2022 Recommendations of the AFU Lithiasis Committee: Medical management - from diagnosis to treatment.

The morphological-compositional analysis of urinary stones allows distinguishing schematically several situations: dietary, digestive, metabolic/hormonal, infectious and genetic problems. Blood and urine testing are recommended in the first instance to identify risk factors of urinary stone disease in order to avoid recurrence or progression. The other objective is to detect a potential underlying pathology associated with high risk of urinary stone disease (e.g. primary hyperparathyroidism, primary or enteric hyperoxaluria, cystinuria, distal renal tubular acidosis) that may require specific management. Lifestyle-diet measures are the basis of the management of all stone types, but pharmacological treatments may be required. METHODOLOGY: These recommendations were developed using two methods: the Clinical Practice Recommendation (CPR) method and the ADAPTE method, depending on whether the question was considered in the European Association of Urology (EAU) recommendations (https://uroweb.org/guidelines/urolithiasis) [EAU 2022] and their adaptability to the French context.

Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling.

Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5-deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5-deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm. Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages.

Composition of urinary calculi: Lessons from a French epidemiologic retrospective study.

INTRODUCTION: Urolithiasis is a common urological disease whose incidence increases in developed countries. We studied relations between composition of urinary calculi, age and gender. MATERIAL: An epidemiologic study was conducted in a French population of patients encountered analysis of urinary calculi between 2013 and 2017. This retrospective cohort study was performed from urinary calculi samples analysed in a clinical biochemistry laboratory of University Hospital of Lyon in France. A total of 5782 samples were included. Data, according to stone composition, presence of a papillary umbilication and a Randall's plaque, age and gender, were investigated. Statistical analyses used the Chi2 test (R software). RESULTS: The overall male to female sex ratio was equal to 1.76. The average and the median of age were 52.1 and 53.0 years, respectively. Whewellite was the most frequent main component in our population (44.4%). Carbapatite, weddellite and uric acid represented the main component in 14.0%, 13.4% and 13.0% of samples, respectively. Differences between genders were shown. Whewellite and uric acid were more frequent in men (P<0.001), while carbapatite and struvite were predominant in women (P<0.001). CONCLUSIONS: Our study provided recent data on the composition of urinary calculi in a French population and the relations between composition of urinary calculi and age and gender. LEVEL OF EVIDENCE: 3.

Pediatric victims involved in urban fires in Paris and its suburbs: Epidemiology, prehospital care, and lessons learned.

AIM: The literature includes few reports on the prehospital care of pediatric casualties of urban house fires. Here we aimed to describe the epidemiology of pediatric fire victims, focusing on their injuries, prehospital care, and survival. METHODS: This retrospective study included children under 15 years of age who were victims of urban house fires and who received care from prehospital medical teams. The variables analyzed included epidemiology, specific care provided by prehospital emergency services, the number of cardiac arrests, and survival rates. RESULTS: Over the 15-month study period, 365 house fires required the presence of at least one prehospital medical team. Casualties of these fires included 121 pediatric victims (median age, 4 years [interquartile range: 2-9 years]). All children were initially treated by a prehospital medical team that was not specialized in pediatrics. Six children (4.9%) received secondary treatment from a pediatric support team. Of the 121 children, 114 (94.2%) suffered from smoke inhalation and seven (5.8%) from burns. Two patients who were in cardiac arrest at their initial medical care did not survive. CONCLUSION: Pediatric fire casualties were initially managed by prehospital medical teams that were not specialized in pediatrics. As in adults, the main injuries were secondary to smoke inhalation, but this has increased toxicity in children. Prehospital teams not specialized in pediatrics can optimize their practice via the sharing of experiences, team training, and cognitive aid checklist for pediatric fire victims.

Omega-3 fatty acid intake and prevalent respiratory symptoms among U.S. adults with COPD.

