Efficacy and Safety of Sarilumab in patients with COVID19 Pneumonia: A Randomized, Phase III Clinical Trial (SARTRE Study).

INTRODUCTION: SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS). METHODS: We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15. RESULTS: A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48-2.20). No relevant safety issues were identified. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.

Involving Individuals with Disorders of Sex Development and Their Parents in Exploring New Models of Shared Learning: Proceedings from a DSDnet COST Action Workshop.

The level of connection between health care professionals and people who experience a condition that affects sex development is variable. These people and associated support groups need to be included in discussions about research and healthcare delivery. The aim of this study was to understand the experiences of individuals with disorders of sexual development (DSD), their parents, health care providers, and support groups. Workshop planning, preparation, delivery, and evaluation involved members of working groups from the COST Action DSDnet. A coordinator, in collaboration with a support group representative, led the workshop design and delivery. Our successful, facilitated workshop involved 33 attendees from 8 EU countries. The workshop provided individuals with DSD, parents, advisory groups, and professionals with an opportunity for shared learning. Outputs focused on 7 key areas, including diagnosis, childhood, and transition to adult care as well as fostering discussion around registries, future research topics, consent processes, and information needs across the life course. The importance of trustworthy and knowledgeable providers, time to understand such rare conditions, and the place support groups have in a life course approach were valuable learning points for all attendees. In conclusion, workshops can be designed and delivered in meaningful ways for all those involved in care of individuals with rare conditions.

Understanding the needs of professionals who provide psychosocial care for children and adults with disorders of sex development.

OBJECTIVE: Disorders in sex development (DSD) can be treated well medically, but families will encounter many psychosocial challenges. Promoting counselling to facilitate acceptance and coping is important yet equality of access is unknown. This study investigated the modalities of psychosocial care provided in centres of DSD care. METHODS: An international survey conducted among 93 providers of psychosocial care, identified through clinical networks, registries and professional forums. RESULTS: Forty-six respondents from 22 different countries filled out the survey (49%). Most respondents (78%) were based in hospital-based expert teams. Referrals came from paediatric endocrinologists (76%), gynaecologists (39%) and paediatric urologists (37%). Psychological counselling was most frequently given to parents (74%), followed by children (39%), adolescents (37%) and adults (11%) and was most frequently focused on coping and acceptance of DSD (54%), education (52%), the atypical body (39%) and genital (41%), decisions on genital surgery (33%), complications with sexual intercourse (29%), disclosure (28%) and acceptance of infertility (11%). Respondents most frequently observed DSD related confusion about gender (54%), acceptance of cross gender behaviour (50%), anxiety (43%) and sadness and depression (38%). CONCLUSIONS: Most psychosocial care is provided to parents. It is assumed that parental support is important as acceptance is conditional to become affectionate caretakers. Although it may be more difficult for youngsters to communicate about their condition and treatment, providing opportunity to bring up issues that are important for them, is imperative. Clinicians and parents should be aware that parental and patients' interests may not correspond completely. Psychosocial management should also include transition and adult care.

Current models of care for disorders of sex development - results from an International survey of specialist centres.

BACKGROUND: To explore the current models of practice in centres delivering specialist care for children with disorders of sex development (DSD), an international survey of 124 clinicians, identified through DSDnet and the I-DSD Registry, was performed in the last quarter of 2014. RESULTS: A total of 78 (63 %) clinicians, in 75 centres, from 38 countries responded to the survey. A formal national network for managing DSD was reported to exist in 12 (32 %) countries. The paediatric specialists routinely involved in the initial evaluation of a newborn included: endocrinologist (99 %), surgeon/urologist (95 %), radiologist (93 %), neonatologist (91 %), clinical geneticist (81 %) and clinical psychologist (69 %). A team consisting of paediatric specialists in endocrinology, surgery/urology, clinical psychology, and nursing was only possible in 31 (41 %) centres. Of the 75 centres, 26 (35 %) kept only a local DSD registry and 40 (53 %) shared their data in a multicentre DSD registry. Attendance in local, national and international DSD-related educational programs was reported by 69, 78 and 84 % clinicians, respectively. Participation in audits/quality improvement exercises in DSD care was reported by 14 (19 %) centres. In addition to complex biochemistry and molecular genetic investigations, 40 clinicians (51 %) also had access to next generation sequencing. A genetic test was reported to be more preferable than biochemical tests for diagnosing 5-alpha reductase deficiency and 17-beta hydroxysteroid dehydrogenase 3 deficiency by 50 and 55 % clinicians, respectively. CONCLUSION: DSD centres report a high level of interaction at an international level, have access to specialist staff and are increasingly relying on molecular genetics for routine diagnostics. The quality of care provided by these centres locally requires further exploration.

Panhypopituitarism due to Absence of the Pituitary Stalk: A Rare Aetiology of Liver Cirrhosis.

Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD). We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism.

Risk of mortality and predisposing factors after osteoporotic hip fracture: a one-year follow-up study.

BACKGROUND AND AIMS: To determine mortality and predisposing factors in patients with fracture of the proximal femur, one year after the initial fracture, in a tertiary hospital in Castile and Leon (Spain). METHODS: Observational case-control study. Patients aged ≥65 years admitted to the orthopedic surgery department of the Rio Hortega Hospital, a tertiary care hospital with approximately 560 beds, due to non-traumatic hip fracture between September 2005 and November 2006, were included. An age-matched control group of 81 institutionalized patients with similar characteristics was recruited. A protocolized telephone interview and a review of hospital medical records was made at 12 months followup. RESULTS: Of the 170 patients recruited, the final analysis was made in 139: 121 (87.1%) women and 18 (12.9%) men. The control group was formed of 81 patients: 64 (79%) women and 17 (21%) men. Mortality was 41.7% in the study group and 2.5% in controls (p; 0.001). Mortality was 31% in month 1, 24.1% between months 2 and 6 and 29.3% between months 6 and 12 (in 15.6% the date of death was unknown). Factors associated with mortality were: age >86 years (p; 0.024); prior cognitive deterioration (p; 0.011); prior locomotor disorder (p; 0.047); male gender (p; 0.017); heart disease (p; 0.042). CONCLUSIONS: Patients with hip fracture, had substantially higher mortality than comparable healthy people, and mortality was highest in the first six months after fracture. Age and prior comorbidities were associated with excess mortality.

HIV type 1 viral encephalitis after development of viral resistance to plasma suppressive antiretroviral therapy.

HIV-1 viral encephalitis produced by antiretroviral-resistant strains in cerebrospinal fluid (CSF), despite suppression of plasma HIV-1 RNA, has been rarely described. We report two cases of symptomatic viral encephalitis demonstrated by clinical, magnetic resonance imaging (MRI), and an inflammatory CSF profile. Viral load in CSF was 24,000 and 6850 copies/ml, whereas plasma HIV RNA level was undetectable since the beginning of therapy. A resistance test in CSF showed genotypic mutations confering resistance to the drugs the patients received for more than 2 years. In the two cases, a high baseline HIV RNA level, a low nadir CD4(+) count, and suboptimal CSF levels of atazanavir were considered as the risk factors for developing encephalitis. The two cases did not resolve with a change to antiretroviral drugs with better CNS penetration, but they had complete clinical and MRI recovery after changing to therapy considering both CNS viral resistance and penetration.