An Unconventional Regimen of Carboplatin and Paclitaxel in Metastatic Colorectal Carcinosarcoma: A Case Report and Review of Literature.

Colorectal carcinosarcoma is an exceedingly rare subtype of colorectal cancer that displays the histological and molecular features of both mesenchymal and epithelial tumors. Due to its rarity, there are no guidelines regarding the systemic treatment of this disease. This report describes a case of a 76-year-old woman with colorectal carcinosarcoma with extensive metastatic burden treated with carboplatin and paclitaxel.

Does embryo quality at transfer affect obstetric outcomes and placental findings?

Study Question: Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality?

Summary Answer: Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions.

What Is Known Already: A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis.

Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions.

Objective: To assess obstetric outcomes and placental findings in pregnancies attained by in vitro fertilization (IVF) in patients with diminished ovarian reserve (DOR).

Design: Retrospective cohort study.

Setting: University-affiliated tertiary hospital.

The discovery of (1R, 3R)-1-(3-chloro-5-fluorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile, a potent and selective agonist of human transient receptor potential cation channel subfamily m member 5 (TRPM5) and evaluation of as a potential gastrointestinal prokinetic agent.

This publication details the discovery of a series of selective transient receptor potential cation channel subfamily M member 5 (TRPM5) agonists culminating with the identification of the lead compound (1R, 3R)-1-(3-chloro-5-fluorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile (39). We describe herein our biological rationale for agonism of the target, the examination of the then current literature tool molecules, and finally the process of our discovery starting with a high throughput screening hit through lead development. We also detail the selectivity of the lead compound 39 versus related family members TRPA1, TRPV1, TRPV4, TRPM4 and TRPM8, the drug metabolism and pharmacokinetics (DMPK) profile and in vivo efficacy in a mouse model of gastrointestinal motility.

Pregnancy complications and placental histology in in vitro fertilization pregnancies with initial low serum β-hCG levels.

Objective: To assess perinatal outcomes and placental findings after in vitro fertilization (IVF) with an initial low serum β-human chorionic gonadotropin (hCG).

Design: A retrospective cohort study.

Setting: University-affiliated tertiary hospital.

The effect of endometriosis on placental histopathology and perinatal outcome in singleton live births resulting from IVF.

Research Question: Does endometriosis have an effect on the placental histopathology pattern and perinatal outcome in singleton live births resulting from IVF treatment?

Design: Retrospective cohort study evaluating the data on all live births following IVF treatment between 2009 and 2017 at one university-affiliated tertiary hospital. All patients had placentas sent for full gross and histopathology assessment, irrespective of complication status or delivery mode. The primary outcomes of the study included anatomical, inflammation, vascular malperfusion and villous maturation placental disorders.

The impact of embryo vitrification on placental histopathology features and perinatal outcome in singleton live births.

Study Question: Does embryo vitrification affect placental histopathology pattern and perinatal outcome in singleton live births?

Summary Answer: Embryo vitrification has a significant effect on the placental histopathology pattern and is associated with a higher prevalence of dysfunctional labor.

What Is Known Already: Obstetrical and perinatal outcomes differ between live births resulting from fresh and frozen embryo transfers. The effect of embryo vitrification on the placental histopathology features associated with the development of perinatal complications remains unclear.

The effect of higher estradiol levels during stimulation on pregnancy complications and placental histology.

Introduction: We aimed to assess obstetric outcomes and placental histology in stimulated in vitro fertilization (IVF) cycles with a high serum estradiol level.

Methods: This was a historic cohort of live singleton deliveries after IVF, at a single university affiliated medical center between 2009 and 2017. Included were pregnancies following controlled ovarian stimulation with fresh embryo transfer.

Pregnancy complications and placental histology following embryo transfer with a thinner endometrium.

Study Question: Are deliveries following IVF with a thinner endometrium associated with adverse perinatal outcomes and placental findings?

Summary Answer: Live births following IVF with a thinner endometrium are associated with an increased rate of placental-mediated obstetric complications and lower birthweight, while the placentas are notable for gross anatomical and histological malperfusion lesions.

What Is Known Already: Past studies have noted a higher rate of adverse outcomes on deliveries following IVF with a thinner endometrium, mainly placental-associated complications. However, no study to date has investigated placental histopathology in such cases.

Usefulness of Hospital Admission Chest X-ray Score for Predicting Mortality and ICU Admission in COVID-19 Patients.

We aimed to investigate the performance of a chest X-ray (CXR) scoring scale of lung injury in prediction of death and ICU admission among patients with COVID-19 during the 2021 peak pandemic in HCM City, Vietnam. CXR and clinical data were collected from Vinmec Central Park-hospitalized patients from July to September 2021. Three radiologists independently assessed the day-one CXR score consisting of both severity and extent of lung lesions (maximum score = 24).

Placental histology following assisted hatching in fresh transfer cycles.

Purpose: To assess placental histological findings following assisted hatching in fresh transfer in vitro fertilization cycles.

Methods: Evaluation of a historic cohort of live singleton deliveries after fresh embryo transfer (ET) at a single university medical center between 2009 and 2017. We compared perinatal outcomes and placental histology in cases where assisted hatching was performed prior to ET (AH group) and cases with no AH (no AH group).

Maternal hypothyroidism and its effect on placental histopathology in singleton live births resulting from fertilization treatment.

We aimed to examine the impact of maternal hypothyroidism on placental pathology and perinatal outcomes in singleton live births resulting from IVF, using medical records of IVF births between 2009 and 2017 at a tertiary hospital. The primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. Secondary outcomes included foetal, maternal, perinatal, and delivery complications.