BACKGROUND: Omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and derivatives, play a key role in the resolution of inflammation. Higher intake has been linked to decreased morbidity in several diseases, though effects on respiratory diseases like COPD are understudied. METHODS: The National Health and Nutrition Examination Survey (NHANES), with a focus on dietary assessment, provides a unique opportunity to explore relationships between omega-3 intake and morbidity in respiratory diseases marked by inflammation in the United States (US) population. We investigated relationships between ALA or EPA + DHA intake and respiratory symptoms among US adults with COPD, as well as variation in relationships based on personal characteristics or exposures. RESULTS: Of 878 participants, mean age was 60.6 years, 48% were current smokers, and 68% completed high school. Omega-3 intake was, 1.71 ± 0.89 g (ALA), and 0.11 ± 0.21 g (EPA + DHA). Logistic regression models, adjusting for age, gender, race, body mass index, FEV1, education, smoking status, pack-years, total caloric intake, and omega-6 (linoleic acid, LA) intake demonstrated no primary associations between omega-3 intake and respiratory symptoms. Interaction terms were used to determine potential modification of relationships by personal characteristics (race, gender, education) or exposures (LA intake, smoking status), demonstrating that at lower levels of LA intake, increasing ALA intake was associated with reduced odds of chronic cough (pint = 0.015) and wheeze (pint = 0.037). EPA + DHA, but not ALA, was associated with reduced symptoms only among current smokers who did not complete high school. CONCLUSIONS: Individual factors should be taken into consideration when studying the association of fatty acid intake on respiratory diseases, as differential responses may reveal susceptible subgroups.

Not only disease activity but also chronic hypertension and overweight are determinants of pregnancy outcomes in patients with systemic lupus erythematosus.

INTRODUCTION: Pregnancies in women with lupus nephritis are at high-risk of complications, while scarcity of scientific knowledge on prognostic factors impedes a fair medical counseling. We aimed to identify determinants associated with maternal and fetal complications. MATERIALS: We retrospectively reviewed medical charts of pregnancies that lasted more than 22 weeks in 66 patients with pre-existing lupus nephritis between 2004 and 2013 in France. Univariate and multivariate analyses were conducted to identify determinants for maternal complications, lupus renal flare and fetal prematurity or death. RESULTS: Eighty-four pregnancies were identified. A maternal complication occurred in 31 pregnancies (36.9%): mostly preeclampsia (17 pregnancies, 20.2%) and renal flares (12 pregnancies, 14.3%). Overall fetal survival was 94.0% (79/84). Maternal pregnancy complications were independently associated with prepregnancy body mass index >25 kg/m2 (OR 3.81, 95% CI 1.03-14.09) and immunological activity (positive anti-dsDNA antibodies or Farr assay lupus) (OR 4.95, 95% CI 1.33-18.43). Renal lupus flares were independently associated with maternal age (OR 1.50, 95% CI 1.12-2.01) and prepregnancy immunological activity (OR 15.99, 95% CI 1.57-162.68) while a remission time >12 months had a protective effect (OR 0.17, 95% CI 0.04-0.68). Three parameters were associated with a higher risk of fetal prematurity or death: a prepregnancy body mass index >25 kg/m2 (HR 3.58, 95% CI 1.45-8.83), hypertension (HR 8.97, 95% CI 3.32-24.25), and immunological activity (HR 3.34, 95% CI 1.30-8.63). CONCLUSION: Maternal age, prepregnancy hypertension, body mass index >25 kg/m2 and lupus immunological activity may be considered as the main determinants for fetal and maternal complications. A remission time above 12 months for patients with lupus nephritis could be associated with a reduced risk of renal flare during pregnancy.

Rehabilitation of distal radioulnar joint instability.

Distal radioulnar joint (DRUJ) instabilities are common and often combined with other injuries of the interosseous membrane and/or the proximal radioulnar joint. Once they are diagnosed and the treatment is chosen, physiotherapists have limited choices due to the lack of validated protocols. The benefits of proprioception and neuromuscular rehabilitation have been brought to light for the shoulder, knee and ankle joints, among others. However, no program has been described for the DRUJ. The purpose of this article is to study the muscular elements responsible for active DRUJ stability, and to propose a proprioceptive rehabilitation program suited to this condition.

Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.

BACKGROUND: There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. CASE PRESENTATION: A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. CONCLUSION: We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.

Estimated or Measured GFR in Living Kidney Donors Work-up?

The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web-based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD-EPI) and on MDRD-eGFR. GFR was measured using 51 Cr- ethylene-diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web-based tool was used to predict those with mGFR < 80 mL/min/1.73 m2 . Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web-based probability of mGFR <90 mL/min/1.73 m2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m2 . The positive predictive value was 0.19. A CKD-EPI-eGFR threshold of 104 mL/min/1.73 m2 and an MDRD-eGFR threshold of 100 mL/min/1.73 m2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m2 . We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web-based application to identify potential donors who should benefit from GFR measurement.

The mechanisms of cardio-protective effects of desflurane and sevoflurane at the time of reperfusion: anaesthetic post-conditioning potentially translatable to humans?

Myocardial conditioning is actually an essential strategy in the management of ischaemia-reperfusion injury. The concept of anaesthetic post-conditioning is intriguing, its action occurring at a pivotal moment (that of reperfusion when ischaemia reperfusion lesions are initiated) where the activation of these cardio-protective mechanisms could overpower the mechanisms leading to ischaemia reperfusion injuries. Desflurane and sevoflurane are volatile anaesthetics frequently used during cardiac surgery. This review focuses on the efficacy of desflurane and sevoflurane administered during early reperfusion as a potential cardio-protective strategy. In the context of experimental studies in animal models and in human atrial tissues in vitro, the mechanisms underlying the cardio-protective effect of these agents and their capacity to induce post-conditioning have been reviewed in detail, underlining the role of reactive oxygen species generation, the activation of the cellular signalling pathways, and the actions on mitochondria along with the translatable actions in humans; this might well be sufficient to set the basis for launching randomized clinical studies, actually needed to confirm this strategy as one of real impact.

Effect of lipopolysaccharide, cytokines, and catecholamines on brain natriuretic peptide release from human myocardium.

BACKGROUND: During sepsis and septic shock, elevated plasma concentrations of brain natriuretic peptide (BNP) have been reported but may be related to several underlying mechanisms. The aim of the present experimental study was to investigate the effect of lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), dobutamine (Dobu), epinephrine (Epi), and norepinephrine (Nor) on BNP synthesis by atrial human myocardium in vitro. METHODS: After the approval of local ethics committee, right atrial appendages were obtained during cannulation for cardiac surgery and pinned in a isolated organ bath containing 15 ml of Tyrode's modified solution. Preparations were oxygenated, maintained at 36 ± 0.5°C and stimulated at a frequency of 1 Hz. A 60-min equilibration period was followed by 180-min exposure to 1 µM endothelin 1 (ET-1; n = 9), 20,000 pg/ml TNF-α (n = 10), 1000 pg/ml IL-1ß (n = 10), 5000 pg/ml IL-6 (n = 10), 10,000 pg/ml LPS (n = 10), 100 µM Epi (n = 9), 100 µM Nor (n = 10), and 100 µM Dobu (n = 8). No product was added in Control group (n = 10). Two BNP dosages were performed: the first after 60 min of stabilization and the second after 180 min of stimulation. Absolute and relative changes in BNP concentration were compared between groups. RESULTS: Exposure to ET-1 significantly increased BNP release as compared with Control group. Dobu, Epi, Nor, and LPS significantly increased BNP concentration but not TNF-α, IL-1ß, or IL-6. CONCLUSIONS: In vitro, LPS, Dobu, Epi, and Nor induced BNP synthesis by human atrial myocardium.

Mechanisms involved in the desflurane-induced post-conditioning of isolated human right atria from patients with type 2 diabetes.

BACKGROUND: Desflurane triggers post-conditioning in the diabetic human myocardium. We determined whether protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels, Akt, and glycogen synthase kinase-3ß (GSK-3ß) were involved in the in vitro desflurane-induced post-conditioning of human myocardium from patients with type 2 diabetes. METHODS: The isometric force of contraction (FoC) of human right atrial trabeculae obtained from patients with type 2 diabetes was recorded during 30 min of hypoxia followed by 60 min of reoxygenation. Desflurane (6%) was administered during the first 5 min of reoxygenation either alone or in the presence of calphostin C (PKC inhibitor) or 5-hydroxydecanoate (5-HD) (mitoK(ATP) channel antagonist). Phorbol 12-myristate 13-acetate (PKC activator) and diazoxide (a mitoK(ATP) channel opener) were superfused during early reoxygenation. The FoC at the end of the 60 min reoxygenation period was compared among treatment groups (FoC(60); mean and sd). The phosphorylation of Akt and GSK-3ß was studied using western blotting. RESULTS: Desflurane enhanced the recovery of force [FoC(60): 79 (3)% of baseline] after 60 min of reoxygenation when compared with the control group (P>0.0001). Calphostin C and 5-HD abolished the beneficial effect of desflurane-induced post-conditioning (both P<0.0001). Phorbol 12-myristate 13-acetate and diazoxide enhanced the FoC(60) when compared with the control group (both P<0.0001). Desflurane increased the level of phosphorylation of Akt and GSK-3ß (P<0.0001). CONCLUSIONS: Desflurane-induced post-conditioning in human myocardium from patients with type 2 diabetes was mediated by the activation of PKC, the opening of the mitoK(ATP) channels, and the phosphorylation of Akt and GSK-3ß.