vNOTES retroperitoneal sentinel lymph node dissection for endometrial cancer staging: First multicenter, prospective case series.

INTRODUCTION: The current standard treatment for endometrial cancer is a laparoscopic hysterectomy with adnexectomies and bilateral sentinel node resection. A retroperitoneal vNOTES sentinel node resection has several theoretical potential advantages. These include being less invasive, leaving no visible scars, operating without Trendelenburg, and therefore offering the anesthetic advantage of easier ventilation in obese patients and following the natural lymph node trajectory from caudally to cranially and therefore a lower risk of missing the sentinel node. The aim of this study is to determine the feasibility of a retroperitoneal vNOTES approach to sentinel lymph node dissection for staging of endometrial cancer. MATERIAL AND METHODS: A prospective multicenter case series was performed in four hospitals. A total of 64 women with early-stage endometrial carcinoma suitable for surgical staging with sentinel lymph node removal were operated via a transvaginal retroperitoneal vNOTES approach. The paravesical space was entered through a vaginal incision after injecting the cervix with indocyanine green. A vNOTES port was placed into this space and insufflation of the retroperitoneum was performed. Sentinel lymph nodes were identified bilaterally using near-infrared light followed by endoscopic removal of these nodes. RESULTS: A total of 64 women with early-stage endometrial cancer underwent sentinel lymph node removal by retroperitoneal vNOTES technique. All patients also underwent subsequent vNOTES hysterectomy and bilateral salpingo-oophorectomy. The median age was 69.5 years, median total operative time was 126 min and the median estimated blood loss was 80 mL. In 97% of the cases bilateral sentinel nodes could be identified. A total of 60 patients had negative sentinel nodes, three had isolated tumor cells and one had macroscopically positive sentinel nodes. No complications with sequel occurred. CONCLUSIONS: This prospective multicenter case series demonstrates the feasibility of the vNOTES approach for identifying and removing sentinel lymph nodes in women with endometrial carcinoma successfully and safely. vNOTES allows sole transvaginal access with exposure of the entire retroperitoneal space, following the natural lymph trajectory caudally to cranially, and without the need for a Trendelenburg position.

vNOTES (vaginal natural orifice transluminal surgery) gynecologic procedures in morbidly and super-morbidly obese women: five year experience.

PURPOSE: To analyze our experience with vNOTES gynecologic procedures in women with morbid and super morbid obesity to determine feasibility and compare outcomes with standard minimally invasive techniques. METHODS: Gynecologic procedures performed by three surgeons on women with a body mass index (BMI) ≥ 40 kg/m2 from 2017 to 2023. A subset of women with a BMI ≥ 50 kg/m2 was also analyzed. RESULTS: 103 women with a BMI ≥ 40 kg/m2 were identified (Class IV), 19 of whom had a BMI ≥ 50 kg/m2 (Class V). For the entire population the mean BMI was 45.7 kg/m2 (40-62). 29 women were nulliparous and 23 had at least one prior cesarean delivery. 51 had no prior abdominal surgery. The procedures performed were hysterectomy and removal of adnexae in 77 patients, hysterectomy alone in six, adnexal surgery alone in nine, and hysterectomy with adnexectomy and lymph nodes in five. Two surgeries were converted to laparoscopy and five to laparotomy. Average surgical time was 87 min (30-232). Average blood loss was 82 mL (10-400). Mean uterine weight was 206 g (29-2890). 53 procedures were performed as outpatient, 44 had overnight observation, four had a length of stay of 2 days, one each for 4 days and 5 days. The laparoscopies occurred in one patient with an obliterated cul-de-sac and in one patient for lymph node removal. The laparotomies occurred for adnexal adhesions in one, bleeding in two, a cystotomy in one requiring urology consultation, and an obliterated cul-de-sac One patient developed a postoperative vaginal cuff hematoma not requiring intervention. CONCLUSION: vNOTES gynecologic procedures are feasible in this high-risk population and may result in shorter recovery times and fewer complications than standard laparoscopy or transvaginal surgery. What does this study add to the clinical work: VNOTES approach is feasible in morbidly obese women and may have distinct advantages over conventional laparoscopic, vaginal or open techniques.

