Morphology Aspects of Hypothyroidism

Hypothyroidism is a common endocrine disorder resulting of low levels of thyroid circulating hormones. The prevalence in the general population varies between 0.3% and 3.7%. Presents as clinical or subclinical disease based on presence of symptoms and levels of serum TSH and free thyroxine and T4, respectively. Hypothyroidism has numerous etiologies, some of them are originated on the thyroid itself and some others are of extrathyroid origin, with variable manifestations. Classified as primary, secondary, tertiary and peripheral. Thyroid autoimmune disease is the principal cause. A new class of drugs against cancer, like the anti-CTLA-4 and anti-PD-L1/PD1 therapies have been associated with primary or secondary hypothyroidism. Endocrine disorders can be difficult to diagnose based only on morphological features because endocrine manifestations are caused primarily by a hormonal imbalance. Hypothyroidism may have a higher risk of morbidity and mortality. Finally, myxedematous coma is the main complication of terminal stages hypothyroidism.

An immune correlate of SARS-CoV-2 infection and severity of reinfections

Background. An immune correlate of protection from SARS-CoV-2 infection is urgently needed. Methods. We used an ongoing household cohort with an embedded transmission study that closely monitors participants regardless of symptom status. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity. Sequencing was performed to determine circulating strains of SARS-CoV-2. We investigated the protection associated with seropositivity resulting from prior infection, the anti-spike antibody titers needed for protection, and we compared the severity of first and second infections. Results. In March 2021, 62.3% of the cohort was seropositive. After March 2021, gamma and delta variants predominated. Seropositivity was associated with 69.2% protection from any infection (95% CI: 60.7%-75.9%), with higher protection against moderate or severe infection (79.4%, 95% CI: 64.9%-87.9%). Anti-spike titers of 327 and 2,551 were associated with 50% and 80% protection from any infection; titers of 284 and 656 were sufficient for protection against moderate or severe disease. Second infections were less severe than first infections (Relative Risk (RR) of moderated or severe disease: 0.6, 95% CI: 0.38-0.98; RR of subclinical disease:1.9, 95% CI: 1.33-2.73). Conclusions. Prior infection-induced immunity is protective against infection when predominantly gamma and delta SARS-CoV-2 circulated. The protective antibody titers presented may be useful for vaccine policy and control measures. While second infections were somewhat less severe, they were not as mild as ideal. A strategy involving vaccination will be needed to ease the burden of the SARS-CoV-2 pandemic.

The natural history of TB disease - a synthesis of data to quantify progression and regression across the spectrum

Background: Prevalence surveys have found a substantial burden of subclinical (asymptomatic but infectious) TB, from which individuals can progress, regress or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of TB disease. Methods: We created deterministic framework of TB disease with progression and regression between three states of pulmonary TB disease: minimal (non-infectious), subclinical, and clinical (symptomatic and infectious) disease. We estimated ranges for each parameter by considering all data from a systematic review in a Bayesian framework, enabling quantitative estimation of TB disease pathways. Findings: Twenty-four studies contributed data from 6030 individuals. Results suggested that, after five years, 24.7%(95% uncertainty interval, UI, 21.3%-28.6%) of individuals with prevalent subclinical disease at baseline had either progressed to clinical disease or died from TB, whereas 16.1%(95%UI, 13.8%-18.5%) had recovered after regressing to minimal disease. Over the course of five years 30% (95%UI, 27.2%-32.6%) of the subclinial cohort never developed symptoms. For those with clinical disease at baseline, 39%(95%UI, 35.8%-41.9%) and 10.3%(95%UI, 8.5%-12.4%) had died or recovered from TB, with the remainder in, or undulating between, the three disease states. The ten-year mortality of people with untreated prevalent infectious disease was 38%. Interpretation: Our results show that for people with subclinical disease, classic clinical disease is neither inevitable nor an irreversible outcome. As such, reliance on symptom- based screening means a large proportion of people with infectious disease may never be detected. Funding: TB Modelling and Analysis Consortium and European Research Council

Influence of calcium concentrations on the metabolic profile of dairy goats during the transitional period

In order to differentiate groups of hypocalcemic (G1) and normocalcemic animals (G2) and infer the influence of subclinical hypocalcemia on metabolic profiles, this study determined calcium concentrations during the transitional period in 35 dairy goats healthy, pregnant, primiparous or multiparous, crossbreed or pure-bred dairy goats producing average 3 kg/day/goat. Therefore, blood samples were collected before (30, 20 and 10 days before parturition), on the day of delivery and after parturition (10, 20, 30, 40, 50 and 60 days postpartum). The variables measured were glucose, nonesterified fatty acids, β-hydroxybutyrate, cholesterol, triglycerides, amylase, total protein, albumin, urea, creatinine, aspartate aminotransferase, gamma glutamyl transferase, creatine kinase, total calcium, phosphorus, magnesium, chlorides, cortisol and insulin, as well as ionized calcium (Ca++), sodium and potassium. Goats were considered to have subclinical hypocalcemia if Ca++ ≤0.72 mmol/L. The data were analyzed by ANOVA. In subclinically hypocalcemic goats, serum concentrations of Ca++ decreased earlier (10dbp) than in normocalcemic goats (parturition) and remained lower throughout the transitional period (p=0,004). Among the measured variables, Ca++ showed greater influence on the NEFA, glucose, insulin and total calcium but also influenced the protein profile. Lower food intake by goats with subclinical hypocalcemia was one of the main factors interfering with the metabolic profile and likely the productivity of these animals. Studies should be conducted to measure the effects of subclinical disease on the production rates and on the emergence of other transitional period diseases.

Mastitis in meat sheep

Mastitis in meat sheep occurs in all flocks, but incidence can vary. It can be a severe disease, resulting in ewe deaths, but chronic and subclinical cases also occur. It is a costly disease, but accurate assesments of the impact, especially of chronic and subclinical disease, are lacking. The most commonly involved pathogens are Mannheimia haemolytica and Staphylococcus aureus. The most important risk factors relate to compromise of teat defences, and increased transmission, but environmental cases do occur. Treatment of acute clinical cases requires systemic antibiosis and non-steroidal anti-inflammatory drug administration, and, where required, supportive care. Prevention involves tackling the risk factors, and using vaccination and breeding to reduce ewe susceptibility.

Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis

Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal fluid (CSF) and serum between early MS and controls and assess its correlation with clinical/radiological measures. Methods: We determined AOC (ability of CSF and serum of patients to inhibit 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidation of dihydrorhodamine) in clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS) (n = 55/11) and non-inflammatory neurological controls (n = 67). MS patients underwent clinical follow-up (median, 4.5; IQR, 5.2 years) and brain MRI at 3 T (baseline/follow-up n = 47/34; median time interval, 3.5; IQR, 2.1 years) to determine subclinical disease activity. Results: CSF AOC was differently regulated among CIS, RRMS and controls (p = 0.031) and lower in RRMS vs. CIS (p = 0.020). Lower CSF AOC correlated with physical disability (r = −0.365, p = 0.004) and risk for future relapses (exp(β) = 0.929, p = 0.033). No correlations with MRI metrics were found. Conclusion: Decreased CSF AOC was associated with increased disability and clinical disease activity in MS. While our finding cannot prove causation, they should prompt further investigations into the role of AOC in the evolution of MS.

Reactivation of Vogt-Koyanagi-Harada disease under control for more than 6 years, following anti-SARS-CoV-2 vaccination

Background/purpose Vogt-Koyanagi-Harada (VKH) disease is a primary stromal choroiditis with bilateral granulomatous panuveitis. If initial-onset VKH is treated early and relentlessly the disease can be controlled and even “cured” in a substantial number of cases. We are reporting on a patient treated early and in a sustained fashion who was inflammation free for seven years but who presented a reactivation 6 weeks after the second dose of anti-SARS-CoV-2 vaccination. Case report A 43-year-old woman presented with severe initial-onset VKH disease which was brought under control using steroidal and non-steroidal Immunosuppression (mycophenolic acid and cyclosporine) with additional infliximab infusions because of the persistence of subclinical choroiditis identified on ICGA. Under infliximab alone disease had been inflammation free with no subclinical disease and absence of sunset glow fundus for 6 years. However, following anti-SARS-CoV-2 vaccination, severe resurgence of the disease occurred with exudative retinal detachments. Disease was rapidly brought again under control with oral prednisone (1 mg/kg) therapy and a new loading scheme of infliximab therapy. Conclusion VKH disease results from an autoimmune process directed against melanocyte associated antigens which can be controlled when early and sustained immunosuppressive treatment is introduced. It seems that anti-SARS-CoV-2 vaccination can be at the origin of reactivation of long-time controlled disease.

Takayasu arteritis: Prevalence and clinical presentation in Switzerland

Objective Takayasu arteritis (TAK) is a rare immune-mediated vasculitis of the aorta and its branches. Aims were to calculate prevalence and incidence in Switzerland, to assess disease activity and performance of MR-Angiography (MRA). Methods 31 patients were recorded in a database, 27 were followed prospectively up to 3 years. Prevalence was calculated based on data of the national statistical bureau. Disease activity was defined using the revised EULAR criteria. MRA depicted stenotic changes and aortic wall enhancement. Results A disease prevalence of 14.5/1.000.000 inhabitants and an incidence of 0.3/1.000.000 per year was calculated. Aortic wall enhancement was found in 10 patients while in clinical and serological remission. EULAR criteria missed 5 patients with disease activity with isolated elevations of ESR/CRP. Arterial stenosis did not change over time in 5 cases, it improved in 2 and increased in 7. At follow-up 16 patients were treated with tocilizumab, 11/16 in monotherapy, 5 patients were treatment-free, 25/27 stayed in remission. Conclusion In addition to prevalence and incidence, our data show that MRA qualifies to detect subclinical disease activity, but, on the other hand, that EULAR criteria may miss disease activity in case of isolated elevation of ESR/CRP.