Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). METHODS: This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. RESULTS: 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). CONCLUSION: G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

Impact of Graft Function on Health Status and Quality of Life in Very Long-Term Survivors Who Received an HSCT for Inborn Errors of Immunity, a Prospective Study of the CEREDIH.

The overall survival rate after hematopoietic stem cell transplantation (HSCT) for inborn errors of immunity (IEI) has improved considerably, and its indications have broadened. As a consequence, addressing the issue of long-term health-related quality of life (HRQoL) has become crucial. Our study focuses on the health and HRQoL of post-HSCT survivors. We conducted a multicenter prospective follow-up study enrolling IEI patients who underwent transplantation in childhood before 2009. Self-reported data from the French Childhood Immune Deficiency Long-term Cohort and the 36-item Short Form questionnaires were compiled. One hundred twelve survivors were included with a median duration period from HSCT of 15 years (range 5-37), of whom 55 underwent transplantation for a combined immunodeficiency. We show that in patients evaluated at least 5 years after HSCT, 55% are still affected by a poor or very poor health status. Poor and very poor health status correlated with an abnormal graft function, defined as host or mixed chimerism, abnormal CD3+ count, or diagnosis of chronic graft-versus-host disease (poor health: odds ratio [OR] = 2.6, 95% confidence interval [CI], 1.1-5.9, P = .028; very poor health: OR = 3.6, 95% CI, 1.1-13, P = .049). Poor health was directly linked to a poorer HRQoL. Significant improvements in graft procedures have translated into better survival rates, but we show here that about half of the transplanted patients remain affected by an altered health status with a correlation to both abnormal graft function and impaired HRQoL. Additional studies are needed to confirm the impact of those improvements on long-term health status and HRQoL.

Functional and oncological outcome of petroclival chondrosarcoma operated on through an extradural anterior petrosectomy approach. A single center experience.

BACKGROUND: Management of skull base chondrosarcoma (SBC) remains challenging due to its deep location and complex growth pattern. Non-total resection and postoperative residual mass are common features, with controversy regarding the need to offer systematic postoperative radiation therapy or additional surgery. METHODS: A single-center retrospective cohort study was conducted on 10 consecutive patients harboring petroclival chondrosarcomas that were operated on between May 2007 and March 2019. After resection, the patients were allocated to a wait-and-rescan policy. RESULTS: Patients were operated on through an extradural anterior petrosectomy (EAP). Subtotal tumor resection was achieved in all patients. The mean duration of follow-up was 70 months (range 25-137/median 67 months). Clinical outcomes dramatically improved in three (30%) patients, while five patients retained preoperative cranial nerve (CN) disturbances after surgery (50%). Two patients reported transient postoperative worsening of their symptoms (20%). All of the postoperative CN new deficits improved within one year, except in one patient who showed permanent facial nerve palsy. The preoperative median Karnofsky Performance Scale (KPS) score was 80 (range 70-100), and then it became 90 (range 70-100) postoperatively. Patients harboring a tumor residue were included in a wait-and-rescan policy. With this regimen, tumor control was obtained in seven patients (70% of cases until the last follow-up). Three patients (30%) showed progression of the residual; two of them were treated with adjuvant therapy, while an extra cranial growth residue was observed in the third. CONCLUSION: Optimal and reasonable surgical resection of petroclival chondrosarcomas could be achieved with good to excellent functional outcomes through an EAP. In spite of a significant percentage of regrowth, only one patient required additional salvage surgery.

Pre-operative distraction using electric ride-on cars for children undergoing elective ambulatory surgery: A randomised controlled trial.

BACKGROUND: Pre-operative anxiety occurs in 18 to 60% of children undergoing surgery and results in poor outcomes. Nonpharmacological methods of distraction are effective in alleviating peri-operative anxiety. In our institution, ride-on electric cars (ride-on e-cars) are routinely used by children undergoing ambulatory surgery as a mean of nonpharmacological distraction. OBJECTIVES: The aim of this study is to assess the effect of pre-operative distraction with ride-on e-cars on children's pre-operative anxiety when undergoing elective ambulatory surgery. DESIGN: This was a prospective, randomised, controlled, open-label study. SETTING: The study was carried out from September 2019 to September 2021 in the ambulatory paediatric surgery unit of our teaching hospital, in Marseille, France. PATIENTS: Children aged 2 to 10 years and weighing less than 35 kg undergoing elective ambulatory surgery were eligible. One hundred and fifteen children were included, 56 in the control group and 59 in the intervention group. INTERVENTION: Children in the control group were transported from the operating room (OR) waiting area to the OR using a trolley, while children in the intervention group used the ride-on e-cars, without pharmacological premedication or parental presence. MAIN OUTCOME MEASURES: The primary outcome was pre-operative anxiety at the end of the transport (prior going into the OR assessed by the modified Yale Preoperative Anxiety Score Short Form (mYPAS-SF). Secondary outcomes were the anxiety levels in children over time, as well as postoperative pain and agitation assessed with the Face Legs Activity Cry Consolability (FLACC) and Paediatric Anaesthesia Emergence Delirium (PAED) scales, respectively. RESULTS: The mYPAS-SF anxiety scores did not differ between the control group and the intervention group (39 ±â€Š19 vs. 37 ±â€Š21, P  = 0.574). The secondary outcomes were similar between the two groups. CONCLUSIONS: Our randomised controlled trial showed that the use of ride-on e-cars did not alter pre-operative anxiety as compared with standard transport in children undergoing elective ambulatory surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03961581.

Ultra-lung-protective ventilation and biotrauma in severe ARDS patients on veno-venous extracorporeal membrane oxygenation: a randomized controlled study.

BACKGROUND: Ultra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO. METHODS: This is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1-2 mL/kg of predicted body weight), low respiratory rate (5-10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group). RESULTS: The primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06). CONCLUSIONS: Despite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www. CLINICALTRIALS: gov ( NCT03918603 ). Registered 17 April 2019.

Local Recurrence Risk Score to Predict Relapse after Stereotactic Body Radiation Therapy for Lung Tumors.

Background: After stereotactic body radiation therapy (SBRT) for lung tumors, follow-up CT scans remain a pitfall. The early detection of local relapse is essential to propose a new treatment. We aim to create a local recurrence predictive score using pre- and post-therapeutic imaging criteria and test it on a validation cohort. Methods: Between February 2011 and July 2016, lung tumors treated by SBRT with available pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and follow-up CT scans were retrospectively analyzed. The risk factors associated with relapse were identified by univariate logistic regression on a train cohort. The score was created using these factors, merging clinical and imaging criteria associated with local relapse, and then tested on an independent validation cohort. Overall and local relapse-free survival at 1 and 3 years were recorded. Results: Twenty-eight patients were included in the train cohort and ten in the derivation cohort (male 74%, median age 70 ± 12 years). Five variables significantly associated with local recurrence (female gender; sequential enlargement; craniocaudal growing; bulging margins; standardized uptake value (SUVmax > 5.5)) were combined to create the score on five points. With the threshold >2.5/5, the sensitivity and specificity of the score on the validation cohort were 100% and 88%, respectively. Overall survival and local relapse-free survival at 1 and 3 years were 89% and 42%, and 89% and 63%, respectively. Conclusion: The local recurrence risk score created has high sensitivity (100%) and specificity (88%), upon independent validation cohort, to detect local relapse. This score is easy to use in daily clinical practice.

Surgical management of large cerebellopontine angle meningiomas: long-term results of a less aggressive resection strategy.

OBJECTIVE: Cerebellopontine angle (CPA) meningiomas present many surgical challenges depending on their volume, site of dural attachment, and connection to surrounding neurovascular structures. Assuming that systematic radical resection of large CPA meningiomas carries a high risk of permanent morbidity, the authors adopted an alternative strategy of optimal resection followed by radiosurgery or careful observation of the residual tumor and assessed the efficiency and safety of this approach to meningioma treatment management. METHODS: This single-center retrospective cohort study included 50 consecutive patients who underwent surgery for meningioma between January 2003 and February 2020. RESULTS: The most common main dural attachments of the meningiomas were posterior (42%) and superior (26%) to the internal auditory meatus. The suboccipital retrosigmoid route was the most routinely used (92%). At the last follow-up examination, 93% of the patients with normal preoperative facial nerve (FN) function retained good House-Brackmann (HB) grades of I and II, whereas 3 patients (7%) displayed intermediate HB grade III FN function. Hearing preservation was achieved in 86% of the patients who presented with preoperative serviceable hearing, and recovery after surgery was achieved in 19% of the patients experiencing preoperative hearing loss. In order to preserve all cranial nerve function, gross-total resection was obtained in 26% of patients. Of the 35 patients who had undergone subtotal resection, 20 (57%) had been allocated into a wait-and-rescan treatment approach and 15 (43%) underwent upfront Gamma Knife surgery (GKS). The mean postoperative tumor volume was 1.20 cm3 in the upfront GKS group and 0.73 cm3 in the wait-and-rescan group (p = 0.08). Tumor control was achieved in 87% and 55% of cases (p < 0.001), with a mean follow-up of 85 and 69 months in the GKS and wait-and-rescan groups, respectively. The 1-, 5-, and 7-year tumor progression-free survival rates were 100%, 100%, and 89% in the GKS group and 95%, 59%, and 47% in the wait-and-rescan group, respectively (p < 0.001). CONCLUSIONS: Optimal nonradical resection of large CPA meningiomas provides favorable long-term tumor control and functional preservation. Adjuvant GKS does not carry additional morbidity and appears to be an efficient adjuvant treatment.

Stereotactic radiosurgery for post operative brain metastasic surgical cavities: a single institution experience.

BACKGROUND: The standard therapy for brain metastasis was surgery combined with whole brain radiotherapy (WBRT). The latter is however, associated with important neurocognitive toxicity. To reduce this toxicity, postoperative stereotactic radiosurgery (SRS) is a promising technique. We assessed the efficacy and the tolerance to postoperative Gamma Knife radiosurgery (GK) on the tumor bed after resection of brain metastases. METHODS: Between February 2011 and December 2016, following macroscopic complete surgical resection, 64 patients and 65 surgical cavities were treated by GK in our institution. The indication for adjuvant radiosurgery was a multidisciplinary decision. The main assessment criteria considered in this study were local control, intracranial metastasis-free survival (ICMFS), overall survival and toxicity. RESULTS: Median follow-up: 11.1 months. Median time between surgery and radiosurgery: 35 days. Median dose was 20 Gy prescribed to the 50% isodose line, for a median treated volume of 5.6 cc. Four patients (7%) suffered from local recurrence. Local recurrence-free, intracranial recurrence-free and overall survival at 1 year were 97.5%, 57.6% and 62.4% respectively. In total, 23 patients (41%) suffered from intracranial recurrence outside the tumor bed. In univariate analysis: concomitant GK treatment of multiple lesions and the tumor bed was associated with a decrease in ICMFS (HR = 1.16 [1.005-1.34] p = 0.04). In multivariate analysis: a non-lung primary tumor was significantly associated with a decrease in ICMFS (HR = 8.04 [1.82-35.4] p = 0.006). An increase in performance status (PS) and in the initial number of cerebral metastases significantly reduced overall survival (HR = 5.4 [1.11-26.3] p = 0.037, HR = 2.7 [1.004-7.36] p = 0.049, respectively) and One radiation necrosis histologically proven. CONCLUSION: Our study confirmed that postoperative GK after resection of cerebral metastases is an efficient and well-tolerated technique, to treat volumes of all sizes (0.8 to 40 cc). Iterative SRS or salvage WBRT can be performed in cases of intracranial relapse, postponing WBRT with its potential side effects.

