Biallelic NPR1 loss of function variants are responsible for neonatal systemic hypertension.

BACKGROUND: Early-onset isolated systemic hypertension is a rare condition of unknown genetic origin. Renovascular, renal parenchymal diseases or aortic coarctation are the most common causes of secondary systemic hypertension in younger children and neonates. We investigated the genetic bases of early-onset isolated systemic hypertension. METHODS: Whole-exome sequencing (WES) was followed by variant filtering and Sanger sequencing for validation and familial segregation of selected variants in a large consanguineous family. mRNA expression was performed to evaluate the impact of the predicted pathogenic variant on gene expression. WES or Sanger sequencing was performed in additional unrelated affected individuals. RESULTS: In one consanguineous family with four children presenting with isolated neonatal-onset systemic hypertension, we identified homozygous stop-gain variant in the NPR1 gene (NM_000906.4:c.1159C>T (p.Arg387Ter)) in the affected individuals. This variant leads to a dramatic reduction of NPR1 RNA levels. NPR1 gene analysis of additional families allowed the identification of another family with two affected children carrying homozygous frameshift variant in NPR1 (NM_000906.4:c.175del (p.Val59TrpfsTer8)). CONCLUSION: We show for the first time that biallelic loss of function of NPR1 is responsible for isolated neonatal-onset systemic hypertension in humans, which represents a new autosomal recessive genetic cause of infantile systemic hypertension or cardiogenic shock. This is consistent with studies reporting early-onset systemic hypertension and sudden death in Npr1-deficient mice. NPR1 gene analysis should be therefore investigated in infants with early-onset systemic hypertension with or without cardiogenic shock of unknown origin.

Access to care for aging former workers living in an immigrant hostel / Accès aux soins d'une population d'anciens travailleurs immigrés vivant en foyer

The Chibanis represent the population of aging former immigrant workers who arrived in France in the 1970s in order to take up employment. Most of them still live in immigrant hostels, which are not appropriate for an older population. This anthropological study was conducted on Chibanis living in an immigrant hostel in the 15th arrondissement of Marseille. The objectives were to assess the medical, economic, and social characteristics of this population, to understand their access to health care, and to measure their adherence to the prevention actions of an association. 67 Chibanis aged 65 and over were included, with a median age of 77: 91% had access to a general practitioner, and 86.6% had more than two chronic diseases. More than half of the Chibanis complained of dental problems, and 20% complained of ophthalmological problems. Only 32.8% of the Chibanis included agreed to follow-up care with the nurses from the association. The population of Chibanis are isolated geographically from their families, live in poor socio-economic conditions, and often have insufficient medico-social coverage. They must "manage" their chronic diseases, as well as costly health problems such as dental or ophthalmic diseases. Improving care pathways for this population requires us to identify their specificities and all the factors hindering prevention actions.

Les Chibanis ­ "cheveux blancs" en arabe dialectal ­ désignent les anciens travailleurs immigrés arrivés en France dans les années 1970 pour exercer un emploi. Ils vivent encore pour la plupart au sein de foyers construits pour des hommes seuls exerçant une profession et non pour accueillir des hommes en situation de vieillissement. Notre travail anthropologique s'est organisé autour d'une population de Chibanis, vivant dans un foyer dans le 15e arrondissement de Marseille. Les objectifs étaient de mieux connaître cette population d'un point de vue médico-socio-culturel, de connaître les modalités de leur accès aux soins et enfin de connaître leur adhésion aux actions de prévention d'une association. 67 Chibanis ≥65 ans ont été inclus, avec une médiane de l'âge de 77 ans : 91 % déclaraient avoir un médecin traitant, 86,6 % avaient plus de 2 maladies chroniques. Plus de la moitié des Chibanis souffraient de problèmes dentaires et près de 20 % présentaient des problèmes ophtalmologiques. Seuls 32,8 % des Chibanis inclus ont accepté de réaliser un suivi par les infirmiers. La population des Chibanis, isolée géographiquement de leur famille, économiquement précaire et avec une couverture médico-sociale souvent insuffisante, doit « gérer ¼ ses pathologies chroniques, et des problèmes de santé notamment dentaires et ophtalmiques couteux. L'amélioration de leurs parcours de santé nécessite de mieux comprendre leurs spécificités et les divers facteurs qui peuvent entraver les actions de prévention.

Prevention of aromatase inhibitor-induced bone loss with anti-resorptive therapy in post-menopausal women with early-stage breast cancer.

We assessed if antiresorptive treatment can prevent aromatase inhibitor-induced bone loss in patients with early breast cancer. We observed that patients who did not receive antiresorptive treatment had a 20.8-fold increase in risk of bone loss after 24 months of aromatase inhibitors therapy. PURPOSE: This study aimed to describe changes in femoral and lumbar bone mineral density (BMD) after 24 months of aromatase inhibitors (AIs) and antiresorptive treatment in postmenopausal women with estrogen receptor-positive breast cancer. METHODS: Prospective, longitudinal study in a real-life setting with a 2-year follow-up. Patients underwent a complete baseline bone assessment including clinical assessment, biological evaluation, BMD measurement, and spine X-ray. Antiresorptive treatment was prescribed to patients with a T-score < - 2 or a T-score < - 1.5 SD with additional osteoporosis risk factors. A follow-up bone assessment was carried out after 24 months. RESULTS: Among 328 patients referred to our center, 168 patients (67.7 ± 10.6 years) were included in our study, and 144 were eligible for antiresorptive treatment. After 24 months, patients receiving antiresorptive treatment experienced a significant increase of + 6.28% in femoral-BMD (F-BMD) and + 7.79% in lumbar-BMD (L-BMD). This increase was not significantly different between osteoporotic and osteopenic patients. Conversely, patients not receiving antiresorptive treatment presented significant F-BMD and L-BMD loss regardless of the baseline BMD. In the multivariate logistic model, the lack of antiresorptive treatment was the only predictive factor for major femoral bone loss with a 20.83 odds ratio (CI95%:4.2-100, p < 0.001). CONCLUSION: This real-life study confirmed that antiresorptive treatment significantly increases femoral and lumbar BMD regardless of the baseline BMD in postmenopausal patients receiving AIs for early breast cancer. Patients who did not receive antiresorptive treatment had a 20.8-fold increased risk of major bone loss. Nevertheless, the best threshold to adopt for starting antiresorptive agents remains undetermined.

Benefits of BNP/NT-proBNP serum level evaluation for dry weight adjustment in pediatric hemodialysis patients.

BACKGROUND: Dry weight (DW) adjustment in children on hemodialysis (HD) can be challenging. It relies on clinical evaluation and additional supports. Our aim was to study the benefits of cardiac biomarker assessment, in addition to the more commonly used technique, bioimpedance spectroscopy (BIS), and clinical signs for DW prescription in pediatric HD patients. METHOD: Observational study including 41 children on HD in three pediatric HD centers in the Paris region. During one session, BIS was performed before the session and serum levels of BNP and NT-proBNP were analyzed before and after the session. RESULTS: Median pre-dialysis level of BNP was 87 ng/L [24-192] and NT-proBNP 968 ng/L [442-4828]. Cardiac biomarker levels showed positive correlation with the BIS hydration status evaluation (p = 0.004). The most appropriate cutoff for pre-dialysis BNP to detect significant overhydration (OH) was 165 ng/L (sensitivity 0.67, specificity 0.84). Based on the BIS evaluation, only 32% of patients with high blood pressure (BP) had OH, whereas in the normal BP group, 33% had significant OH. CONCLUSIONS: DW prescription for children on HD should not only rely on clinical evaluation, particularly BP, but should also include additional helpful parameters. BIS is well-validated in children, but it has limitations in non-cooperative patients, and its cost can limit its use in some settings. Cardiac biomarkers, especially BNP, were well-correlated to hydration status evaluated by BIS, and thus could add valuable information for individual patient management and DW assessment. A higher resolution version of the Graphical abstract is available as Supplementary information.

Renal vein thrombosis in neonates: a case series of diagnosis, treatment and childhood kidney function follow-up.

BACKGROUND: Neonatal renal vein thrombosis (NRVT) is a rare condition with little data available. METHODS: We retrospectively analyzed newborns diagnosed with NRVT admitted to 3 pediatric nephrology units in Paris from 2005 to 2020. RESULTS: Twenty-seven patients were analyzed (male = 59%). The median age at diagnosis was 2.5 days (1 - 4.5). Diagnosis was suspected based on at least one of the three cardinal signs of renal vein thrombosis in 93%: flank mass (67%), hematuria (67%) and thrombocytopenia (70%). In all patients, diagnosis was confirmed by ultrasound. All patients had at least one known perinatal risk factor. A prothrombotic risk factor was found in 13 patients (48%). NRVT was unilateral in 70%, involving the left renal vein in 58%. Among 25 treated patients, 19 (76%) received low molecular weight heparin (LMWH) as initial therapy, 2 (8%) received unfractionated heparin and 4 (16%) received fibrinolysis. Median duration of treatment was 8 weeks (4 - 12). Bleeding occurred significantly more often with fibrinolysis than with LMWH/supportive therapy (3 of 4: 75% vs 0 of 4: 0%, p = 0.05). Clot resolution in patients treated with fibrinolysis did not differ significantly from those treated with LMWH/supportive therapy. After a median follow-up of 5.7 years (3 years - 9.9 years), pathological kidney features were observed in 73% of the patients (19 of 26), kidney atrophy in 18 (69%), hypertension in 2 (8%), chronic kidney disease (CKD) in 1 (4%) and proteinuria in 2 (8%). CONCLUSIONS: NRVT remains a challenging condition, which still requires further study because of its associated morbidity. A higher resolution version of the Graphical abstract is available as Supplementary information.

Accès aux soins d'une population d'anciens travailleurs immigrés vivant en foyer.

The Chibanis represent the population of aging former immigrant workers who arrived in France in the 1970s in order to take up employment. Most of them still live in immigrant hostels, which are not appropriate for an older population. This anthropological study was conducted on Chibanis living in an immigrant hostel in the 15th arrondissement of Marseille. The objectives were to assess the medical, economic, and social characteristics of this population, to understand their access to health care, and to measure their adherence to the prevention actions of an association. 67 Chibanis aged 65 and over were included, with a median age of 77: 91% had access to a general practitioner, and 86.6% had more than two chronic diseases. More than half of the Chibanis complained of dental problems, and 20% complained of ophthalmological problems. Only 32.8% of the Chibanis included agreed to follow-up care with the nurses from the association. The population of Chibanis are isolated geographically from their families, live in poor socio-economic conditions, and often have insufficient medico-social coverage. They must "manage" their chronic diseases, as well as costly health problems such as dental or ophthalmic diseases. Improving care pathways for this population requires us to identify their specificities and all the factors hindering prevention actions.

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

BACKGROUND: Sarcopenia 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. METHODS: This 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. DISCUSSION: The 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 REGISTRATION: The 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 ).

Specific immune biomarker monitoring in two children with severe IgA nephropathy and successful therapy with immunoadsorption in a rapidly progressive case.

BACKGROUND: Childhood IgA nephropathy (cIgAN) is one of the most common primary glomerulonephritides with the potential to evolve to kidney failure. IgAN is an autoimmune disease involving 3 key factors: galactose-deficient IgA1 (Gd-IgA1), anti-IgA1 autoantibodies, and soluble (s)CD89 IgA Fc receptor. These molecules and immune complexes have been described recently as potential biomarkers of disease progression in childhood IgAN but their evolution in time under immunosuppressive treatment remains unknown. METHODS: We performed a prospective study of two proliferative cIgAN patients by sequentially biomonitoring immune IgA complexes (sCD89-IgA, IgG-IgA), sCD89, and Gd-IgA1 and correlating them with clinical and histological outcome after treatment. RESULTS: After patient 1's treatment, a decrease in sCD89-IgA, IgG-IgA, and free sCD89 was linked to a decrease in proteinuria whereas eGFR (estimated glomerular filtration rate) and Gd-IgA1 levels remained stable. Patient 1 received tacrolimus and monthly intramuscular steroid injections of Kenacort for 10 months. At the end, a relapse induced an increase in proteinuria consistent with an increase of the 3 biomarkers. Patient 2 displayed rapidly progressive IgAN with crescents in more than 90% of glomeruli and received intense immunosuppression treatment associated with the immunoadsorption (IA) approach. During IA, proteinuria decreased rapidly, as well as levels of CD89-IgA, IgG-IgA, sCD89, and Gd-IgA1 biomarkers. After discontinuation of IA, proteinuria increased as well as IgG-IgA complexes whereas sCD89-IgA and sCD89 remained low. Further re-intensification of IA and addition of cyclophosphamide improved proteinuria again with reduced IgG-IgA. A second biopsy was performed showing a reduction of extracapillary proliferation to 6% of glomeruli and only 9% glomerulsoclerosis. CONCLUSIONS: In conclusion, sequential biomonitoring of Gd-IgA1, IgA-immune complexes, and sCD89 in cIgAN was found to be valuable, by correlating with clinical features and glomerular proliferative lesions in cIgAN. These biomarkers could represent useful tools to evaluate kidney injury without repeat kidney biopsies.

