Subject(s)
Gynecology , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , United States/epidemiology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Papillomavirus Infections/diagnosis , Papillomavirus Infections/prevention & control , Early Detection of Cancer , Mass ScreeningABSTRACT
Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.
Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Humans , SARS-CoV-2 , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , COVID-19 Vaccines , Antibodies , Interleukin-2 Receptor alpha Subunit , Immunity, Cellular , Antibodies, Viral , VaccinationABSTRACT
The Longfin Smelt (Spirinchus thaleichthys) population in the San Franscisco Bay/Sacramento-San Joaquin Delta (Bay-Delta) has declined to â¼1% of its pre-1980s abundance and, as a result, is listed as threatened under the California Endangered Species Act. The reasons for this decline are multiple and complex, including the impacts of contaminants. Because the spawning and rearing seasons of Longfin Smelt coincide with the rainy season, during which concentrations of contaminants increase due to runoff, we hypothesized that early life stages may be particularly affected by those contaminants. Bifenthrin, a pyrethroid insecticide commonly used in agricultural and urban sectors, is of concern. Concentrations measured in the Bay-Delta have been shown to disrupt the behavior, development, and endocrine system of other fish species. The objective of the present work was to assess the impact of bifenthrin on the early developmental stages of Longfin Smelt. For this, embryos were exposed to 2, 10, 100, and 500 ng/L bifenthrin from fertilization to hatch, and larvae were exposed to 2, 10, and 100 ng/L bifenthrin from one day before to 3 days post-hatch. We assessed effects on size at hatch, yolk sac volume, locomotory behavior, and upper thermal susceptibility (via cardiac endpoints). Exposure to these environmentally relevant concentrations of bifenthrin did not significantly affect the cardiac function of larval Longfin Smelt; however, exposures altered their behavior and resulted in smaller hatchlings with reduced yolk sac volumes. This study shows that bifenthrin affects the fitness-determinant traits of Longfin Smelt early life stages and could contribute to the observed population decline.
Subject(s)
Osmeriformes , Pyrethrins , Water Pollutants, Chemical , Animals , Pyrethrins/toxicity , Endangered SpeciesABSTRACT
Adeno-associated viral (AAV) vectors have emerged as gene therapy and vaccine delivery systems. Differential scanning fluorimetry or differential scanning calorimetry is commonly used to measure the thermal stability of AAVs, but these global methods are unable to distinguish the stabilities of different AAV subpopulations in the same sample. To address this challenge, we combined charge detection-mass spectrometry (CD-MS) with a variable temperature (VT) electrospray source that controls the temperature of the solution prior to electrospray. Using VT-CD-MS, we measured the thermal stabilities of empty and filled capsids. We found that filled AAVs ejected their cargo first and formed intermediate empty capsids before completely dissociating. Finally, we observed that pH stress caused a major decrease in thermal stability. This new approach better characterizes the thermal dissociation of AAVs, providing the simultaneous measurement of the stabilities and dissociation pathways of different subpopulations.
Subject(s)
Capsid , Dependovirus , Capsid/chemistry , Capsid Proteins/chemistry , Dependovirus/chemistry , Mass Spectrometry , TemperatureABSTRACT
We report a comprehensive assessment of Lewis acidity for a series of carbone-stibenium and -bismuthenium ions using the Gutmann-Beckett (GB) method. These new antimony and bismuth cations have been synthesized by halide abstractions from (CDC)PnBr3 and [(pyCDC)PnBr2][Br] (CDC = carbodicarbene; Pn = Sb or Bi; py = pyridyl). The reaction of (CDC)SbBr3 (1) with one or two equivalents of AgNTf2 (NTf2 = bis(trifluoromethanesulfonyl)imide) or AgSbF6 gives stibaalkene mono- and dications of the form [(CDC)SbBr3-n][A]n (2-4; n = 1,2; A = NTf2 or SbF6). The stibaalkene trication [(CDC)2Sb][NTf2]3 (5) was also isolated and collectively these molecules fill the gap among the series of cationic pnictaalkenes. The Sb cations are compared to the related CDC-bismaalkene complexes 6-9. With the goal of preparing highly Lewis acidic compounds, a tridentate bis(pyridine)carbodicarbene (pyCDC) was used as a ligand to access [(pyCDC)PnBr2][Br] (10, 12) and trications [(pyCDC)Pn][NTf2]3 (Pn = Sb (11), Bi (13)), forgoing the need for a second CDC as used in the synthesis of 5. The bonding situation in these complexes is elucidated through electron density and energy decomposition analyses in combination with natural orbital for chemical valence theory. In each complex, there exists a CDC-Pn double bonding interaction, consisting of a strong σ-bond and a weaker π-bond, whereby the π-bond gradually strengthens with the increase in cationic charge in the complex. Notably, [(CDC)SbBr][NTf2]2 (4) has an acceptor number (AN) (84) that is comparable to quintessential Lewis acids such as BF3, and tricationic pnictaalkene complexes 11 and 13 exhibit strong Lewis acidity with ANs of 109 (Pn = Sb) and 84 (Pn = Bi), respectively, which are among the highest values reported for any antimony or bismuth cation. Moreover, the calculated fluoride ion affinities (FIAs) for 11 and 13 are 99.8 and 94.3 kcal/mol, respectively, which are larger than that of SbF5 (85.1 kcal/mol), which suggest that these cations are Lewis superacids.
ABSTRACT
Amplicons-large, highly identical segmental duplications-are a prominent feature of mammalian Y chromosomes. Although they encode genes essential for fertility, these amplicons differ vastly between species, and little is known about the selective constraints acting on them. Here, we develop computational tools to detect amplicon copy number with unprecedented accuracy from high-throughput sequencing data. We find that one-sixth (16.9%) of 1,216 males from the 1000 Genomes Project have at least one deleted or duplicated amplicon. However, each amplicon's reference copy number is scrupulously maintained among divergent branches of the Y chromosome phylogeny, including the ancient branch A00, indicating that the reference copy number is ancestral to all modern human Y chromosomes. Using phylogenetic analyses and simulations, we demonstrate that this pattern of variation is incompatible with neutral evolution and instead displays hallmarks of mutation-selection balance. We also observe cases of amplicon rescue, in which deleted amplicons are restored through subsequent duplications. These results indicate that, contrary to the lack of constraint suggested by the differences between species, natural selection has suppressed amplicon copy number variation in diverse human lineages.
Subject(s)
Chromosomes, Human, Y/genetics , DNA Copy Number Variations/genetics , Selection, Genetic/genetics , Animals , Cell Line , Evolution, Molecular , Gene Dosage/genetics , Gene Duplication/genetics , Genome/genetics , High-Throughput Nucleotide Sequencing/methods , Humans , Male , PhylogenyABSTRACT
The synthesis and thermal redox chemistry of the first antimony (Sb)- and bismuth (Bi)-phosphaketene adducts are described. When diphenylpnictogen chloride [Ph2PnCl (Pn = Sb or Bi)] is reacted with sodium 2-phosphaethynolate [Na[OCP]·(dioxane)x], tetraphenyldipnictogen (Ph2Pn-PnPh2) compounds are produced, and an insoluble precipitate forms from solution. In contrast, when the N-heterocyclic carbene adduct (NHC)-PnPh2Cl is combined with [Na[OCP]·(dioxane)x], Sb- and Bi-phosphaketene complexes are isolated. Thus, NHC serves as an essential mediator for the reaction. Immediately after the formation of an intermediary pnictogen-phosphaketene NHC adduct [NHC-PnPh2(PCO)], the NHC ligand transfers from the Pn center to the phosphaketene carbon atom, forming NHC-C(O)P-PnPh2 [Pn = Sb (3) or Bi (4)]. In the solid state, 3 and 4 are dimeric with short intermolecular Pn-Pn interactions. When compounds 3 and 4 are heated in THF at 90 and 70 °C, respectively, the pnictogen center PnIII is thermally reduced to PnII to form tetraphenyldipnictines (Ph2Pn-PnPh2) and an unusual bis-carbene-supported OCP salt, [(NHC)2OCP][OCP] (5). The formation of compound 5 and Ph2Pn-PnPh2 from 3 or 4 is unique in comparison to the known thermal reactivity for group 14 carbene-phosphaketene complexes, further highlighting the diverse reactivity of [OCP]- with main-group elements. All new compounds have been fully characterized by single-crystal X-ray diffraction, multinuclear NMR spectroscopy (1H, 13C, and 31P), infrared spectroscopy, and elemental analysis (1, 2, and 5). The electronic structure of 5 and the mechanism of formation were investigated using density functional theory (DFT).
