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Neoadjuvant immune checkpoint inhibitors for patients with resectable stage III/IV melanoma: A nationwide real-life study in France (NEOMEL)
No full textInternational audienceDespite the clear therapeutic benefits of neoadjuvant treatment (NT) with immune checkpoint inhibitors (ICIs) in clinical trials, the efficacy of NT ICIs (NT-ICI) and the optimal regimen for patients (pts) with resectable metastatic melanoma (RMM) remain to be confirmed in real life. Objective To assess the efficacy and safety of NT-ICI among pts with RMM in real life. Methods NEOMEL is a French retrospective multicentric cohort study. Dermato-oncologists from the French group of skin cancers included pts treated with NT-ICI for RMM (AJCC 8th stage III or IV) between July 2016 and April 2024. Pts were treated either with NT anti-programmed cell death protein-1 (anti-PD-1) monotherapy or with the combination of anti–cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) plus anti-PD-1 (1-mg/kg ipilimumab (IPI) and 3-mg/kg nivolumab (NIVO); or 3-mg/kg IPI and 1-mg/kg NIVO). The primary endpoint was the pathological complete response (pCR) rate. The secondary endpoints were pathological response according to the International Neoadjuvant Melanoma Consortium criteria, radiological response, the occurrence of immune-related adverse events (irAEs) including those of ≥ grade 3 and outcomes with recurrence-free survivals (RFS) and event-free survivals (EFS). Results Among the 174 included pts, 149 (86%) underwent surgery. NT-ICI achieved a high pCR rate of 43% (95% CI, 34.9-51.3), including 44.7% (95% CI, 35.4–54.3) with NT-anti-PD-1 and 37.1% (95% CI, 21.5–55.1) with NT-IPI-NIVO (p=0.427). The major (complete + near-complete) pathological response rate was 53.2%. Radiological responses were observed in 49.9% of pts, including 12 complete responses (12.1%), of which 91.7% (n=11) corresponded to pCR. Severe immune-related adverse events (irAEs) occurred more frequently with NT-IPI-NIVO (24.4%) compared to NT-anti-PD-1 (3.1%) (p<0.001). The median RFS was 29.61 months (95% CI, 27.70-not reached [NR]) with significantly higher RFS in pts with pCR than no-pCR (HR, 0.218 [95% CI, 0.082–0.583], p=0.0009). The median EFS was 35.7 months 2 (95% CI, 28-NR). Conclusion In this retrospective real-life study, NT-ICI confirms its efficacy in RMM pts, achieving high pathological response rates. However, dual checkpoint inhibition with IPI-NIVO was associated with a higher risk of severe irAEs. These findings underscore the relevance of NT-ICI for RMM in clinical practice and required further confirmation
Defibrillation Testing During Implantation of Subcutaneous Implantable Cardioverter Defibrillators
No full textInternational audienceBackground: Defibrillation testing (DT) remains recommended during subcutaneous implantable cardioverter defibrillator (S-ICD) implantation due to limited supporting evidence.Objectives: The objective of this study was to evaluate the long-term impact of DT during S-ICD implantation.Methods: The HONEST (coHOrte fraNcaise des dEfibrillateurs Sous cuTanés) study is a nationwide, ongoing observational study, including all S-ICD recipients in France (2012-2019). Five-year endpoints were centrally adjudicated, and propensity score-weighted analyses compared outcomes by DT status.Results: Among 4,924 patients, DT was performed in 4,066 (82.6%), decreasing from 85.4% (2012-2014) to 66.9% in 2019 (P < 0.001). Nontested patients were older (51.2 vs 49.6 years; P = 0.007), had lower left ventricular ejection fraction (37.6% vs 43.3%; P < 0.001), and were more frequently implanted for primary prevention (68.0% vs 62.4%; P = 0.002) and structural heart disease (84.9% vs 76.8%; P < 0.001). DT-related complications occurred in 0.1%, including 2 deaths. Failure rate was 1.0%, with 87.8% undergoing corrective reinterventions. Independent predictors of DT failure were elevated shock impedance (≥89 Ω; OR: 4.60; 95% CI: 2.32-9.66; P < 0.001) and obesity (body mass index ≥30 kg/m2; OR: 2.17; 95% CI: 1.01-4.55; P = 0.007). After adjustment, DT omission was not associated with increased risks of overall mortality (HR: 1.17; 95% CI: 0.86-1.61; P = 0.313), cardiovascular mortality (HR: 1.04; 95% CI: 0.70-1.56; P = 0.846), sudden cardiac death (HR: 0.27; 95% CI: 0.04-1.72; P = 0.167), and appropriate (HR: 1.01; 95% CI: 0.78-1.30; P = 0.945) or inappropriate shocks (HR: 0.98; 95% CI: 0.78-1.23; P = 0.865). Combined rates of ineffective shocks or undetected ventricular arrhythmias were similar (0.05 vs 0.06 per 100 person-years).Conclusions: Our findings suggest that DT can be safely omitted in the majority of S-ICD recipients, whereas selective DT may be considered in higher-risk subgroups. (S-ICD French Cohort Study (HONEST); NCT05302115)
Mechanical Insufflation-Exsufflation in Older In-Patients With Impaired Cough
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“The captain wanted to stay with the sinking … (can't say boat)”: How hypomanic personality traits interfere with inhibitory control?
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Risk of refeeding syndrome: an observational study in primary healthcare
No full textInternational audienceBackground: Refeeding syndrome (RFS) is a complex phenomenon associated with increased mortality. However, the prevalence of risk factors for RFS has never been assessed in primary care. Our aim was to assess the prevalence of risk for developing RFS in primary care.Methods: A retrospective observational study was conducted in a general practitioner (GP) surgery in June 2022. The study included older adult patients (aged ≥75 years) or adult patients with chronic disease (aged 18-74 years), living at home and receiving care at home or at the GP's surgery between January 1 and June 30, 2021. Patients at high risk of developing RFS were identified using the National Institute for Health and Clinical Excellence (NICE) criteria. The risk of RFS was also assessed in patients aged ≥70 years using an adaptation of the NICE criterion for body mass index based on the Global Leadership Initiative on Malnutrition guidelines.Results: The prevalence of patients at risk for RFS was 2.8% (95% CI: 1.5%-4.1%) in the full population of 611 patients and 8.8% (95% CI: 6.1%-6.4%) in the subset of patients aged ≥70 years assessed using the adapted NICE criterion. The prevalence of patients at risk for RFS increased with age and chronic conditions. More severe comorbidity and home care were factors associated with higher risk of RFS.Conclusion: The risk of developing RFS in primary care settings is not negligible. GPs should consider this risk in their practice to develop a more comprehensive care programme
Benefit of splenectomy in distal pancreatectomy for neuroendocrine tumours: multicentre retrospective study
No full textInternational audienceBackground: Distal pancreatectomy is frequently indicated for left-sided pancreatic neuroendocrine tumour (NET). When combined lymphadenectomy is warranted, distal pancreatectomy with splenectomy (DPS) is generally advocated to optimize lymph node dissection. The spleen-preserving distal pancreatectomy (SPDP) may represent an alternative approach. This study aimed to evaluate postoperative and oncological results of distal pancreatectomy with and without splenectomy for pancreatic NET.Methods: This multicentre retrospective study included all distal pancreatectomy for pancreatic NET performed between 2014 and 2018. Patients with functional NET or multiple endocrine neoplasia type 1 were excluded. Indications and results were compared between DPS, distal pancreatectomy according to Kimura (K-SPDP) and distal pancreatectomy according to Warshaw (W-SPDP), before and after propensity score matching (PSM).Results: Among 251 patients included (108 DPS (43%), 73 K-SPDP (29%), and 70 W-SPDP (28%)), there was no difference in terms of patients' characteristics, surgical approach, and conversion. Tumour size (P = 0.005), grade (P < 0.001) and the number of nodes analysed (P < 0.001) were significantly lower in patients undergoing K-SPDP as compared to W-SPDP or DPS. Apart from a difference in readmission rate (P = 0.002), there was no difference in terms of mortality rate or severe morbidity rate between the three techniques. After PSM comparing DPS (n = 70) and W-SPDP (n = 70), there was no difference in morbidity and mortality rates. R0 resection rate (91% versus 97%; P = 0.165), the number of nodes analysed (8 versus 7; P = 0.495), and median overall survival (P = 0.493) were not different.Conclusion: In cases of distal pancreatectomy for NET, splenectomy did not seem to improve lymph node dissection or survival. When lymph node dissection associated with distal pancreatectomy is justified, the benefit of splenectomy appears questionable
Caries risk assessment by dental students and dentists in the Netherlands – a survey study to assess knowledge and implementation
No full textInternational audienceIntroduction: To prevent caries with targeted strategies and to act conservatively, it is essential oral healthcare providers perform an individual caries risk assessment (CRA). This study aimed to explore knowledge and application regarding CRA by Dutch fifth-year dental students (D5DSs) and practitioners (DDPs). Methods: A survey was conducted through a questionnaire sent at random to a group of 1,500 members of the Royal Dutch Dental Association (KNMT) and to 213 D5DSs from all three dental schools in the Netherlands. Results: Of the 374 DDP respondents (25%), 79% reported to perform CRA in routine practice. Female dentists reported using CRA in their daily practice more often than males (p = 0.008). The questionnaire was completed by 118 D5DSs (55%). All D5DS respondents reported using CRA and most students were familiar with Dutch prevention-oriented methods. Eighteen percent of them did not make an individual treatment plan based on caries risk. The familiarity of DDPs regarding Dutch prevention-oriented methods was lower than that of students (p < 0.001). In both groups of respondents, oral hygiene and diet were the two most important factors considered when assessing caries risk in patients, whatever their age. Conclusion: CRA is applied less frequently in the general practice compared to student clinics at university. Our results suggest that dentists in the Netherlands could improve their knowledge about cariology by continuing education. Dental schools should emphasize implementation of the knowledge in clinical practice. In addition, a uniform and evidence-based method to perform CRA in the dental practice is needed.</div
Antimony used as rescue therapy in a kidney transplant recipient unresponsive to liposomal amphotericin B for chronic visceral leishmaniasis
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Intra-arterial hepatic chemotherapy in metastatic colorectal cancer: differences between oxaliplatin-naive versus oxaliplatin-pretreated patients
No full textInternational audienceBackground: Oxaliplatin-based hepatic arterial infusions (HAI) combined with intravenous therapy is a therapeutic option for colorectal cancer with liver-only metastasis, notably in the palliative setting, either initially or after failure of systemic chemotherapy. Our study aimed to assess efficacy and tolerance between oxaliplatin-naive patients and oxaliplatin-pretreated patients. Methods: Between 2008 and 2022, single-center consecutive patients presenting with liver metastasis secondary to colorectal cancer who received at least one cycle of HAI-oxaliplatin combined with systemic therapy were included. Results: The oxaliplatin-naive arm included 63 patients (median age 58 years) and the pretreated arm included 244 patients (median age 53 years). Patient characteristics were well balanced between the groups. All patients in the oxaliplatin-naive arm received HAI-oxaliplatin while 13% of the pretreated patients received HAI-FOLFIRINOX. After a median follow-up of 36 months, median progression-free survival was 14 months in the oxaliplatin-naive group (range 11.8-24 months) and 10.1 months in the pretreated group (range 9.4-12.5 months) (P ¼ 0.016). The objective response rate was 66.7% and the disease control rate was 79.4% in the oxaliplatin-naive group, versus 32.4% and 77.5% (P < 0.001) in the pretreated group. Grade 3-4 toxicities were comparable between the two groups, including neuropathy. Secondary resection/ablation rate was 22.2% in oxaliplatin-naive patients and 17.6% in pretreated patients. Conclusion: Oxaliplatin use as an intra-arterial hepatic infusion is feasible and efficient after previous systemic oxaliplatin; it showed significant response rates without increased toxicities. It can provide alternative treatments and spare late-setting drugs such as regorafenib and tipiraciletrifluridine for a further palliative intent treatment.</div
Sarcopenia, myosteatosis and inflammation are independent prognostic factors of SARS-CoV-2 pneumonia patients admitted to the ICU
No full textInternational audienceThe aims of our study were to assess the correlations between sarcopenia and myosteatosis assessed by CT-scan at T4 and/or L3 levels and inflammation in critically ill COVID patients on ICU admission, and their respective prognostic value on day 90 death (D90-death). It is a retrospective monocentric study. Sarcopenia was defined by skeletal muscle cross sectional surface area (CSA) and myosteatosis by skeletal muscle density (SMD) at L3 and T4 levels. Inflammatory biomarkers were collected on ICU admission. Of the 239 patients, 74 died by D90; 66.6% get sarcopenia on ICU admission. CSA at T4 level was an independent risk factor for D90-death (1.66[1.03; 2.66]; p = 0.04), as were procalcitonin (2.03[1.2; 3.43]; p = 0.01) and IL-6 levels (1.56[0.96; 2.54]; p = 0.07). In addition, we found correlation factors of 0.79 (p < 0.01) between SMD at T4 and L3 levels, and a correlation factor of 0.64 (p < 0.01) between CSA at T4 and L3 levels.These results indicate a poorer prognosis following a decrease in muscle surface area, a decrease in density, and an increase in inflammatory biomarkers such as Il6. It also suggests that incorporating indices of sarcopenia with inflammatory biomarkers may improve prognostic accuracy