Thyroid hormones modifications among COVID-19 patients undergoing pulmonary rehabilitation.

Introduction: Patients with severe COVID-19 often experience long-lasting disabilities that can improve after pulmonary rehabilitation. Moreover patients with severe COVID-19 display thyroid function alterations due to a non-thyroidal illness syndrome (NTIS). The aim of our study was to evaluate thyroid function parameters among patients hospitalized for COVID-19 who were eligible or not to respiratory rehabilitation and their modifications during follow-up. Materials and methods: Post-COVID-19 patients referred to a Respiratory Rehabilitation Unit were evaluated. Outpatients, not candidate for rehabilitation, were enrolled as Control group. Patients who had completed a 4-week-rehabilitation program were enrolled as Rehabilitation Group. All patients were evaluated at T0 (4 weeks after the discharge home in Control Group and after completion of rehabilitation in Rehabilitation Group) and at T1 (3 months after T0). Results: The final study group included 39 patients (20 in the Rehabilitation group and 19 in the Control group). Patients in the Rehabilitation Group had more frequently received invasive or non-invasive ventilation, had a longer length-of-stay in referring hospitals, had a higher number of comorbidities and displayed a worse performance at 6-minute-walking-test (6MWT) and Short-Physical-Performance-Battery-test (SPPB). FT3 values were lower at T0 in the Rehabilitation Group, while TSH and FT4 values were similar in the two groups. While no significant modifications in thyroid-function-parameters were observed in the Control Group, a significant increase in FT3 value was observed in the Rehabilitation Group at T1. Participants of both groups had improved the results of 6MWT at T1, while SPPB values improved only in the Rehabilitation Group. Conclusions: COVID-19 patients after pulmonary rehabilitation experience an increase in FT3 values during follow-up, paralleled with an amelioration of functional capabilities.

Efficacy of intra-articular polynucleotides in the treatment of knee osteoarthritis: a randomized, double-blind clinical trial.

This randomized, double-blind clinical trial was conducted over 16 weeks to assess the efficacy and safety profile of intra-articular polynucleotides gel injections in the treatment of knee osteoarthritis associated with persistent knee pain. 60 patients were enrolled and randomized to receive intra-articular polynucleotides (n = 30) or hyaluronan (n = 30); patients received five weekly intra-articular knee injections and the follow-up period was 3 months after the end of treatment. Primary endpoint was to determine polynucleotides (PN) efficacy in reducing knee pain at the end of the study, over baseline value and over standard hyaluronan viscosupplementation (HA). Pain levels were measured using a 0-10 cm Visual Analogue Scale (VAS). Secondary endpoints included Knee Osteoarthritis Outcome Score (KOOS), NSAIDs consumption, crackling during movement and articular mobility limitation. The mean global VAS pain decreased from 5.7 + or - 1.9 cm (T0) to 1.9 + or - 1.5 cm (T16) in polynucleotide group and from 4.9 + or - 2.0 cm (T0) to 2.1 + or - 1.4 cm (T16) in hyaluronan group. The reduction in pain was statistically significant for both groups. KOOS increases from baseline values were statistically significant in both groups. No significant adverse events were reported. These findings suggest that intra-articular polynucleotides can be a valid alternative to traditional hyaluronan supplementation for the treatment of knee osteoarthritis.

Neonatal Screening for Congenital Hypothyroidism: What Can We Learn From Discordant Twins?

CONTEXT: Newborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates. OBJECTIVES: To estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH. DESIGN AND PATIENTS: Forty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH. RESULTS: Seven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors. CONCLUSIONS: This study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.

Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis.

CONTEXT: Congenital hypothyroidism (CH) is a common endocrine disorder with an incidence of 1:3000-4000 at birth. In 80-85% of cases, CH is caused by defects in thyroid organogenesis, resulting in absent, ectopically located, and/or severely reduced gland [thyroid dysgenesis (TD)]. Mutations in genes controlling thyroid development have demonstrated that in a few cases, TD is a Mendelian trait. However, accumulating evidence supports the view that the genetics of TD are complex, possibly with a polygenic/multifactorial basis. A higher prevalence of congenital heart disease has been documented in children with CH than in the general population. Such an association suggests a possible pathogenic role of genes involved in both heart and thyroid development. NKX2-5 encodes a homeodomain-containing transcription factor with a major role in heart development, and mutations affecting this gene have been reported in individuals with congenital heart disease. OBJECTIVE: In the present work we investigated the possible involvement of NKX2-5 mutations in TD. RESULTS: Our results indicate that Nkx2-5(-/-) embryos exhibit thyroid bud hypoplasia, providing evidence that NKX2-5 plays a role in thyroid organogenesis and that NKX2-5 mutations contribute to TD. NKX2-5 mutational screening in 241 patients with TD allowed the identification of three heterozygous missense changes (R25C, A119S, and R161P) in four patients with TD. Functional characterization of the three mutations demonstrated reduced DNA binding and/or transactivation properties, with a dominant-negative effect on wild-type NKX2-5. CONCLUSION: Our results suggest a previously unknown role of NKX2-5 in the pathogenesis of TD.

Risk factors for congenital hypothyroidism: results of a population case-control study (1997-2003).

OBJECTIVE: To identify risk factors for permanent and transient congenital hypothyroidism (CH). DESIGN: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. METHODS: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrollment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. RESULTS: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) = 12.2, 95% confidence interval (CI): 2.4-62.3). A statistically significant association with additional birth defects, female gender and gestational age >40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR = 1.9, 95% CI: 0.7-5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR = 15.7, 95% CI: 0.9-523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. CONCLUSION: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease.