Suppression of Pituitary Hormone Genes in Subjects Who Died From COVID-19 Independently of Virus Detection in the Gland.

CONTEXT: Involvement of the pituitary gland in SARS-CoV-2 infection has been clinically suggested by pituitary hormone deficiency in severe COVID-19 cases, by altered serum adrenocorticotropic hormone (ACTH) levels in hospitalized patients, and by cases of pituitary apoplexy. However, the direct viral infection of the gland has not been investigated. OBJECTIVE: To evaluate whether the SARS-CoV-2 genome and antigens could be present in pituitary glands of lethal cases of COVID-19, and to assess possible changes in the expression of immune-related and pituitary-specific genes. METHODS: SARS-CoV-2 genome and antigens were searched in the pituitary gland of 23 patients who died from COVID-19 and, as controls, in 12 subjects who died from trauma or sudden cardiac death. Real-time reverse transcription polymerase chain reaction (PCR), in situ hybridization, immunohistochemistry, and transmission electron microscopy were utilized. Levels of mRNA transcripts of immune-related and pituitary-specific genes were measured by the nCounter assay. RESULTS: The SARS-CoV-2 genome and antigens were detected in 14/23 (61%) pituitary glands of the COVID-19 group, not in controls. In SARS-CoV-2-positive pituitaries, the viral genome was consistently detected by PCR in the adeno- and the neurohypophysis. Immunohistochemistry, in situ hybridization, and transmission electron microscopy confirmed the presence of SARS-CoV-2 in the pituitary. Activation of type I interferon signaling and enhanced levels of neutrophil and cytotoxic cell scores were found in virus-positive glands. mRNA transcripts of pituitary hormones and pituitary developmental/regulatory genes were suppressed in all COVID-19 cases irrespective of virus positivity. CONCLUSION: Our study supports the tropism of SARS-CoV-2 for human pituitary and encourages exploration of pituitary dysfunction after COVID-19.

Evaluation of Safety and Efficacy of ReHub in Patients Who Underwent Primary Total Knee Arthroplasty: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Total Knee Arthroplasty (TKA) is an intervention that can significantly improve the quality of life of patients with advanced knee osteoarthritis. Early start of rehabilitation and its continuation at home once the patient is discharged are key factors for the success of the process.This study aims to assess the effectiveness of a home-based telerehabilitation solution (ReHub) on improving functional capacity and clinical outcomes for patients who underwent TKA. METHODS/DESIGN: The study is a randomized, open-label with blinded outcome assessor, parallel assignment clinical trial with a sample size of 52 patients that is conducted according to the SPIRIT recommendations. After the TKA intervention, the patients are randomly allocated to the control group or the experimental group with a 1:1 ratio. Both groups follow a Fast Track recovery protocol which includes discharge after 2-3 days from surgery, a daily plan of 5 exercises for autonomous rehabilitation and domiciliary visits by a physiotherapist starting approximately 2 weeks after surgery. The experimental group uses the sensor-based telerehabilitation system ReHub to perform the exercises. The primary outcome measure is the range of motion of the knee. Secondary outcomes include physical performance, quality of life, pain intensity, muscle strength, treatment adherence and satisfaction with the ReHub system. The outcomes assessment is performed at hospital discharge (baseline), at stitch removal (2 weeks after baseline) and 2 weeks after stitch removal (4 weeks after baseline).The study conforms to the guidelines of the Declaration of Helsinki and was approved by the hospital's ethics committee. DISCUSSION: The study will address an important gap in the evidence base by reporting the effectiveness of an affordable and low-cost home-based telerehabilitation solution in patients who underwent TKA. ETHICS AND DISSEMINATION: The study was approved by the hospital's ethics committee ("Comité Ético de Investigación Clínica del HCB", reg. HCB/2019/0571). The trial was registred at ClinicalTrials.gov (NCT04155957). The results of this study will be published in peer-reviewed journals as well as national and international conferences. TRIAL REGISTRATION: NCT04155957 (ClinicalTrials.gov). HIGHLIGHTS: Assessing a home-based telerehabilitation solution effectiveness in knee surgery.In situations such as the CoVid-19 pandemic, it is a resolutive intervention method.Telerehabilitation is an alternative to conventional face-to-face physical therapy.This system is far less demanding in terms of human resources.Range of motion assessment is the primary outcome measure.

Give more data, awareness and control to individual citizens, and they will help COVID-19 containment.

The rapid dynamics of COVID-19 calls for quick and effective tracking of virus transmission chains and early detection of outbreaks, especially in the "phase 2" of the pandemic, when lockdown and other restriction measures are progressively withdrawn, in order to avoid or minimize contagion resurgence. For this purpose, contact-tracing apps are being proposed for large scale adoption by many countries. A centralized approach, where data sensed by the app are all sent to a nation-wide server, raises concerns about citizens' privacy and needlessly strong digital surveillance, thus alerting us to the need to minimize personal data collection and avoiding location tracking. We advocate the conceptual advantage of a decentralized approach, where both contact and location data are collected exclusively in individual citizens' "personal data stores", to be shared separately and selectively (e.g., with a backend system, but possibly also with other citizens), voluntarily, only when the citizen has tested positive for COVID-19, and with a privacy preserving level of granularity. This approach better protects the personal sphere of citizens and affords multiple benefits: it allows for detailed information gathering for infected people in a privacy-preserving fashion; and, in turn this enables both contact tracing, and, the early detection of outbreak hotspots on more finely-granulated geographic scale. The decentralized approach is also scalable to large populations, in that only the data of positive patients need be handled at a central level. Our recommendation is two-fold. First to extend existing decentralized architectures with a light touch, in order to manage the collection of location data locally on the device, and allow the user to share spatio-temporal aggregates-if and when they want and for specific aims-with health authorities, for instance. Second, we favour a longer-term pursuit of realizing a Personal Data Store vision, giving users the opportunity to contribute to collective good in the measure they want, enhancing self-awareness, and cultivating collective efforts for rebuilding society.

Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients.

PURPOSE: The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. METHODS: From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. RESULTS: Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5-28) days since symptoms' onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06-3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11-0.89, p = 0.029). CONCLUSION: Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.

Protocols and self-checking plans for the safety of post-COVID-19 balneotherapy.

During the COVID-19 pandemics, balneotherapic establishments were closed in Italy like in the rest of Europe. The Italian Foundation for Research in balneotherapy (FoRST) was asked to prepare a safety protocol to be proposed to the National Health Authorities to allow the establishments to restart their activity when possible, under safe conditions (the so-called Phase-2). The group of experts proposed the following hygienic and sanitary protocols of risk management for the initial reopening of the balneology settings in Italy. The plan aims to define the operating procedures to be implemented at the balneology establishments for the beginning of Phase-2 and to keep them constantly updated in the different periods that will characterize Phase-2 in relation to the trends of the disease. To this end the procedures, defined on the basis of the scientific state-of-the-art available today, will be updated and revised from time to time whenever further scientific evidence and directives from the Health Authorities make it necessary and/or useful.