Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

Development of laparoscopic skills in skills-naïve trainees using self-directed learning with take-home laparoscopic trainer boxes.

Background: To determine if take home laparoscopic trainer boxes with only self-directed learning can develop laparoscopic skills in surgically naive learners. Methods: 74 starting PGY1 OB/Gyn residents and OB/Gyn clerkship medical students volunteered for the study. Learners performed a laparoscopic peg transfer task with only task instructions and no additional training. Initial tasks were recorded and scored. The participants took home a laparoscopic trainer box for 3 weeks to practice without guidance and returned to perform the same task for a second/final score. Initial and final scores were compared for improvement. This improvement was compared to practice and variables such as demographics, surgical interest, comfort with laparoscopy, and past experiences. Results: Mean peg transfer task scores improved from 287 (SD = 136) seconds to 193 (SD = 79) seconds (p < 0.001). Score improvement showed a positive correlation with number of home practice sessions with a linear regression R2 of 0.134 (p = 0.001). More practice resulted in larger increases in comfort levels, and higher comfort levels correlated with better final task scores with a linear regression R2 of 0.152 (p < 0.001). Interest in a surgical specialty had no impact on final scores or improvement. Playing a musical instrument and having two or more dexterity-based hobbies was associated with a better baseline score (p = 0.032 and p = 0.033 respectively), but no difference in the final scores or score improvement. No other past experiences impacted scores. Conclusions: Our study demonstrates that the use of home laparoscopic box trainers can develop laparoscopic skills in surgical novices even without formal guidance or curriculum.

Risk of endometrial polyp and surgical intervention in postmenopausal women with proliferative endometrium.

OBJECTIVE: To study the long-term risks of postmenopausal women with proliferative endometrium developing benign uterine pathologies (endometrial polyps and uterine fibroids) and requiring future gynecological interventions, and to compare them with women with atrophic endometrium. DESIGN: Retrospective cohort study of all women aged 55 or over who underwent endometrial biopsy between 1/1997 and 12/2008. Outcome data were available through to 2/2018. Women with proliferative endometrium were compared with those with atrophic endometrium for the presence of endometrial polyps, uterine fibroids, future endometrial biopsy for recurrent vaginal bleeding, and future hysteroscopy or hysterectomy. Logistic regression models were used to evaluate the association of endometrial histology and other covariates with the risk of morbidities. MAIN FINDINGS: Postmenopausal women with proliferative endometrium are at higher risk of developing endometrial polyps, uterine fibroids and need for surgical intervention. Of 1808 women who underwent endometrial biopsy during the study period, 962 met inclusion criteria: 278 had proliferative and 684 had atrophic endometrium. Length of surveillance was similar in the two groups (11.9 vs. 11.5 years, p = 0.2). Compared with women with atrophic endometrium, women with proliferative endometrium had significantly higher rates of endometrial polyps (17.3 % vs 9.7 % p = 0.001). Multivariable logistic regression confirmed that women with proliferative endometrium had more fibroids on ultrasound (62.1 % vs 50.3 % 3 = 0.02), and had increased risks of developing endometrial polyps (aOR 1.9, 95 % CI 1.28-3.07, p = 0.002), repeat endometrial biopsy (34.9 % vs. 16.8%p < 0.001) and future hysterectomy or hysteroscopy (26.6 % vs 16.2 % p < 0.001). CONCLUSIONS: In addition to the long-term increased risk of cancer, postmenopausal women with proliferative endometrium are more likely to have future bleeding, surgical interventions and diagnosis of endometrial polyps. Medical management to reduce estrogenic activity and associated risks may be considered in these cases.

Stress, anxiety, and illness perception in patients experiencing delay in operative care due to the COVID-19 pandemic.

Background: Amid the height of the COVID-19 pandemic in the US, the US Surgeon General ordered hospitals and healthcare systems to stop all elective surgical procedures. The aim of our study was to evaluate the additional mental health impact of surgical delay on patients awaiting surgery for benign, pre-malignant and malignant conditions within the context of the COVID-19 pandemic. Study design: All patients over the age of 18 awaiting surgery for benign, pre-malignant or malignant conditions within the gynecologic oncology, surgical oncology and colorectal services across Northwell Health were eligible for participation. Upon successful enrollment, participants completed a baseline questionnaire consisting of the Generalized Anxiety Disorder Questionnaire, the Penn State Worry Questionnaire, and Brief-Illness Patient Questionnaire. Results: The surgical delay was considered moderately to extremely concerning by 72 % of survey respondents, with one third indicating the highest (10/10) level of concern. Fifty-five percent of patients with a pre-operatively suspected/confirmed cancer or pre-malignant condition demonstrated mild to severe anxiety in their completion of the GAD-7 scale. The average time awaiting surgery was 117 days (range 8-292); and 63 % of respondents indicated that the delay had a moderate to severe impact on their daily life. Conclusions: Patients awaiting surgery for confirmed, suspected or pre-malignant conditions expressed decreased sense of control and increased levels of distress compared to patients awaiting procedures for benign conditions (p < 0.05, 95 % CI [-2.65, -0.08]). Future research will focus on the effects of COVID-19 related delays in operative care on clinical outcomes, including cancer morbidity and mortality.

Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma.

The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK/STAT3 signaling to increase ∆Np63α-a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention.

Video Didactic Preparation Augments Problem-Based Learning for First Year Medical Students.

Problem-based learning (PBL) utilizes a self-directed strategy. This process relies on group participation to succeed. Students without a background in biology or medicine can feel overwhelmed by the complexity of the subject matter and unable to participate in the group learning process. We incorporated curated educational videos in the PBL curriculum to help address this situation. First year medical students participated in this study in the form of a typical PBL session. They were then assessed on basic and clinical science knowledge and their learning experience. Student basic science and clinical knowledge were similar between the student groups. However, the students given a list of suggested videos scored higher in their learning experience, perception of feeling prepared, and participating in the group PBL experience than students who were not given the video list. Results from this study indicate that videos can be utilized to enhance the PBL process.

Establishing patient-derived organoids from human endometrial cancer and normal endometrium.

Endometrial cancer is the most common gynecologic malignancy in the United States and is one of the few malignancies that had an increasing incidence and mortality rate over the last 10 years. Current research models fail to recapitulate actual characteristics of the tumor that are necessary for the proper understanding and treatment of this heterogenous disease. Patient-derived organoids provide a durable and versatile culture system that can capture patient-specific characteristics such as the mutational profile and response to therapy of the primary tumor. Here we describe the methods for establishing, expansion and banking of endometrial cancer organoids to develop a living biobank. Samples of both endometrial tumor tissue and matched normal endometrium were collected from 10 patients. The tissue was digested into single cells and then cultured in optimized media to establish matched patient endometrial cancer and normal endometrial tissue organoids. Organoids were created from all major endometrial cancer histologic subtypes. These organoids are passaged long term, banked and can be utilized for downstream histological and genomic characterization as well as functional assays such as assessing the response to therapeutic drugs.

Assessing burnout among Obstetrics & Gynecology residents during night float versus day float in a large academic hospital.

BACKGROUND: The prevalence estimates of burnout among residents vary widely. Resident physicians working overnight have additional stressors and therefore, may be at higher risk of developing burnout. OBJECTIVE: To determine the rates of burnout among residents working night rotations versus day rotations. METHODS: This is a prospective, cross sectional, survey-based assessment of the prevalence of burnout among Obstetrics and Gynecology (OBGYN) residents on nights versus days rotations conducted at a large academic residency program that spans two separate hospitals in New York. All residents in the residency program were asked to complete the Maslach Burnout Inventory - Human Services Survey for Medical Personnel (MBI-HSS (MP)) after the first rotation of the academic year in 2018, 2019, and 2020. The results for each of the three aspects of the MBI-HSS (MP): emotional exhaustion, depersonalization, and personal accomplishment, were then compared for those on nights versus day rotations using students t-test. RESULTS: A total of 76 responses were received, 13 from residents on night rotations and 63 from residents on day rotations with a response rate of 61.8%. Comparing resident responses for a night versus day rotation, the residents averaged a low level of emotional exhaustion (a score of 17 ± 9) on day shift, compared to a moderate level of emotional exhaustion (a score of 18 ± 14) on nights (p = 0.37). Similarly, 55.6% of respondents reports low personal accomplishment on days, compared to 76.9% while on nights. CONCLUSIONS: Emotional exhaustion scores were lower for residents on daytime rotations (mean score 17, SD 9), compared to those on nights rotations (mean 18, SD 14). Although there was no difference in depersonalization when comparing the day and night shift, 45% of the responses indicated high levels of depersonalization regardless of the type of shift. These results highlight the need to continue efforts to minimize burnout in medical training.

Maackia amurensis seed lectin (MASL) ameliorates articular cartilage destruction and increases movement velocity of mice with TNFα induced rheumatoid arthritis.

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. For example, the transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN on chondrocytes to decrease inflammatory signaling cascades and reduce cartilage destruction in a lipopolysaccharide induced osteoarthritis mouse model. Here, we investigated the effects of MASL on rheumatoid arthritis progression in a TNFα transgenic (TNF-Tg) mouse model. Results from this study indicate that MASL can be administered orally to ameliorate joint malformation and increase velocity of movement exhibited by these TNF-Tg mice. These data support the consideration of MASL as a potential treatment for rheumatoid arthritis.

Intestinal type adenocarcinoma of the endometrium with signet ring cells, a rare aggressive variant.

Objective: Intestinal type mucinous adenocarcinoma (iMACE) is a rare and unusual variant of mucinous carcinoma of the endometrium that can show focal features of poorly differentiated adenocarcinomas of gastric, pancreatic or intestinal origin by producing signet ring cells. To date, only two reported cases of signet ring cells as a morphological feature of iMACE have been reported. Alterations in E-cadherin expression have been linked to increased metastatic potential, tumor dedifferentiation, and deep myometrial invasion in endometrial carcinomas. The presence or absence of E-cadherin in iMACE with signet-ring cells has not been studied. Thus, we sought to analyze E-cadherin expression in this aggressive variant of endometrial carcinoma. Cases: Diagnosis of iMACE with signet ring cells was rendered with the aid of immunohistochemical staining and histological analysis. Average age of diagnosis was 72 with the presenting complaint of postmenopausal bleeding in all three women. Focal loss or weakly positive E-cadherin expression was seen in areas of signet-rings cell morphology in all three cases. Conclusion: This case report adds to the body of literature that demonstrates the aggressive nature of intestinal differentiation in the endometrium. In addition, this report suggests that the presence of signet-rings cells and loss of E-cadherin expression may render a poorer prognosis as seen in other parts of the body.

Minimally invasive versus open surgery for women with stage 1A1 and stage 1A2 cervical cancer: A retrospective database cohort study.

Background: Recent studies comparing minimally invasive versus open radical hysterectomy in patients with early-stage cervical cancer have reported a worse overall survival with minimally invasive surgery (MIS). However, in the patients with microscopic disease, there was no survival difference and the optimal surgical approach for microscopic cervical cancer remains unclear. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy as the primary treatment for stage IA1/IA2 cervical cancer between January 2010 and December 2016. Using multivariable logistic regression, our primary outcome was to compare overall survival between the open and MIS groups. The data was stratified for simple and radical hysterectomies. Secondary endpoint was comparison of readmission rates and length of stay (LOS). Results: We identified 6230 patients with stage IA1 and IA2 cervical cancer that underwent hysterectomy as primary treatment. 4054 of these women (65%) underwent MIS. There was no difference in age, lympho-vascular invasion, number of lymph nodes retrieved and histology between the two groups. In the overall cohort, there was no difference in survival between the open and the MIS group (Hazard ratio for the open group 1.23; CI 0.92-1.63). Post-operative radiation therapy was more common in the open group (5.24% vs 4.09%, p value < 0.02). The mean LOS (1.35 days vs 3.08 days) was shorter in MIS group (p value < 0.0001). No difference was found in the readmission rates (60% for the MIS group vs 55% for the open group; p value 0.14). Conclusions: Our data suggest that MIS is associated with similar overall survival and shorter length of hospital stay compared to the open hysterectomy in women with stage IA cervical cancer. Based on this large data set, MIS appears to be a safe and effective surgical approach for women with stage IA1/IA2 cervical cancer.

Surgeon Attitudes Toward Concurrent Urogynecologic and Gynecologic Oncology Procedures: A Cross-sectional Survey.

