A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization.

Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM contributes to ZIKV immunity in pregnancy, mediating neutralization up to 3 months post-symptoms. From a ZIKV-infected pregnant woman, we isolated a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets an envelope dimer epitope within domain II. The epitope arrangement on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not available to IgG. DH1017.IgM protected mice against viremia upon lethal ZIKV challenge more efficiently than when expressed as an IgG. Our findings identify a role for antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunotherapeutic, particularly during pregnancy.

Tall-columnar glandular cells in SurePath™ liquid-based cytology Pap sample: Learning from mimics/pitfalls.

We offer a comprehensive depiction of the cytomorphological characteristics of lobular endocervical glandular hyperplasia (LEGH) as observed in SurePath™ liquid-based cytology (LBC), subsequently confirmed on cone biopsy. Lobular endocervical glandular hyperplasia (LEGH), a precursor to gastric-type adenocarcinoma (GAE) of the endocervix, is rare and reports of it in cervical cytology are scarce. We provide a thorough description of the cytomorphological features of LEGH observed in SurePath™ liquid-based cytology (LBC), later confirmed by cone biopsy. To the best of our knowledge, this is the first report documenting cytology of LEGH in LBC of a Pap sample.

Bugs' eyes and black monsters: Ascitic fluid cytology in an elderly male with hematochezia.

Anorectal malignant melanomas are rare, accounting for less than 2% of all melanomas. Malignant effusions developing secondary to malignant melanoma are highly uncommon. Herein, we present the cytomorphological features of a metastatic anorectal malignant melanoma presenting with ascites at the initial clinical presentation.

Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America.

Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a near expected life span, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the life span. To receive optimal medical care and achieve desired outcomes, persons with HIV must be consistently engaged in care and able to access uninterrupted treatment, including ART. Comprehensive evidence-based HIV primary care guidance is, therefore, more important than ever. Creating a patient-centered, stigma-free care environment is essential for care engagement. Barriers to care must be decreased at the societal, health system, clinic, and individual levels. As the population ages and noncommunicable diseases arise, providing comprehensive healthcare for persons with HIV becomes increasingly complex, including management of multiple comorbidities and the associated challenges of polypharmacy, while not neglecting HIV-related health concerns. Clinicians must address issues specific to persons of childbearing potential, including care during preconception and pregnancy, and to children, adolescents, and transgender and gender-diverse individuals. This guidance from an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America updates previous 2013 primary care guidelines.

Impact of three-dimensional chemoradiation on pelvic bone mineral density, low back pain, and disability in cervical cancer: a prospective study.

OBJECTIVE: To prospectively analyze the effect of three-dimensional chemoradiation on the bone mineral density of pelvic bones and its association with low back pain and disability in patients with locally advanced cervical cancer. METHODS: In biopsy proven locally advanced cervical cancer patients, bone mineral density and T scores for lumbar vertebrae 5, dorsal thoracic vertebrae 12, and T scores for the femoral neck were analyzed. Low back pain was scored using the visual analog scale while disability scoring was done using the Oswestry low back pain disability scale. Furthermore, a subgroup analysis for patients (classified according to menopausal status) was performed. RESULTS: In total, 106 patients were analyzed. A statistically significant decline in mean bone mineral density was observed at all three sites (vertebrae 5 and 12, and the femoral neck) post-chemoradiation therapy compared with pretreatment bone mineral density (0.671 vs 0.828, -2.083 vs -1.531, -2.503 vs -1.626; all p<0.001). Similarly, in subgroup analyses, at all three sites, pre-menopausal patients showed a statistically significant association (0.876 vs 0.697, -1.203 vs -0.2.761, -1.403 vs -2.232; all p<0.001) while a non-significant association was observed for post-menopausal patients at vertebrae 12 (-1.707 vs -1.719; p=0.09) with a statistically significant association at vertebrae 5 and the femoral neck (0.803 vs 0.656, -1.746 vs -2.648; p<0.01). Although statistically significant low back pain and disability scores were observed overall and irrespective of menopausal status, no correlation between bone mineral density and low back pain and disability was observed. CONCLUSION: Pelvic bone mineral density decreases significantly after chemoradiation, irrespective of menopausal status. However, no correlation with low back pain and disability was observed. Pelvic bone mineral density analysis should be considered before chemoradiation in cervical cancer.

Lessons From COVID-19 in Children: Key Hypotheses to Guide Preventative and Therapeutic Strategies.

The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), reveals a peculiar trend of milder disease and lower case fatality in children compared with adults. Consistent epidemiologic evidence of reduced severity of infection in children across different populations and countries suggests there are underlying biological differences between children and adults that mediate differential disease pathogenesis. This presents a unique opportunity to learn about disease-modifying host factors from pediatric populations. Our review summarizes the current knowledge of pediatric clinical disease, role in transmission, risks for severe disease, protective immunity, as well as novel therapies and vaccine trials for children. We then define key hypotheses and areas for future research that can use the pediatric model of disease, transmission, and immunity to develop preventive and therapeutic strategies for people of all age groups.

Weight gain after curative parathyroidectomy predicts increase in bone mineral density in patients with symptomatic primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) results in reduction of bone mineral density (BMD) and an increased risk of pathological fractures. Curative surgery does improve BMD; however, the magnitude of rise and predictive factors are highly variable amongst the hitherto available studies. OBJECTIVES: To quantify the magnitude of improvement in BMD after curative surgery in patients with symptomatic PHPT and dissect out the possible clinical and biochemical parameters predicting the BMD rise. METHODS: We conducted a retrospective study of symptomatic PHPT patients undergoing surgery between August 2016 and July 2018. Patients achieving biochemical cure with pre- and post-operative (at least 1 year after surgery) dual-energy X-ray absorptiometry scans performed were included in the study. RESULTS: After exclusion, 63 patients were included in the study (M:F = 2:5; mean age = 44.8 years). At a median interval of 15 months, the median per cent change in BMD (ΔBMD) at lumbar spine (LS), total hip (TH), femoral neck (FN) and one-third distal radius (forearm) was 6.5%, 7.0%, 8.1% and 6.9%, respectively. Following multiple linear regression analysis, baseline BMD was found to inversely predict ΔBMD at LS, TH and forearm. Pre-operative iPTH positively predicted ΔBMD at LS and FN. Interestingly, 82.5% of the patients had a gain in body weight following curative surgery and change in body weight emerged as a significant positive predictor of ΔBMD at all sites. CONCLUSIONS: Curative surgery improves BMD at all sites in patients with symptomatic PHPT. Weight gain following surgery can be used as a positive clinical predictor of BMD rise.

A Screening CAD Tool for the Detection of Microcalcification Clusters in Mammograms.

Breast cancer is the most common cancer diagnosed in women worldwide. Up to 50% of non-palpable breast cancers are detected solely through microcalcification clusters in mammograms. This article presents a novel and completely automated algorithm for the detection of microcalcification clusters in a mammogram. A multiscale 2D non-linear energy operator is proposed for enhancing the contrast between the microcalcifications and the background. Several texture, shape, intensity, and histogram of oriented gradients (HOG)-based features are used to distinguish microcalcifications from other brighter mammogram regions. A new majority class data reduction technique based on data distribution is proposed to counter data imbalance problem. The algorithm is able to achieve 100% sensitivity with 2.59, 1.78, and 0.68 average false positives per image on Digital Database for Screening Mammography (scanned film), INbreast (direct radiography) database, and PGIMER-IITKGP mammogram (direct radiography) database, respectively. Thus, it might be used as a second reader as well as a screening tool to reduce the burden on radiologists.

Role of perfusion CT in the evaluation of adnexal masses.

The objective of this study was to evaluate the role of perfusion computed tomography (PCT) in differentiating benign from malignant adnexal masses. Twenty patients, each of pathologically proven malignant and benign adnexal masses who had undergone PCT on 64-slice CT scanner, were included in the study. The PCT parameters, viz. blood volume (BV), blood flow (BF), permeability surface index area (PS) and time to maximum of the tissue residue function (Tmax) of the adnexal masses were calculated. Statistical analysis to study the association between PCT parameters and histopathological diagnosis was done. In the malignant group, the mean PS, BV and BF values were elevated. The mean Tmax of the benign lesions was higher compared to that of the malignant lesions. There was a significant statistical difference in the PCT parameters between the malignant and benign groups (p value = .001). PCT can be a useful tool for differentiating benign and malignant adnexal masses. Impact statement What is already known on this subject? It is not always possible to distinguish benign from malignant adnexal lesions despite the application of various imaging techniques. Perfusion CT (PCT) is an imaging technique with which we can obtain both the morphological and functional information of tumours. Perfusion-based imaging enables us to objectively evaluate the neovascularity in a lesion. This helps in differentiating the benign lesions from aggressive malignant lesions. What do the results of this study add? The PCT parameters, viz. blood volume (BV), blood flow (BF), permeability surface index area (PS) and time to maximum of the tissue residue function (Tmax) were calculated from adnexal masses on a 64-multi-slice CT scanner and correlated with their histopathological diagnoses. The values of the mean PS, BV and BF values were significantly higher in the malignant adnexal masses. The mean Tmax in the benign masses was more compared to that of the malignant lesions. Significant statistical difference was seen in PCT parameters between malignant and benign groups. What are the implications of these findings for clinical practice and/or further research? PCT can be a useful tool for differentiating benign from malignant adnexal masses. However, more collaborative research and robust validation are imperative to further evaluate this innovative evolving technique.

Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection.

Zika virus (ZIKV) is an emerging flavivirus that can cause birth defects and neurologic complications. Molecular tests are effective for diagnosing acute ZIKV infection, although the majority of infections produce no symptoms at all or present after the narrow window in which molecular diagnostics are dependable. Serology is a reliable method for detecting infections after the viremic period; however, most serological assays have limited specificity due to cross-reactive antibodies elicited by flavivirus infections. Since ZIKV and dengue virus (DENV) widely cocirculate, distinguishing ZIKV infection from DENV infection is particularly important for diagnosing individual cases or for surveillance to coordinate public health responses. Flaviviruses also elicit type-specific antibodies directed to non-cross-reactive epitopes of the infecting virus; such epitopes are attractive targets for the design of antigens for development of serological tests with greater specificity. Guided by comparative epitope modeling of the ZIKV envelope protein, we designed two recombinant antigens displaying unique antigenic regions on domain I (Z-EDI) and domain III (Z-EDIII) of the ZIKV envelope protein. Both the Z-EDI and Z-EDIII antigens consistently detected ZIKV-specific IgG in ZIKV-immune sera but not cross-reactive IgG in DENV-immune sera in late convalescence (>12 weeks postinfection). In contrast, during early convalescence (2 to 12 weeks postinfection), secondary DENV-immune sera and some primary DENV-immune sera cross-reacted with the Z-EDI and Z-EDIII antigens. Analysis of sequential samples from DENV-immune individuals demonstrated that Z-EDIII cross-reactivity peaked in early convalescence and declined steeply over time. The Z-EDIII antigen has much potential as a diagnostic antigen for population-level surveillance and for detecting past infections in patients.

Breast density in screening mammography in Indian population - Is it different from western population?

Mammography is the only method presently considered appropriate for mass screening of breast cancer. However, higher breast density was strongly associated with lower mammographic sensitivity. Breast density is also identified as independent and strongest risk factors for breast cancer. Studies have shown women with high breast density have four to six times increased risk of breast cancer as compare to women with fatty breast. It varies between different age group it generally decreases with increasing age in postmenopausal women and it can be different in different ethnic groups and people from different geographical areas. This study evaluates the breast density in Indian population and its relationship with the age. We reviewed of all screening mammography examinations performed from May 2012 to January 2015 at our institute PGIMER, Chandigarh, INDIA. Descriptive analyses were used to examine the association between age and breast density. A total of 6132 screening mammograms were performed. Each subgroup categorized by decade of age. There was a significant inverse relationship between age and breast density (P < .001). Twenty-two percent of patients between 40 and 49 years old had dense breasts. This percentage decreased to 9% of women in their 50s. Only 7% of women in their 60s and 8% of women in their 70s had dense breasts. This data has been compared with the Western study done in New York University (NYU) shows there is significant difference (P value <.05) in the breast density in Indian and Western population with more Indians having ACR Grade 1 and 2 and Western population having 2 and 3. We found an inverse relationship between patient age and mammographic breast density. However, there were a large proportion of young women who had lower grades of mammographic density which could potentially benefit from the use of routine screening mammography in this subgroup of patients. Moreover, the breast density of Indian population is less when compared to the Western population. This might suggest that mammography is a good modality of choice for screening Indian population.

Spectrum of magnetic resonance imaging findings in ovarian torsion.

PURPOSE: Ovarian torsion is the twisting of the ovary on its vascular pedicle resulting in vascular compromise. Diagnosis of ovarian torsion is challenging in patients who have atypical clinical or ultrasound (US) findings. The objective of our study was to demonstrate the magnetic resonance imaging (MRI) features of ovarian torsion to help radiologists make a conclusive diagnosis when the clinical and US findings are unclear. MATERIAL AND METHODS: We retrospectively reviewed the clinical and MRI features in 10 females with surgically proven ovarian torsion, who had inconclusive clinical, US, or computed tomography findings. RESULTS: All patients showed a significantly enlarged ovary with size ranging from 5 to 18 cm. 'Twisted ovarian pedicle' sign was seen in seven patients. Eight cases showed areas of haemorrhage within the ovarian stroma. Non-enhancement of ovarian stroma was observed in six patients. Seven patients showed an ipsilateral deviation of the uterus. CONCLUSIONS: MRI features of ovarian torsion include ovarian enlargement, twisted ovarian pedicle, ovarian haemorrhage, abnormal ovarian enhancement, and ipsilateral deviation of the uterus. Awareness of these imaging features will enable the radiologist to recognise ovarian torsion and differentiate it reliably from other benign or malignant ovarian lesions.

Comparison of Absolute Apparent Diffusion Coefficient (ADC) Values in ADC Maps Generated Across Different Postprocessing Software: Reproducibility in Endometrial Carcinoma.

OBJECTIVE: Apparent diffusion coefficient (ADC) maps are usually generated by builtin software provided by the MRI scanner vendors; however, various open-source postprocessing software packages are available for image manipulation and parametric map generation. The purpose of this study is to establish the reproducibility of absolute ADC values obtained using different postprocessing software programs. MATERIALS AND METHODS: DW images with three b values were obtained with a 1.5-T MRI scanner, and the trace images were obtained. ADC maps were automatically generated by the in-line software provided by the vendor during image generation and were also separately generated on postprocessing software. These ADC maps were compared on the basis of ROIs using paired t test, Bland-Altman plot, mountain plot, and Passing-Bablok regression plot. RESULTS: There was a statistically significant difference in the mean ADC values obtained from the different postprocessing software programs when the same baseline trace DW images were used for the ADC map generation. CONCLUSION: For using ADC values as a quantitative cutoff for histologic characterization of tissues, standardization of the postprocessing algorithm is essential across processing software packages, especially in view of the implementation of vendor-neutral archiving.

Multimodality imaging of acute gynecological emergencies-a pictorial essay.

Gynecological emergencies can often present with a myriad of non-specific signs and symptoms, posing a diagnostic challenge to the clinician. They can be grossly divided into uterine or adnexal pathologies. Uterine pathologies can be secondary to intracavitary accumulation of blood [like in patients with transverse vaginal septum, Robert's uterus, accessory and cavitated uterine mass, unicornuate uterus with contralateral non-communicating functional horn], bleeding per vaginum [like in patients with retained products of conception, enhanced myometrial vascularity], pyometra [secondary to pelvic inflammatory disease, cervical obstruction secondary to benign and malignant causes] or complications of fibroids [like red degeneration, torsion of subserosal fibroid]. The adnexal pathologies can range from ectopic pregnancy in a urine pregnancy test (UPT) positive patient to haemorrhagic ovarian cyst, ovarian torsion, ruptured dermoid cyst and tubo-ovarian abscess in a UPT negative patient. Multimodality imaging including ultrasound (USG), computed tomography (CT) scan and magnetic resonance imaging (MRI) can narrow down the differentials and help in formulating an accurate diagnosis. The objective of this article is to familiarize the readers with multimodality imaging findings in common as well as uncommon acute gynecological emergencies and provide an algorithmic imaging approach for acute gynecological emergencies. USG is typically used as the first line diagnostic modality in diagnosis of acute gynecological emergencies. CT scan & MRI are helpful as a problem-solving tool in acute gynecological emergencies when USG findings are indeterminate.