Occupational class suicide risk: 12-year study of national coronial data.

BACKGROUND: Previous research showed that the Global Financial Crisis (GFC) was associated with a widening disparity in suicide rates between lower-class occupations and the highest-class occupations in Australia. There has been no research investigating whether this trend continued post-GFC. AIMS: This study aimed to investigate suicide rates by occupational class among employed Australians aged 15 years and over, between 2007 and 2018. METHOD: A population-level retrospective mortality study was conducted using data from the National Coronial Information System. Adjusted suicide rates were calculated over the period 2007 to 2018. Negative binomial regression models were used to assess the relationship between occupational class, gender and time, comparing post-GFC years (2010-2012, 2013-2015 and 2016-2018) with GFC years (2007-2009). RESULTS: Relative to the GFC period of 2007-2009, a significant reduction in suicide disparity between managers and other occupation groups was only observed among male labourers (rate ratios (RR) = 0.65, 95% CI 0.49-0.86) and male technicians/trades workers (RR = 0.73, 95% CI 0.56-0.96) for the period 2013-2015. CONCLUSION: Skilled manual and lower-skilled occupational classes remain at elevated risk of suicide in Australia. While a decreasing divergence in suicide rates was only observed between labourer and manager occupational classes post-GFC, this trend was not maintained over the later part of the study period (2016-2018). There is a need to further understand the relationship between contextual factors associated with suicide among the employed population, especially during periods of economic downturn.

Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

Non-disclosing youth: a cross sectional study to understand why young people do not disclose suicidal thoughts to their mental health professional.

BACKGROUND: Prevalence of suicidal ideation increases rapidly in adolescence, and many choose not to seek help and disclose their ideation. Young people who do disclose suicidal ideation, prefer to do so with peers and family compared to mental health professionals, who are best placed to provide evidence-based treatment. This study aimed to identify key factors associated with young people's decision to, or not to disclose suicidal thoughts to their mental health practitioner. METHODS: A community-based sample of young Australians (16 - 25 years), who had experienced suicidal ideation and engaged with a mental health professional, completed an online questionnaire (N=513) which assessed demographic characteristics, severity of depression, anxiety, psychological distress, and suicidal ideation, lifetime suicide attempts, exposure to suicide loss, personal suicide stigma, prioritisation of mental health issues, and therapeutic alliance. Logistic regression analyses were used to identify factors associated with disclosure. RESULTS: Though the full sample had engaged in therapy, 39% had never disclosed suicidal ideation to their clinician. Those who had disclosed were more likely to report greater therapeutic alliance (OR=1.04, 95% CI=1.02-1.06), personal suicide stigma (OR=1.04, 95% CI=1.01-1.06), prioritisation of suicidal ideation (OR=.24, 95% CI=0.14-0.42), and lifetime history of suicide attempt (OR=.32, 95% CI=0.18-0.57). The most common reason for not disclosing was concern that it would not remain confidential. CONCLUSION: These findings provide new insights into why young people may not seek help by disclosing suicidal ideation, despite having access to a mental health professional, and establish evidence to inform practice decisions and the development of prevention strategies to support young people for suicide.

Suicide among hospitality workers in Australia, 2006-2017.

PURPOSE: Suicide among hospitality workers has recently attracted attention in the media. To date, little is known about suicide among hospitality workers in Australia. METHODS: Suicide data were obtained from the National Coronial Information System (NCIS). Occupational suicide rates were calculated using the Australian Bureau of Statistics population-level data from the 2011 census. Negative binomial regression, univariate logistic regression, and multivariate logistic regression were used to estimate the association between suicide and employment as a hospitality worker over the period 2006-2017, compared to all other occupations. RESULTS: Suicide rates for chefs was significantly higher than for persons in non-hospitality occupations [incidence rate ratio (IRR), 3.93; 95% CI 2.53-5.79; P < 0.001]. The interaction between occupation and sex was examined with follow-up testing. Suicide rates for female chefs were significantly higher than for females in non-hospitality occupations (IRR, 3.93; 95% CI 2.60-5.94). Suicide rates for male chefs were also significantly higher than males in non-hospitality occupations (IRR, 1.38; 95% CI 1.14-1.67). Compared with non-hospitality occupations, hospitality workers who died by suicide had significantly greater odds of being female (OR 0.63, 95% CI 0.50-0.79), residing in residential Socio-Economic Indexes for Areas (SEIFA) classified as most disadvantaged (OR 1.62, 95% CI 1.19-2.20), and being born outside of Australia (OR 1.74, 95% CI 1.34-2.25). CONCLUSION: Results indicate the need for targeted prevention of suicide by Australian hospitality workers. Overall, results suggest that specific hospitality occupations present a higher risk of suicidal behaviour than other non-hospitality occupations.

Spatial Errors in Automated Geocoding of Incident Locations in Australian Suicide Mortality Data.

BACKGROUND: There is increasing interest in the spatial analysis of suicide data to identify high-risk (often public) locations likely to benefit from access restriction measures. The identification of such locations, however, relies on accurately geocoded data. This study aims to examine the extent to which common completeness and positional spatial errors are present in suicide data due to the underlying geocoding process. METHODS: Using Australian suicide mortality data from the National Coronial Information System for the period of 2008-2017, we compared the custodian automated geocoding process to an alternate multiphase process. Descriptive and kernel density cluster analyses were conducted to ascertain data completeness (address matching rates) and positional accuracy (distance revised) differences between the two datasets. RESULTS: The alternate geocoding process initially improved address matching from 67.8% in the custodian dataset to 78.4%. Additional manual identification of nonaddress features (such as cliffs or bridges) improved overall match rates to 94.6%. Nearly half (49.2%) of nonresidential suicide locations were revised more than 1,000 m from data custodian coordinates. Spatial misattribution rates were greatest at the smallest levels of geography. Kernel density maps showed clear misidentification of hotspots relying solely on autogeocoded data. CONCLUSION: Suicide incidents that occur at nonresidential addresses are being erroneously geocoded to centralized fall-back locations in autogeocoding processes, which can lead to misidentification of suicide clusters. Our findings provide insights toward defining the nature of the problem and refining geocoding processes, so that suicide data can be used reliably for the detection of suicide hotspots. See video abstract at, http://links.lww.com/EDE/B862.

Radiation treatment for refractory endometriosis: a 38-year-old female presenting with vaginal bleeding.

BACKGROUND: Endometriosis is typically managed with a medical or surgical approach, though some patients have medically refractory disease and are poor surgical candidates. CASE PRESENTATION: A 39-year-old woman presented to our facility with uncontrolled bleeding and pain from an endometriotic mass at the vaginal cuff. She had a history of abdominal hysterectomy with bilateral salpingo-oophorectomy, now with medically refractive and inoperable disease due to prior history of vesicovaginal fistula. We prescribed 30 Gy in 10 fractions with 10 MV and 18 MV photons to the target. At follow-up our patient reported a complete resolution of bleeding and pelvic pain. CONCLUSION: Radiation treatment can be an effective treatment for refractory endometriosis.

Use of Metformin in Obese Women With Type I Endometrial Cancer Is Associated With a Reduced Incidence of Cancer Recurrence.

OBJECTIVES: Recent evidence suggests that hyperinsulinemia associated with obesity may be a significant risk factor for the development of endometrial cancer. Metformin is used in type II diabetes to lower circulating insulin levels. We sought to examine our obese patients with endometrial cancer and examine those who were on metformin to determine any impact on their cancer course. METHODS: A retrospective review of all women with the diagnosis of endometrial cancer and a body mass index of 30 kg/m(2) or higher during a 6-year period (2005-2011) at our institution was conducted. Records were reviewed for standard demographic data, use of metformin, cancer characteristics, treatment, and cancer follow-up. RESULTS: A total of 351 women were identified who were obese and diagnosed as having endometrial cancer. Of these, 64 were on metformin (M+) at the time of diagnosis of endometrial cancer. The women on metformin had a significantly higher mean body mass index (44.6 vs 41.6, P < 0.05). Age, grade, stage, and adjuvant therapy did not differ between the 2 groups. Recurrence occurred in 15.3% of the M- women versus 7.8% of the M+ women (not significant). However, for those patients with type I endometrial cancer, only 1 patient (1.9%) who was on metformin recurred versus 10.3% who were not on the drug (P = 0.05). With a minimum of 24 months of follow-up, 89.1% of metformin users were alive and free of disease versus 83.9% of nonusers (not significant). CONCLUSIONS: Obese women who developed endometrial cancer while on metformin did not seem to have pathologic risk factors different from those not on metformin. However, the type I cancer patients on metformin were less likely to recur than those not on the drug. This suggests that a prospective trial of metformin at the time of diagnosis of endometrial cancer in the obese population may be warranted.

Multimodal hyperspectroscopy as a triage test for cervical neoplasia: pivotal clinical trial results.

OBJECTIVE: To prospectively evaluate a new non invasive device that combines fluorescence and reflectance spectroscopy in a population in women at risk for cervical dysplasia. METHODS: A total of 1607 women were evaluated with multimodal hyperspectroscopy (MHS), a painless test with extremely high spectral resolution. Subjects who were referred to colposcopy based on abnormal screening tests or other referral criteria underwent the MHS test and also had a sample taken for additional cytology and presence of high risk human papilloma virus (HPV) prior to undergoing biopsy. RESULTS: Sensitivity of MHS for cervical intraepithelial neoplasia (CIN) 2+ was 91.3% (252/276). Specificity, or the potential reduction in referrals to colposcopy and biopsy, was 38.9% (222/570) for women with normal or benign histology and 30.3% (182/601) for women with CIN1 histology. Two year follow-up data, collected for a subgroup of 804 women, revealed 67 interval CIN2+ that originally were diagnosed at enrollment as normal or CIN1. MHS identified 60 of these (89.6%) as positive for CIN2+ prior to their discovery during the two year follow-up period. CONCLUSIONS: MHS provides an immediate result at the point of care. Recently, the limitations of cytology have become more obvious and as a consequence greater emphasis is being placed on HPV testing for cervical cancer screening, creating a need for an inexpensive, convenient and accurate test to reduce false positive referrals to colposcopy and increase the yield of CIN2+ at biopsy. MHS appears to have many of the attributes necessary for such an application.

Risk of repeat self-harm and suicide death following an episode of hospital self-harm presentation among adolescents and young adults.

BACKGROUND: Self-harm is a critical issue affecting young people which could result in adverse outcomes including repeat episodes and suicide. In this study, we aimed to estimate the short-term and long-term risk of repeat self-harm and subsequent suicide death following self-harm presentations among adolescents and young adults. METHODS: Using linked data from the New South Wales (NSW) Emergency Department Data Collection (EDDC), the NSW Admitted Patient Data Collection (APDC), and cause of death unit record file (COD-URF), we collected all self-harm presentations to emergency departments and/or hospitals and suicide deaths between 2012 and 2019 in NSW, Australia. We used survival analysis models to estimate the incidence of repeat self-harm and suicide by time since the index self-harm and relative risks by sex, type of hospital presentation and count of self-harm records. RESULTS: In total, we identified 81,133 self-harm episodes among 48,547 individuals aged 10-29 years. Of 48,547 individuals who engaged in an index self-harm during the study period, 39.5 % (19,180) were aged between 15 and 19 years. The incidence of both repeat self-harm and suicide were highest in the year following the index self-harm presentation (repeat self-harm: 188.84 per 1000 person-years; suicide: 3.30 per 1000 person-years) and declined to 14.51 and 0.28 per 1000 person-years after five years. Among individuals indexed for self-harm at 15-29 years, males and those who were admitted to hospital for the index self-harm had the highest risk of both subsequent repeat self-harm and suicide death and those with 2 or more self-harm presentation records had the higher risk for subsequent suicide death. CONCLUSION: Adolescents and young adults with self-harm presentations were at a high risk of subsequent repeat self-harm and suicide death, especially the first year after presentations. Youth-specific early intervention and long-term management should be delivered accordingly, especially for those at early adolescence .