IMPORTANCE: There is increasing overlap in the urogynecologic and gynecologic oncologic patient populations. To improve patient advocacy and access to care, a collaborative surgical approach may benefit this cohort. OBJECTIVE: The aim of the study was to evaluate surgeon attitudes toward performing concurrent urogynecologic and gynecologic oncology procedures. We hypothesized that most surgeons are amenable to collaboration. STUDY DESIGN: We conducted a cross-sectional questionnaire of members of the Society of Gynecologic Oncology and the American Urogynecologic Society from August to November 2020. A 23-item online survey was created to assess surgeon demographics, practice and screening patterns, and attitudes toward surgical collaboration. We also evaluated obstacles to performing joint procedures and assessed whether attitudes could be influenced by new information. RESULTS: A total of 338 surveys were included in the analysis, including 158 urogynecologists and 226 gynecologic oncologists (GOs). Most surgeons (77.8%) will recommend concurrent procedures with another specialty, and 97.8% of urogynecologists and 95.7% of oncologists currently perform joint surgical procedures. Male surgeons, regardless of specialty, were more likely to recommend staged procedures (44% vs 31%, P < 0.001), as were GOs (28% vs 10.1%, P < 0.001). However, oncologists were more likely than urogynecologists to initiate referrals for surgical collaboration (33.3% vs 14.4%, P < 0.001). CONCLUSIONS: A total of 22.2% of urogynecologists and oncologists prefer staging surgical procedures. The most common barrier to a combined procedure was logistics. Urogynecologists were more concerned about the effects of cancer treatments on healing, the use of mesh implants, and financial reimbursements as compared with GOs. Treatment delay was a significantly greater concern for the oncologists.

Independent effects of Src kinase and podoplanin on anchorage independent cell growth and migration.

The Src tyrosine kinase is a strong tumor promotor. Over a century of research has elucidated fundamental mechanisms that drive its oncogenic potential. Src phosphorylates effector proteins to promote hallmarks of tumor progression. For example, Src associates with the Cas focal adhesion adaptor protein to promote anchorage independent cell growth. In addition, Src phosphorylates Cas to induce Pdpn expression to promote cell migration. Pdpn is a transmembrane receptor that can independently increase cell migration in the absence of oncogenic Src kinase activity. However, to our knowledge, effects of Src kinase activity on anchorage independent cell growth and migration have not been examined in the absence of Pdpn expression. Here, we analyzed the effects of an inducible Src kinase construct in knockout cells with and without exogenous Pdpn expression on cell morphology migration and anchorage independent growth. We report that Src promoted anchorage independent cell growth in the absence of Pdpn expression. In contrast, Src was not able to promote cell migration in the absence of Pdpn expression. In addition, continued Src kinase activity was required for cells to assume a transformed morphology since cells reverted to a nontransformed morphology upon cessation of Src kinase activity. We also used phosphoproteomic analysis to identify 28 proteins that are phosphorylated in Src transformed cells in a Pdpn dependent manner. Taken together, these data indicate that Src utilizes Pdpn to promote transformed cell growth and motility in complementary, but parallel, as opposed to serial, pathways.

The significance of "atrophic endometrium" in women with postmenopausal bleeding.

We evaluated the interpretation of atrophic endometrium (AE) histology as the most common cause for postmenopausal bleeding (PMB). This theory has been accepted for several generations by gynecologists and gynecologic oncologists and has been published in past and current major gynecology textbooks. In our review of the literature, we did not find sufficient histological or clinical proof for this concept. In our view, AE is not a cause of PMB and we back this up with a review of old and current medical literature. The old studies are based on information which was obtained prior to the existence of transvaginal sonogram, sonohysterogram and hysteroscopy. Focal lesions are notorious for being missed by endometrial sampling and curettage. Recent studies show that focal endometrial lesions are a crucial cause for PMB and some of those lesions can harbor cancer. In our opinion, AE is the most common histology found because it is physiologic and a ubiquitous finding in postmenopausal women, but it is not a cause of PMB. Referring to AE as a cause of PMB may result in misdiagnosis of cancer, management delay and unnecessary intervention. To avoid misdiagnosis of cancer, transvaginal sonogram should be considered in all women with PMB and AE on pathology. If endometrial thickness is found, AE is unlikely to be the cause of the PMB and further workup is warranted to reveal the true etiology for the bleeding.

Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial.

OBJECTIVE: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19. DESIGN: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory). RESULTS: Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms. CONCLUSIONS: Famotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required.

