagnosis of complicated skin and soft-tissue infection caused by suspected or confirmed gram-positive organisms were randomized to receive either intravenously administered telavancin once daily or standard therapy (antistaphylococcal penicillin 4 times daily or vancomycin twice daily)., Results: For the study, 167 patients were randomized and received at least 1 dose of study medication. Success rates were similar in all analysis populations at the test-of-cure evaluation. Of patients with S. aureus infection at baseline (n = 102), 80% of the telavancin group were cured and 77% of the standard therapy group were cured. For patients with MRSA infection at baseline (n = 48), cure rates were 82% for the telavancin group and 69% for the standard therapy group. Microbiologic eradication in patients with MRSA infection was 84% for the telavancin group versus 74% for the standard therapy group. MIC90 values were lower for telavancin in all tested strains of S. aureus (< or = 0.25 ug/mL) compared with the MIC90 values for vancomycin and oxacillin. Similar proportions of patients discontinued therapy for adverse events in both treatment groups (approximately 5%). Fewer serious adverse events were reported in the telavancin group (4 events) than were for the standard therapy group (9)., Conclusion: Clinical and microbiological results of this study support the further development of telavancin, especially for treatment of infection due to MRSA.

In 2000, the American Legacy Foundation (Legacy) launched truth, a national, multi-medium tobacco control social marketing campaign targeting youth age 12-17. This paper provides a brief description of one aspect of that campaign, the truth tour, and compares and contrasts the truth tour with commercial field marketing approaches used by the tobacco industry. The methods used for the tour's process evaluation are also described, and two important lessons learned about using field marketing techniques and using youth to implement field marketing techniques in social marketing campaigns are discussed. Social marketing campaigns that target youth may want to launch field marketing activities. The truth tour experience can inform the development of those efforts.

Objective: To assess the incidence of Pneumocystis carinii pneumonia (PCP) after discontinuation of either primary or secondary prophylaxis., Design: This was a prospective, non-randomized, non-blinded study., Setting: Twenty-five University-based AIDS Clinical Trials Group units., Participants: Participants either had a CD4 cell count < or = 100 x 106/l at any time in the past and no history of confirmed PCP (group I; n = 144), or had a confirmed episode of PCP > or = 6 months prior to study entry (group II; n = 129). All subjects had sustained CD4 cell counts > 200 x 106/l in response to antiretroviral therapy., Interventions: Subjects discontinued PCP prophylaxis within 3 months or at the time of study entry. Evaluations for symptoms of PCP and CD4 cell counts were performed every 8 weeks. Prophylaxis was resumed if two consecutive CD4 cell counts were < 200 x 106/l., Main Outcome Measure(s): The main outcome was development of PCP., Results: No cases of PCP occurred in 144 subjects (median follow-up, 82 weeks) in group I or in the 129 subjects (median follow-up, 63 weeks) in group II (95% upper confidence limits on the rates of 1.3 per 100 person-years and 1.96 per 100 person-years for groups I and II, respectively). Eight subjects (five in group I and three in group II) resumed PCP prophylaxis after two consecutive CD4 cell counts < 200 x 106/l., Conclusions: The risk of developing initial or recurrent PCP after discontinuing prophylaxis is low in HIV-infected individuals who have sustained CD4 cell count increases in response to antiretroviral therapy. Neither lifelong primary nor secondary PCP prophylaxis is necessary.

Nanoelectrospray ionization (nanoESI) mass spectrometry was performed on naturally occurring steroid sulfates and unconjugated steroids derivatized to their sulfate esters using precursor ion monitoring. Initially, an extraction method was developed based on a combinatorial approach employed to obtain the most efficient liquid/liquid extraction protocol. The new method allowed unconjugated steroids and their sulfated analogues to be isolated separately in a two-step procedure using diethyl ether/hexane (90:10, v/v) in the first step to extract the unconjugated steroids and chloroform/2-butanol (50:50, v/v) in the second step to extract steroid sulfates. Precursor ion scanning performed with a triple-quadrupole mass spectrometer was used to examine quantitatively the extracted unconjugated and sulfated steroids, where the recovery efficiency averaged 70 and 87%, respectively. In addition, some steroids could be structurally elucidated by employing tandem mass spectrometry. The limit of detection for steroid sulfates from the biological matrix was 200 amol/microL (approximately 80 fg/microL) with only 1 microL of sample being injected. Endogenous levels of the unconjugated and sulfated steroids were detected and quantified from physiological samples including urine and blood. Internal standards, pregnenolone-d4 sulfate and dehydroepiandrosterone-d2 (DHEA), were used for quantitation. Extraction and nanoESI analyses were also performed on cerebrospinal fluid where the neurosteroid DHEA sulfate was detected. The small amount of material consumed (typically less than 20% of the injection volume) suggests that nanoESI has even greater potential for high sensitivity when combined with nanoLC approaches, especially for monitoring reproductive and adrenal steroids, as well as for the analysis of the less abundant neurosteroids.