Self-harm in 5-to-24 year olds: Retrospective examination of hospital presentations to emergency departments in New South Wales, Australia, 2012 to 2020.

There is some evidence that self-harm presentations in children and young people have increased over the past decade, yet there are few up-to-date studies examining these trends. This study aims to describe trends in the rates and severity of emergency department self-harm presentations for youth aged 5-24 years in New South Wales, Australia between 1 January 2012 and 31 December 2020. We analysed self-harm hospital presentations using join point analysis to compare quarterly growth in rates and urgency of presentation since 2012 by age group and sex. Binomial logistic modelling was used to identify risks for re-presentation for self-harm, including age group, sex, country of birth, mode of arrival, inpatient status, triage category, rurality, and socio-economic disadvantage. In total, 83,111 self-harm presentations for 51,181 persons were analysed. Overall rates of self-harm among those aged 5-24 years increased by 2.4% (p < .001) per quarter in females and 1.6% (p < .001) per quarter in males, with statistically significant average quarterly increases observed across all age groups. Overall and age-specific self-harm triage urgency rates increased statistically significantly for potentially serious, and potentially- and immediately life-threatening categories. A higher likelihood of re-presentation to any emergency department for self-harm was associated with younger age, female, residing in a regional area, arriving by ambulance, admitted as an in-patient, and a more severe index self-harm presentation. Hospital self-harm presentations have been growing steadily over the past decade, with the greatest growth in the youngest people. Understanding the reasons for these sustained upward trends is a priority for suicide prevention.

A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

Machine learning algorithms to classify self-harm behaviours in New South Wales Ambulance electronic medical records: A retrospective study.

BACKGROUND: There is increasing interest in suicide surveillance solutions to identify non-fatal suicidal and self-harming behaviours in the Australian community not currently captured through national administrative datasets. OBJECTIVE: The aim of the present study was to develop machine learning models to classify self-harm related behaviours using unstructured clinical note text from New South Wales (NSW) Ambulance data and compare their performance via traditional methods. METHODS: Primary data were derived from NSW Ambulance electronic medical records (eMRs) for potential self-harm related NSW Ambulance attendances for the period 2013-2019. Data included paramedic clinical notes detailing the nature of the attendance, clinical outcome, and narrative information. We assessed sensitivity, specificity, positive predictive value, negative predictive value, F-score, and the Matthews correlation coefficient (MCC) for four algorithms (Support Vector Machine, random forest, decision tree, and logistic regression). RESULTS: The performance of these algorithms was compared using the MCC measure. In a test sample of 3157 ambulance attendances (1349 self-harm related behaviours and 1808 unrelated), the MCC for classification of self-harm related behaviour ranged from +0.681 to +0.730. The Support Vector Machine (sensitivity = 82.7%, specificity = 89.6%, MCC = 0.730) and the logistic regression (sensitivity = 83.1%, specificity = 89.3%, MCC = 0.727) models performed best. CONCLUSIONS: This study demonstrates that machine learning models can be applied to paramedic notes within unstructured medical records to classify self-harm related behaviours. The resulting model could be used to compliment current manual abstraction of self-harm behaviours and provide more timely approximations to be used for self-harm surveillance.

The performance of machine learning models in predicting suicidal ideation, attempts, and deaths: A meta-analysis and systematic review.

Research has posited that machine learning could improve suicide risk prediction models, which have traditionally performed poorly. This systematic review and meta-analysis evaluated the performance of machine learning models in predicting longitudinal outcomes of suicide-related outcomes of ideation, attempt, and death and examines outcome, data, and model types as potential covariates of model performance. Studies were extracted from PubMed, Web of Science, Embase, and PsycINFO. A bivariate mixed effects meta-analysis and meta-regression analyses were performed for studies using machine learning to predict future events of suicidal ideation, attempts, and/or deaths. Risk of bias was assessed for each study using an adaptation of the Prediction model Risk Of Bias Assessment Tool. Narrative review included 56 studies, and analyses examined 54 models from 35 studies. The models achieved a very good pooled AUC of 0.86, sensitivity of 0.66 (95% CI [0.60, 0.72)], and specificity of 0.87 (95% CI [0.84, 0.90]). Pooled AUCs for ideation, attempt, and death were similar at 0.88, 0.87, and 0.84 respectively. Model performance was highly varied; however, meta-regressions did not provide evidence that performance varied by outcome, data, or model types. Findings suggest that machine learning has the potential to improve suicide risk detection, with pooled estimates of machine learning performance comparing favourably to performance of traditional suicide prediction models. However, more studies with lower risk of bias are necessary to improve the application of machine learning in suicidology.

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study.

PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Krüppel-like factor 9 loss-of-expression in human endometrial carcinoma links altered expression of growth-regulatory genes with aberrant proliferative response to estrogen.

Endometrial cancer is the most commonly diagnosed female genital tract malignancy. Krüppel-like factor 9 (KLF9), a member of the evolutionarily conserved Sp family of transcription factors, is expressed in uterine stroma and glandular epithelium, where it affects cellular proliferation, differentiation, and apoptosis. Deregulated expression of a number of Sp proteins has been associated with multiple types of human tumors, but a role for KLF9 in endometrial cancer development and/or progression is unknown. Here, we evaluated KLF9 expression in endometrial tumors and adjacent uninvolved endometrium of women with endometrial carcinoma. KLF9 mRNA and protein levels were lower in endometrial tumors coincident with decreased expression of family member KLF4 and growth-regulators FBJ murine osteosarcoma viral oncogene homolog (FOS) and myelocytomatosis viral oncogene homolog (MYC) and with increased expression of telomerase reverse transcriptase (TERT) and the chromatin-modifying enzymes DNA methyltransferase 1 (DNMT1) and histone deacetylase 3 (HDAC3). Expression of estrogen receptor alpha (ESR1) and the tumor-suppressor phosphatase and tensin homolog deleted in chromosome 10 (PTEN) did not differ between tumor and normal tissue. The functional relevance of attenuated KLF9 expression in endometrial carcinogenesis was further evaluated in the human endometrial carcinoma cell line Ishikawa by siRNA targeting. KLF9 depletion resulted in loss of normal cellular response to the proliferative effects of estrogen concomitant with reductions in KLF4 and MYC and with enhancement of TERT and ESR1 gene expression. Silencing of KLF4 did not mimic the effects of silencing KLF9 in Ishikawa cells. We suggest that KLF9 loss-of-expression accompanying endometrial carcinogenesis may predispose endometrial epithelial cells to mechanisms of escape from estrogen-mediated growth regulation, leading to progression of established neoplasms.

Lower extremity glandography (LEG): a new concept to identify and enhance lymphatic preservation.

BACKGROUND: Lower extremity edema remains a major postoperative complication after inguinal lymphadenectomy for vulvar cancer. This study documents the lymphatic drainage of the vulva versus the lymphatic drainage of the lower extremity coming through the femoral triangle. METHODS: Seven patients underwent either unilateral or bilateral inguinal lymphadenectomy in conjunction with a radical vulvar resection. Preoperatively, patients had technetium-99 injected into the vulvar cancer. Isosulfan blue was injected into the medioanterior thigh 10 cm below the inguinal ligament. The femoral triangle was opened, and a neoprobe was used to locate the "hot" node bearing the technetium-99. Gentle dissection located the blue lymphatic channel and any blue lymph nodes. The blue and hot nodes were resected and submitted separately. The patients then underwent a complete inguinal lymphadenectomy. RESULTS: A total of 11 groin dissections were performed. In 9 of the 11 groins, the hot node was identified, and in 8 of the 11 groins, blue node or lymphatic channel was identified. The hot nodes were uniformly located on the superior medial aspect of the femoral triangle. The blue nodes were uniformly located on the lateral aspect of the femoral triangle just anterior to the femoral artery or vein. Three patients had hot lymph nodes containing cancer. Of those 3 patients, one had an additional node positive. None of the blue lymph nodes contained cancer. CONCLUSIONS: This procedure demonstrates the alternative lymphatic drainage of the leg versus the vulva. Larger studies are necessary to document the exclusivity of these 2 drainage systems. Preservation of the lymphatic drainage of the leg may result in decreased lymphedema.