Heterocellular N-cadherin junctions enable nontransformed cells to inhibit the growth of adjacent transformed cells.

BACKGROUND: The Src tyrosine kinase phosphorylates effector proteins to induce expression of the podoplanin (PDPN) receptor in order to promote tumor progression. However, nontransformed cells can normalize the growth and morphology of neighboring transformed cells. Transformed cells must escape this process, called "contact normalization", to become invasive and malignant. Contact normalization requires junctional communication between transformed and nontransformed cells. However, specific junctions that mediate this process have not been defined. This study aimed to identify junctional proteins required for contact normalization. METHODS: Src transformed cells and oral squamous cell carcinoma cells were cultured with nontransformed cells. Formation of heterocellular adherens junctions between transformed and nontransformed cells was visualized by fluorescent microscopy. CRISPR technology was used to produce cadherin deficient and cadherin competent nontransformed cells to determine the requirement for adherens junctions during contact normalization. Contact normalization of transformed cells cultured with cadherin deficient or cadherin competent nontransformed cells was analyzed by growth assays, immunofluorescence, western blotting, and RNA-seq. In addition, Src transformed cells expressing PDPN under a constitutively active exogenous promoter were used to examine the ability of PDPN to override contact normalization. RESULTS: We found that N-cadherin (N-Cdh) appeared to mediate contact normalization. Cadherin competent cells that expressed N-Cdh inhibited the growth of neighboring transformed cells in culture, while cadherin deficient cells failed to inhibit the growth of these cells. Results from RNA-seq analysis indicate that about 10% of the transcripts affected by contact normalization relied on cadherin mediated communication, and this set of genes includes PDPN. In contrast, cadherin deficient cells failed to inhibit PDPN expression or normalize the growth of adjacent transformed cells. These data indicate that nontransformed cells formed heterocellular cadherin junctions to inhibit PDPN expression in adjacent transformed cells. Moreover, we found that PDPN enabled transformed cells to override the effects of contact normalization in the face of continued N-Cdh expression. Cadherin competent cells failed to normalize the growth of transformed cells expressing PDPN under a constitutively active exogenous promoter. CONCLUSIONS: Nontransformed cells form cadherin junctions with adjacent transformed cells to decrease PDPN expression in order to inhibit tumor cell proliferation. Cancer begins when a single cell acquires changes that enables them to form tumors. During these beginning stages of cancer development, normal cells surround and directly contact the cancer cell to prevent tumor formation and inhibit cancer progression. This process is called contact normalization. Cancer cells must break free from contact normalization to progress into a malignant cancer. Contact normalization is a widespread and powerful process; however, not much is known about the mechanisms involved in this process. This work identifies proteins required to form contacts between normal cells and cancer cells, and explores pathways by which cancer cells override contact normalization to progress into malignant cancers. Video Abstract.

Intraoperative Indocyanine Green Dye Use in Ovarian Torsion: A Feasibility Study.

STUDY OBJECTIVE: To determine the feasibility of  intravenous indocyanine green (ICG) dye use in patients with adnexal torsion to intraoperatively evaluate ovarian perfusion after detorsion. DESIGN: A prospective multicenter single-arm feasibility study. SETTING: A teaching hospital. PATIENTS: A total of 12 nonpregnant patients, 18 to 45 years old with surgically confirmed adnexal torsion. INTERVENTIONS: Torsion was surgically confirmed, the involved adnexa were untwisted laparoscopically, and ICG dye was injected intravenously. The absence or presence of ICG perfusion was documented, and the clinical decision for ovarian conservation or removal was determined by the surgeon. MEASUREMENTS AND MAIN RESULTS: The primary outcome was feasibility of using ICG dye including measures such as time to visualized perfusion and operative time. Secondary outcomes included presence or absence of ovarian preservation and postoperative follow-up measures. Intraoperative visualization of ICG perfusion to the detorsed adnexa was achieved in 10 patients (83%) in a median time of 1 minute (0, 2), resulting in entire (n = 9) or partial (n = 1) ovarian conservation. Perfusion was absent in 2 cases, and postoophorectomy histologic necrosis was confirmed in one case. Median operative time was 74 minutes (48, 94). There were no adverse events related to ICG dye use. CONCLUSION: Intraoperative ICG dye use in this study was logistically feasible and conservation of the entire or partial ovary was observed in 83% of patients, including one case where preoperative Doppler flow was absent.

