Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

Cutaneous drug-induced lupus erythematosus: Clinical and immunological characteristics and update on new associated drugs.

Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE.

Spontaneous heterotopic triplets - A review of literature.

OBJECTIVE: Spontaneous heterotopic triplets, a tubal ectopic pregnancy and a twin pregnancy, are rare disorders. The study aimed to examine all available evidence regarding signs and symptoms, imaging findings, management and newborn outcome of spontaneous heterotopic triplets. DESIGN: A literature search in Medline and EMBASE databases from 2000 to 2016 was conducted. The following key words were employed: 'spontaneous heterotopic pregnancy', OR 'heterotopic triplets'. Only cases of spontaneous heterotopic triplets without assisted reproduction techniques were included. RESULTS: Six cases were identified and included in the present review. All cases presented with abdominal pain and one case presented in shock. Hemoperitoneum was present in five cases. Laterouterine mass with adnexal gestational sac is not systematically described (3 cases/6), but was a good ultrasonographic sign of heterotopic pregnancy. All patients had tubal rupture, but anyone had vaginal bleeding. The surgical treatment was made by salpingectomy in five cases to ensure successful treatment. The mean and median gestational age at delivery were 29.9 and 37.54 weeks, respectively (range 6-41 weeks). The neonatal outcome was good for 6 newborns. CONCLUSION: Spontaneous heterotopic triplets are rare. Early surgical intervention is the key to successful treatment of heterotopic triplet pregnancy and allows good neonatal outcome.

Hemoglobin level variability in hemodialysis patients treated with epoetin-ß during 1 year.

AIM: This analysis was performed to assess the prevalence and the factors associated with hemoglobin (Hb) variability during treatment with erythropoiesis-stimulating agents (ESA) in France. METHODS: Hb variability was evaluated in a subgroup of hemodialysis (HD) patients of the French cohort DiaNE. Eligible patients had received epoetin-ß at least 6 months before entering DiaNE, 12 months during DiaNE and had no missing monthly Hb measurements. Up and down excursions (Hb variations > 1.5 g/dl with duration > 8 weeks) were assessed. RESULTS: Of the 499 patients evaluated in this analysis, 295 (59%) had Hb levels inside the target range of 11 - 13 g/dl at baseline. The number of patients with constantly stable Hb level inside the target range decreased from baseline to 27.5% at 6 months and 10.8% at 12 months. More than 70% of patients experienced Hb variability. The number of excursions was 1.7 ± 0.8 per patient/year. The amplitude of up excursions was 2.8 ± 1.0 g/ dl with a duration of 14.7 ± 4.7 weeks. The amplitude of down excursions was 2.6 ± 0.9 g/dl with a duration of 14.5 ± 4.6 weeks. The main factors associated with Hb variability were number of epoetin-ß dose changes, adverse events and iron therapy changes. CONCLUSION: Hb variability is frequent in French ESA-treated HD patients and closely related to practices. Further efforts are needed to improve anemia management.

Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome.

INTRODUCTION: Gitelman syndrome (GS) is a tubulopathy caused by SLC12A3 gene mutations, which lead to hypokalaemic alkalosis, secondary hyperaldosteronism, hypomagnesaemia and hypocalciuria. AIM: The aim of this study was to assess the prevalence of SLC12A3 gene mutations in adult hypokalaemic patients; to compare the phenotype of homozygous, heterozygous and non-mutated patients; and to determine the efficiency of treatment. METHODS: Clinical, biological and genetic data were recorded in 26 patients. RESULTS: Screening for the SLC12A3 gene detected two mutations in 15 patients (six homozygous and nine compound heterozygous), one mutation in six patients and no mutation in five patients. There was no statistical difference in clinical symptoms at diagnosis between the three groups. Systolic blood pressure tended to be lower in patients with two mutations (P=0.16). Hypertension was unexpectedly detected in four patients. Five patients with two mutated alleles and two with heterozygosity had severe manifestations of GS. Significant differences were observed between the three groups in blood potassium, chloride, magnesium, supine aldosterone, 24 h urine chloride and magnesium levels and in modification of the diet in renal disease. Mean blood potassium levels increased from 2.8 ± 0.3, 3.5 ± 0.5 and 3.2 ± 0.3 before treatment to 3.2 ± 0.5, 3.7 ± 0.6 and 3.7 ± 0.3 mmol/l with treatment in groups with two (P=0.003), one and no mutated alleles respectively. CONCLUSION: In adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of the SLC12A3 gene in 80% of cases. GS was more severe in patients with two mutated alleles than in those with one or no mutated alleles. High blood pressure should not rule out the diagnosis, especially in older patients.

[Transperineal repair of rectocele with prosthetic mesh. A prospective study]. / Traitement de la rectocèle par voie périnéale avec prothèse. Une étude prospective.

PURPOSE: To assess the long term results of a transperineal repair of rectocele with a prosthetic mesh and the criteria for selecting the patients. METHODS: Twenty-five consecutive patients (median age: 60 years) with a symptom-giving rectocele have been operated upon. Indication for surgery was: an obstructed defecation (N = 22); a fecal incontinence (N = 1); a pelvic heaviness with dyspareunia (N = 1) or a severe rectal syndrome (N = 1). Patients were evaluated by physical examination and, preoperatively, by defecography and anorectal manometry. The rectovaginal septum was repaired, through a perineal approach, with an absorbable (N = 5) or non absorbable (N = 20) prosthetic mesh. Long term results were assessed after a median follow-up of 45 (range 12-120) months by physical examination and a standardized questionnaire. The presence of the following three symptoms was evaluated: feeling of incomplete emptying, prolonged and unsuccessful straining at stool, digital assistance. Outcome was considered as successful when none of these symptoms were present, as good when minor emptying difficulties persisted, as moderate when emptying difficulties were associated with straining, as a failure when the symptomatic triad was unchanged. A general satisfaction score was established. RESULTS: All the patients had the defect of the rectovaginal septum corrected. Four patients had a low residual rectocele associated, in two cases, with a rectal prolapse subsequently treated by a Delorme's operation. Outcome in patients complaining of obstructed defecation was considered excellent or good in 80% of patients, moderate in 9% and poor in 9%. Subjective scoring showed a significantly better result in cases of success. Among 11 incontinent patients, seven (63.5%) improved or regained full continence. Dyspareunia in three cases was corrected. Age, parity, digital assistance, previous gynecologic surgery, use of laxatives, size of rectocele, type of mesh, anatomical result of repair had no significant prognostic value. On the other hand, in patients with obstructed defecation, clinical and manometric signs of anal hyperactivity of the pelvic floor or anismus (N = 4) were significantly related to a poor result (P < 0.001). CONCLUSION: Surgical repair with a prosthetic mesh is an efficient therapy in patients with obstructed defecation and/or incontinence caused by a rectocele. Clinical and defecographic parameters have no influence on outcome. Preoperative manometric data may help in selecting patients. In case of anal hyperactivity or anismus, given the risk of functional failure, behavioral retraining must be considered as first-line treatment.

[Randomized trials in the prevention of recurrent calcium oxalate stones]. / Les essais cliniques randomisés dans la prévention des récidives des lithiases oxalo-calciques.

Kidney stone, with or without lumbar pain, is a major health care problem because of its prevalence and cost for both the patient and the society. Although, surgical procedures are well known, medical treatment and recurrences prophylaxis are uncodified. Fifteen stone recurrence prevention studies have been reviewed, evaluating dietary intake and drugs. The most important factor is a daily diuresis of at least 2 liters. Calcium intake shouldn't be restricted, whereas oxalate, sodium, and protein intakes have to be limited. Hyper and normocalciuretic kidney stone formers improve their outcome with thiazide or indapamide treatment. Hyperuricosuria justifies allopurinol. Potassium citrate (without sodium) may decrease recurrence risk, even in patients without hypocitraturia.

[Factors determining the choice of a modality of treatment by dialysis: a study of nine dialysis centers]. / Facteurs déterminant le choix d'une modalité de traitement par dialyse: une enquête dans neuf centres de dialyse.

BACKGROUND: The objective of this cross-sectional study in a population of 1472 dialysis patients was to identify the main factors involved in the choice of a specific option for dialysis therapy, taking into account three different types of criteria such as medical dependence (DM), nurse care requirement (SI) and independence for dialysis therapy (CA). METHODS: Each patient has been analysed, independently of present treatment modality, according to the above three criteria, namely DM, SI and CA. For each type of parameter, patients have been allocated to one of three levels, each level being established to evaluate whether dialytic treatment should be undertaken as hospital centre dialysis (HDC) or in a facility off the hospital. Level 3 of any one category corresponded to the inability of doing haemodialysis at home (HHD) or in self-care unit (AD). Level 2 included patients who could be treated in AD or by peritoneal dialysis (PD) with the assistance of a nurse. CAPD or HHD were considered as potential treatment modalities only in patients qualifying for level 1 of each criterion. RESULTS: In the patient population as a whole, the following treatment options were observed: HHD 3.6%, CAPD 6%, PD 1.8%, AD 16.3% and HDC 72.2%. For medical dependence (DM) there was a relatively even distribution for the three levels in six centres. In contrast, two centres were characterized by a predominance of DM level 3. Differences in DM levels between centres were greatly reduced when considering separately only those patients who were actually treated by CAPD, HDC and AD. SI levels were more uniformly distributed within all centres, and this was true for HCD and AD patients. When considering CA levels in HDC patients, a large predominance of CA level 3 was observed in all centres whereas CA level 1 was nearly in existent. CONCLUSION: The major finding of this study was that the inability or the refusal of dialysis patients to participate at treatment, independently of medical condition and nurse care requirement, was the main factor in the choice of hospital centre dialysis.

[Renal and hypertensive complications of extracorporeal lithotripsy]. / Complications rénales et hypertensives de la lithotritie extracorporelle: les patients à risque.

HISTOLOGICAL AND FUNCTIONAL CONSEQUENCES OF ESWL: Extracorporeal shock wave litotripsy is now used for the treatment of about 90% of stones. Because of the nonpunctual delivery of energy into the stone, a small volume of renal parenchyma is injured, giving rise to a fibrous scar which can be visualized by morphological techniques such as magnetic nuclear resonance. Isotopic techniques point out a 15% reduction of renal plasma flow on the side of the litotripsy. For a majority of patients, this alteration is transient. HYPERTENSION: In a few cases, abrupt onset of transient hypertension has been reported in clear relation with a compressive perirenal hematoma. The causal effect of ESWL on late occurrence of permanent hypertension is however still uncertain, probably because of the difficulty to show that this occurrence is not related to the older age of the patient alone. The FDA sponsored multicentric study begun in 1993 should solve this issue in the future. PATIENTS AT RISK: Recent articles suggest that altered renal function prior to ESWL would predict late occurrence of hypertension and worsening of renal failure. Furthermore, age and the resistance index of arcuate or interlobular renal arteries (measured by Doppler) could help to screen the patients at risk of developing hypertension. Practical attitude: In practice, renal function and blood pressure should be carefully monitored in patients aged over 60 and/or who have a serum creatinine > 300 mumol/l.

Renal and hypertensive complications of extracorporeal shock wave lithotripsy: who is at risk?

Extracorporeal shock wave lithotripsy (ESWL) is now used in the treatment of about 90% of renal and ureteral stones. Because of the non-punctual delivery of energy to the stone, a small volume of renal parenchyma is injured giving place to a fibrous scar which can be shown by highly resolutive imaging techniques like magnetic nuclear resonance. Isotopic clearances point to a reduction of 15% in the renal plasma flow on the side of the lithotripsy, but this alteration appears to be transient in nature. In a few cases an abrupt onset of transient hypertension has been reported in clear relation to a compressive perirenal hematoma. The responsibility of ESWL in the late occurrence of permanent hypertension is, however, still uncertain, probably because of the difficulty in showing that this occurrence is not only related to the older age of the patient. The American Food and Drug Administration-sponsored multicentric study begun in 1992 should solve this issue in the future. Recent articles suggest that altered renal function prior to ESWL would predict the late occurrence of hypertension and worsening of renal failure. Furthermore, age and the resistance index of arcuate or interlobar renal arteries (measured by Doppler) could help to screen patients at risk of developing hypertension. In practice in patients over 60 years of age and/or with a plasma creatinine of >to 300 micromol/l, ESWL should be performed with caution, and renal function and blood pressure should be carefully monitored.

Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis.