Anti-rituximab antibodies in pediatric steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab is a chimeric anti-CD20 monoclonal antibody that induces sustained remission in children with steroid-dependent nephrotic syndrome. However, there is no consensus on the optimal regimen and monitoring of rituximab. In other autoimmune diseases, anti-rituximab antibodies (ARA) have been reported in 10-40% of patients, but their clinical relevance remains unclear. In nephrotic syndrome, data are scarce. METHODS: We report a single-center retrospective study with immuno- and pharmacological monitoring of rituximab treatment in children with frequent relapsing (FR) or steroid-dependent nephrotic syndrome (SDNS). We analyzed the monthly monitoring of 24 children, receiving a dose of rituximab (375 mg/m2) between December 2017 and April 2018 at the Pediatric Nephrology Department of Robert-Debré hospital, Paris. RESULTS: ARA were detected in 7/24 patients (29%), sometimes after the first infusion of rituximab. ARA were present at baseline in two patients previously treated with rituximab. Both displayed no B-cell depletion. ARA were also reported in 5/22 patients during follow-up, with antibodies always detected in the first month following B-cell recovery. An incomplete CD19+CD20- B-cell depletion at M1 (5-25/mm3) and low serum rituximab levels was predictive of developing ARA. The development of de novo ARA during follow-up was not associated with shorter B-cell depletion. CONCLUSIONS: This study shows that ARA are frequent in children with FR/SDNS and that close immuno- and pharmacological monitoring may help personalizing rituximab treatment in patients needing repeated injections.

Functional status in older patients with lung cancer: an observational cohort study.

PURPOSE: An assessment of the impact of functional status (FS) evaluated using a combination of Activities of Daily Living (ADL) and the short version of the Instrumental Activities of Daily Living (IADL), on 3- and 6- month mortality and on 3-month unplanned hospitalizations in older patients treated for lung cancers. METHOD AND OBJECTIVES: This observational retrospective study was conducted between September 2015 and January 2019 at Marseille University Hospital (AP-HM). During this period, all consecutive outpatients aged 70 years or older referred for a comprehensive geriatric assessment (CGA) before the initiation of lung cancer treatment were enrolled. RESULTS: Two hundred twenty-seven patients were analyzed: the median age was 78.7 years and 74.0% were male. Almost half of the patients were metastatic (45.4%). Concerning FS, 41.9% of patients had no ADL-IADL impairment, 30.0% had either IADL or ADL impairment, and both ADL-IADL were impaired for 28.1%. Impaired ADL-IADL was associated with poor nutritional status, depression, mobility, and cognitive disorders. In a logistic regression model, ADL or IADL impairment (aOR = 2.1; 95% CI [1.0-4.2]; p = 0.037) and impaired ADL-IADL (aOR = 2.6; 95% CI [1.2-5.3]; p = 0.012) were independently associated with a higher risk of unplanned hospitalizations within 3 months. In the multivariate Cox model, 6-month mortality risk was independently associated with impaired ADL-IADL (aHR = 2.3; 95% CI [1.3-4.4]; p = 0.008). CONCLUSION: The combination of ADL and IADL scales to assess FS is a prognostic marker of the mortality risk at 6 months in older patients with lung cancer and should be more largely used by oncologists in treatment decision making.

Prenatal bone abnormalities in three cases of familial hypocalciuric hypercalcemia.

INTRODUCTION: Prenatal diagnosis of bone and mineralization anomalies is associated with a wide range of etiologies and prognoses. The improvement of antenatal ultrasound combined with the development of molecular diagnosis in genetics has transformed antenatal medicine into a challenging discipline. Of the various known causes of bone abnormalities and hypomineralization, calcium and phosphate metabolism disorders are exceptional. An accurate diagnosis is crucial for providing appropriate genetic counseling and medical follow-up after birth. CASE: We report on three siblings with severe bone abnormalities diagnosed during the second trimester ultrasound of pregnancy. Postnatal follow-up showed transitory hyperparathyroidism, with hypercalcemia and hypocalciuria. METHODS: Sanger sequencing performed after birth in the three newborns revealed a monoallelic pathogenic variant in the CASR gene, encoding the calcium sensing receptor, confirming the diagnosis of familial hypocalciuric hypercalcemia, paternally inherited. Postnatal evolution was favorable after treatment with a calcimimetic agent. CONCLUSIONS: Previously, prenatal bone abnormalities caused by familial hypocalciuric hypercalcemia had only been described in one patient. This entity should be considered as differential diagnosis of bones abnormalities. Knowing about this unusual etiology is important to guide the diagnosis, the prenatal counseling and to improve medical management.

