Purpose
Despite the importance of follow-up and multidisciplinary care after bariatric surgery, many patients do not attend postoperative appointments, particularly those with the medical team. The ...present study aimed to identify factors associated with loss to follow-up after bariatric surgery.
Materials and Methods
We recruited patients who underwent bariatric surgery between 01/01/2012 and 31/12/2013. Data were collected on demographic and socioeconomic information and comorbidities. Ten baseline psychological evaluations were blindly reviewed to evaluate the relationship between emotions and compliance with follow-up. During the 3-year postoperative period, we defined frequent attendees as those who attended at least two visits, whereas non-attendees were those who attended one visit or none
.
We evaluated baseline variables associated with non-adherence with follow-up schedules.
Results
Among 92 patients, 41 patients (44.6%) attended at least two postoperative appointments, while 51 (55.4%) were classified as non-attendees. Among the non-attendees, significantly more were younger than 45 years compared with attendees. No other statistically significant differences were found in terms of socioeconomic variables. Multivariate logistic regression revealed male gender and psychological issued related to obesity to be independent predictors of poor compliance with follow-up. Blinded psychological evaluation of ten patients did not suggest that psychological factors are predictive of follow-up attendance.
Conclusion
Identifying factors associated with loss to follow-up after bariatric surgery is challenging. However, this is important in order to enable the design of personalized follow-up plans, especially for younger patients and those with psychological issues.
Rabies virus (RABV) transcription and replication take place within viral factories having liquid properties, called Negri bodies (NBs), that are formed by liquid-liquid phase separation (LLPS). The ...co-expression of RABV nucleoprotein (N) and phosphoprotein (P) in mammalian cells is sufficient to induce the formation of cytoplasmic biocondensates having properties that are like those of NBs. This cellular minimal system was previously used to identify P domains that are essential for biocondensates formation. Here, we constructed fluorescent versions of N and analyzed by FRAP their dynamics inside the biocondensates formed in this minimal system as well as in NBs of RABV-infected cells using FRAP. The behavior of N appears to be different of P as there was no fluorescence recovery of N proteins after photobleaching. We also identified arginine residues as well as two exposed loops of N involved in condensates formation. Corresponding N mutants exhibited distinct phenotypes in infected cells ranging from co-localization with NBs to exclusion from them associated with a dominant-negative effect on infection. We also demonstrated that in vitro, in crowded environments, purified P as well as purified N0-P complex (in which N is RNA-free) form liquid condensates. We identified P domains required for LLPS in this acellular system. P condensates were shown to associate with liposomes, concentrate RNA, and undergo a liquid-gel transition upon ageing. Conversely, N0-P droplets were disrupted upon incubation with RNA. Taken together, our data emphasize the central role of P in NBs formation and reveal some physicochemical features of P and N0-P droplets relevant for explaining NBs properties such as their envelopment by cellular membranes at late stages of infection and nucleocapsids ejections from the viral factories.
miRNAs, small non-coding RNAs that regulate gene expression, are involved in various pathological processes, including viral infections. Virus infections may interfere with the miRNA pathway through ...the inhibition of genes involved in miRNA biogenesis. A reduction in the number and the levels of miRNAs expressed in nasopharyngeal swabs of patients with severe COVID-19 was lately observed by us, pointing towards the potential of miRNAs as possible diagnostic or prognostic biomarkers for predicting outcomes among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The objective of the present study was to investigate whether SARS-CoV-2 infection influences the expression levels of messenger RNAs (mRNAs) of key genes involved in miRNA biogenesis. mRNA levels of
,
,
,
, and Exportin-5 (
) were measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal swab specimens from patients with COVID-19 and controls, as well as in cells infected with SARS-CoV-2 in vitro. Our data showed that the mRNA expression levels of
,
,
,
, and
were not significantly different in patients with severe COVID-19 when compared to patients with non-severe COVID-19 and controls. Similarly, the mRNA expression of these genes was not affected by SARS-CoV-2 infection in NHBE and Calu-3 cells. However, in Vero E6 cells,
,
,
, and
mRNA levels were slightly upregulated 24 h after infection with SARS-CoV-2. In conclusion, we did not find evidence for downregulation of mRNA levels of miRNA biogenesis genes during SARS-CoV-2 infection, neither ex vivo nor in vitro.
Primary Mediastinal large B-cell Lymphoma (PMLBL) is a rare entity predominantly affecting adolescents and young adults. Recently, an international phase 2 trial in pediatric patients using ...dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) failed to reproduce excellent survival reported in some adult studies. The optimal therapy regimen needs to be determined in this disease. French prospective LMB2001 trial included all patients < 18 years with mature B-cell lymphoma treated in French centers. For patients with PMLBL, treatment included 4 to 8 courses of Lymphomes Malins B (LMB)-based chemotherapy without radiotherapy. From 2008, rituximab was added before each chemotherapy course. From 09/2001 to 03/2012, 42 patients with PMLBL were registered. The median age was 15 years (range 8-18). 21 patients were treated by chemotherapy plus rituximab. The median follow-up was 7.1 years (Interquartile range, 5.8-11.1). Five-year event-free (EFS) and overall survival (OS) were 88.1% (95%Confidence Interval (CI), 75.0%-94.8%) and 95.2% (95%CI, 84.0%-98.7%) for the whole population. The 5-year EFS was 81.0% (95%CI, 60.0%-92.3%) and 95.2% (95%CI, 77.3%-99.2%) (HR=0.24 (95%CI 0.03-2.2)) and 5-year OS was 90.5% (95%CI, 71.1%-97.3%) and 100% for patients treated without and with rituximab, respectively. Only 1/21 patients treated with rituximab and LMB-based chemotherapy had local early treatment failure but achieved prolonged complete remission with second-line chemotherapy and radiotherapy. Intensive LMB-based chemotherapy with rituximab achieved excellent survival in children/adolescents with PMLBL. Further international prospective studies are required to confirm these results in this population.
Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown.
Blood viscosity, red ...blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients.
Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age.
The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.
Documenting bacteremia at the onset of fever in immunosuppressed children is challenging; therefore, it leads to the early administration of broad-spectrum antibiotics. We aimed to analyse the ...evolution of antibiotic resistance profiles of bacterial bloodstream infections (BSI) and gut colonisations in a large cohort of immunocompromised children carrying a central venous catheter, in comparison with a prior, similar study conducted in our centre from 2014 to 2017. A retrospective, observational cohort study was conducted from January 2018 to December 2021, in a tertiary centre for paediatric immuno-haematology and oncology. Empirical antibiotic therapy was adapted to the immunosuppression risk group and prior bacterial colonisation. There was a mean of 6.9 BSI/1000 patient bed days. Multidrug-resistant bacteria (MDRB) associated BSI accounted for 35/273 (12.8%). The incidence of MDRB gum/gut colonisation and MDRB associated BSI increased annually and correlated with the level of immunosuppression (
= 0.024). One third (34.7%) of the BSI episodes were not associated with neutropenia. As compared to the previous study, an alarming emergence of MDRB responsible for gut colonisations and BSI in immunosuppressed children was reported over the last four years. The degree of immunosuppression directly correlates with the risk of having an MDRB gut colonisation or MDRB BSI.
Benjamini-Hochberg false discovery rate correction Of the miRNAs found of interest to discriminate between severe and non-severe COVID-19 in our study, some were reported to be implicated in viral ...and other infections: miR-455-5p was up-regulated in rabies virus infection in vitro, decreased suppressor of cytokine signaling 3 (SOCS3) expression and increased signal transducer and activator of transcription 3 (STAT3) activity, resulting in enhanced viral replication and the production of IL-6.6 Furthermore, this miRNA targeted the C-C motif chemokine receptor 5 (CCR5).7 Of interest, CCR5 is involved in severe COVID-19 and has been proposed as anti-inflammatory treatment target.8 Taken together, this underlines the role of hsa-miR-455-5p in viral infections and the inflammatory response and its potential as target of therapeutic interventions. hsa-miR-532-3p diminished the levels of ASK1 and downstream phosphorylation/translocation of p38 MAPK during lipopolysaccharide (LPS)/ tumor necrosis factor-α (TNF-α)-induced inflammation in macrophages and reduced the release of various pro-inflammatory cytokines and chemokines, including IL-6 and TNF-alpha.9 IL-6 is a proinflammatory cytokine that has been reported to be involved in the cytokine storm observed in severe COVID-19.10 The down-regulation of anti-inflammatory miRNAs, such as hsa-miR-532-3p, hsa-miR-340-5p and hsa-miR-455-5p, in severe COVID-19 (Table 1) is in line with a hyperinflammatory state in severe COVID-19. Recently, direct and indirect miRNA interactions with other miRNAs have been described (reviewed11). ...it cannot be excluded that the miRNAs identified in this study directly or indirectly influence expression of other miRNAs and thus have a broad impact on miRNA and gene expression. ...our analysis of miRNA expression in nasopharyngeal swabs revealed a general reduction of miRNA expression in severe COVID-19 patients.
While outcome for pediatric T lymphoblastic lymphoma (T‐LL) has improved with acute leukemia‐type therapy, survival after relapse remains rare. Few prognostic markers have been identified: NOTCH1 ...and/or FBXW7 (N/F) mutations identify good prognosis T‐LL and high‐level minimal disseminated disease (MDD) is reported to be of poor prognosis. We evaluated MDD and/or MRD status by 8‐color flow cytometry and/or digital droplet PCR in 82 pediatric T‐LL treated according to the EURO‐LB02 prednisone reference arm. Both techniques gave identical results for values ≥0.1%, allowing compilation. Unlike historical studies, an MDD threshold of 1% had no prognostic significance. The 54% (42/78) of patients with MDD ≥0.1% had a relatively favorable outcome (5‐y overall survival OS 97.6% versus 80.6%, P = 0.015, 5‐y event‐free‐survival EFS 95.2% versus 80.6%, P = 0.049). MDD lower than 0.1% had no impact in N/F mutated T‐LL, but identified the N/F germline patient with a high risk of relapse. Combining oncogenetic and MDD status identified 86% of patients (n = 49) with an excellent outcome and 14% of N/F germline/MDD <0.1% patients (n = 8) with poor prognosis (5y‐OS 95.9% versus 37.5%, P < 0.001; 5y‐EFS 93.9% versus 37.5%, P < 0.001). If confirmed by prospective studies, MDD and N/F mutational status would allow identification of a subset of patients who merit consideration for alternative front‐line treatment.
This study’s objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with ...sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006–2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival without SCD-related events was 10.7% for SS/SB° patients. In contrast, hydroxyurea was prescribed in 13.7% and bone marrow transplant performed in nine patients only. In this study, residual risks of severe complications were low, probably resulting from a good national TCD, vaccination, and healthcare system coverage. Nonetheless, burden of disease remained high, stressing the need for disease-modifying or curative therapy.
(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β
) or under different ...treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment.
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