BMAL1 and CLOCK proteins exhibit differential association with mitochondrial dynamics, protein synthesis pathways and muscle strength in human muscle.

Murine models lacking CLOCK/BMAL1 proteins in skeletal muscle (SkM) present muscle deterioration and mitochondria abnormalities. It is unclear whether humans with lower levels of these proteins in the SkM have similar alterations. Here we evaluated the association between BMAL1 and CLOCK protein mass with mitochondrial dynamics parameters and molecular and functional SkM quality markers in males. SkM biopsies were taken from the vastus lateralis of 16 male (non-athletes, non-obese and non-diabetic) subjects (8-9 a.m.). The morphology of mitochondria and their interaction with the sarcoplasmic reticulum (mitochondria-SR) were determined using transmission electron microscopy images. Additionally, protein abundance of the OXPHOS complex, mitochondria fusion/fission regulators, mitophagy and signalling proteins related to muscle protein synthesis were measured. To evaluate the quality of SkM, the cross-sectional area and maximal SkM strength were also measured. The results showed that BMAL1 protein mass was positively associated with mitochondria-SR distance, mitochondria size, mitochondria cristae density and mTOR protein mass. On the other hand, CLOCK protein mass was negatively associated with mitochondria-SR interaction, but positively associated with mitochondria complex III, OPA1 and DRP1 protein mass. Furthermore, CLOCK protein mass was positively associated with the protein synthesis signalling pathway (total mTOR, AKT and P70S6K protein mass) and SkM strength. These findings suggest that the BMAL1 and CLOCK proteins play different roles in regulating mitochondrial dynamics and SkM function in males, and that modulation of these proteins could be a potential therapeutic target for treating muscle diseases. KEY POINTS: In murine models, reductions in BMAL1 and CLOCK proteins lead to changes in mitochondria biology and a decline in muscle function. However, this association has not been explored in humans. We found that in human skeletal muscle, a decrease in BMAL1 protein mass is linked to smaller intermyofibrillar mitochondria, lower mitochondria cristae density, higher interaction between mitochondria and sarcoplasmic reticulum, and reduced mTOR protein mass. Additionally, we found that a decrease in CLOCK protein mass is associated with a higher interaction between mitochondria and sarcoplasmic reticulum, lower protein mass of OPA1 and DRP1, which regulates mitochondria fusion and fission, lower protein synthesis signalling pathway (mTOR, AKT and P70S6K protein mass), and decreased skeletal muscle strength. According to our findings in humans, which are supported by previous studies in animals, the mitochondrial dynamics and skeletal muscle function could be regulated differently by BMAL1 and CLOCK proteins. As a result, targeting the modulation of these proteins could be a potential therapeutic approach for treating muscle diseases and metabolic disorders related to muscle.

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study.

OBJECTIVE: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. METHODS: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. RESULTS: Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. CONCLUSION: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Ideal vascular health and cognitive performance in the Brazilian Longitudinal Study of Adult Health.

BACKGROUND AND PURPOSE: Most evidence for the association between ideal vascular health (IVH) and cognitive performance comes from high income countries. The aim was to investigate this association in the Brazilian Longitudinal Study of Adult Health. METHODS: Cognition was assessed using the word list, verbal fluency and trail making tests. The IVH score included ideal metrics for body mass index, smoking, physical activity, diet, blood pressure, fasting glucose and total cholesterol. Poor, intermediate and optimal health were characterized in those presenting 0-2, 3-4, 5-7 ideal metrics, respectively. To determine the association between IVH score and cognitive performance, linear regression models adjusted for age, sex, education, race, alcohol use, depression and thyroid function were used. RESULTS: In 12 271 participants, the mean age was 51.3 ± 8.9 years, 54% were women, 57% White and 53% had poor vascular health. Participants with intermediate (ß = 0.064, 95% confidence interval 0.033; 0.096) and optimal health (ß = 0.108, 95% confidence interval 0.052; 0.164) had better global cognitive Z-scores. In addition, interactions of IVH score with age, education and race were found, suggesting a better cognitive performance with higher IVH in older adults, Black/Brown participants and those with lower levels of education. CONCLUSION: Ideal vascular health was associated with better cognitive performance. Older, Black/Brown and low-educated participants had better cognition in the presence of higher IVH scores.

Accuracy of computer-aided image analysis in the diagnosis of odontogenic cysts: A systematic review.

BACKGROUND: This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing odontogenic cysts. MATERIAL AND METHODS: A systematic review was conducted according to the PRISMA statements and considering eleven databases, including the grey literature. Protocol was registered in PROSPERO (CRD [Blinding]). The PECO strategy was used to define the eligibility criteria and only studies involving diagnostic accuracy were included. Their risk of bias was investigated using the Joanna Briggs Institute Critical Appraisal tool. RESULTS: Out of 437 identified citations, five papers, published between 2006 and 2019, fulfilled the criteria and were included in this systematic review. A total of 5,264 images from 508 lesions, classified as radicular cyst, odontogenic keratocyst, lateral periodontal cyst, glandular odontogenic cyst, or dentigerous cyst, were analyzed. All selected articles scored low risk of bias. In three studies, the best performances were achieved when the two subtypes of odontogenic keratocysts (solitary or syndromic) were pooled together, the case-wise analysis showing a success rate of 100% for odontogenic keratocysts and radicular cysts, in one of them. In two studies, the dentigerous cyst was associated with the majority of misclassifications, and its omission from the dataset improved significantly the classification rates. CONCLUSIONS: The overall evaluation showed all studies presented high accuracy rates of computer-aided systems in classifying odontogenic cysts in digital images of histological tissue sections. However, due to the heterogeneity of the studies, a meta-analysis evaluating the outcomes of interest was not performed and a pragmatic recommendation about their use is not possible.

Self-initiated changes in physical activity levels improve cardiometabolic profiles: A longitudinal follow-up study.

BACKGROUND AND AIMS: While studies have described the importance of higher physical activity levels (PAL) in weight loss, the impact of self-initiated PAL on health status warrants further study. We aimed to prospectively examine the effects of self-initiated longitudinal PAL changes on body mass index (BMI) and cardiometabolic parameters in normal weight, overweight and obese adults. METHODS AND RESULTS: We included 4840 adults (mean age 41.6 ± 7.9 years, 79% male) undergoing routine health screening examinations. Self-reported PAL, height, weight, blood pressure and blood samples were collected at baseline and after a mean (95% confidence interval) follow up of 536 (531-541) days. Subjects were stratified according to BMI [39.8% normal weight (<25 kg/m2), 45.1% overweight (25.0-29.9 kg/m2), and 19.1% obese (≥30 kg/m2)]. In normal weight individuals, BMI increased from baseline to follow-up, irrespective of PAL changes. On the other hand, overweight and obese individuals that increased PAL experienced a decrease in BMI by -0.9% and -3.1%, respectively (p < 0.05). Overweight and obese individuals that increased PAL also experienced a decrease in -5.8% -4.6% in non-HDL concentrations from baseline to follow-up (p < 0.05). Finally, in overweight individuals, LDL cholesterol concentrations decreased from baseline to follow-up, irrespective of PAL changes whereas in obese individuals, a maintenance or increased PAL were associated with a decrease in -4.7% and -6.1% (p < 0.05), respectively. CONCLUSIONS: In a large cohort of screening patients, longitudinal self-initiated PAL is associated with improved BMI and cardiometabolic profile in overweight and obese individuals.

Low-level laser therapy for treatment of neurosensory disorders after orthognathic surgery: A systematic review of randomized clinical trials.

BACKGROUND: Low-level laser has been widely used in Dentistry and many studies have focused on its application in oral surgeries. This study was conducted with the aim of searching for scientific evidence concerning the effectiveness of laser to reduce pain or paresthesia related to orthognathic surgery. MATERIAL AND METHODS: An electronic search was performed in PubMed, Scopus, Science Direct, LILACS, SciELO, CENTRAL, Google Scholar, OpenGrey, and ClinicalTrials.gov, up to November 2016, with no restrictions on language or year of publication. Additionally, a hand search of the reference list of the selected studies was carried out. The PICOS strategy was used to define the eligibility criteria and only randomized clinical trials were selected. RESULTS: Out of 1,257 identified citations, three papers fulfilled the criteria and were included in the systematic review. The risk of bias was assessed according to the Cochrane Guidelines for Clinical Trials and results were exposed based on a descriptive analysis. One study showed that laser therapy was effective to reduce postoperative pain 24 hours (P=0.007) and 72 hours (P=0.007) after surgery. Other study revealed the positive effect of laser to improve neurosensory recovery 60 days after surgery, evaluated also by the two-point discrimination (P=0.005) and sensory (P=0.008) tests. The third study reported an improvement for general sensibility of 68.75% for laser group, compared with 21.43% for placebo (P=0.0095), six months after surgery. CONCLUSIONS: Individual studies suggested a positive effect of low-level laser therapy on reduction of postoperative pain and acceleration of improvement of paresthesia related to orthognathic surgery. However, due to the insufficient number and heterogeneity of studies, a meta-analysis evaluating the outcomes of interest was not performed, and a pragmatic recommendation about the use of laser therapy is not possible. This systematic review was conducted according to the statements of PRISMA and was registered at PROSPERO under the number CRD42016043258.

Subclinical hypothyroidism is associated with higher carotid intima-media thickness in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND AND AIM: Although subclinical hypothyroidism (SCH) is associated with cardiovascular risk, there is scarce data about subclinical atherosclerosis in subjects with SCH. We aimed to analyze the association between SCH and carotid intima-media thickness (IMT) using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS AND RESULTS: We included subjects with normal thyroid function (TSH: 0.4-4.0 mIU/l, and normal free thyroxine (FT4): 0.8-1.9 ng/dl) and SCH (TSH ≥ 4.0 mIU/l and normal FT4) evaluated for IMT in a cross-sectional analysis. We excluded individuals using medications that affect thyroid function and those with a history of cardiovascular disease. We performed logistic and linear regression models to evaluate the association with IMT (mean values and categorized at the 75th percentile) as a dependent variable and SCH as an independent variable, adjusted for other cardiovascular risk factors. From 8623 subjects (median age of 50 years; interquartile range: 44-57), 4624 (53.6%) were women, 8095 (93.9%) were euthyroid, and 528 (6.1%) had SCH. Groups varied in age, body mass index, Framingham risk score, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein, as well as, IMT, that were all higher in SCH compared to euthyroid participants. SCH is associated with IMT as a continuous variable (ß = 0.010, P = 0.036) and IMT >75th percentile: OR = 1.30 (95% CI = 1.06-1.59) in logistic models. CONCLUSION: Individuals with SCH presented higher IMT compared with euthyroid subjects, even after adjustment for potential confounders. IMT was independently associated with SCH in the baseline of the ELSA-Brasil study.

Neck circumference is associated with carotid intimal-media thickness but not with coronary artery calcium: Results from The ELSA-Brasil.

BACKGROUND AND AIMS: It is uncertain whether neck circumference can be a risk indicator for subclinical atherosclerosis. We aimed to investigate their relationships measured by coronary artery calcium (CAC) and common carotid intima-media thickness (cc-IMT) with neck circumference in ELSA-Brasil. METHODS AND RESULTS: In cross-sectional and sex-specific analyses of 2266 women (50.6 ± 8.4 yrs) and 1886 men (50.7 ± 9.0 yrs) with both cc-IMT and CAC, free from previous cardiovascular disease at baseline, we built logistic models using diverse cut-off points for CAC score (0 vs > 0, < 100 vs ≥ 100, < 400 vs ≥ 400 Agatston units) and cc-IMT (< 75 th percentile vs ≥ 75 th; <90th percentile vs ≥ 90 th) as dependent variables, after which adjustments for age and traditional cardiovascular risk factors were made. Mean neck circumference was 33.6 (± 2.4 cm) for women and 38.8 (± 2.6 cm) for men. In fully adjusted models including sociodemographic, cardiovascular risk factors and body-mass index and waist circumference, for each 1 standard deviation increase in neck circumference we found an odds ratio (OR, 95% CI) for IMT above the 75th percentile of (1.52, 1.16; 1.99) for women and (1.66, 1.28; 2.14) for men, and above the 90th cc-IMT percentile [1.66 (1.19; 2.32) for men but not for women [1.21 (0.80; 1.82)]. We found no association between neck circumference and CAC using different cut-off points (p > 0.05 for all). CONCLUSION: Neck circumference was significantly and independently associated with cc-IMT but not with CAC in women and men, indicating a possible effect of perivascular fat tissue on atherosclerosis.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Eight-year change in carotid intima-media thickness and associated risk factors in adults with and without psoriasis - the ELSA-Brasil cohort study.

The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 [44.0-57.0] years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (ß=0.002, P=0.002) and hypertension (ß=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (ß=-0.004, P=0.042) and White ethnicity (ß=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (ß=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (ß=-0.005, P<0.001), past smoking (ß=-0.048, P=0.009), and hypertension (ß=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.

Validation of the North America expert consensus statement on reporting CT findings for COVID-19 in individuals with lung cancer.

The aim of our study was to validate the use of the standardized Radiological Society of North America (RSNA) reporting system in individuals with known lung cancer who presented to the emergency department with suspected COVID-19. We included patients aged 18 years or older from the Cancer Institute of the State of São Paulo (ICESP) with a confirmed diagnosis of lung cancer, admitted to the emergency department and undergoing chest computed tomography (CT) for suspicion of COVID-19. Comparison between SARS-CoV2 RT-PCR across RSNA categories was performed in all patients and further stratified by diagnosis of lung cancer progression. Among 58 individuals included in the analysis (65±9 years, 43% men), 20 had positive RT-PCR. Less than a half (43%) had no new lung findings in the CT. Positive RT-PCR was present in 75% of those with typical findings according to RSNA and in only 9% when these findings were classified as atypical or negative (P<0.001). Diagnostic accuracy was even higher when stratified by the presence or absence of progressive disease (PD). Extent of pulmonary inflammatory changes was strongly associated with higher mortality, reaching a lethality of 83% in patients with >25% of lung involvement and 100% when there was >50% of lung involvement. The lung involvement score was also highly predictive of prognosis in this population as was reported for non-lung cancer individuals. Collectively, our results demonstrated that diagnostic and prognostic values of chest CT findings in COVID-19 are robust to the presence of lung abnormalities related to lung cancer.

Post-TB health and wellbeing.

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases clinical management.

Anti-Ro52 (or anti-TRIM21) antibodies are part of the family of anti-Ro/SSA antibodies, historically markers of Sjögren syndrome and systemic lupus erythematosus. Anti-Ro52 antibodies represent one the most frequently encountered autoantibodies in patients with connective tissue disease (primary Sjögren syndrome, systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myopathies). Because of their lack of specificity and detection in patients with non-autoimmune disorders, the usefulness of anti-Ro52 testing in connective tissue diseases is still matter of debate among clinicians and immunologists. Autoantibodies are mainly diagnostic markers for autoimmune diseases but some of them can also be directly involved in the generation of tissue damage. Over the past decade several authors reported associations of anti-Ro52 antibodies with some clinical features - especially interstitial lung disease - and survival in patients with connective tissue diseases. There is also a growing evidence of the role of anti-Ro52 antibodies in the pathogenesis of connective tissue diseases. In this review, we comprehensively discuss the clinical associations of anti-Ro52 antibodies in the different connective tissue diseases and the recent advances on their potential role in the inflammatory response.

Clinical presentation and in-hospital prognosis of lung cancer patients presenting with suspected and confirmed COVID-19.

We sought to compare the clinical presentation and prognosis of patients with lung cancer and confirmed COVID-19 infection to those with negative RT-PCR SARS-CoV-2 results. We included patients with confirmed lung cancer and suspected COVID-19 who presented to the emergency department. The primary outcome was in-hospital mortality and secondary outcomes included admission to intensive care unit (ICU) or mechanical ventilation. We analyzed the characteristics according to RT-PCR results and primary outcome. We constructed a logistic regression for each RT-PCR result group to find potential predictors of the primary outcome. Among 110 individuals with confirmed lung cancer (65±9 years, 51% male), 38 patients had positive RT-PCR and 72 patients had negative RT-PCR. There was no difference between groups for any clinical characteristic or comorbidities though individuals with confirmed COVID-19 had higher functionality in the ECOG scale. Leucocytes and lymphocytes were lower in individuals with positive tests. The primary outcome occurred in 58 (53%) individuals, 37 (34%) were admitted to the ICU, and 29 (26%) required mechanical ventilation. Although mortality was similar between the two groups, individuals with confirmed COVID-19 were significantly more likely to be admitted to the ICU or receive mechanical ventilation. Only lower lymphocytes and higher CRP were significantly associated with higher mortality. The clinical presentation of COVID-19 in lung cancer is not sufficient to identify higher or lower probability groups among symptomatic individuals, the overall mortality is high irrespective of RT-PCR results, and lymphopenia on admission was associated with the diagnosis and prognosis for COVID-19.

Reduced levels of both circulating CD4+ CD25+ CD127(low/neg) and CD4+ CD8(neg) invariant natural killer regulatory T cells in stable heart transplant recipients.

A cross-regulation between two regulatory T cell (T(reg) ) subsets [CD4(+) CD25(+) and invariant natural killer (NK) T - iNK T] has been described to be important for allograft tolerance induction. However, few studies have evaluated these cellular subsets in stable recipients as correlates of favourable clinical outcome after heart transplantation. T(reg) and iNK T cell levels were assayed by flow cytometry in peripheral blood samples from 44 heart transplant recipients at a 2-year interval in 38 patients, and related to clinical outcome. Multi-parameter flow cytometry used CD4/CD25/CD127 labelling to best identify T(reg) , and a standard CD3/CD4/CD8/Vα24/Vß11 labelling strategy to appreciate the proportions of iNK T cells. Both subtypes of potentially tolerogenic cells were found to be decreased in stable heart transplant recipients, with similar or further decreased levels after 2 years. Interestingly, the patient who presented with several rejection-suggesting incidents over this period displayed a greater than twofold increase of both cell subsets. These results suggest that CD4(+) CD25(+) CD127(low/neg) T(reg) and iNK T cells could be involved in the local control of organ rejection, by modulating immune responses in situ, in clinically stable patients. The measurement of these cell subsets in peripheral blood could be useful for non-invasive monitoring of heart transplant recipients, especially in the growing context of tolerance-induction trials.

Kidney Injury Molecule-1 in the detection of early kidney injury in dogs with leptospirosis.

Renal damage, a common feature in canine leptospirosis, ranges from a subclinical affection to kidney dysfunction and death. Chances of recovery can be improved by early intervention. However, traditional biomarkers (serum urea and creatinine) have limited relevance for precocity. Kidney Injury Molecule-1 (KIM-1) is a transmembrane protein upregulated in early stages of tubular injury. This study evaluated the use of urinary KIM-1 to detect early renal injury in naturally occurring canine leptospirosis. This exploratory research included 30 dogs divided into two groups: (1) dogs with leptospirosis (n = 25) and (2) healthy dogs (n = 5). Leptospira sp. infection was diagnosed through urine PCR and/or direct bacteriologic culture and/or serology (single MAT titters ≥800). Additionally, stage of infection was further characterized in acute and subacute phases based on the onset of clinical symptoms from 3 to 7 days. Urinary KIM-1 (uKIM-1) concentrations were measured in both groups with a commercial canine ELISA kit. uKIM-1 levels were statistically different (P < 0.01) between the studied groups, especially in non-azotemic dogs (P = 0.0042). The biomarker showed 88 % sensibility to diagnosis of kidney injury at> 1.49 ng/mL cut-off. Urine KIM-1 was negatively correlated with urine specific gravity (USG) but accompanied histopathological evidence of renal degeneration, necrosis and regeneration processes, extending information on kidney health. Measurement of KIM-1 in the urine of canine patients was able to detect naturally occurring acute and subacute leptospirosis accompanied by tubular injury in early non-azotemic infections.

Association of coronary calcification with prognosis of Covid-19 patients without known heart disease.

Risk factors that determine the severity of Covid-19 have not been fully elucidated. The aim of this study was to evaluate the role of coronary artery calcification (CAC) as a risk factor for death or mechanical ventilation (MV) of patients without known heart disease infected with Covid-19. We analyzed 283 consecutive in-patients with acute respiratory symptoms with chest computed tomography (chest-CT), without previous heart disease, and criteria for Covid-19 (RT-PCR positive and/or typical clinical and chest-CT findings). CAC was classified by the number of coronary segments affected as absent (0), mild (1-3), and severe calcification (more than 3). The association between CAC, CAC severity, and death or MV due to severe respiratory failure was assessed by logistic regression. The mean age was 58.7±15.7 years and 54.1% were men. Patients with CAC were older, more likely to have hypertension, and less likely to be obese. CAC was present in 75 patients (26.5%), of which 42 had a mild calcification and 33 had severe calcification, and was associated with death (OR=2.35, 95%CI: 1.01-5.48) or MV (OR=2.72, 95%CI: 1.20-6.20) adjusted for multiple confounders, with significant and increased odds ratio for the severe form of CAC (death: OR=3.70, 95%CI: 1.20-11.42; MV: OR=3.30, 95%CI: 1.09-9.95). We concluded that CAC was an independent risk factor for death or MV in Covid-19 patients without previous heart disease, particularly for those with severe calcification. CAC can be easily visualized on common chest-CT, widely used in evaluation of moderate to severe Covid-19.

Eight-year change in carotid intima-media thickness and associated risk factors in adults with and without psoriasis - the ELSA-Brasil cohort study

The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 [44.0-57.0] years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (β=0.002, P=0.002) and hypertension (β=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (β=-0.004, P=0.042) and White ethnicity (β=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (β=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (β=-0.005, P<0.001), past smoking (β=-0.048, P=0.009), and hypertension (β=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.

Thyrotropin and free thyroxine levels and coronary artery disease: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Data on the association between subclinical thyroid dysfunction and coronary artery disease (CAD) is scarce. We aimed to analyze the association between thyroid function and CAD using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We included subjects with normal thyroid function (0.4-4.0 mIU/L, and normal free thyroxine, FT4, or 0.8 to 1.9 ng/dL), subclinical hypothyroidism (SCHypo; TSH>4.0 mIU/L and normal FT4), and subclinical hyperthyroidism (SCHyper; TSH<0.4 mIU/L and normal FT4) evaluated by coronary computed tomography angiography. We excluded individuals using medications that interfere in thyroid function or with past medical history of cardiovascular disease. Logistic regression models evaluated the presence of CAD, segment involvement score (SIS) >4, and segment severity score (SSS) >4 of coronary arteries as the dependent variables, and quintiles of TSH and FT4 as the independent variables, adjusted for demographical data and cardiovascular risk factors. We included 767 subjects, median age 58 years (IQR=55-63), 378 (49.3%) women, 697 euthyroid (90.9%), 57 (7.4%) with SCHypo, and 13 (1.7%) with SCHyper. No association between TSH and FT4 quintiles and CAD prevalence was noted. Similarly, no association between TSH levels and the extent or severity of CAD, represented by SIS>4 and SSS>4 were seen. Restricting analysis to euthyroid subjects did not alter the results. TSH levels were not significantly associated with the presence, extent, or severity of CAD in a middle-aged healthy population.

Early vedolizumab trough levels predict mucosal healing in inflammatory bowel disease: a multicentre prospective observational study.

BACKGROUND: The correlation between vedolizumab trough levels during induction therapy and mucosal healing remains unknown. AIM: To compare early vedolizumab trough levels in patients with and without mucosal healing within the first year after treatment initiation. METHODS: We prospectively collected vedolizumab trough levels in all inflammatory bowel disease patients at weeks 2, 6 and 14 of vedolizumab treatment in three French referral centres between 1 June 2014 and 31 March 2017. Results of every patient that underwent mucosal assessment by magnetic resonance imaging and/or endoscopy in the first year after treatment initiation were analysed. RESULTS: Median vedolizumab trough levels in the overall population (n = 82) were 27 µg/mL (interquartile range, IQR 21.2-33.8 µg/mL) at week 2, 23 µg/mL (IQR 15-34.5 µg/mL) at week 6 and 10.7 µg/mL (IQR 4.6-20.4 µg/mL) at week 14. Only median vedolizumab trough levels at week 6 differed between patients with and without mucosal healing within the first year after treatment initiation (26.8 vs 15.1 µg/mL, P = 0.035). A cut-off trough level of 18 µg/mL at week 6 predicted mucosal healing within the first year after the start of vedolizumab with an area under the receiver operating curve of 0.735 (95% confidence interval 0.531-0.939). A vedolizumab trough level above 18 µg/mL at week 6 was the only independent variable associated with mucosal healing within the first year of treatment (odds ratio 15.7, 95% confidence interval 2.4-173.0, P = 0.01). CONCLUSION: Early therapeutic drug monitoring might improve timely detection of vedolizumab-treated patients in need for an intensified dosing regimen.