Geriatric syndromes in a centenarians population.

BACKGROUND: Centenarians develop diseases later than younger populations. AIMS: Assessment of geriatric syndromes in centenarians living in Marseille in 2020. METHODS: Observational preliminary study describing centenarians living in the Marseille area, being part of the patients base of the general practitioners (GPs). RESULTS: Twenty-two centenarians were enrolled, including seventeen women (77.3%). Thirteen centenarians lived in nursing homes (NH) and nine in private housing (PH). All were dependent for daily living activities and 78.9% used walkers to get around. GPs consultations were exclusively home visits (in NH or PH). Centenarians living in NH presented more cognitive impairments, more comorbidities, and fewer hospitalizations during the past year compared to centenarians living in PH. DISCUSSION: Although centenarians represent a model of successful aging for society, all were dependent and had at least one geriatric syndrome. CONCLUSIONS: Maintaining centenarians at home requires technical aids and intervention of several professional caregivers relying on family support.

Telemedication Reviews to Optimize Medication Prescription for Older People in Nursing Homes.

Introduction: Older people living in nursing homes (NH) are at a higher risk of preventable drug-related adverse events because of age-related physiological changes, polypathology, and polypharmacy. NH residents are particularly exposed to potentially inappropriate medications (PIMs). Many strategies have been developed to improve the quality and the safety of drug prescription in NH, including medication reviews (MRs). Methods: In the context of the application of telemedicine, we developed and are currently implementing a novel hospital expert-based MRs through tele-expertise (or "telemedication review," telemedication reviews hereafter [TMR]) in French NH residents. The impact of these TMR on unplanned hospitalizations 3 months after implementation is assessed. TMR consider all available sociodemographic, clinical, biological, and pharmaceutical data pertaining to the patient and are performed in accordance with their health care objectives. Results: The preliminary results for the 39 TMRs performed to date (September 2021) showed that a total of 402 PIMs were detected, and all residents had at least one PIM. We also present the feasibility and the usefulness of this novel TMR for NH, illustrating these preliminary results with two concrete TMR experiences. Among the 39 TMR performed, the average acceptance rate of expert recommendations made to general practitioners (GP) working in NH was ∼33%. Discussion and Conclusions: The success of this novel TMR depends on how the proposed prescription adjustments made by the hospital expert team are subsequently integrated into health care practices. The low acceptance rate by GP highlights the need to actively involve these professionals in the process of developing TMR, with a view to encouraging them to act on proposed adjustments.

Clinical characteristics and outcomes of patients with haematologic malignancies and COVID-19 suggest that prolonged SARS-CoV-2 carriage is an important issue.

Specificities of COVID-19 disease course in patients with haematologic malignancies are still poorly studied. So, we aimed to compare patients with haematologic malignancies to patients without malignancies, matched by sex and age and hospitalised for COVID-19 at the same time and in the same centre. Among 25 patients with haematologic malignancies, we found that mortality (40% versus 4%, p < 0.01), number of days with RT-PCR positivity (21.2 ± 15.9 days [range, 3-57] versus 7.4 ± 5.6 days [range, 1-24], p < 0.01), maximal viral load (mean minimal Ct, 17.2 ± 5.2 [range, 10-30] versus 26.5 ± 5.1 [range, 15-33], p < 0.0001) and the delay between symptom onset and clinical worsening (mean time duration between symptom onset and first day of maximum requirement in inspired oxygen fraction, 14.3 ± 10.7 days versus 9.6 ± 3.7 days, p = 0.0485) were higher than in other patients. COVID-19 course in patients with haematologic malignancies has a delayed onset and is more severe with a higher mortality, and patients may be considered as super-spreaders. Clinicians and intensivists need to be trained to understand the specificity of COVID-19 courses in patients with haematological malignancies.

Lessons learned from the investigation of a COVID-19 cluster in Creil, France: effectiveness of targeting symptomatic cases and conducting contact tracing around them.

BACKGROUND: This study presents the methods and results of the investigation into a SARS-CoV-2 outbreak in a professional community. Due to the limited testing capacity available in France at the time, we elaborated a testing strategy according to pre-test probability. METHODS: The investigation design combined active case finding and contact tracing around each confirmed case with testing of at-risk contact persons who had any evocative symptoms (n = 88). One month later, we performed serology testing to test and screen symptomatic and asymptomatic cases again (n = 79). RESULTS: Twenty-four patients were confirmed (14 with RT-PCR and 10 with serology). The attack rate was 29% (24/83). Median age was 40 (24 to 59), and the sex ratio was 15/12. Only three cases were asymptomatic (= no symptoms at all, 13%, 95% CI, 3-32). Nineteen symptomatic cases (79%, 95% CI, 63-95) presented a respiratory infection, two of which were severe. All the RT-PCR confirmed cases acquired protective antibodies. Median incubation was 4 days (from 1 to 13 days), and the median serial interval was 3 days (0 to 15). We identified pre-symptomatic transmission in 40% of this cluster, but no transmission from asymptomatic to symptomatic cases. CONCLUSION: We report the effective use of targeted testing according to pre-test probability, specifically prioritizing symptomatic COVID-19 diagnosis and contact tracing. The asymptomatic rate raises questions about the real role of asymptomatic infected people in transmission. Conversely, pre-symptomatic contamination occurred frequently in this cluster, highlighting the need to identify, test, and quarantine asymptomatic at-risk contact persons (= contact tracing). The local lockdown imposed helped reduce transmission during the investigation period.

Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood. METHODS: Neonatal survivors and patients diagnosed in postnatal period with ARPKD between 1985 January and 2017 December from 3 French pediatric centers were retrospectively enrolled in the study. RESULTS: Fifty patients with mean follow-up 12.5 ± 1 years were enrolled. ARPKD was diagnosed before birth in 24%, and at mean age 1.8 years in others. Thirty-three patients were < 1 year of age at first symptoms, which were mostly kidney-related. These most often presented high blood pressure during follow-up. Portal hypertension was diagnosed in 29 patients (58%), 4 of them with bleeding from esophageal varices. Eight patients presented cholangitis (> 3 episodes in three children). Liver function was normal in all patients. Nine children received a kidney transplant without liver complications. A 20-year-old patient received a combined liver-kidney transplant (CLKT) for recurrent cholangitis, and a 15-year-old boy an isolated liver transplant for uncontrollable variceal bleeding despite portosystemic shunt. CONCLUSIONS: Long-term outcome in patients with ARPKD is heterogeneous, and in this cohort did not depend on age at diagnosis except for blood pressure. Few patients required liver transplantation. Indications for liver or combined liver-kidney transplantation were limited to recurrent cholangitis or uncontrollable portal hypertension. Liver complications after kidney transplantation were not significant.

Impact of care pathway for nursing home residents treated for cancer: ONCO-EHPAD study.

PURPOSE: Few data are known about cancer management in frail nursing home residents. METHODS: Objective of our prospective, interventional study was to set up in the Marseille area, a care pathway for nursing homes residents with a suspected cancer. It combined cancer diagnosis procedures and comprehensive geriatric assessment (CGA), both made in our geriatric oncology outpatient unit, before oncologic advice for treatment decision. In standard care, CGA is carried out after therapeutic decision, to determine whether the planned treatment is compatible with the patient's frailties. CGA and quality of life were performed at enrolment and at 6 months. This study was registered in ClinicalTrials.gov (NCT03103659). RESULTS: Between April 2017 and March 2020, 48 residents from 38 nursing homes were included: 24 had the care pathway (PP), and 24 the standard care (NPP). Six were excluded (no cancer). PP had more frailties than NPP. All PP and 75% of NPP had outpatient care. Curative treatment was given to 77% of NPP (including chemotherapy in 10 cases), and 25% of PP (surgery, radiotherapy, hormone therapy). A majority of PP (75%) had supportive care. At 6 months, 16 patients died (11 NPP, 5 PP). Quality of life evolution was available for 11 PP and 7NPP: it showed stability in PP and degradation in NPP. CONCLUSION: Even if part of residents were too frail to get curative treatment, the care pathway enabled them to benefit from oncologic advice and appropriate supportive care while preserving their quality of life. Further investigations are needed to confirm these findings.

High Serum Vitamin B12 Levels Associated with C-Reactive Protein in Older Patients with Cancer.

BACKGROUND: A Comprehensive Geriatric Assessment (CGA) has been proposed to assess prognosis and to adapt oncological care in older patients with cancer. However, few biological markers are incorporated in the CGA. METHODS: This comparative study on older patients with cancer was realized before final therapeutic decision and during a CGA that included biological markers. Our objective study was to know if the serum vitamin B12-C-reactive protein index (BCI) can help to estimate early death and unplanned hospitalization. Associations between BCI and unplanned hospitalization or mortality were analyzed using ordered multivariate logistic regression. FINDINGS: We included 621 older cancer adults in outpatient care with a median age of 81 years (range, 70-98 years) from September 2015 to May 2018. In this study, 5.6% of patients died within 3 months, 8.8% had unplanned hospitalization within 1 month, and 11.4% had unplanned hospitalization within 3 months. Hypercobalaminemia was present in 83 patients (13.4%), and 34 patients (5.5%) had BCI >40,000. According to the multivariate analysis, BCI was a prognostic factor of mortality within 3 months and unplanned hospitalizations at 1 and 3 months. Impaired activities of daily living (ADL) and palliative care were also risk factors for mortality within 3 months. Impaired instrumental ADL, low albumin level, and palliative care were risk factors for unplanned hospitalization at 1 month. INTERPRETATION: BCI could be routinely added to the CGA process, as part of a pretreatment workup, in order to assess more precisely the frailties and to adapt oncological care in older patients treated for cancer. IMPLICATIONS FOR PRACTICE: Aging comes with an increase of frailties and comorbidities. To identify frailties in older patients with cancer, this study used a Comprehensive Geriatric Assessment, which allowed for the adaptation of each treatment plan in accordance with the individual needs of the patients. However, biological characteristics were not included in this assessment. This study showed that hypercobalaminemia and vitamin B12 -C-reactive protein index may be potential markers for cancer with poor prognosis, particularly in the older population. These biological markers can be used in geriatric oncology and general medicine.

Steroid therapy in children with IgA nephropathy.

IgA nephropathy (IgAN) is one the most common primary glomerulonephritis in children and adolescents worldwide, with 20% of children developing end-stage kidney disease (ESKD) within 20 years of diagnosis. There is a need for treatment guidelines, especially for steroids in children with primary IgAN, since the STOP-IgA trial casts doubts on the use of steroids in adults with intermediate risk. Pediatricians are prone to prescribe steroids in addition to renin-angiotensin system blockade (RASB) when proteinuria is > 0.5 g/l, eGFR deteriorates < 70 ml/min/1.73 m2, or when a biopsy sample shows glomerular inflammation. Lack of randomized controlled trials (RCTs) in children with IgAN has led to an absence of consensus on the use of immunosuppressive agents in the treatment of progressive IgAN. This literature review evaluates the available evidence on steroid treatment in children with IgAN.

Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome.

BACKGROUND: Several studies have demonstrated that rituximab (RTX) improves relapse-free survival in patients with steroid-dependent nephrotic syndrome (SDNS). However, these studies used various RTX regimens and there are few data comparing these regimens in children with SDNS. In this retrospective study, we assessed the effect of three different initial RTX regimens on both time to B cell reconstitution and to first relapse. METHODS: Sixty-one SDNS patients receiving a first course of RTX were included. Group 1 received one injection of 100 mg/m2, group 2 received one injection of 375 mg/m2, and group 3 received two injections of 375 mg/m2 at day 0 and day 7. Time to B cell reconstitution and time to first relapse and respective risk factors were studied. RESULTS: Median time to B cell reconstitution was 2.5 [1.8-3.5], 5.0 [3.9-6.0], and 6.6 [4.6-7.8] months in groups 1, 2, and 3, respectively. RTX regimen was associated with time to B cell reconstitution (HRs group 2 vs. 3, 4.07 [1.96-8.48]; group 1 vs. 3, 11.13 [4.04-30.67]). One-year relapse-free survival was 50% [58-77], 59% [42-76], and 72% [46-87] in groups 1, 2, and 3, respectively. RTX regimen was associated with risk of relapse (HRs group 2 vs. 3, 1.55 [0.51-4.65]; group 1 vs. 3, 4.98 [1.15-21.60]). CONCLUSIONS: The initial dose of rituximab impacts time to B cell reconstitution and the probability of relapse. Risk of relapse is also associated with patient characteristics, suggesting that RTX regimen could be modified for each patient to balance efficacy, cost, and side effects.