ABSTRACT
Gabapentin is approved to treat postherpetic neuralgia and epilepsy with partial-onset seizures. The large majority of gabapentin prescribing is off label. Gabapentin may be abused for euphoria, potentiating the high from opiates, reduction of alcohol cravings, a cocaine-like high, as well as sedation or sleep. Individuals at the highest risk for abusing gabapentin include those with opioid abuse, mental illness, or previous history of prescription drug abuse. States are now taking action to track gabapentin use through prescription monitoring programs, and some states have reclassified it as a Schedule V controlled substance. This commentary summarizes gabapentin's abuse potential, identifies state-level actions regarding gabapentin monitoring, and discusses possible clinical implications and ways to enhance patient safety when prescribing gabapentin.
Subject(s)
Cyclohexanecarboxylic Acids , Epilepsy , Substance-Related Disorders , Amines/adverse effects , Controlled Substances , Cyclohexanecarboxylic Acids/adverse effects , Gabapentin/therapeutic use , Humans , Substance-Related Disorders/prevention & controlABSTRACT
ABSTRACT: The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.
Subject(s)
Guidelines as Topic , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adult , Aged , American Cancer Society , Female , Humans , Middle Aged , Papillomaviridae , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines , United States , Uterine Cervical Neoplasms/virology , Vaginal SmearsABSTRACT
We report a combined experimental and theoretical study on the first examples of carbodicarbene (CDC)-stabilized bismuth complexes, which feature low-coordinate cationic bismuth centers with C=Bi multiple-bond character. Monocations [(CDC)Bi(Ph)Cl][SbF6 ] (8) and [(CDC)BiBr2 (THF)2 ][SbF6 ] (11), dications [(CDC)Bi(Ph)][SbF6 ]2 (9) and [(CDC)BiBr(THF)3 ][NTf2 ]2 (12), and trication [(CDC)2 Bi][NTf2 ]3 (13) have been synthesized via sequential halide abstractions from (CDC)Bi(Ph)Cl2 (7) and (CDC)BiBr3 (10). Notably, the dications and trication exhibit C â Bi double dative bonds and thus represent unprecedented bismaalkene cations. The synthesis of these species highlights a unique non-reductive route to C-Bi π-bonding character. The CDC-[Bi] complexes (7-13) were compared with related NHC-[Bi] complexes (1, 3-6) and show substantially different structural properties. Indeed, the CDC ligand has a remarkable influence on the overall stability of the resulting low-coordinate Bi complexes, suggesting that CDC is a superior ligand to NHC in heavy pnictogen chemistry.
ABSTRACT
AIM: To describe the results of a feasibility phase and the expected results of a new approach to increase the participation rate in a Colorectal Cancer Organized Screening Program (CRCSP) through Facebook awareness messages. METHOD: This approach targets people aged 50-74 years, who reside in an urban deprived area and regularly connect to Facebook. The feasibility phase ran over 2 months (December 2018 and January 2019) in six municipalities (Seine-Saint-Denis, France). The full provisional campaign will run over a year. The approach consists of sending electronic awareness messages on the importance of screening for colorectal cancer using a specific Facebook module. Subjects who consent to screening complete a test-kit application form. The eligibility of each subject to participate in screening is determined by a doctor before the kit is sent out. RESULTS: A total of 39 900 people were reached by the feasibility phase campaign, and 9200 were able to watch at least one Facebook message/video. Of those, 4450 people logged to learn more about the CRCSP, 298 applied for a test kit, 160 test kit applicants were eligible to participate and the test completion rate was 41.9%. According to these feasibility results, 366 120 targeted people would connect regularly in the tested area, 141 541 of whom would be interested in a specific promotional message posted on Facebook. Requests could be made for 9770 kits, with 5246 people being eligible to participate in screening. The expected test-completion rate is estimated at 42%-89%. This would represent 5%-11% of the tests carried out in the area during the same period by 'classical' CRCSP. CONCLUSION: Implementation of the Facebook strategy would significantly improve the rate of participation in the CRCSP by mobilizing people with no previous participation, including younger subjects.
Subject(s)
Colorectal Neoplasms , Social Media , Colorectal Neoplasms/diagnosis , Early Detection of Cancer , Feasibility Studies , Humans , Mass Screening , