Marseille University Hospital Research Articles

F2c.*C20209T mutation in patients with a history of thrombosis: A case report, retrospective 2 site-results and review of the literature.

G20210A (c.*97G>A) prothrombin gene variant, found in white population has been associated with an increased risk of venous thromboembolism (VTE). Other rare polymorphisms in F2 gene (C20209T) have been reported, more rare and touching black people, but its potential association with VTE remain uncertain. About a 69 years-old Caucasian woman presenting an unprovoked deep venous thrombosis of the leg, we analyzed retrospectively 25.000 thrombophilia tests on a 11-year period of time (2007-2018), at Nice and Marseille University Hospitals, and performed extensive review of the literature. Genetic determination included a similar PCR protocol and sequencing. Twenty-one heterozygous cases out of 25.585 determinations (0.08%) was found. The C20209T mutation detected in our Caucasian patient is rare, with a frequency that differed from what was reported in the previous literature, mainly in non-Caucasian patients (Africans, Africans-Americans, and Caribbeans). One hundred and thirteen patients with this mutation have been described in the literature, of which only one homozygous. This study is the most important on C20209T mutation performed at present, allowing to precise its frequency and its potential role in venous thromboembolism.

Risk factors associated with progression from papilloedema to optic atrophy: results from a cohort of 113 patients

BackgroundThe aim of this study was to assess the risk factors for atrophic progression of patients with papilloedema secondary to intracranial hypertension, using optical coherence tomography parameters.MethodsA retrospective study was...

Identification of Follow-Up Markers for Rehabilitation Management in Patients with Vestibular Schwannoma.

This study delves into the absence of prognostic or predictive markers to guide rehabilitation in patients afflicted with vestibular schwannomas. The objective is to analyze the reweighting of subjective and instrumental indicators following surgery, at 7 days and 1 month postoperatively. This retrospective cohort encompasses 32 patients who underwent unilateral vestibular schwannoma surgery at the Marseille University Hospital between 2014 and 2019. Variations in 54 indicators and their adherence to available norms are calculated. After 1 month, one-third of patients do not regain the norm for all indicators. However, the rates of variation unveil specific responses linked to a preoperative error signal, stemming from years of tumor adaptation. This adaptation is reflected in a postoperative visual or proprioceptive preference for certain patients. Further studies are needed to clarify error signals according to lesion types. The approach based on variations in normative indicators appears relevant for post-surgical monitoring and physiotherapy.

Temporal Shift of the Respiratory Syncytial Virus Epidemic Peak for the Years 2020-2023 in Marseille, Southern France.

Respiratory syncytial virus is among the most common causes of respiratory infections. Typically, this viral infection has a seasonality during the cold months but with the SARS-CoV-2 pandemic this has been considerably modified. Here, we studied the epidemiology of this virus in university hospitals of Marseille, South of France, over the period 2020 to 2023. We tested in our laboratory from July 2020 to October 2021 16,516 nasopharyngeal swabs from 16,468 patients for RSV infection using different qPCR assays. We then analyzed data from previous and subsequent winters (from 2018 to 2023) and previous summers (from 2015 to 2021). A total of 676 patients were RSV-positive; their mean age was 3 years and 91 were under 5 years of age. We observed a delay of 4 months of the RSV epidemic's onset compared to other years with an epidemic that peaked in March 2021. We had significantly more RSV-positive cases during summer 2021 compared to previous summers, whereas the incidence of RSV infections was not significantly higher during winter 2022 versus previous winters. Moreover, 494 patients were diagnosed as RSV-positive in the emergency unit and 181 were subsequently hospitalized, and 34 patients were diagnosed RSV-positive while already in the intensive care unit. Over all the study periods, 38 patients diagnosed as RSV-positive died, the majority of whom (23/28) were over 65 years of age. These data show an atypical evolution of the incidence of RSV infections in our city and is another example of the unpredictability of infectious disease epidemiology.

Impact of cardiac surgery on left-sided infective endocarditis with intermediate-length vegetations

ObjectiveThe best strategy to manage patients with left-sided infective endocarditis (IE) and intermediate-length vegetations (10–15 mm) remains uncertain. We aimed to evaluate the role of surgery in patients with intermediate-length...

Dynamics of community-acquired meningitis syndrome outbreaks in southern France.

In southern France, cases of community-acquired meningitis syndrome (CAM) are typically clustered as outbreaks with determinants which remain unknown. This 61-month retrospective investigation in Nîmes and Marseille university hospital laboratories, yielded 2,209/20,779 (10.63%) documented CAM cases caused by 62 different micro-organisms, represented by seasonal viral etiologies (78.8%), including Enterovirus, Herpes Simplex Virus (HSV), and Varicella-Zoster Virus (VZV; 1,620/2,209 = 73.4%). Multi correspondence analysis revealed an association of infection with age and sex, with the risk of infection being relatively higher in young men, as confirmed by Fisher's exact test (p < 10-3). Bacterial meningitis accounted for 20% of cases, mostly caused by Streptococcus pneumoniae (27.4% of cases), Neisseria meningitidis (12.5%), and Haemophilus influenzae (9.5%) with bacteria/virus coinfection (0.9%), and only six cases of documented fungal meningitis. In total, 62.6% of cases, of which 88.7% were undocumented, arose from 10 outbreaks. 33.2% of undocumented cases were aged >60 years compared to 19.2% of documented cases (p < 0.001), and viral infection was more common in the summer (87.5%) compared to other seasons (72.3%; p < 0.001). Outbreaks most often started in Nîmes and moved eastward toward Marseille at a speed of ~9 km/day, and these dynamics significantly correlated with atmospheric temperature, especially during summer outbreaks. In particular, the incidence of Enterovirus-driven outbreaks correlated with temperature, revealing correlation coefficients of 0.64 in Nîmes and 0.72 in Marseille, and its occurrence in Marseille lagged that in Nîmes by 1-2 weeks. Tracing the dynamics of CAM outbreak during this retrospective investigation in southern France yielded a speed of displacement that correlated with the variation in temperature between both cities, and these results provide clues for the next occurrence of undocumented outbreaks.

Correlation between assessment of cytochrome P450 1A2 activity and enzyme activity scores, and their relation to clozapine exposure.

Cytochrome P450 1A2 (CYP1A2) is involved in the metabolism of antipsychotic drugs such as clozapine and olanzapine. Personalization of these treatments requires an accurate estimation of CYP1A2 activity. In this study, we aimed (1) to evaluate the correlation between activity score (AS), covariate-corrected activity score (CCS) and the phenotype of CYP1A2 using a caffeine test probe and (2) to investigate their relationship with dose-adjusted clozapine concentrations in a subgroup of the cohort. A multicentric, retrospective and observational study was carried out in the French university hospitals of Marseille and Tours. CYP1A2 activity was calculated by the paraxanthine/caffeine (17X/137X) ratio determined 4h after an oral intake of 100 mg caffeine. AS was calculated according to the CYP1A2*1F alleles. CCS was calculated according to the CYP1A2*1F alleles, smoking status and the presence of concomitant inhibitors. As expected, among the 89 patients included, the 17X/137X ratio was significantly higher in patients who smoked. We found a significant but modest correlation between the 17X/137X ratio and CCS (R2 = 0.3, P = 1.74 × 10-8 ) but none between the 17X/137X ratio and AS (R2 = -0.007, P = 0.52). AS was not correlated with dose-adjusted clozapine levels, contrary to CCS (R2 = 0.19, P = 0.016) and especially the 17X/137X ratio (R2 = 0.42, P = 1.7 × 10-5 ). Correlation with clozapine concentrations showed the advantage of the 17X/137X ratio over the CCS in clozapine dose optimization. CYP1A2 activity, especially when determined by the caffeine probe, may be used to personalize clozapine dosing for patients experiencing treatment failure.

A 21L/BA.2-21K/BA.1 "MixOmicron" SARS-CoV-2 hybrid undetected by qPCR that screen for variant in routine diagnosis.

Among the multiple SARS-CoV-2 variants identified since summer 2020, several have co-circulated, creating opportunities for coinfections and potentially genetic recombinations that are common in coronaviruses. Viral recombinants are indeed beginning to be reported more frequently. Here, we describe a new SARS-CoV-2 recombinant genome that is mostly that of a Omicron 21L/BA.2 variant but with a 3′ tip originating from a Omicron 21K/BA.1 variant. Two such genomes were obtained in our institute from adults sampled in February 2022 in university hospitals of Marseille, southern France, by next-generation sequencing carried out with the Illumina or Nanopore technologies. The recombination site was located between nucleotides 26,858-27,382. In the two genomic assemblies, mean sequencing depth at mutation-harboring positions was 271 and 1362 reads and mean prevalence of the majoritary nucleotide was 99.3 ± 2.2% and 98.8 ± 1.6%, respectively. Phylogeny generated trees with slightly different topologies according to whether genomes were depleted or not of the 3′ tip. This 3′ terminal end brought in the Omicron 21L/BA.2 genome a short transposable element of 41 nucleotides named S2m that is present in most SARS-CoV-2 except a few variants among which the Omicron 21L/BA.2 variant and may be involved in virulence. Importantly, this recombinant is not detected by currently used qPCR that screen for variants in routine diagnosis. The present observation emphasizes the need to survey closely the genetic pathways of SARS-CoV-2 variability by whole genome sequencing, and it could contribute to gain a better understanding of factors that lead to observed differences between epidemic potentials of the different variants.

Acceptance, efficacy, and safety of COVID-19 vaccination in older patients with cancer

PurposeThe COVID-19 vaccination campaign began in December 2020, in France, and primarily targeted the oldest people. Our study aimed to determine the level of acceptance of vaccination in a population of older patients with cancer. MethodsFrom January 2021, we offered vaccination with the BNT162b2 COVID-19 vaccine to all patients 70 years and older referred to our geriatric oncology center in Marseille University Hospital (AP-HM) for geriatric assessment before initiation of an oncological treatment. Objectives were to evaluate acceptance rate of COVID-19 vaccination and to assess vaccine safety, reactogenicity, and efficacy two months after the first dose. ResultsBetween January 18, 2021 and May 7, 2021, 150 older patients with cancer were offered vaccination after a geriatric assessment. The majority were men (61.3%), with a mean age of 81 years. The two most frequent primary tumors were digestive (29.4%) and thoracic (18%). The vaccine acceptance rate was 82.6% and the complete vaccination rate (2 doses) reached 75.3%. Among the vaccinated patients, 15.9% reported mild side effects after the first dose and 23.4% after the second dose, mostly arm pain and fatigue. COVID-19 cases were observed in 5.1% of vaccinated patients compared with 16.7% in unvaccinated patients. Of the 22 vaccinated patients who agreed to have their serum tested, 15 had antibodies against the spike protein at day 21 after the first dose. ConclusionOur study showed a high acceptance rate of COVID-19 vaccination, with good tolerance in this frail population. These results highlight the benefits of organizing vaccination campaigns at the very beginning of oncological management in older patients.Clinical trial registration: This study was registered May 23, 2019 in ClinicalTrials.gov (NCT03960593).

Herpetic encephalitis: which treatment for which body weight?

Prognosis of herpetic encephalitis remains severe, with a high proportion of deaths and sequelae. Its treatment is based on acyclovir, but the precise and most effective modalities of this treatment are not established. The objective of this study was to determine them. For this, we carried out a descriptive, retrospective, monocentric study, using the current coding database at Marseille University Hospitals. Cohort was intended to be exhaustive for the disease, from January 2000 to June 2019, including patients hospitalized in intensive care and conventional hospitalization sector. Patients (n = 76) included were at least 16years of age and had a clinical presentation, cerebral Magnetic Resonance Imaging, and/or electroencephalogram abnormalities consistent with herpetic encephalitis confirmed by a positive HSV-PCR in the CSF. Clinical data and treatment, including the doses actually administered to the patient, were compared according to patient's outcome. The mortality rate was 12%, whereas 49% had complete recovery and 39% sequelae impeding independence. Poor outcome was statistically associated with persistence of confusion, aphasia, and impaired consciousness lasting more than 5days, superinfection, status epilepticus, and length of stay in intensive care unit. A statistical decision tree, constructed using the Classification And Regression Tree model, to prioritize treatment management, showed two main factors that influence the outcome: the patient's weight, and the average daily acyclovir dose actually administered. These results suggest to modify acyclovir management in herpetic encephalitis, for low-weight patients (< 79kg) with a minimum dosage of 2550mg/day (850mg/ 8h), when possible.

HoSAGE: sarcopenia in older patient with intermediate / high-risk prostate cancer, prevalence and incidence after androgen deprivation therapy: study protocol for a cohort trial

BackgroundSarcopenia is defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. Ageing greatly contributes to sarcopenia as may many other factors such as cancer or androgen deprivation therapies (ADT). This cohort study aims to evaluate (1) the prevalence of muscle disorders and sarcopenia in older patients before initiation of intermediate to high risk prostate cancer treatment with ADT and radiotherapy, and (2) the occurrence and/or aggravation of muscle disorders and sarcopenia at the end of cancer treatment.MethodsThis cohort study is monocentric and prospective. The primary objectives are to determine the risk factor of sarcopenia prevalence and to study the relationship between ADT and sarcopenia incidence, in patients 70 years and older with histologically proven localized or locally advanced prostate cancer, addressed to a geriatrician (G8 score ≤14) for comprehensive geriatric assessment (CGA) in Marseille University Hospital. Secondary objectives encompass, measurement of sarcopenia clinical criteria along prostate oncological treatment; evaluation of the quality of life of patients with sarcopenia; evaluation of the impact of socio-behavioral and anthropological factors on sarcopenia evolution and incidence; finally the evaluation of the impact of ADT exposure on sarcopenia. Sarcopenia prevalence was estimated to be between 20 and 30%, therefore the study will enroll 200 patients.DiscussionThe current guidelines for older patients with prostate cancer recommend a pelvic radiotherapy treatment associated to variable duration (6 to 36 months) of ADT. However ADT impacts muscle mass and could exacerbate the risks of sarcopenia. Our study intends to assess the specific effect of ADT on sarcopenia incidence and/or worsening as well as to estimate sarcopenia prevalence in this population. The results of this cohort trial will lead to a better understanding of sarcopenia prevalence and incidence necessary to further elaborate a prevention plan.Trial registrationThe protocol was registered to the French drug and device regulation agency under the number 2019-A02319-48, before beginning the study (11/12/2019). The ClinicalTrials.gov identifier is NCT04484246, registration on the ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04484246).

Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients.

Simple SummaryDecisions on cancer treatment for older patients take into account not only comorbidities but also physical and cognitive resources. Comprehensive geriatric assessment (CGA) in older patients assesses geriatric frailties but does not include standardized biological tests. The B12/CRP index (BCI) was first intended as a prognosis tool to predict 90-day mortality after advanced cancer diagnosis. This study shows the prognostic link between BCI value and overall cancer survival time in older people, and the association between BCI value and geriatric frailty before cancer treatment in this population.Background: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. Method: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. Results: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 < BCI ≤ 40,000) and high-BCI (BCI > 40,000) groups (HR = 0.327, CI95% [0.26–0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. Conclusion: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment.

Incidence and Outcome of Coinfections with SARS-CoV-2 and Rhinovirus.

Background: We aimed to compare the clinical severity in patients who were coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and rhinovirus or monoinfected with a single one of these viruses. Methods: The study period ranged from 1 March 2020 to 28 February 2021 (one year). SARS-CoV-2 and other respiratory viruses were identified by real-time reverse-transcription-PCR as part of the routine work at Marseille University hospitals. Bacterial and fungal infections were detected by standard methods. Clinical data were retrospectively collected from medical files. This study was approved by the ethical committee of our institute. Results: A total of 6034/15,157 (40%) tested patients were positive for at least one respiratory virus. Ninety-three (4.3%) SARS-CoV-2-infected patients were coinfected with another respiratory virus, with rhinovirus being the most frequent (62/93, 67%). Patients coinfected with SARS-CoV-2 and rhinovirus were significantly more likely to report a cough than those with SARS-CoV-2 monoinfection (62% vs. 31%; p = 0.0008). In addition, they were also significantly more likely to report dyspnea than patients with rhinovirus monoinfection (45% vs. 36%; p = 0.02). They were also more likely to be transferred to an intensive care unit and to die than patients with rhinovirus monoinfection (16% vs. 5% and 7% vs. 2%, respectively) but these differences were not statistically significant. Conclusions: A close surveillance and investigation of the co-incidence and interactions of SARS-CoV-2 and other respiratory viruses is needed. The possible higher risk of increased clinical severity in SARS-CoV-2-positive patients coinfected with rhinovirus warrants further large scale studies.

Increased Gray Matter Density in the Right Mesencephalic Tegmentum Is Associated With Better Engel Classes I and II After Radiosurgery for Hypothalamic Hamartomas.

Hypothalamic hamartomas (HHs) are disabling congenital lesions, responsible for gelastic seizures frequently associated with catastrophic epilepsies, epileptogenic encephalopathy, and cognitive and psychiatric severe comorbidities. Stereotactic radiosurgery (SRS) is a well-established minimally invasive therapeutic approach. To assess whether pretherapeutic gray matter density (GMD) correlates with seizure outcome. We used voxel-based morphometry at whole-brain level, as depicted on pretherapeutic standard structural magnetic resonance neuroimaging. We examined 24 patients (10 male patients, 14 female patients; mean age, 12.7 yr; median, 9; range, 5.9-50) treated in Marseille University Hospital, France, between May 2001 and August 2018. Most relevant anatomic area predicting postoperative Engel classes I and II vs III and IV after SRS for HHs was mesencephalic tegmentum. Higher pretherapeutic GMD in this area was associated with better outcomes for seizure cessation. The only other statistically significant clusters were right cerebellar lobule VIIIb and VIIIa. Lower pretherapeutic GMD in both clusters correlated with better Engel class outcomes. GMD decreased with age in the left mediodorsal thalamus. Seizure cessation after SRS for HHs was associated with higher GMD in mesencephalic tegmental area, acknowledged to be involved in the neural control of explosive vocal behavior in animals. This area is connected by the mamillotegmental bundle to the lateral tuberal nucleus area of the hypothalamus, where HHs are known to rise. In the future, the detection of more gray matter in this "laugh" tegmental area based on pretherapeutic routine structural neuroimaging might help in patient selection for minimally invasive radiosurgery for HH.

Acquired diaphragmatic hernia after hepatectomy and liver transplantation in adults and children: A case series and literature review.

Backgrounds/AimsAcquired diaphragmatic hernia is a rare complication following liver surgery in adult and pediatric patients. This study aims to describe main features occurring in adult and pediatric patients after liver surgery and report an up-date review of the literature.MethodsAll adult and pediatric patients who were diagnosed with postoperative acquired diaphragmatic hernia in Lyon and Marseille University Hospitals were included in this study. Diagnosis, clinical, radiologic, and therapeutic data were analysed retrospectively from medical papers and/or electronic records.ResultsThirteen adults with a median age of 50 years (range, 30–67 years) and 5 children aged 2.4 years (range, 0.9–4 years) were diagnosed with acquired diaphragmatic hernia after a median time of 65.1 (range, 1.8–244.7) and 2 (range, 0.33–10.9) months, respectively, following surgeries (5 live-donor right hepatectomies, 5 right and 1 left hepatectomies for tumors and cysts, and 2 whole liver transplantations in adults; and 5 liver transplantations with left lateral section in children). Eleven patients presented digestive and/or thoracic symptoms whereas seven were asymptomatic and diagnosed by routine imaging follow-up. All patients were re-operated with a median delay of 2.4 months (range, 0–25.3 months) for adults and 1 day (range, 0–2 days) for children. Two recurrences resulted in a secondary surgical repair.ConclusionsAcquired diaphragmatic hernia is a rare and potentially serious event after liver surgery. Recognition and surgical repair of this particular complication should be considered in the setting of unexplained abdominal and/or thoracic symptoms. Preventive measures should be taken intraoperatively.

Prognostic study in patients with repaired Tetralogy of Fallot (TOF) who underwent pulmonary valve replacement (PVR) for pulmonary regurgitation (PR) at a “senior” age

The optimal timing for surgical management of severe PR in patients with repaired TOF is still controversial due to lack of prognostic data. Due to ageing of this population we wanted to analyse the prognostic factors associated with this surgery at a “senior” age. The aim of this study was to define clinical and paraclinical criteria associated with morbidity-mortality of RVP in “senior” patients with repaired TOF. We conducted a single-centre, retrospective study of 48 patients aged 30 years old and above with repaired TOF who underwent RVP at Marseille University Hospital from January 2009 to December 2018. RVP for other congenital cardiopathy or endocarditis and RVP for TOF in patients younger than 30 years old were excluded. The primary outcome was to assess morbidity-mortality with composite criterion including supraventricular arrhythmia, rehospitalization due to any cardiologic cause or death due to any cause. Mean age at PVR was 41 ± 9.8 years old. Mean patient follow-up was 52 months. Twenty-three (48%) patients had the primary outcome. Preoperative signs of late management of patients with repaired TOF complicated of PR, whether left ventricular dysfunction on echocardiography ( P = 0.005), right heart failure ( P = 0.002), syncope or ventricular tachycardia ( P = 0.006), are associated with increased postoperative morbidity-mortality. In multivariate analysis, only elevated right ventricular end-diastolic pressure (RVEDP) was associated with our primary outcome. Preoperative right ventricular volumes on MRI were not associated with our primary endpoint. RVEDP was a risk factor for postoperative morbidity-mortality of PVR. Right heart catheterization could be helpful in deciding the best timing for PVR in “senior” patients with repaired TOF. Our study supports recent research highlighting the limitations of considering right ventricular volumes in MRI as a therapeutic target.

Cytomegalovirus Viral Load in Transplanted Patients Using the NeuMoDx™ (Qiagen) Automated System: A 1-Month Experience Feedback

Cytomegalovirus (CMV) reactivations represent a significant morbidity and mortality problem in transplant patients. Reliable and rapid measurement of CMV viral load is a key issue for optimal patient management. We report here the evaluation of NeuMoDx™ (Qiagen) in a routine hospital setting (University Hospitals of Marseille, France) in comparison with our classical reference technique R-GENE. During one month, 719 CMV viral loads from 507 patients were measured in parallel in both techniques. Using the ROC (receiver operating characteristic) curve and our biological experience we suggest that values <52 IU/mL (geometric mean) correspond to negative samples, values >140 IU/mL (Fowlkes–Mallows index) correspond to quantifiable positive results and values ranging from 52 to 140 IU/mL represent non-quantifiable positive results. Follow-up of 15 transplant patients who developed CMV reactivation during the study showed that NeuMoDx™ provided higher viral load measurement during the first two weeks of follow-up for three patients. These important intra-individual variations resulted in a significant median increase considering the whole data set (6.7 points of difference expressed as a percentage of the initial viral load). However, no difference between the two techniques was noticeable after two weeks of treatment. Subsequent to this first study we conclude that NeuMoDx™, used with optimized logistics and an adapted threshold, allows a rapid CMV viral load measurement and that its use does not lead to any difference in patient management compared to the reference technique R-GENE®.

Functional status in older patients with cancer

BackgroundFunctional Status (FS) is an important domain in Comprehensive Geriatric Assessment (CGA) and is most often evaluated using the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales separately. Method and objectivesThis secondary analysis of a previous prospective cohort study was conducted between September 2015 and May 2018 at Marseille University Hospital, France, on 613 cancer outpatients aged ≥70 years.The first objective of this study was to determine the prevalence of FS impairment in older outpatients with cancer using a combination of the information collected with the ADL and short IADL scales. Our second objective was to describe the potential impact of this combined FS on three-month unplanned hospitalizations and three-month mortality in this population. ResultsThe median age was 81 years and 61.2% were men. The most common types of tumours were lung and thoracic (22.3%). Concerning FS, 255 patients (41.6%) had unimpaired ADL-IADL, 131 patients (21.4%) had IADL impairment, 38 patients (6.2%) had ADL impairment, and 189 patients (30.8%) had impaired ADL-IADL. In the multivariate Cox analysis, metastatic stage (adjusted Hazard Ratio (aHR) = 1.79; 95% CI [1.14–2.80]) and impaired ADL-IADL (aHR = 3.46; 95% CI [1.89–6.33]) were independently associated with three-month mortality. In the logistic regression model, impaired ADL-IADL (adjusted Odd ratio (aOR) = 3.64; 95% CI [1.84–7.20]) was the only factor independently associated with three-month unplanned hospitalizations. InterpretationThe combined use of the ADL and IADL scales to evaluate functional status in older patients with cancer is of significant prognostic value regarding the risks of three-month unplanned hospitalizations and mortality.

Beta-lactam allergy labeling in intensive care units: An observational, retrospective study.

This retrospective study aimed to describe the association between the “β-lactam allergy” labeling (BLAL) and the outcomes of a cohort of intensive care unit (ICU) patients.Retrospective cohort study.Seven ICU of the Aix Marseille University Hospitals from Marseille in France.We collected the uses of the label “β-lactam allergy” in the electronic medical files of patients aged 18 years or more who required more than 48 hours in the ICU with mechanical ventilation and/or vasopressors admitted to 7 ICUs of a single institution.We retrospectively compared the patients with this labeling (BLAL group) with those without this labeling (control group).The primary outcome was the duration of ICU stay. Among the 7146 patients included in the analysis, 440 and 6706 patients were classified in the BLAL group and the control group, respectively. The prevalence of BLAL was 6.2%. In univariate and multivariate analyses, BLAL was weakly or not associated with the duration of ICU and hospital stays (respectively, 6 [3–14] vs 6 [3–14] days, standardized beta −0.09, P = .046; and 18 [10–29] vs 15 [8–28] days, standardized beta −0.09, P = .344). In multivariate analysis, the ICU and 28-day mortality rates were both lower in the BLAL group than in the control group (aOR 0.79 95% CI [0.64–0.98] P = .032 and 0.79 [0.63–0.99] P = .042). Antibiotic use differed between the 2 groups, but the outcomes were similar in the subgroups of septic patients in the BLAL group and the control group.In our cohort, the labeling of a β-lactam allergy was not associated with prolonged ICU and hospital stays. An association was found between the labeling of a β-lactam allergy and lower ICU and 28-day mortality rates.Trial registration: Retrospectively registered.

Inter-center comparison of good manufacturing practices-compliant stromal vascular fraction and proposal for release acceptance criteria: a review of 364 productions

BackgroundEven though the manufacturing processes of the stromal vascular fraction for clinical use are performed in compliance with the good manufacturing practices applying to advanced therapy medicinal products, specifications related to stromal vascular fraction quality remain poorly defined. We analyzed stromal vascular fraction clinical batches from two independent good manufacturing practices-compliant manufacturing facilities, the Swiss Stem Cell Foundation (SSCF) and Marseille University Hospitals (AP-HM), with the goal of defining appropriate and harmonized release acceptance criteria.MethodsThis retrospective analysis reviewed the biological characteristics of 364 batches of clinical-grade stromal vascular fraction. Collected data included cell viability, recovery yield, cell subset distribution of stromal vascular fraction, and microbiological quality.ResultsStromal vascular fraction from SSCF cohort demonstrated a higher viability (89.33% ± 4.30%) and recovery yield (2.54 × 105 ± 1.22 × 105 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% ± 5.96% and 2.25 × 105 ± 1.11 × 105 VNCs per mL). AP-HM batches were significantly less contaminated (95.71% of sterile batches versus 74.15% for SSCF batches). The cell subset distribution was significantly different (higher proportion of endothelial cells and lower proportion of leukocytes and pericytes in SSCF cohort).ConclusionsBoth centers agreed that a good manufacturing practices-compliant stromal vascular fraction batch should exert a viability equal or superior to 80%, a minimum recovery yield of 1.50 × 105 VNCs per mL of adipose tissue, a proportion of adipose-derived stromal cells at least equal to 20%, and a proportion of leukocytes under 50%. In addition, a multiparameter gating strategy for stromal vascular fraction analysis is proposed.