Vitamin D Levels as a Marker of Severe SARS-CoV-2 Infection.

The SARS-CoV-2 virus may cause severe infection, which is associated with diverse clinical manifestations. Vitamin D has immunomodulating properties and may enhance the body's defense system against invading pathogenic organisms. The aim was to assess 25(OH)D3 levels in patients hospitalized for severe infection from the SARS-CoV-2 virus and explore the relationship between 25(OH)D3 and outcomes. In a group of 88 patients hospitalized for severe infection from the SARS-CoV-2 virus and a control group matched for age and sex, the levels of 25(OH)D3 were analyzed. Levels of 25(OH)D3 were 17.36 ± 8.80 ng/mL (mean ± SD) compared with 24.34 ± 10.34 ng/mL in patients with severe SARS-CoV-2 infection and the control group, respectively, p < 0.001 (Student's t-test). 25(OH)D3 levels were significantly related to outcomes, i.e., survival as opposed to non-survival, as more patients with 25(OH)D3 deficiency (0-10 ng/mL) and insufficiency (10-20 ng/mL) had a fatal outcome as compared with those with vitamin D sufficiency (p < 0.001, chi-square test, p < 0.001, Fisher's exact test). Levels of 25(OH)D3 were inversely related to C-reactive protein (CRP), ferritin, d-dimer, and fibrinogen levels (p < 0.001, linear regression analysis, beta coefficient of variation, -0.176, -0.160, -0.178, and -0.158, respectively). Vitamin D deficiency observed in severe SARS-CoV-2 infection was related to disease outcomes.

Thyroid Disease and Systemic Lupus Erythematosus.

Background and Objectives: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. Materials and Methods: A cohort of 45 consecutive patients with a mean age of 47.97 years (range 21-79 years) and 45 age- and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. Results: Four patients (8.9%) were found to suffer from primary hypothyroidism, five (11.11%) from subclinical hypothyroidism and one (2.22%) from hyperthyroidism, whereas one (2.22%) of the controls had primary hypothyroidism and one (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile that was compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively (p < 0.05, chi-square test). Conclusions: In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population, and in a significant number of these patients, antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease, and this should be considered when evaluating patients with SLE.

Vitamin D and Autoimmune Rheumatic Diseases.

Vitamin D is a steroid hormone with potent immune-modulating properties. It has been shown to stimulate innate immunity and induce immune tolerance. Extensive research efforts have shown that vitamin D deficiency may be related to the development of autoimmune diseases. Vitamin D deficiency has been observed in patients with rheumatoid arthritis (RA) and has been shown to be inversely related to disease activity. Moreover, vitamin D deficiency may be implicated in the pathogenesis of the disease. Vitamin D deficiency has also been observed in patients with systemic lupus erythematosus (SLE). It has been found to be inversely related to disease activity and renal involvement. In addition, vitamin D receptor polymorphisms have been studied in SLE. Vitamin D levels have been studied in patients with Sjogren's syndrome, and vitamin D deficiency may be related to neuropathy and the development of lymphoma in the context of Sjogren's syndrome. Vitamin D deficiency has been observed in ankylosing spondylitis, psoriatic arthritis (PsA), and idiopathic inflammatory myopathies. Vitamin D deficiency has also been observed in systemic sclerosis. Vitamin D deficiency may be implicated in the pathogenesis of autoimmunity, and it may be administered to prevent autoimmune disease and reduce pain in the context of autoimmune rheumatic disorders.

Sarcopenia in patients with diabetes mellitus.

