Is cholecalciferol a potential disease-modifying anti-rheumatic drug for the management of rheumatoid arthritis?

Vitamin D is a pleiotropic molecule with a well-characterised immunomodulatory activity in vitro; however, its potential clinical application in autoimmune conditions has yet to be clarified. Several authors have investigated the use of vitamin D as a disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA), obtaining divergent conclusions. This systematic review summarises and critically analyses the findings of papers assessing the impact of vitamin D supplementation on pain relief, disease activity, functional status and flare rate. We conclude that the correction of hypovitaminosis D may have a beneficial effect on pain perception; moreover, the achievement of an adequate plasma vitamin D concentration obtained with high-dose regimens might evoke immunomodulatory activities of vitamin D and favourably impact on disease control. Nevertheless, the current evidence is still not strong enough to support the use of cholecalciferol as a DMARD in RA, and further studies are required to clarify this issue.

Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

BACKGROUND: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV). METHODS: Patients with COVID-19 pneumonia admitted up to May 28th, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan. RESULTS: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes. CONCLUSIONS: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Pattern of Emergency Department referral during the COVID-19 outbreak in Italy.

BACKGROUND: The Coronavirus disease (COVID-19) outbreak is putting the European National Health Systems under pressure. Interestingly, Emergency Department (ED) referrals for other reasons than COVID-19 seem to have declined steeply. In the present paper, we aimed to verify how the COVID-19 outbreak changed ED referral pattern. METHODS: We retrospectively reviewed the clinical records of patients referred to the ED of a University Hospital in Northern Italy from 1 March to 13 April 2020. We compared the following data with those belonging to the same period in 2019: number of EDs accesses, rate of hospital admission, frequencies of the most common causes of ED referral, priority codes of access. RESULTS: The number of ED referrals during the COVID-19 outbreak was markedly reduced when compared to the same period in 2019 (3059 vs. 5691; -46.3%). Conversely, the rate of hospital admission raised from 16.9% to 35.4% (P<0.0001), with a shift toward higher priority codes of ED admission. In 2020, we observed both a reduction of the number of patients referred for both traumatic (513, 16.8% vs. 1544, 27.1%; χ2=118.7, P<0.0001) and non-traumatic (4147 vs. 2546) conditions. Among the latter, suspected COVID-19 accounted for 1101 (43.2%) accesses. CONCLUSIONS: The COVID-19 pandemic completely changed the pattern of ED referral in Italy, with a marked reduction of the accesses to the hospitals. This could be related to a limited exposure to traumas and to a common fear of being infected during EDs in-stay. This may limit the misuse of EDs for non-urgent conditions but may also delay proper referrals for urgent conditions.

Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge.

Importance: Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown. Objective: To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge. Design, Setting, and Participants: This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription-polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results. Exposure: Severe COVID-19 requiring hospitalization. Main Outcomes and Measures: The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (Dlco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as Dlco <60% expected value); proportion of patients with posttraumatic stress symptoms (measured using the Impact of Event Scale-Revised total score); proportion of patients with functional impairment (assessed using the Short Physical Performance Battery [SPPB] score and 2-minute walking test); and identification of factors associated with Dlco reduction and psychological or functional sequelae. Results: Among 767 patients hospitalized for severe COVID-19, 494 (64.4%) refused to participate, and 35 (4.6%) died during follow-up. A total of 238 patients (31.0%) (median [interquartile range] age, 61 [50-71] years; 142 [59.7%] men; median [interquartile range] comorbidities, 2 [1-3]) consented to participate to the study. Of these, 219 patients were able to complete both pulmonary function tests and Dlco measurement. Dlco was reduced to less than 80% of the estimated value in 113 patients (51.6%) and less than 60% in 34 patients (15.5%). The SPPB score was suggested limited mobility (score <11) in 53 patients (22.3%). Patients with SPPB scores within reference range underwent a 2-minute walk test, which was outside reference ranges of expected performance for age and sex in 75 patients (40.5%); thus, a total of 128 patients (53.8%) had functional impairment. Posttraumatic stress symptoms were reported in a total of 41 patients (17.2%). Conclusions and Relevance: These findings suggest that at 4 months after discharge, respiratory, physical, and psychological sequelae were common among patients who had been hospitalized for COVID-19.

Role of positron emission tomography in the assessment of disease burden and risk of relapse in patients affected by giant cell arteritis.

Giant cell arteritis (GCA) is characterized by two subsets: cranial GCA and large-vessel GCA (LV-GCA); positron emission tomography (PET) is an essential tool in the diagnosis of LV-GCA. In this study, we aimed to investigate its potential prognostic value in the stratification of relapse risk. We retrospectively revised all the clinical records of patients who received a diagnosis of GCA at an immuno-rheumatology clinic of a University Hospital along 6 years and who underwent to a PET-CT examination at diagnosis. Clinical, laboratory, and imaging data were collected. Relapses were recorded. The study population included 19 patients (10 females, 52.6%; median age 74.0 [65.5-76.0] years), 12 with typical cranial GCA (63%) and 7 (37%) with LV-GCA. Based on PET findings, a diagnosis of aortitis was made in 15/19 patients, including 8/12 patients with a classical cranial GCA (58%). Along a median follow-up of 15 months [4.5-26.5], 4 relapses were observed. All relapsers were male; indeed, the difference in gender distribution was the only variable reaching statistical difference between relapsers and non-relapsers. Specifically, aortitis was not more frequent among relapsers. Our study confirms PET as a valid tool in the identification of LV-GCA with no cranial involvement. We failed to demonstrate a role for PET in the prognostic stratification of GCA, while male gender is suggested as a potential risk factor for GCA relapse.Key Points• A significant proportion of patients with GCA presents with non-cranial disease, the identification of which requires imaging studies, among which PET is particularly useful.• Aortitis might be detected also in patients with the classical, cranial GCA type but does not seem to have prognostic implications, at least in terms of relapse risk.• Male gender is suggested as a risk factor for relapse in GCA.

Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring ß-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases.