Serum Osteoprotegerin Is an Independent Marker of Metabolic Complications in Non-DialysisDependent Chronic Kidney Disease Patients

Background: Osteoprotegerin (OPG) belongs to the tumour necrosis factor superfamily and is known to accelerate endothelial dysfunction and vascular calcification. OPG concentrations are elevated in patients with chronic kidney disease. The aim of this study was to investigate the association between OPG levels and frequent complications of chronic kidney disease (CKD) such as anaemia, protein energy wasting (PEW), inflammation, overhydration, hyperglycaemia and hypertension. Methods: One hundred non-dialysis-dependent men with CKD stage 3–5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure overhydration, fat amount and lean body mass. We also measured the serum concentrations of haemoglobin, albumin, total cholesterol, C-reactive protein (CRP), fibrinogen and glycated haemoglobin (HgbA1c), as well as blood pressure. Results: We observed a significant, positive correlation between OPG and age, serum creatinine, CRP, fibrinogen, HgbA1c concentrations, systolic blood pressure and overhydration. Negative correlations were observed between OPG and glomerular filtration rate (eGFR), serum albumin concentrations and serum haemoglobin level. Logistic regression models revealed that OPG is an independent marker of metabolic complications such as anaemia, PEW, inflammation and poor renal prognosis (including overhydration, uncontrolled diabetes and hypertension) in the studied population. Conclusion: Our results suggest that OPG can be an independent marker of PEW, inflammation and vascular metabolic disturbances in patients with chronic kidney disease.

Low FT3 is an independent marker of disease severity in patients hospitalized for COVID-19

Aim: To study the prevalence of thyroid dysfunction and its association with disease severity in hospitalized patients of coronavirus disease-19 (COVID-19). Methods: In this retrospective cohort study, thyroid function tests (TFT) of 236 hospitalized patients of COVID-19, along with demographic, comorbid, clinical, biochemical, and disease severity records were analysed. Patients were divided into previous euthyroid or hypothyroid status to observe the effect of prior hypothyroidism on severity of COVID-19. Results: TFT abnormalities were common. Low free T3 (FT3), high thyroid stimulating hormone (TSH) and low TSH were seen in 56 (23.7%), 15 (6.4%) and 9 (3.8%) patients, respectively. The median levels of TSH (2.06 vs 1.26 mIU/mL, p=0.001) and FT3 (2.94 vs 2.47 pg/mL, p=0.000) were significantly lower in severe disease. Previous hypothyroid status (n=43) was associated with older age, higher frequency of comorbidities, higher FT4 and lower FT3. TFT did not correlate with markers of inflammation (except lactate dehydrogenase), however, FT3 and TSH negatively correlated with outcome severity score and duration of hospital stay. Cox-regression analysis showed that low FT3 was associated with severe COVID-19 (p=0.032, HR 0.302; CI 0.101-0.904), irrespective of prior hypothyroidism. Conclusions: Functional thyroid abnormalities (low FT3 and low TSH) are frequently seen in hospitalized patients of COVID-19. Although these abnormalities did not correlate with markers of inflammation, this study shows that low FT3 at admission independently predicts severity of COVID-19.

Echocardiogram in critically ill patients with COVID-19

Background Describe echocardiographic characteristics in patients admitted to an intensive care unit by COVID-19 and identify clinical and laboratory findings associated with an abnormal echocardiogram and its association with in-hospital mortality. Methods Included all patients with RT-PCR-confirmed COVID-19 who underwent echocardiography during hospitalization. Echocardiographic characteristics were assessed in the entire population and subgroups. We also analyzed clinical characteristics associated with an abnormal echocardiogram. An echocardiogram was defined as abnormal when it demonstrates systolic ventricular dysfunction of any degree (left and/or right ventricle) and/or high filling pressures (E/E' ratio>16; SPAP>40mmHg, RAP>15mmHg or diastolic dysfunction ≥ grade 2) and/or moderate to severe pericardial effusion. Clinical variables were also assessed using a classification tree and binary logistic regression was performed with characteristics that showed a statistical significance in univariate analysis. Finally, echocardiographic variables were assessed for in-hospital mortality outcome using the chi-square test. Results 272 admissions to ICU by COVID-19 were identified. Of these, 159 underwent echocardiography (58.5%). 39 were excluded by incomplete demographic data. 72 echocardiograms (60%) were abnormal according to pre-established criteria. Low occurrence of left and right ventricular systolic dysfunction was observed, as well as 30.8% of the population had a normal diastolic function. In univariate analysis, characteristics associated with abnormal echocardiogram were age, elevated troponin, previous heart failure, and SAPS3 score. In the regression model, troponin was the independent marker of abnormal echocardiography in patients admitted to the intensive care unit by COVID19. This finding was corroborated by the classification tree. The abnormal echocardiogram was not associated with in-hospital mortality (OR 1.60; CI95% 0.75–3.41), but the presence of systolic ventricular dysfunction of any degree was associated with a higher occurrence of this outcome (OR 3.52; CI95% 1.12–11.1). Conclusions In intensive care COVID-19 patients, many manifested elevated ventricular filling pressures, but the occurrence of ventricular dysfunction was low. Elevated serum troponin level was the independent marker associated with an abnormal echocardiogram. Systolic ventricular dysfunction was the only echocardiographic variable associated with in-hospital mortality. FUNDunding Acknowledgement Type of funding sources: None.

Elevated tumor expression of Astroprincin (FAM171A1) is an independent marker of poor prognosis in colon cancer

Background Colon cancer (CC) is one of the most commonly diagnosed malignancies worldwide. Several biomarkers have been suggested for improved prognostic evaluation, but few have been implemented in clinical practice. There is a need for biomarkers that predict the tumor behavior in CC and allow stratification of patients that would benefit from adjuvant therapy. We recently identified and functionally characterized a previously unknown protein that we called ASTROPRINCIN (APCN) due to its abundance in astrocytes. APCN, also annotated as FAM171A1, is found in trophoblasts of early placenta. We demonstrated that high expression levels of APCN in cancer cells induced motility and ability of invasive growth in semisolid medium. Methods We screened by immunohistochemistry a tissue microarray material from the tumors of 429 CC patients with clinical follow-up in a test series and 255 CC patients in a validation series. Results We showed that low or absent APCN expression correlates with a favorable prognosis while high APCN expression was a sign of an adverse outcome. Cox uni- and multivariable analysis revealed that elevated tumor expression of APCN constitutes a robust marker of poor prognosis independent of stage, grade, patient’s age, or gender. Conclusion Our findings demonstrate that APCN is a novel independent prognostic marker in CC and could potentially select patients for more intense postoperative adjuvant treatment and follow-up.

Effect of Pelvic Floor Muscle Training on Urinary Incontinence in Gynecologic Cancer: A Review

PURPOSE: Menopause is associated with increased carotid–femoral pulse wave velocity (cfPWV), an indicator of arterial stiffness, which is an independent marker of cardiovascular risk. This study aimed to investigate the cfPWV, blood pressure, and body composition with habitual exercise for at least 1 year in postmenopausal women performing habitual aquatic walking versus age-matched sedentary postmenopausal and premenopausal women.METHODS: A total of 115 postmenopausal and premenopausal women were divided into the following groups: (1) postmenopausal women performing habitual aquatic walking (HAW; n=57), (2) sedentary postmenopausal women (SPO; n=41), and (3) sedentary premenopausal women (SPR, n=17). The HAW group participated 3 days per week, 60 minutes per day, for at least 1 year, whereas the SPO and SPR groups performed no regular exercise, for less than 2 days per week, 30 minutes per day, for at least 1 year. The cfPWV, BP, and body composition were assessed in all groups.RESULTS: The cfPWV (p<.05), augmentation pressure (p<.05), and DBP were significantly lower in the SPR group than in the SPO group. AIx@75, BMI, %BF, and SBP were significantly lower in the SPR group than in the SPO and HAW groups. Lean body mass was higher in the SPR group than in the SPO and HAW groups (p<.05). The cfPWV, AP, AIx@75, SBP, and %BF were lower in the HAW group than in the SPO group (p<.05). Furthermore, the cfPWV was significantly correlated with aging and SBP.CONCLUSIONS: This cross-sectional study indicates that sedentary postmenopausal women may be at a higher risk of cardiovascular disease than postmenopausal women who participate in habitual aquatic walking.

Role of the nigrosome 1 absence as a biomarker in amyotrophic lateral sclerosis

Introduction The absence of nigrosome 1 on brain MRI and the hyperechogenicity of substantia nigra (SNh) by transcranial sonography are two useful biomarkers in the diagnosis of parkinsonisms. We aimed to evaluate the absence of nigrosome 1 in amyotrophic lateral sclerosis (ALS) and to address its meaning. Methods 136 ALS patients were recruited, including 16 progressive muscular atrophy (PMA) and 22 primary lateral sclerosis (PLS) patients. The SNh area was measured planimetrically by standard protocols. The nigrosome 1 status was qualitatively assessed by two blind evaluators in susceptibility weight images of 3T MRI. Demographic and clinical data were collected and the C9ORF72 expansion was tested in all patients. Results Nigrosome 1 was absent in 30% of ALS patients (36% of PLS, 29% of classical ALS and 19% of PMA patients). There was no relationship between radiological and clinical laterality, nor between nigrosome 1 and SNh area. Male sex (OR = 3.63 [1.51, 9.38], p = 0.005) and a higher upper motor neuron (UMN) score (OR = 1.10 [1.02, 1.2], p = 0.022) were independently associated to nigrosome 1 absence, which also was an independent marker of poor survival (HR = 1.79 [1.3, 2.8], p = 0.013). Conclusion In ALS patients, the absence of nigrosome 1 is associated with male sex, UMN impairment and shorter survival. This suggests that constitutional factors and the degree of pyramidal involvement are related to the substantia nigra involvement in ALS. Thus, nigrosome 1 could be a marker of a multisystem degeneration, which in turn associates to poor prognosis.

Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

The aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXRα expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXRα was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXRα expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXRα expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXRα was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXRα expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXRα expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXRα was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXRα plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXRα is correlated with a more aggressive course of the disease, whereas nuclear RXRα expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy.

Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery

Purpose Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient’s early postoperative pain is an independent marker of anastomotic leakage. Methods By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014–2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data. Results In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4–10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21–2.38), as well as reoperation (OR 2.17, 95% CI 1.41–3.32). Severe pain (NRS 8–10) was more strongly related to leakage (OR 2.38, 95% CI 1.44–3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome. Conclusion In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.