INTRODUCTION: Diseases such as diabetes mellitus may be associated with adverse changes in body composition. Sarcopenia is characterized by a progressive and generalized loss of skeletal muscle mass and functionality. AIM: To investigate the relationship between type 2 diabetes mellitus (T2DM) and sarcopenia. MATERIALS AND METHODS: In a retrospective, non-randomized study, 35 T2DM patients, aged 20-80 years, were assessed for sarcopenia prevalence compared to controls (n=16). Appendicular skeletal mass (ASM) (kg) was measured, and sarcopenia was defined as SMI <7.0 and <5.7 kg/m2, in males and females, respectively, using the European Working Group on Sarcopenia in Elderly (EWGOSP) definition. Low physical performance was defined as a walking speed of <0.8 m/s. RESULTS: Incidence of sarcopenia was significantly higher in T2DM patients vs. controls (27% vs. 20%, p=0.01) and elderly vs. young participants (40% vs. 12%, p<0.001), respectively. Walking velocity was significantly lower in T2DM patients compared to male and female controls (1.08±0.22 vs. 1.23±0.18 and 1.07±0.26 vs. 1.26±0.16, respectively, p<0.001,). CONCLUSIONS: A moderate prevalence of sarcopenia in patients with type 2 diabetes mellitus was observed, which appeared to increase significantly in older men. Finally, incidence of T2DM displayed decreased physical performance in both genders.

Vitamin D Deficiency in Primary Sjögren's Syndrome: Association with Clinical Manifestations and Immune Activation Markers.

Vitamin D is an agent involved in bone and mineral homeostasis. It has been recognized as a potent immunomodulator. It has immune-enhancing properties, and it induces immune tolerance. Vitamin D deficiency has been shown to be related to the development of autoimmune disorders. Vitamin D deficiency has been observed in patients with rheumatoid arthritis (RA) and it has been shown to be related with disease activity. Vitamin D deficiency has also been found in patients with systemic lupus erythematosus (SLE) and it was shown to be related to disease activity and renal involvement. Vitamin D deficiency has also been observed in multiple sclerosis. Vitamin D has been found to act as a supplemental therapeutic agent in multiple sclerosis. Sjögren's syndrome is a systemic autoimmune disease affecting the exocrine glands, known as an autoimmune epithelitis. The disease has a complex pathogenesis, requiring a genetic background, immune cell activation, and autoantibody production. The disease affects the exocrine glands, lacrimal, and salivary glands leading to ocular and oral dryness. Vitamin D levels have been measured in patients with Sjögren's syndrome and an association was observed between low vitamin D levels, peripheral neuropathy and the presence of lymphoma. In other cohorts, such as a Turkish cohort, vitamin D deficiency was observed in patients with Sjögren's syndrome. The aim is to measure serum vitamin D levels in consecutive patients with primary Sjögren's syndrome and investigate the relationship between vitamin D levels and the presence of immunologic markers, clinical, serological, and histopathological characteristics.

Vitamin D levels in Greek patients with systemic lupus erythematosus.

OBJECTIVES: Vitamin D deficiency has been observed in autoimmune rheumatic diseases, such as rheumatoid arthritis. The aim was to study vitamin D in patients with systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: In a cohort of 45 patients with SLE, 41 females and 4 males, aged 47.07 ± 2.17 years (mean ± SEM), and range = 21-79 years, 25(OH)D3 levels were determined by electrochemiluminescence. C3 and C4 levels were also analyzed. SLE disease activity was estimated by SLEDAI-2K. Observations were also performed in a control group matched for age and sex. RESULTS: In this cohort of SLE patients, 25(OH)D3 levels were 40.36 ± 2.41 nmol/L (mean ± SEM) as opposed to 60.98 ± 4.28 nmol/L in the control group (p < 0.001, Student's t test). Vitamin D levels were related to C3 (p < 0.001, linear regression analysis), correlation coefficient 0.106, r2 = 0.011, and C4 (p < 0.001); correlation coefficient 0.316 and r2 = 0.100; and inversely related to disease activity (p < 0.001), correlation coefficient -0.572 and r2 = 0.327. 25(OH)D3 levels were 17.73 ± 1.20 nmol/L and 12.24 ± 0.93 nmol/L, in the groups without and with renal involvement, respectively (p = 0.001, Student's t test). CONCLUSIONS: Vitamin D levels are low in SLE patients and are inversely related to disease activity. Routine screening for vitamin D levels should be performed in SLE patients.

Nutritional Pearls: Diet and Rheumatoid Arthritis.

Various studies have investigated the effect of diet on rheumatoid arthritis (RA) as a complimentary treatment along with standard drug therapy. Various types of diet have been investigated. Fasting, the Mediterranean diet, the Cretan Mediterranean diet, vegetarian diet, an anti-inflammatory diet and the use of various specific food substances have been in the focus of research interest. The relationship of obesity with disease activity in RA has also been investigated. A period of fasting followed by Mediterranean diet, the Cretan Mediterranean diet and an anti-inflammatory diet have been found to have a beneficial effect on disease activity in RA. Obesity has been found to be associated with increased disease activity in RA. However, weight loss appears to be related to increased mortality in RA. The use of flavonoids, resveratrol and curcumin may have a beneficial effect in RA. It appears that diet may aid in RA management as a complimentary factor to standard drug treatment.

The Effect of Omega-3 Fatty Acids on Rheumatoid Arthritis.

Omega-3 fatty acids are unsaturated fatty acids thought to play a role in health and disease. They are known as essential fatty acids, as they cannot be synthesized in mammals. Omega-3 fatty acids have a beneficial effect on the secondary prevention of coronary artery disease and stroke and are essential for the development and function of the nervous system and the retina in man. Omega-3 fatty acids are thought to have immunomodulatory properties as they act as precursors to lipid mediators of inflammation which may limit or modulate the inflammatory response. Omega-3 fatty acids seem to prevent or attenuate experimental arthritis. They may have a beneficial effect in the treatment of rheumatoid arthritis. Clinical studies have shown that omega-3 fatty acids may have a modulatory effect on disease activity, namely on the number of swollen and tender joints. It appears that omega-3 fatty acids may modulate disease activity in rheumatoid arthritis.

Low Prevalence of TERT Promoter, BRAF and RAS Mutations in Papillary Thyroid Cancer in the Greek Population.

Thyroid cancer is a common endocrine malignancy and displays a variety of histological patterns ranging from adenoma to malignant tumors. Molecular diagnostics have given significant insights into the genetic basis of thyroid tumorigenesis, known to be linked with signaling pathways affected by oxidative stress. We report for the first time a genotype study of TERT promoter combined with BRAF and RAS mutations in Papillary Thyroid Cancer (PTC) cases in the Greek population. Polymerase Chain Reaction and sequencing were used to identify TERT promoter (C228T, C250T, CC243-243TT) mutations, the BRAF (T1799A) mutation and mutations in codons 12, 13, 61 of the HRAS, KRAS and NRAS genes. The most common C228T TERT promoter mutation was identified in 2 PTC cases co-existing with the BRAF mutation. The BRAF T1799A mutation was detected in 10 PTC cases, while two different NRAS mutations in codon 61 (C181A and A182G) were found in 2 PTC cases. These mutations occur in a mutually exclusive manner. Our results indicate that despite the low frequencies, the study of the specific mutations should be encouraged because they are indicative of aggressive forms of thyroid cancer of the papillary histotype in this patient cohort, thus providing insights towards their therapeutic management.

Vitamin D in acutely ill patients.

Objective To investigate 25(OH)D3 levels and their relationship to survival in a cohort of acutely ill patients on admission to an intensive care unit. Methods This study enrolled acutely ill patients at admission to an intensive care unit and a group of sex- and age-matched healthy control subjects. The 25(OH)D3 levels were measured using an enzyme immunoassay. C-reactive protein and procalcitonin levels were also measured using immunoassays. Results A total of 50 acutely ill patients and 50 healthy control subjects were enrolled in the study. The mean ± SEM 25(OH)D3 levels were significantly lower in the acutely ill patients compared with the control group (11.74 ± 0.88 ng/ml versus 24.66 ± 1.60 ng/ml, respectively). The 25(OH)D3 levels were not related to survival. An inverse relationship was observed between 25(OH)D3 levels and C-reactive protein levels. A weak inverse relationship was also observed between 25(OH)D3 levels and procalcitonin levels. Conclusions The 25(OH)D3 levels were decreased in acutely ill patients admitted to an intensive care unit compared with healthy control subjects. 25(OH)D3 levels may be inversely related to C-reactive protein and procalcitonin levels.

Anti-synthetase syndrome presenting with interstitial lung disease.

Anti-synthetase syndrome is an idiopathic inflammatory myopathy characterized by interstitial lung involvement, arthritis, Raynaud's phenomenon, mechanic's hands and fever. The case of anti-synthetase syndrome in a young female is reported. The patient presented with interstitial lung disease, initially subclinical muscle involvement, Raynaud's phenomenon, arthritis and mechanic's hands. Induction therapy was administrated, that consisted of intravenous methylprednisolone and cyclophosphamide, followed by azathioprine and prednisone with good response, and finally, complete remission. The presence of mechanic's hands in a patient with lung involvement should prompt for specific investigations such as anti-synthetase antibodies and muscle enzymes. Anti-synthetase syndrome should be aggressively managed by immunosuppressive therapy, as interstitial lung disease is a severe manifestation of the disease which may affect quality of life and life expectancy.

High incidence of thyroid cancer among patients with acromegaly.

PURPOSE: Several studies have suggested that patients with acromegaly have an increased risk of thyroid, colorectal, breast and prostate cancers. In this study we determined the prevalence of malignant neoplasms in patients with acromegaly. METHODS: Cancer risk was evaluated in a cohort of 110 patients (M/F 48/62, age 58.63±13.8 years, range 30-86) with acromegaly. Mean age at diagnosis of acromegaly was 46.37±13.11 years. Mean period of time since diagnosis of acromegaly was 12.26+9.6 years. RESULTS: From 110 patients, cancer was diagnosed in 26 (23.6%) patients. Thyroid cancer was the most common cancer and was diagnosed in 13 patients (11.8%); other cancers encountered were gastric cancer (N=2), endometrial cancer (N-2), and breast cancer, colon cancer, prostate cancer (N-2), myelodysplastic syndrome, renal cell carcinoma, lung cancer and pancreatic carcinoma, one case each. Age, gender, age at the time of diagnosis of acromegaly, tumor size of pituitary adenoma and duration of disease were not associated with cancer development. CONCLUSIONS: This study suggests that patients with acromegaly have an increased risk of thyroid cancer and therefore they should undergo regular screening with hormonal and ultrasound evaluation of the thyroid and FNAB when required.

Vitamin D deficiency in a patient with HDR syndrome.

The case of a patient with clinical symptoms, laboratory and imaging findings of hypoparathyroidism, sensorineural deafness, renal dysplasia HDR, or Barakat syndrome (hypoparathyroidism, deafness, renal dysplasia), and vitamin D deficiency, is presented. A Caucasian man aged 51 years with a history of chronic hypocalcaemia since childhood, was admitted with hypertonia of the body and extremities, and loss of consciousness. On admission, he was found to have severe hypocalcaemia, hyperphosphataemia, severe hypoparathyroidism, low serum magnesium and mild renal insufficiency. Calcium gluconate was administered intravenously supplemented with magnesium, and the patient recovered consciousness while clinical and laboratory findings improved. Evaluation revealed left renal aplasia and sensorineural deafness affecting both ears. Vitamin D deficiency was also present. He was given calcium and vitamin D supplements orally, and the hypocalcaemia was corrected. This case is described as it is an extremely rare case of HDR syndrome with concurrent vitamin D deficiency.

Vitamin D and glycemic control in diabetes mellitus type 2.

OBJECTIVES: The extraskeletal effects of vitamin D have attracted considerable interest. Vitamin D deficiency appears to be related to the development of diabetes mellitus type 2 and the metabolic syndrome. Vitamin D may affect glucose homeostasis, vitamin D levels having been found to be inversely related to glycosylated hemoglobin levels in gestational diabetes mellitus. In addition, vitamin D appears to protect from the development of gestational diabetes mellitus. The aim was to study levels of 25-hydroxy vitamin D3 [25(OH)D3] and the relationship between 25(OH)D3 levels and glycemic control in patients with diabetes mellitus type 2. METHODS: Glycosylated hemoglobin (HbA1c) and 25(OH)D3 levels were measured in a group of 120 diabetes mellitus type 2 patients. The same measurements were performed in a group of 120 control subjects of the same age and sex. 25(OH)D3 was measured by radioimmunoassay and glycosylated hemoglobin (HbA1c) was measured by high-performance liquid chromatography. RESULTS: 25(OH)D3 levels were lower in the diabetes mellitus type 2 patients than in the control group, being 19.26 ± 0.95 ng/ml and 25.49 ± 1.02 ng/ml, in the patient and control groups, respectively (p < 0.001, Student's t-test). 25(OH)D3 levels were found to be inversely associated with HbA1c levels in the diabetic patients (p = 0.008, r (2) = 0.058, linear regression). 25(OH)D3 levels were found to be inversely associated with HbA1c when the patient and control groups were analysed together (p < 0.001, r (2) = 0.086). CONCLUSIONS: Vitamin D levels appeared to be lower in diabetes mellitus type 2 patients than in the control group, vitamin D levels being related to glycemic control in diabetes mellitus type 2. These findings may have therapeutic implications as cautious vitamin D supplementation may improve glycemic control in diabetes mellitus type 2.

Therapeutic applications of melatonin.

Melatonin is a methoxyindole synthesized within the pineal gland. The hormone is secreted during the night and appears to play multiple roles within the human organism. The hormone contributes to the regulation of biological rhythms, may induce sleep, has strong antioxidant action and appears to contribute to the protection of the organism from carcinogenesis and neurodegenerative disorders. At a therapeutic level as well as in prevention, melatonin is used for the management of sleep disorders and jet lag, for the resynchronization of circadian rhythms in situations such as blindness and shift work, for its preventive action in the development of cancer, as additive therapy in cancer and as therapy for preventing the progression of Alzheimer's disease and other neurodegenerative disorders.

Vitamin D and rheumatoid arthritis.

OBJECTIVES: Vitamin D deficiency has been implicated in the pathogenesis of autoimmune diseases, such as diabetes mellitus type 1 and multiple sclerosis. Reduced vitamin D intake has been linked to increased susceptibility to the development of rheumatoid arthritis (RA) and vitamin D deficiency has been found to be associated with disease activity in patients with RA. The objective was to evaluate vitamin D status in patients with RA and to assess the relationship between vitamin D levels and disease activity. METHODS: In a cohort of 44 patients with RA, 25-hydroxyvitamin D(3) [25(OH)D(3)] levels, parathyroid hormone levels, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured. Disease activity was evaluated by calculating the 28-joint Disease Activity Score (DAS28). A control group (n = 44), matched for age and sex, was evaluated as well. RESULTS: In the cohort of 44 patients with RA 25(OH)D(3) levels were found to be low compared with the control group, 25(OH)D(3) being 15.26 ± 1.07 ng/ml [mean ± standard error of the mean (SEM)] and 25.8 ± 1.6 ng/ml in the patient and control group respectively (Student's t test, p < 0.001). Parathyroid hormone levels were 71.08 ± 7.02 pg/ml (mean ± SEM) (normal values 10.0-65.0 pg/ml), CRP 7.6 ± 1.57 mg/litre (mean ± SEM) (normal values < 3 mg/litre) and ESR was 38.0 ± 4.6 mm/h (mean ± SEM) in the group of patients with RA. Levels of 25(OH)D(3) were found to be negatively correlated to the DAS28, the correlation coefficient being -0.084. Levels of 25(OH)D(3) were also found to be negatively correlated to CRP and ESR, the correlation coefficient being -0.115 and -0.18, respectively. CONCLUSION: It appears that vitamin D deficiency is highly prevalent in patients with RA, and that vitamin D deficiency may be linked to disease severity in RA. As vitamin D deficiency has been linked to diffuse musculoskeletal pain, these results have therapeutic implications. Vitamin D supplementation may be needed both for the prevention of osteoporosis as well as for pain relief in patients with RA.