The Impact of COVID-19 on the Response to Hypoxia.

Louis, Alexandre, Charlotte Pröpper, Yann Savina, Corentin Tanne, Guy Duperrex, Paul Robach, Pascal Zellner, Stéphane Doutreleau, Jean-Michel Boulet, Alain Frey, Fabien Pillard, Cristina Pistea, Mathias Poussel, Thomas Thuet, Jean-Paul Richalet, and François Lecoq-Jammes. The impact of COVID-19 on the response to hypoxia. High Alt Med Biol. 24:321-328, 2023. Background: Severe high-altitude illness (SHAI) and coronavirus disease 2019 (COVID-19), while differing in most aspects of pathophysiology, both involve respiratory capacity. We examined the long-term impact of COVID-19 on response to hypoxia in individuals free of symptoms but having tested positive during the pandemic. The need for recommendations for such individuals planning a stay at high altitude are discussed. Methods: This multicenter study recruited participants from the multiSHAI cohort, all of whom had previously undergone a hypoxic exercise test. These participants were classified into two groups depending on whether they had since suffered mild-to-moderate COVID-19 (COVID+) or not (Control) and then asked to retake the test. Primary outcomes were: desaturation induced by hypoxia at exercise (ΔSpE), hypoxic cardiac response at exercise, hypoxic ventilatory response at exercise, and SHAI risk score. Results: A total of 68 participants retook the test, 36 classified in the COVID+ group. Analyses of primary outcomes showed no significant differences between groups. However, the COVID+ group showed significantly increased ventilation (VE) parameters during both hypoxic (p = 0.003) and normoxic exercise (p = 0.007). However, only the VE/oxygen consumption relationship during hypoxic exercise was significantly different. Conclusion: This study demonstrates no negative impact of COVID-19 on response to hypoxia as evaluated by the Richalet test. Clinical Trial Registration: NTC number: NCT05167357.

What altitude is safe for infants? An expert panel survey.

AIM: To assess advice given to parents who wish to travel to high altitudes with an infant and to provide guidance on this topic. METHOD: Using an anonymous self-report survey online, we collected information on the advice provided by practitioners, who practice in mountain environments, to parents who wish to travel to altitude with an infant. General practitioners and pediatricians working in the French Alps were asked about the maximum allowable altitude for different ages and the specific recommendations given. RESULTS: A total of 104 practitioners (39% general practitioners) responded to the study. Overall, to spend 1 day at altitude, practitioners recommended a median altitude of 1200, 1500, 1600, and 2000 m for infants under 1, 3, 12, and 24 months, respectively. Their main recommendations for infant protection focused on cold protection, increased hydration, and increased humidity level in the ambient air. Prevention of sudden infant death syndrome was essential according to the respondents. For infants with upper airway infection, most of the participants (90%, n = 94) recommended against traveling to altitude. CONCLUSION: This survey revealed a certain consensus about the maximum travel altitude to be recommended for infants.

Epidemiology, prevention methods, and risk factors of foot blisters in French trail ultramarathons.

BACKGROUND: Blisters are a common running injury and are known to limit runners' performance. There have been many studies on the subject with contrasting results. It would therefore be useful to describe more clearly blister epidemiology, blister prevention methods, and risk factors of blister development. METHODS: This study is a retrospective anonymous, post-race survey. Runners were contacted by email after races in France during the summer and autumn of 2021 and asked to fill-in an online survey about their experience with blisters and running experiences. RESULTS: Five hundred and thirty-three runners participated, of whom were 468 (88%) men and 47 women (12%), mean age 42±9.75. Sixty-one percent (N.=329) of runners applied blister prevention methods before the start of the race and 29% (N.=155) reported blisters at the end of the race. Most commonly used blisters prevention methods were: anti-friction cream 79% (N.=260), "anti-blister socks" 33% (N.=107), paper tape 13% (N.=44), and topical lemon application 11% (N.=36). Having a history of blisters in the past is strongly associated with blisters onset OR=15.950 (9.135-29.640; P<0.0001). Distances ran between 40 to 74 km appeared to be the less likely to cause blisters OR 0.188 (0.045-0.729; P=0.019). None of the studied blister prevention methods seemed to match the protective effect of running shorter distances. CONCLUSIONS: Having a history of previous blisters is a major risk factor for blister occurrence, while running shorter distances seems protective.

Cardiac involvement in pediatric hemolytic uremic syndrome.

BACKGROUND: Cardiac involvement is a known but rare complication of pediatric hemolytic uremic syndrome (HUS). We conducted a nationwide observational, retrospective case-control study describing factors associated with the occurrence of myocarditis among HUS patients. METHODS: Cases were defined as hospitalized children affected by any form of HUS with co-existent myocarditis in 8 French Pediatric Intensive Care Units (PICU) between January 2007 and December 2018. Control subjects were children, consecutively admitted with any form of HUS without coexistent myocarditis, at a single PICU in Lyon, France, during the same time period. RESULTS: A total of 20 cases of myocarditis were reported among 8 PICUs, with a mean age of 34.3 ± 31.9 months; 66 controls were identified. There were no differences between the two groups concerning the season and the typical, Shiga toxin-producing Escherichia coli (STEC-HUS), or atypical HUS (aHUS). Maximal leukocyte count was higher in the myocarditis group (29.1 ± 16.3G/L versus 21.0 ± 9.9G/L, p = 0.04). The median time between admission and first cardiac symptoms was of 3 days (range 0-19 days), and 4 patients displayed myocarditis at admission. The fatality rate in the myocarditis group was higher than in the control group (40.0% versus 1.5%, p < 0.001). Thirteen (65%) children from the myocarditis group received platelet transfusion compared to 19 (29%) in the control group (p = 0.03). CONCLUSION: Our study confirms that myocarditis is potentially lethal and identifies higher leukocyte count and platelet transfusion as possible risk factors of myocarditis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Renal Prognosis in Children With Tubulointerstitial Nephritis and Uveitis Syndrome.

INTRODUCTION: Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome. METHODS: We performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018. RESULTS: A total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m2 (4.9-62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (-4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m2 (60.3-152.7) and <90 ml/min per 1.73 m2 in 20 patients. CONCLUSION: In our study, nearly half of the patients had renal sequelae at last follow-up. Given the possible progression to chronic kidney disease, long-term monitoring of children with TINU syndrome is mandatory. Approximately a quarter of the children had asymptomatic uveitis suggesting all children presenting with TIN should undergo systematic ophthalmologic screening even in the absence of ocular signs.

Chronic kidney disease consecutive to chemotherapy for chondroblastic osteosarcoma: A report on 6 pediatric cases.

BACKGROUND: The management of osteosarcoma in children and adolescents is based on poly-chemotherapy including several nephrotoxic drugs (e.g. ifosfamide, methotrexate, and cisplatinum). Chronic renal toxicity is a frequent complication but stage 5 chronic kidney disease requiring dialysis is rare. We report here a series of six pediatric patients with osteosarcoma displaying chronic kidney disease after chemotherapy. CASE-DIAGNOSIS/TREATMENT: We retrospectively reviewed the medical charts, mainly for clinical history, timing between chemotherapy and development of tubulopathy and CKD, type of therapies and global evolution (chronic dialysis and further renal transplantation, n=2; death, n=1). Notably, all patients suffered from chondroblastic osteosarcoma. CONCLUSIONS: Advanced chronic kidney disease can be a complication of osteosarcoma management that could more frequently lead to dialysis and further transplantation. It would be interesting to identify specific risk factors of such renal toxicity. The chondroblastic sub-type may be associated with such susceptibility, but this needs to be confirmed.

Pediatric atypical hemolytic-uremic syndrome due to auto-antibodies against factor H: is there an interest to combine eculizumab and mycophenolate mofetil?

BACKGROUND: Atypical hemolytic and uremic syndrome (aHUS), a thrombotic micro-angiopathy (TMA) caused by deregulation in the complement pathway, is sometimes due to the presence of anti-complement factor H (CFH) auto-antibodies. The "standard" treatment for such aHUS combines plasma exchange therapy and immunosuppressive drugs. Eculizumab, a monoclonal antibody that blocks the terminal pathway of the complement cascade, could be an interesting alternative in association with an immunosuppressive treatment for maintenance regimen. CASE-DIAGNOSIS/TREATMENT: We report on two children, diagnosed with mildly severe aHUS due to anti-CFH antibodies, who were treated with the association eculizumab-mycophenolate mofetil (MMF). Neither side effects nor relapses were observed during the 3 years of follow-up; MMF was even progressively tapered and withdrawn successfully in one patient. CONCLUSIONS: The association of eculizumab and MMF appears to be an effective and safe option in pediatric cases of aHUS due to anti-CFH antibodies of mild severity.

Outbreak of Shiga toxin-producing Escherichia coli (STEC) O26 paediatric haemolytic uraemic syndrome (HUS) cases associated with the consumption of soft raw cow's milk cheeses, France, March to May 2019.

We report an outbreak of Shiga toxin-producing Escherichia coli (STEC) associated paediatric haemolytic uraemic syndrome linked to the consumption of raw cow's milk soft cheeses. From 25 March to 27 May 2019, 16 outbreak cases infected with STEC O26 (median age: 22 months) were identified. Interviews and trace-back investigations using loyalty cards identified the consumption of raw milk cheeses from a single producer. Trace-forward investigations revealed that these cheeses were internationally distributed.

Cytomegalovirus infection in the first year after pediatric kidney transplantation.

Cytomegalovirus is common in adult recipients (prevalence of 40-90%). Children are typically seronegative but immunosuppression may prone to primary-infection or viral reactivation, with potentially severe consequences. CMV infection incidence in pediatric kidney transplant recipients has seldom been investigated. The aim of our study was to evaluate the incidence and timing of CMV infection during the first year after renal transplantation. We assembled a retrospective cohort of 136 children who had received a kidney transplant between 2003 and 2014 with a year follow-up. The patients were classified regarding CMV infection as high risk (D+/R-), intermediate risk (R+) or low risk (D-/R-). CMV infection was defined by the viral replication remaining asymptomatic whereas CMV disease concerned viral replication with clinical and/or biological symptoms. Oral valganciclovir was used as prophylaxis for high-risk recipients. A total of 38 patients (27.9%) developed CMV infection, 13 (40.6%) of the 32 D+/R-, 24 (45.3%) of the 53 R+ and 1 (2.0%) of the 51 D-/R-. Of these 38 infected patients, 10 developed tissue-invasive disease. During the first year after kidney transplantation, 27.9% of recipients developed CMV infection. This study confirms the influence of donor and recipient CMV status on infection propensity and highlights the importance of adequate follow-up for intermediate risk patients.

Donor-Related Coccidioidomycosis Transmitted Through Left-Liver Transplant to a Child Recipient in a Nonendemic Area.

This first observation of donor-transmitted coccidioidomycosis in a pediatric liver-transplant recipient underlines a rare condition in transplanted patients in a nonendemic area. This transmission was observed after a liver split, the patient being contaminated by the left liver while the right-liver recipient was not.