Modeling High-Grade Serous Ovarian Carcinoma Using a Combination of Fallopian Tube Electroporation and CRISPR-Cas9-Mediated Genome Editing.

Ovarian cancer is the most lethal gynecologic cancer to date. High-grade serous ovarian carcinoma (HGSOC) accounts for most ovarian cancer cases, and it is most frequently diagnosed at advanced stages. Here, we developed a novel strategy to generate somatic ovarian cancer mouse models using a combination of electroporation and CRISPR-Cas9-mediated genome editing.

Interobserver Reliability for Identifying Specific Patterns of Placental Injury as Defined by the Amsterdam Classification.

Context.—: Placental pathology is an essential tool for understanding neonatal illness. The recent Amsterdam international consensus has standardized criteria and terminology, providing harmonized data for research and clinical care.

Exploring Patient-Reported Costs Related to Hepatitis C on the Medical Crowdfunding Page GoFundMe®.

Background: Successful medical crowdfunding campaigns may alleviate or even eliminate the financial burden of expensive, cumulative medical bills. GoFundMe crowdfunding pages for hepatitis C virus (HCV) patients were reviewed and analyzed to better understand the characteristics that contribute to a successful fundraising campaign in a disease often associated with patients with a lower social standing or stigma.

Methods: A pilot cross-sectional study of all publicly available GoFundMe crowdfunding pages was conducted for posts related to HCV on GoFundMe in June 2019.

Effect of embryo stage at transfer on placental histopathology features in singleton live births resulting from fresh embryo transfers.

Objective: To evaluate the effect of embryo stage at transfer on placental histopathology and perinatal outcome in singleton live births resulting from fresh embryo transfers (ETs).

Design: Retrospective cohort study.

Setting: Not applicable.

Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design-Part 1.

Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and structural biology to quickly identify and elaborate an indazole fragment into a series of reversible MetAP2 inhibitors with <10nM potency, excellent selectivity, and favorable in vitro safety profiles.

Loss of SMARCA4 (BRG1) protein expression as determined by immunohistochemistry in small-cell carcinoma of the ovary, hypercalcaemic type distinguishes these tumours from their mimics.

Aims: Molecular investigation of small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) has revealed that it is a monogenetic tumour characterized by alteration of SMARCA4 (BRG1), encoding a member of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complex. A large majority of cases show loss of expression of the corresponding SMARCA4/BRG1 protein. Furthermore, three cases of SCCOHT with retained SMARCA4 protein expression showed loss of SMARCB1/INI1 expression.

The value of the "suspicious for urothelial carcinoma" cytology category: a correlative study of 4 years including 337 patients.

Background: The terminology used in reporting urine cytology lacks uniformity and the significance of the "atypical" and "suspicious" categories is still not well established. This results in variable clinical follow-up and management of those cases. The authors sought to investigate the prognostic value of a diagnosis of "suspicious for high-grade urothelial carcinoma" (HGUCA).

Direct measurement of vena contracta area by real-time 3-dimensional echocardiography for assessing severity of mitral regurgitation.

We tested the hypothesis that the vena contracta (VC) cross-sectional area in patients with mitral regurgitation (MR) can be reproducibly measured by real-time 3-dimensional (3D) echocardiography and correlates well with the volumetric effective regurgitant orifice area (EROA). Earlier MR repair requires accurate noninvasive measures, but practically, the VC area is difficult to image in 2-dimensional views, which are often oblique to it. 3D echocardiography can provide an otherwise unobtainable true cross-sectional view.

Assessment of right ventricular function by real-time three-dimensional echocardiography improves accuracy and decreases interobserver variability compared with conventional two-dimensional views.

Aims: Two-dimensional echocardiographic (2DE) assessment of right ventricular (RV) function is difficult, often resulting in inconsistent RV evaluation. Real-time three-dimensional echocardiography (RT3DE) allows the RV to be viewed in multiple planes, which can potentially improve RV assessment and limit interobserver variability when compared with 2DE.

Methods And Results: Twenty-five patients underwent 2DE and RT3DE.

Assessing mitral valve area and orifice geometry in calcific mitral stenosis: a new solution by real-time three-dimensional echocardiography.

Background: Planimetry of mitral valve area (MVA) is difficult in calcific mitral stenosis (CaMS) in which limiting orifice is near the annulus, and unlike rheumatic mitral stenosis (RhMS), does not present an area for planimetry at the leaflet tips. Moreover, pressure half time (PHT)-derived MVA (MVA(PHT)) has limitations in patients with CaMS in whom there are coexisting conditions that affect LV chamber compliance. We tested the hypothesis that real-time 3-dimensional echocardiography (RT3D) can guide measurement at the narrowest orifice in CaMS.

Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes.

The aim of this study was to determine whether severe mitral regurgitation (MR) is progressive and whether tissue-Doppler (TD)-derived indexes can detect early left ventricular (LV) dysfunction in chronic severe MR. Percutaneous rupture of mitral valve chordae was performed in pigs (n = 8). Before MR (baseline), immediately after MR (post-MR), and at 1 and 3 mo after MR, cardiac function was assessed using conventional and TD-derived indexes.

Myocardial adaptation and efficiency in response to intensive physical training in elite speedskaters.

Background: Physiological cardiac adaptations to exercise training resulting in the 'athlete's heart' are well known. Most of these studies, however, were included either those who exercise to exhaustion, non-elite athletes or those who participate primarily in sports requiring extensive weight training. Studies utilizing conventional and tissue Doppler echocardiographic studies in highly competitive elite athletes whose training includes both aerobic and weight training are limited.

Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon.

Background: Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction.

Methods And Results: We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers.