Prediction of the relationship of cesarean section scar niche and postmenstrual spotting: is there any relation?

Background Postmenstrual spotting has recently been related to a discontinuation of the myometrium at the site of a previous cesarean section called "CS scar niche". There was no consensus regarding the gold standard method for the assessment of the niche. Recently, Magnetic resonance imaging (MRI) has shown promise in the evaluation of the niche. Our study aims to assess the role of MRI in the evaluation of the CS scar niche characters and its association with post-menstrual spotting. Results A total of 65 patients with CS niche were prospectively included in this study and subdivided into two groups, according to presence or absence of postmenstrual spotting (Group A; 34 patients with postmenstrual spotting and Group B; 31 patients without spotting). All patients were examined using a 1.5 T MRI unit. CS scar niche volume was significantly higher among women with post-menstrual spotting (0.57 ± 0.07 vs. 0.07 ± 0.05 (cm3); P < 0.001). Also, women with post-menstrual spotting have significantly higher scar length (9.38 ± 3.06 vs. 5.02 ± 2.10 (mm); P < 0.001), scar depth (6.95 ± 3.16 vs. 3.23 ± 0.99 (mm); P < 0.001), scar width (15.78 ± 3.94 vs. 9.87 ± 1.84 (mm); P < 0.001) in comparison to those without post-menstrual spotting. Scar depth (> 7.4 mm) had 81% sensitivity and 97% specificity for prediction of post-menstrual spotting with overall accuracy was 88.7%. While scar width (> 12.8 mm) had 71% sensitivity and 97% specificity for prediction of post-menstrual spotting with overall accuracy was 83.3%. Scar volume (> 0.15 cm3) had 97% sensitivity and 100% specificity for prediction of post-menstrual spotting with overall accuracy was 98.4%. Conclusion MRI measures (CS scar volume, depth, and width) are predictors for postmenstrual spotting in patients with CS scar niche, and scar volume is the most powerful predictor.

Use of Circulating Tumour DNA (ctDNA) for Measurement of Therapy Predictive Biomarkers in Patients with Cancer

Biomarkers that predict likely response or resistance to specific therapies are critical in personalising treatment for cancer patients. Such biomarkers are now available for an increasing number of anti-cancer therapies, especially targeted therapy and immunotherapy. The gold-standard method for determining predictive biomarkers requires tumour tissue. Obtaining tissue, however, is not always possible and even if possible, the amount or quality of tissue obtained may be inadequate for biomarker analysis. Tumour DNA, however, can be released into the bloodstream, giving rise to what is referred to as circulating tumour DNA (ctDNA). In contrast to tissue, blood can be obtained from effectively all patients in a minimally invasive and safe manner. Other advantages of blood over tissue for biomarker testing include a shorter turn-around time and an ability to perform serial measurements. Furthermore, blood should provide a more complete profile of mutations present in heterogeneous tumours than a single-needle tissue biopsy. A limitation of blood vis-à-vis tissue, however, is lower sensitivity and, thus, the possibility of missing an actionable mutation. Despite this limitation, blood-based predictive biomarkers, such as mutant EGFR for predicting response to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer and mutant PIK3CA for predicting response to alpelisib in combination with fulvestrant in advanced breast cancer, may be used when tissue is unavailable. Although tissue remains the gold standard for detecting predictive biomarkers, it is likely that several further blood-based assays will soon be validated and used when tissue is unavailable or unsuitable for analysis.

Comparison of Anterior Nares Viral Loads in Asymptomatic and Symptomatic Individuals Diagnosed with SARS-CoV-2 in a University Screening Program

RT-qPCR has been used as the gold standard method for detecting SARS-CoV-2 since early in the pandemic. At our university based high throughput screening program, we test all members of our community weekly. RT-qPCR cycle threshold (CT) values are inversely proportional to the amount of viral RNA in a sample, and thus are a proxy for viral load. We hypothesized that CT values would be higher, and thus the viral loads at the time of diagnosis would be lower in individuals who were infected with the virus but remained asymptomatic throughout the course of the infection. We collected the N1 and N2 CT values from 1633 SARS-CoV-2 positive RT-qPCR tests of individuals sampled between August 7, 2020, and March 18, 2021, at the BU Clinical Testing Laboratory. We matched this data with symptom reporting data from our clinical team. We found that asymptomatic patients had CT values significantly higher than symptomatic individuals on the day of diagnosis. Symptoms were followed by the clinical team for 10 days post the first positive test. Within the entire population, 78.1% experienced at least one symptom during surveillance by the clinical team (n=1276/1633). Of those experiencing symptoms, the most common symptoms were nasal congestion (73%, n=932, 1276), cough (60.0%, n=761/1276), fatigue (59.0%, n=753/1276), and sore throat (53.1%, n=678/1276). The least common symptoms were diarrhea (12.5%, n=160/1276), dyspnea on exertion (DOE) (6.9%, n=88/1276), foot or skin changes (including rash) (4.2%, n=53/1276), and vomiting (2.1%, n= 27/1276). Presymptomatic individuals, those who were not symptomatic on the day of diagnosis but became symptomatic over the following 10 days, had CT values higher for both N1 (median= 27.1, IQR 20.2- 32.9) and N2 (median=26.6, IQR 20.1-32.8) than the symptomatic group N1 (median= 21.8, IQR 17.2- 29.4) and N2 (median= 21.4, IQR 17.3- 28.9) but lower than the asymptomatic group N1 (median=29.9, IQR 23.6-35.5) and N2 (median= 30.0, IQR 23.1- 35.7). This study supports the hypothesis that viral load in the anterior nares on the day of diagnosis is a measure of disease intensity at that time.

molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history

Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV, a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.

Approach To The Pediatric Patient: Central Diabetes Insipidus

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of disorders affecting the hypothalamic-posterior pituitary network. The differential diagnosis is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating congenital or acquired cerebral and pituitary stalk lesions. Pituitary stalk size at presentation could be normal, but it may change over time, depending on the underlying condition, while other brain areas or organs may become involved during follow up. Early diagnosis and treatment are crucial in order to avoid central nervous system damage, germ cell tumor dissemination, and to minimize complications of multiple pituitary hormone defects. We provide a practical update on the diagnosis and management of patients with CDI and highlight several pitfalls that may complicate the differential diagnosis of conditions presenting with polyuria and polydipsia. The need for a careful and close follow-up of patients with “apparently” idiopathic CDI is particularly emphasized, because the underlying condition may be recognized over time. The clinical scenario that we outline at the beginning of this article represents the basis for the discussion about how the etiological diagnosis of CDI can be overlooked, and demonstrates how a water intake and urine output improvement can be a sign of progressive damage of both hypothalamus and anterior pituitary gland with associated pituitary hormonal deficiencies.

The Functional Polymorphism of DDAH2 rs9267551 Is an Independent Determinant of Arterial Stiffness

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA.Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P &lt; 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P &lt; 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels.Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.

Spectrum of Oral Cavity Lesions and its Clinico-Histopathological Correlation

Introduction: Oral cavity lesions comprise a wide spectrum of diseases that varies from non-neoplastic to neoplastic. The clinical evaluation alone is insufficient for proper diagnosis in most cases. So, histopathological examination is the gold standard method for diagnosis and management of patients accordingly. Objective: The present study was done to evaluate the histopathological spectrum of oral cavity lesions and compare them in relation to age, sex, site, clinical features, risk factors, and clinical diagnoses. Methods: This prospective cross-sectional study enrolled 127 cases of oral biopsies which were received at the Department of Pathology, Tribhuvan University and Teaching Hospital, Kathmandu Nepal, from May 2018 to April 2019 for histopathological examination. Specimens were fixed in 10% formalin and subjected for tissue processing and Hematoxylin and Eosin stained sections. Data entry and analysis were done by using SPSS 24 version where frequency and percentile were calculated. Results: Total cases were 127 with slight female predilection and the age group of 50-60 years (mean age of 44.24 years) were commonly affected. The tongue being the most common site, frequently lesions presented as swelling. Most of the lesions were non-neoplastic comprising 45% whereas malignant lesions comprised 23.6%. Smoking increased the risk of malignancy by 2 fold. The most common benign lesions were squamous papilloma & fibroepithelial polyp whereas the malignant lesion was squamous cell carcinoma. Sixty percent of clinical diagnoses didn’t show correlation. Conclusions: Oral cavity lesions have a wide spectrum of distribution in age, sex, site, and clinical presentation. Initially, oral lesions may present with subtle symptoms which may cause underdiagnosis. Thus, histopathological diagnosis is a must to rule out malignancy. Keywords: Clinical presentation; correlation; oral cavity; risk factors.

Comparative Study of Electrocardiographic and Echocardiographic Evidence of Left Ventricular Hypertrophy in Systemic Hypertension

Background and Aims: Hypertension is a common health problem. Left ventricular hypertrophy, a condition in hypertension is a risk factor for myocardial infarction, stroke and heart failure. This study aims to detect left ventricular hypertrophy in hypertensive patients using Electrocardiography and echocardiography. Methods: In this descriptive cross-sectional study; 143 patients of Hypertension from February 2019 to August 2019 were enrolled. They were evaluated for left ventricular hypertrophy using electrocardiography and echocardiography. Sokolow-Lyon and Cornell Voltage electrocardiographic criteria were used and their sensitivities and specificities to detect left ventricular hypertrophy were calculated taking echocardiography as a gold standard method. Results: The mean age of the study population was 58.69 ± 11.33 years. Mean duration of hypertension was 4.72 ±3.2 years. The mean systolic and diastolic blood pressure were 137 ± 15.42 mmHg and 84 ± 10.5 mmHg respectively. Out of 143 study population, 30(21%) of them had left ventricular hypertrophy on electrocardiography as defined by Sokolow-Lyon criteria, and 29(20.3%) had left ventricular hypertrophy on electrocardiography as per Cornell Voltage criteria. On combining both Sokolow-Lyon and Cornell Voltage criteria, 37(25.9%) of the study population had left ventricular hypertrophy on electrocardiography (either as per Sokolow-Lyon or Cornell Voltage criteria). On echocardiography, 62(43.4%) of them were found to have left ventricular hypertrophy. Conclusions: Electrocardiography is a less sensitive tool to diagnose Left Ventricular Hypertrophy in hypertension but its specificity is high (>95%). Investigation of choice to detect Left Ventricular Hypertrophy in hypertensive people is still the echocardiography.

Invasive Right Ventricular Pressure-Volume Analysis: Basic Principles, Clinical Applications, and Practical Recommendations

Right ventricular pressure-volume (PV) analysis characterizes ventricular systolic and diastolic properties independent of loading conditions like volume status and afterload. While long-considered the gold-standard method for quantifying myocardial chamber performance, it was traditionally only performed in highly specialized research settings. With recent advances in catheter technology and more sophisticated approaches to analyze PV data, it is now more commonly used in a variety of clinical and research settings. Herein, we review the basic techniques for PV loop measurement, analysis, and interpretation with the aim of providing readers with a deeper understanding of the strengths and limitations of PV analysis. In the second half of the review, we detail key scenarios in which right ventricular PV analysis has influenced our understanding of clinically relevant topics and where the technique can be applied to resolve additional areas of uncertainty. All told, PV analysis has an important role in advancing our understanding of right ventricular physiology and its contribution to cardiovascular function in health and disease.