PURPOSE: To assess the value of serial determinations of antineutrophil cytoplasmic autoantibodies (ANCA) for monitoring disease activity in patients with systemic vasculitis. PATIENTS AND METHODS: Forty-three patients with histologically proven vasculitis (21 with Wegener's granulomatosis, 17 with microscopic polyangiitis, and 5 with renal-limited vasculitis) were studied for a median follow-up of 22 months. Disease activity was prospectively assessed and quantified by the Birmingham Vasculitis Activity Score. A total of 347 sera were analyzed for ANCA determination. RESULTS: Relapses occurred in 23 (54%) of 43 patients. Diagnostic category (Wegener's granulomatosis vs micropolyangiitis and renal-limited vasculitis), severity of initial symptoms (mean vasculitis activity score, mean number of organs involved), and ANCA pattern [cytoplasmic-ANCA (c-ANCA) vs perinuclear-ANCA (p-ANCA)] did not significantly differ between relapsers and nonrelapsers. Lung involvement was more frequent at onset among relapsers [16 of 23 (70%) vs 6 of 20 (30%); P = 0.02]. Relapses were slightly, but not significantly, more frequent in patients with Wegener's granulomatosis or a c-ANCA pattern. The percentage of relapsers was greater in patients with persistently positive ANCA than in patients with negative or decreasing ANCA titers (86% vs 20%, P = 0.0001). However, the predictive value of an increase in ANCA titers for the occurrence of a subsequent relapse was only 28% (4 of 14) for c-ANCA, 12% (2 of 17) for anti-proteinase 3-ANCA, and 43% (6 of 14) for anti-myeloperoxidase-ANCA. An increase in ANCA occurred before or during relapse in 33% (10 of 30) of cases for c-ANCA/anti-proteinase 3 antibodies, and 73% (11 of 15) of cases for anti-myeloperoxidase antibodies. CONCLUSION: The persistence of ANCA positivity is strongly associated with relapses. However, an increase in ANCA titers has a poor value for the early prediction of a subsequent relapse and should not be used as a sole parameter for therapeutic intervention. In addition, our results suggest that serial anti-myeloperoxidase determination may be useful as a prognostic marker in patients who are p-ANCA positive.

Pathophysiology and treatment of idiopathic hypercalciuria.

Nearly 50 years after its initial description by Dr. F. Albright, the term idiopathic hypercalciuria (IH) is still in use. The exact mechanism of hypercalciuria is still unknown despite extensive pathophysiologic investigations; recent advances represent the focus of this review. A precise definition of true IH is proposed, taking into account the various nutritional conditions influencing calcium excretion. The potential pathogenic mechanisms are discussed, and the limits of the classical Pak's pathophysiological classification are recalled. The evidence supporting the role of an increased intestinal calcium absorption, a defect in renal tubular calcium reabsorption, or an increased bone loss as a primary mechanism in IH are successively examined. Since overall available human data indicates that all three mechanisms may be found in IH, the hypothesis that a broader disorder encompassing all these various abnormalities may be involved in IH is discussed. Three global hypotheses to account for IH physiopathology are examined: a diffuse defect in fatty acid content of cell membranes, an increased expression of the vitamin D receptor of the 25(OH) vitamin D 1 alpha-hydroxylase, or of the calcium sensor receptor and a monocyte disease. Finally, the available clinical data justifying the therapeutic approaches are reviewed, and guidelines for dietary recommendations regarding calcium and also animal protein, sodium chloride, alcohol, carbohydrate, phosphate, and potassium intakes are proposed, and drug therapy indications are discussed.

Low bone mineral density and peripheral blood monocyte activation profile in calcium stone formers with idiopathic hypercalciuria.

Calcium stone formers (CaSF) with idiopathic hypercalciuria (IH) have been shown to have decreased bone mineral density (BMD). The mechanism of their bone loss remains obscure. Monokines like interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte macrophage stimulating factor (GM-CSF) are involved in bone remodeling, but only IL-1 excess has been incriminated in the bone loss of CaSF with IH. Therefore, to more precisely delineate the role of monocyte activation in the pathogenesis of bone loss in these patients, we studied the production of IL-1 beta, IL-6, TNF-alpha, and GM-CSF by unstimulated or lipopolysaccharide (LPS)-stimulated cultured peripheral blood monocytes in 15 CaSF with IH, in 10 CaSF with dietary calcium-dependent hypercalciuria (DH), and in 10 healthy controls (C). Cytokines were measured in the culture medium by sensitive enzyme-linked immunosorbent assay and vertebral BMD by single energy computed tomography. The decrease of vertebral BMD in IH compared with DH, was confirmed (Z score: -1.2 +/- 0.2 vs. -0.5 +/- 0.2; P = 0.04; Mann-Whitney). In the supernatant of unstimulated peripheral blood monocytes, IL-1 beta and TNF-alpha levels were higher in IH than in C (respectively, 40 +/- 21 vs. 7 +/- 1 pg/mL, P = 0.008 and 236 +/- 136 vs. 39 +/- 23 pg/mL, P = 0.03); those of GM-CSF were greater in IH than in DH and C (respectively, 52 +/- 27 vs. 6 +/- 2, P = 0.04 and 6 +/- 2 pg/mL, P = 0.01) and those of IL-6 were not significantly different among the groups. After in vitro stimulation by LPS (10 micrograms/mL), the levels of the various monokines were not significantly different. In IH patients, the post-LPS levels of IL-6 were negatively correlated to vertebral BMD (n = 15, Z = -1.97, P = 0.04; Spearman), whereas those of GM-CSF were positively related to vertebral BMD (n = 15, Z = 2.01, P = 0.04). In this study, calcium stone formers with IH have bone mineral decrease and a particular profile of peripheral blood monocytes activation. This latter is characterized by a spontaneously increased synthesis of IL-1 beta, TNF-alpha, and GM-CSF. Furthermore, post-LPS levels of IL-6 and GM-CSF are correlated with vertebral BMD. These results suggest that monocyte activation may be involved in the bone loss of calcium stone formers with IH.

[Bone involvement in idiopathic calcium lithiasis]. / Atteinte osseuse dans la lithiase calcique idiopathique.

Bone involvement in idiopathic calcium nephrolithiasis is characterized by the following abnormalities: a) the bone density is decreased, the severity of bone loss being dependent upon the existence of hypercalciuria and upon the pathophysiology of this latter: it is inconsistent in the absence of hypercalciuria or when hypercalciuria is of the absorptive type I or II, whereas it is almost constant in fasting hypercalciuria without secondary hyperparathyroidism and constant and severe in the rare true renal hypercalciuria. b) The bone histology (which has been evaluated only in idiopathic hypercalciuric patients) mainly shows a defect in bone formation at the exception of the rare renal hypercalciuria. Osteoclastic hyperresorption is only seen in this latter type of hypercalciuria whereas in the other types of hypercalciuria only an increase of the total or inactive resorption surface is observed. This phenomenon is possibly explained only by a delayed refilling of the resorption lacunae secondary to the decreased bone formation. The osteoid thickness is either normal or decreased despite decrease in mineralization apposition rate which seems therefore to be secondary to the decreased bone formation. c) Symptomatic bone disease in hypercalciuric stone formers is exceptional and always related to a severe long term calcium restriction. d) The biochemical markers of bone resorption tend to be increased in idiopathic hypercalciuria. Hydroxyprolinuria is more often elevated than pyridinolinuria. However pyridinolinuria is negatively correlated to bone density. The contrast between the increase of these bone resorption markers and the usual normality of plasma PTH and of the osteoclastic resorptive surfaces, suggest the role of meat induced acid load which may favor inactive resorption by dissolution of bone buffers. A disturbed profile synthesis of cytokines which induce differentiation and proliferation of the osteoclasts and which modulate the osteoblastic proliferation and function (IL-1, IL-6, TNF-alpha, GM-CSF...) may play a role in the bone loss of calcium stone formers but further studies are necessary to precise its transient or permanent involvement in their bone disease. e) The decrease of bone formation may be explained by the suppressed PTH secretion which may be explained by hypercalcitriolemia. This excess of calcitriol synthesis may be secondary either to monocyte increased synthesis of IL-1 which stimulates the renal 1 alpha-hydroxylase by the mean of an increased PGE2 synthesis or to the relative hypophosphatemia of the calcium stone formers comparatively to healthy controls. Hypercalcitriolemia may originate from the activated monocyte itself. The decrease in bone formation may also be secondary to the action of monokines on the osteoblast differentiation and/or function.