Predictors of visual function after resection of skull base meningiomas with extradural anterior clinoidectomy.

Skull base meningiomas threatening the optic nerves may require performing an extradural anterior clinoidectomy (EAC) to optimally decompress the optic pathways. The present study evaluated the functional results and morbidity after surgical resection of skull base meningiomas including EAC, focusing on visual acuity (VA) and oculomotricity. Eighty-seven consecutive patients harboring skull base meningiomas who underwent surgical resection that included an EAC between 2003 and 2020 were retrospectively analyzed (86% women, median age 53 years). Decreased visual acuity (DVA) was graded as functional (VA ≥ 5/10) and nonfunctional (VA < 5/10). Statistical analyses were performed on VA and oculomotor nerve (OcN) dysfunction. Ninety surgical procedures were performed. Meningiomas were located at the anterior clinoid process (39%), cavernous sinus (31%), and spheno-orbital (30%) levels. Patients with a preoperative functional vision (normal or functional DVA) had a 90.9% (IC95% = [84.0; 97.8]) probability of preserving it at 6 months and an 84.8% (IC95% = [76.2; 93.5]) probability at last follow-up. Patients with preoperative nonfunctional vision (nonfunctional DVA or blindness) had a 19.0% (IC95% = [2.3; 35.8]) probability of recovery of functional vision at 6 months and a 23.8% (IC95% = [5.6; 42.0]) probability at last follow-up. Preoperative DVA was significantly associated with early postoperative DVA in univariate analyses (p = 0.04). Concerning the OcN, 65% of the patients experienced a postoperative dysfunction, and 78% of those cases recovered. Our study confirms EAC as a useful technical option for skull base meningiomas threatening the optic nerve, especially relevant for patients with preoperative functional vision, and supports early surgical management for these meningiomas.

Is salvage surgery for large vestibular schwannomas after failed gamma knife radiosurgery more challenging?

In order to verify whether a previous gamma knife surgery (GKS) treatment could influence the oncological and functional outcome in large vestibular schwannoma (VS) surgery, we have compared group of patients operated on for large VS after failed GKS to a group of genuine VS that underwent the same functional nerve-sparing resection technique regimen in the same period. Single center retrospective cohort study of 23 consecutive GKS failure and 170 genuine VS patients operated on between April 2003 and March 2019. After resection, patients were allocated to a Wait-&-rescan or an upfront GKS policy. At last follow-up examination, the facial nerve function was good (House-Brackmann grades I or II) in 95% of the GKS failure and 84% of the genuine VS patients (p = .25). The median volume of tumor residue was .56 cc in the GKS failure group and .62 cc in the genuine VS group (p = .70). Tumor control was achieved in 91% and 83% of cases with a mean follow-up of 74 and 63 months in the GKS failure and the genuine VS populations, respectively. The 1-, 5-, and 7-year progression-free survival were 100%, 95%, and 85% respectively in the GKS failure group and 97%, 80%, and 81% in the genuine VS group (p = .27). Despite significant modifications of the microsurgical environment associated to salvage surgery after GKS failure, a functional nerve-sparing resection is an effective strategy to optimize the results on facial nerve function, with similar long-term tumor control to those observed in the genuine VS population.

Neighborhood Disadvantage and Early Respiratory Outcomes in Very Preterm Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: To investigate the impact of neighborhood conditions on respiratory-related hospital admissions in the first year after discharge from the neonatal unit in a population of infants born very preterm with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Very preterm infants (gestational age <33 weeks) who had BPD at 36 weeks postconceptional age and who received follow-up in a French regional medical network were included. Socioeconomic context was estimated using a neighborhood-based Socioeconomic Deprivation Index. Poisson regression analysis was used to identify risk factors associated with rehospitalization. RESULTS: The study included 423 infants with a mean gestational age of 27 ± 2 weeks and mean birth weight of 941 ± 277 g; 51% of the population lived in a disadvantaged area. The hospital admission rate was increased by 8.8% for infants living in affluent areas and by 24% for those living in disadvantaged areas (P <.01) and reached 30% in extremely preterm infants from disadvantaged areas. After adjusting for perinatal characteristics, home oxygen therapy, and season of birth, the respiratory-related hospitalization rate was almost 3-fold higher in infants living in disadvantaged areas, with an adjusted incidence rate ratio of 2.79 (95% CI, 1.29-6.09; P <.01). CONCLUSIONS: Disadvantaged neighborhoods adversely impact early respiratory outcomes in infants born very preterm with BPD. The social context should be considered in routine follow-up care of children born preterm. Further studies investigating the underlying mechanisms are warranted for implementing preventive strategies.

Association of kidney biopsy findings with short- and medium-term outcomes in children with moderate-to-severe IgA vasculitis nephritis.

Assessing the initial severity of immunoglobulin A vasculitis nephritis (IgAV-N) is important due to its determining effect on kidney management and outcomes. This paper describes a multicentre paediatric cohort of IgAV-N patients and discusses relationships among clinical presentation, histological features, and kidney outcome. We retrospectively studied a cohort of 170 children with biopsy-proven IgAV-N, diagnosed between 2007 and 2017. One-quarter of the cohort (27%) presented with initial nephrotic syndrome (NS). Kidney biopsy revealed International Study of Kidney Disease (ISKDC) grade II or grade III in 83% of cases. Endocapillary proliferation was observed in 73% of patients, and chronic lesions were observed in 25%. Data analysis showed a significant association between NS at onset and endocapillary proliferation and cellular crescents. After a median follow-up of 21 months (IQR 12-39), 30% of patients had persistent proteinuria or decreased eGFR. At the end of follow-up, kidney impairment was more often observed in patients with NS at onset and those with cellular crescents and chronic lesions on initial kidney biopsy.Conclusion: This study highlights the relationship between the clinical and histological presentation of IgAV-N and the factors that affect kidney outcome. The ISKDC classification may be improved by including lesions that are more discriminating for disease severity and prognosis. What is Known: • Nephrotic syndrome (NS) or kidney failure at diagnosis and cellular crescents in more than 50% of the glomeruli are recognized as risk factors for poor kidney outcome in immunoglobulin A vasculitis nephritis (IgAV-N). • The reference histological classification of the International Study of Kidney Disease in Children (ISKDC) is primarily based on the presence and number of affected glomeruli (mesangial proliferation, cellular crescents). The updated Oxford classification, which emphasizes tubular atrophy and interstitial fibrosis, is also used to group pathological features of IgAV-N. Both classifications have limitations. What is New: • Medical treatment should not be postponed in patients with IgAV-N and NS until after biopsy, as NS at diagnosis is associated with initial histological severity and poorer kidney outcome. This proposal needs to be verified in further studies. • Endocapillary proliferation is associated with the initial severity of IgAV-N at diagnosis, while chronic glomerular changes and interstitial fibrosis are associated with poorer short- and medium-term kidney outcomes.

Ipsilateral vs controlateral approach in tuberculum sellae meningiomas surgery: a retrospective comparative study.

Most of tuberculum sellae meningiomas (TSM) show asymmetric growth. They are usually resected through ipsilateral approaches. The access of the inferior-medial side of the ipsilateral optic nerve might be challenging, which result in increased manipulation of the compromised optic nerve. The contralateral approach has been described to avoid these technical difficulties. Assessing the long-term visual and olfactory outcome, as well as recurrence rate in patients operated for TSM through ipsilateral or contralateral approaches. Single center retrospective cohort study about 94 patients operated on between March 2000 and April 2018. Seventy percent of the preoperative visual acuity loss totally resolved (44%) or showed varying degrees of improvement (26%) after surgery. Seventy-two percent of the preoperative visual field defects evolved favorably (44% recovery, 28% improvement). Eight patients showed aggravated visual disturbances (9%). A contralateral approach seemed to be predictive of visual field defects improvement after surgery (OR = 0.4), with borderline significant results (p = .08). There was a higher rate of postoperative olfactory nerve impairment after a contralateral approach (37% vs 17%, p = .03). Total removal of the tumor fragment entering the optic canal was accomplished in 96% in the contralateral vs 75% in the ipsilateral group (p = .04). The 2-, 5-, and 7-year tumor progression-free survival were 100% in the Simpson grade 2 group, and 85% (n = 17), 74% (n = 11), and 67% (n = 5) in the Simpson grade 4 group, respectively (p = .00). Resection of tuberculum sellae meningiomas through a contralateral approach seems to provide better visual outcome and tumor control at the cost of increased olfactory nerve disorders.

Chiasmapexy for secondary empty sella syndrome: diagnostic and therapeutic considerations.

PURPOSE: Secondary empty sella syndrome (SESS) following pituitary surgery remains a diagnostic and therapeutic challenge. The aim of this study was to specify the diagnostic criteria, surgical indications and results of chiasmapexy in the SESS. METHODS: Three cases from two experienced neurosurgical centers were collected and the available literature was reviewed. RESULTS: The 3 patients were operated for a giant non-functioning pituitary adenoma, a cystic macroprolactinoma, and an arachnoid cyst respectively. Postoperative visual outcome was initially improved, and then worsened progressively. At the time of SESS diagnosis, visual field defect was severe in all cases with optic nerve (ON) atrophy in 2 cases. Patients were operated via an endoscopic endonasal extradural approach. One patient was re-operated because of early fat reabsorption. Visual outcome improved in 1 case and stabilized in 2 cases. Statistical analyses performed on 24 cases from the literature review highlighted that patient age and severity of the preoperative visual defect were respectively significant and nearly significant prognostic factors for visual outcome, unlike the surgical technique. CONCLUSION: T2-weighted or CISS/FIESTA sequence MRI is mandatory to visualize adhesions, ON kinking and neurovascular conflict. TS approach is the most commonly used approach. The literature review could not conclude on the need for an intra or extradural approach suggesting case by case adapted strategy. Intrasellar packing with non-absorbable material such as bone should be considered. Severity of the visual loss clearly decreases the visual outcome suggesting early chiasmapexy. In case of severe and long standing symptoms before surgery, benefits and surgical risks should be carefully balanced.

Supportive use of platelet-rich plasma and stromal vascular fraction for cell-assisted fat transfer of skin radiation-induced lesions in nude mice.

BACKGROUND: External radiotherapy has become indispensable in oncological therapies. Unfortunately, radiation is responsible for serious side effects, such as radiodermatitis. The skin is weakened and ulcerated. Our study aimed to evaluate the subcutaneous transfer of microfat (MF) alone and two mixes: MF+Platelet-rich plasma (PRP) and MF+stromal vascular fraction (SVF) to treat radiation-induced skin lesions. METHOD: We defined randomly five experimental groups of nine mice: 1 healthy control group and 4 irradiated (60 Grey) and treated groups. The skin lesions were treated 3 months after irradiation by MF, MF+PRP (50%-50%), MF+SVF (90%-10%) or Ringer-lactate subcutaneous injections. Wound healing was evaluated at 1, 2 and 3 months post-injection and histological wound analysis at 3 months, after euthanasia. RESULTS: All the irradiated mice presented with wounds. After sham-injection, the wound area increased by 91.1±71.1% versus a decrease of 15.9±23.1% after MF alone (NS), 27.3±23.8% after MF+SVF (NS) and 76.4±7.7% after MF+PRP (P=0.032). A significative reduction of skin thickness in wound periphery was measured for the three treated groups compared to sham-injection (P<0.05) but not in the healed wounds (NS). The most important subcutaneous neo-vessel density was shown after MF+SVF injection. CONCLUSION: The MF+PRP mix was the most efficient product to increase healing. The MF+SVF mix showed the highest rate of neo-angiogenesis but was disappointing in terms of healing. LEVEL OF EVIDENCE: Not gradable.

Functional and genetic testing in adults with HLH reveals an inflammatory profile rather than a cytotoxicity defect.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition. Primary HLH occurs early in life as a result of monogenic biallelic mutations affecting lymphocyte cytotoxicity. Secondary HLH occurs mostly in adults secondary to infection, lymphoma, or rheumatic disease. In this latter setting, lymphocyte cytotoxicity status is not known. We conducted a systematic evaluation of natural killer (NK) cell cytotoxicity in adult patients with secondary HLH. Adult patients with secondary HLH were prospectively studied ex vivo for total lymphocyte count and subtype, NK cell phenotype, perforin expression and degranulation, and natural or antibody-dependent cell cytotoxicity, in comparison with patients affected by the same underlying disease without HLH (disease controls [DCs]) and with healthy controls (HCs). Screening for variants of cytotoxity genes was systematically performed. 68 patients were included in the HLH group and 34 each in the DC and HC groups. In HLH patients, severe and transient lymphopenia, activated NK cell phenotype (eg, increased CD69, ICAM-1, HLADR, and CCR5 expression), and decreased capacity of interferon γ production were observed; mean perforin expression was normal; and degranulation tests and NK cell cytotoxicity were not different from those in DCs. A monoallelic variant of uncertain significance affecting a lymphocyte cytotoxicity gene or the perforin variant A91V was observed in almost 50% of the patients. We detected no major intrinsic cytotoxicity dysfunction in secondary HLH patients compared with DCs and no predicted pathogenic gene variant. The activated NK phenotype profile associated with decreased interferon γ production seems similar to those of other hyperinflammatory diseases such as sepsis or systemic juvenile idiopathic arthritis.

Prospective study on predictability of complications by pancreatic surgeons.

PURPOSE: We evaluated the intuition of expert pancreatic surgeons, in predicting the associated risk of pancreatic resection and compared this "intuition" to actual operative follow-up. The objective was to avoid major complications following pancreatic resection, which remains a challenge. METHODS: From January 2015 to February 2018, all patients who were 18 years old or more undergoing a pancreatic resection (pancreaticoduodenectomy [PD], distal pancreatectomy [DP], or central pancreatectomy [CP]) for pancreatic lesions were included. Preoperatively and postoperatively, all surgeons completed a form assessing the expected potential occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF: grade B or C), postoperative hemorrhage, and length of stay. RESULTS: Preoperative intuition was assessed for 101 patients for 52 PD, 44 DP, and 5 CP cases. Overall mortality and morbidity rates were 6.9% (n = 7) and 67.3% (n = 68), respectively, and 38 patients (37.6%) developed a POPF, including 27 (26.7%) CR-POPF. Concordance between preoperative intuition of CR-POPF occurrence and reality was minimal, with a Cohen's kappa coefficient (κ) of 0.175 (P value = 0.009), and the same result was obtained between postoperative intuition and reality (κ = 0.351; P < 0.001). When the pancreatic parenchyma was hard, surgeons predicted the absence of CR-POPF with a negative predictive value of 91.3%. However, they were not able to predict the occurrence of CR-POPF when the pancreas was soft (positive predictive value 48%). CONCLUSIONS: This study assessed for the first time the surgeon's intuition in pancreatic surgery, and demonstrated that pancreatic surgeons cannot accurately assess outcomes except when the pancreatic parenchyma is hard.

Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial.

PURPOSE: Aggressive meningiomas that progress after surgery/radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect in vitro. The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas. PATIENTS AND METHODS: Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1-28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety. RESULTS: A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored NF2 germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%-73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%-97.4%) and 75% (95% CI, 50.0%-88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months (P < 0.0002) and 0.48%/3 months at 6 months after treatment (P < 0.0003). CONCLUSIONS: The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas.