Gynecologic infection rates after ablation treatment for cervical intraepithelial neoplasia grade 2 and higher (CIN2+): Secondary analysis of a non-inferiority randomized trial.

Although concerns have been raised regarding potential infection and morbidity in women undergoing ablation treatment for cervical precancer in low- and middle-income countries (LMIC), there is extremely limited data to substantiate this claim. This is a secondary analysis of a randomized non-inferiority trial (id: NCT03084081) that compares the efficacy and safety of three ablation treatments for biopsy-confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+): CO2 gas-based cryotherapy, non-gas cryotherapy, and thermal ablation (TA). Here, we present findings regarding the incidence of sexually transmitted infections (STI) and vaginitis post-treatment.

Consistency of endometrial receptivity array and histologic dating of spatially distinct endometrial samplings: a prospective, blinded study.

Objective: To compare the consistency of endometrial receptivity array (ERA) and histologic dating among 3 spatially distinct endometrial samples obtained during a cycle of exogenous estrogen and progesterone.

Design: Prospective blinded study.

Setting: University practice.

Profibrotic COVID-19 subphenotype exhibits enhanced localized ER-dependent HSP47 expression in cardiac myofibroblasts in situ.

We recently described a subgroup of autopsied COVID-19 subjects (∼40%), termed 'profibrotic phenotype,' who exhibited clusters of myofibroblasts (Mfbs), which were positive for the collagen-specific chaperone heat shock protein 47 (HSP47) in situ. This report identifies increased, localized (hot spot restricted) expression of αSMA, COLα1, POSTN and FAP supporting the identity of HSP47 cells as myofibroblasts and characterizing a profibrotic extracellular matrix (ECM) phenotype. Coupled with increased GRP78 in COVID-19 subjects, these data could reflect induction of the unfolded protein response for mitigation of proteostasis (i.

Analytical validation and implementation of a pan cancer next-generation sequencing panel, CANSeqKids for molecular profiling of childhood malignancies.

Next-Generation Sequencing (NGS) allows rapid analysis of multiple genes for the detection of clinically actionable variants. This study reports the analytical validation of a targeted pan cancer NGS panel CANSeqKids for molecular profiling of childhood malignancies. Analytical validation included DNA and RNA extracted from de-identified clinical specimens including formalin fixed paraffin embedded (FFPE) tissue, bone marrow and whole blood as well as commercially available reference materials.

Collagen-Specific HSP47 Myofibroblasts and CD163 Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections.

Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47 cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections.

Safety and Acceptability of Three Ablation Treatments for High-Grade Cervical Precancer: Early Data From a Randomized Noninferiority Clinical Trial.

Purpose: This ongoing trial is comparing the efficacy and safety of three ablation treatments for cervical intraepithelial neoplasia grade 2 or higher. Here, we present early data regarding pain, side effects, and acceptability of CO gas-based cryotherapy (CO), nongas cryotherapy, and thermal ablation (TA). Efficacy results are expected to become available in late 2023.

Cervical Cancer Prevention in El Salvador: Gains to Date and Challenges for the Future.

Cervical cancer is preventable through vaccination, early detection, and the treatment of pre-cancerous lesions. However, global inequalities mean that the disease remains a leading cause of cancer death around the world, with over 80% of new cases and 90% of deaths occurring in low- and middle-income countries (LMICs). In El Salvador, joint efforts between the Ministry of Health (MoH) and the non-profit organization Basic Health International (BHI) have been in place since 2008, with the goal of reducing the country's disease burden.

A Proof-of-Concept IoT System for Remote Healthcare Based on Interoperability Standards.

The Internet of Things paradigm in healthcare has boosted the design of new solutions for the promotion of healthy lifestyles and the remote care. Thanks to the effort of academia and industry, there is a wide variety of platforms, systems and commercial products enabling the real-time information exchange of environmental data and people's health status. However, one of the problems of these type of prototypes and solutions is the lack of interoperability and the compromised scalability in large scenarios, which limits its potential to be deployed in real cases of application.

Cytotoxic CD8-positive T-lymphocyte infiltration in the lungs as a histological pattern of SARS-CoV-2 pneumonitis.

Despite millions of PCR confirmed cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, the long-term pathophysiological changes induced by this infection in the lungs and their relationship with possible immune triggers remain incompletely understood. Acute respiratory distress syndrome and subsequent respiratory failure are the most common causes of mortality in hospitalised patients. Severe lung tissue destruction can be due to an overactive immune system that far exceeds the harm that would have been caused by direct virus replication.

Multisite Clinical Validation of Isothermal Amplification-Based SARS-CoV-2 Detection Assays Using Different Sampling Strategies.

Isothermal amplification-based tests have been introduced as rapid, low-cost, and simple alternatives to real-time reverse transcriptase PCR (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. The clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP coronavirus disease of 2019 [COVID-19] detection test and OptiGene COVID-19 direct plus RT-loop-mediated isothermal amplification [LAMP] test) was compared with that of clinical RT-PCR assays using different sampling strategies. A total of 1,378 participants were tested across 4 study sites.

Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies.

Vaccinations are widely credited with reducing death rates from COVID-19, but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation, and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose-regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2.

Sensitive and Specific Immunohistochemistry Protocol for Nucleocapsid Protein from All Common SARS-CoV-2 Virus Strains in Formalin-Fixed, Paraffin Embedded Tissues.

Human coronavirus disease 2019 (COVID-19) is a life-threatening and highly contagious disease caused by coronavirus SARS-CoV-2. Sensitive and specific detection of SARS-CoV-2 viral proteins in tissues and cells of COVID-19 patients will support investigations of the biologic behavior and tissue and cell tropism of this virus. We identified commercially available affinity-purified polyclonal antibodies raised against nucleocapsid and spike proteins of SARS-CoV-2 that provide sensitive and specific detection of the virus by immunohistochemistry in formalin-fixed, paraffin-embedded tissue.

Human papillomavirus vaccination history and diagnosis of cervical intraepithelial neoplasia grade ≥2 severe lesions among a cohort of women who underwent colposcopy in Kaiser Permanente Southern California.

Background: The risk of a high-grade lesion in women undergoing colposcopy following an abnormal screening result may be different by human papillomavirus vaccination status, because women who are vaccinated are presumably less likely to harbor human papillomavirus types 16 and 18.

Objective: This study aimed to evaluate whether the risk of high-grade cervical lesion diagnosed through colposcopy is lower in women with human papillomavirus vaccination than in women without vaccination referred to colposcopy based on equal abnormal screening findings.

Study Design: Kaiser Permanente Orange County female patients between ages 21 and 38 years were included following an abnormal screening if they had ≥1 colposcopies between July 2017 and August 2018 and had at least 1 pathology diagnosis from the colposcopy visits.

Multi-site clinical validation of Isothermal Amplification based SARS-COV-2 detection assays using different sampling strategies.

Background: Isothermal amplification-based tests were developed as rapid, low-cost, and simple alternatives to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-COV-2 detection.

Methods: Clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP COVID-19 detection test and OptiGene COVID-19 Direct Plus RT-LAMP test) was compared to clinical RT-PCR assays using different sampling strategies. A total of 1378 participants were tested across four study sites.

Diffuse interstitial pneumonia-like/macrophage activation syndrome-like changes in patients with COVID-19 correlate with length of illness.

Objectives: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness.

Methods: Lungs of 12 consecutive COVID-19 decedents consented for autopsy were evaluated for gross and histopathologic abnormalities. A complete Ghon "en block" dissection was performed on all cases; lung weights and gross characteristics recorded.

Acute SARS-CoV-2 pneumonitis with cytotoxic CD8 positive T-lymphocytes: Case report and review of the literature.

As of October 2020, there are over 40 million confirmed cases, and more than 1 million confirmed deaths of Covid-19 worldwide. The main cause of death in hospitalized patients is a respiratory failure due to acute respiratory distress syndrome. It has been suggested that the very intense immune response induces diffuse alveolar damage that far exceeds the harm that would have been caused by virus replication per se, resulting in lethal tissue destruction.

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study.

Context.—: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting.

Cervical cancer prevention in El Salvador: A prospective evaluation of screening and triage strategies incorporating high-resolution microendoscopy to detect cervical precancer.

Cervical cancer remains a leading cause of cancer death for women in low- and middle-income countries. The goal of our study was to evaluate screening and triage strategies, including high-resolution microendoscopy (HRME), to detect cervical abnormalities concerning for precancer at the point of care. Women (n = 1824) were enrolled at the Instituto de Cáncer de El Salvador.

Kras-Deficient T Cells Attenuate Graft-versus-Host Disease but Retain Graft-versus-Leukemia Activity.

Acute graft-versus-host disease (aGVHD) is one major serious complication that is induced by alloreactive donor T cells recognizing host Ags and limits the success of allogeneic hematopoietic stem cell transplantation. In the current studies, we identified a critical role of Kras in regulating alloreactive T cell function during aGVHD. Kras deletion in donor T cells dramatically reduced aGVHD mortality and severity in an MHC-mismatched allogeneic hematopoietic stem cell transplantation mouse model but largely maintained the antitumor capacity.

A rapid, high-volume cervical screening project using self-sampling and isothermal PCR HPV testing.

Objective: Rapid, high-volume screening programs are needed as part of cervical cancer prevention in China.

Methods: In a 5-day screening project in Inner Mongolia, 3345 women volunteered following a community awareness campaign, and self-swabbed to permit rapid HPV testing. Two AmpFire™ HPV detection systems (Atila Biosystems) were sufficient to provide pooled 15-HPV type data within an hour.

Outcomes for Step-Wise Implementation of a Human Papillomavirus Testing-Based Cervical Screen-and-Treat Program in El Salvador.

Purpose: The Cervical Cancer Prevention in El Salvador (CAPE) project is a public-sector intervention introducing lower-cost human papillomavirus (HPV) testing in all four departments of the Paracentral region that screened a total of 28,015 women. After demonstrating success of an HPV screen-and-treat (S&T) algorithm over colposcopy management in the first two phases, the third phase scaled up the S&T strategy. We present results from phase III and evaluate S&T components across the entire project.

The cost-effectiveness of human papillomavirus self-collection among cervical cancer screening non-attenders in El Salvador.

Cervical cancer screening with human papillomavirus (HPV) DNA testing has been incorporated into El Salvador's national guidelines. The feasibility of home-based HPV self-collection among women who do not attend screening at the clinic (i.e.

Evaluation of two alternative ablation treatments for cervical pre-cancer against standard gas-based cryotherapy: a randomized non-inferiority study.

Introduction: Gas-based cryotherapy is the conventional ablative treatment for cervical pre-cancer in low-income settings, but the use of gas poses significant challenges. We compared the depth of necrosis induced by gas-based cryotherapy with two gas-free alternatives: cryotherapy using CryoPen,and thermoablation.

Methods: We conducted a five-arm randomized non-inferiority trial: double-freeze carbon dioxide (CO) cryotherapy (referent), single-freeze CO cryotherapy, double-freeze CryoPen, single-freeze CryoPen, and thermoablation.