Nosocomial COVID-19 infection in women undergoing elective cesarean delivery: a prospective cohort study.

BACKGROUND: The COVID-19 pandemic placed obstetricians in a difficult position of continuing to perform elective cesarean delivery without the knowledge of the risk of the spread of nosocomial infection of the COVID-19 virus. OBJECTIVE: This study aimed to determine the nosocomial infection rate in women undergoing elective cesarean delivery at 2 academic institutions. STUDY DESIGN: This nonrandomized prospective cohort trial evaluated patients undergoing elective cesarean delivery during the reopening phase of the COVID-19 pandemic in the state of New York at 2 large volume labor and delivery units. Eligible patients with a negative preoperative reverse transcriptase-polymerase chain reaction test and immunoglobulin G antibody test for COVID-19 were retested 6 to 9 days after discharge. The primary objective was the COVID-19 test conversion rate defined as a positive polymerase chain reaction test for SARS-CoV-2 after discharge with a negative preoperative test. This was used as a proxy for the nosocomial infection rate. RESULTS: A total of 136 patients were screened for participation. Of these patients, 2 tested positive for COVID-19 on preoperative testing, and 25 declined to participate. Overall, 111 patients consented to participate, and 96 patients underwent both preoperative and postoperative testing. No patient with a negative polymerase chain reaction test preoperatively, had a positive polymerase chain reaction test for the COVID-19 virus postoperatively. CONCLUSION: With strict and methodical perioperative and postpartum protocols, we can limit nosocomial COVID-19 infection in women undergoing elective cesarean delivery.

Is minimally invasive surgery for clinical stage I uterine carcinosarcoma safe?

Minimally invasive surgery (MIS) has been a mainstay of the surgical management of uterine cancer since the mid-2000s. We aim to determine the role and safety of MIS in women with uterine carcinosarcoma (UCS). An Institutional Review Board-approved study identified all patients with UCS between January 2011 and December 2017 at our institution. Demographic and outcome measures were abstracted from the medical records and tumor registry. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). 129 women with UCS were identified during the study period. 62 cases (48%) were open procedures and 67 cases (52%) were MIS with the majority of the MIS group having robotic surgery. 55% of the patients had pathological stage 1 disease. Thirty-eight percent of UCS tumors were heterologous. 93% of patients received adjuvant therapy in the form of chemotherapy and/or radiation therapy. There was no difference in the recurrence-free survival (RFS) or overall survival (OS) between the open surgery and the MIS groups as well as between the heterologous and homologous UCS groups (p > 0.05). UCS represents a rare and aggressive subtype of endometrial cancer. Our data suggest that MIS is a safe surgical approach for staging in women with UCS.

BRD4 Regulates Transcription Factor ΔNp63α to Drive a Cancer Stem Cell Phenotype in Squamous Cell Carcinomas.

Bromodomain containing protein 4 (BRD4) plays a critical role in controlling the expression of genes involved in development and cancer. Inactivation of BRD4 inhibits cancer growth, making it a promising anticancer drug target. The cancer stem cell (CSC) population is a key driver of recurrence and metastasis in patients with cancer. Here we show that cancer stem-like cells can be enriched from squamous cell carcinomas (SCC), and that these cells display an aggressive phenotype with enhanced stem cell marker expression, migration, invasion, and tumor growth. BRD4 is highly elevated in this aggressive subpopulation of cells, and its function is critical for these CSC-like properties. Moreover, BRD4 regulates ΔNp63α, a key transcription factor that is essential for epithelial stem cell function that is often overexpressed in cancers. BRD4 regulates an EZH2/STAT3 complex that leads to increased ΔNp63α-mediated transcription. Targeting BRD4 in human SCC reduces ΔNp63α, leading to inhibition of spheroid formation, migration, invasion, and tumor growth. These studies identify a novel BRD4-regulated signaling network in a subpopulation of cancer stem-like cells, elucidating a possible avenue for effective therapeutic intervention. SIGNIFICANCE: This study identifies a signaling cascade driven by BRD4 that upregulates ΔNp63α to promote cancer stem-like properties, which has potential therapeutic implications for the treatment of squamous cell carcinomas.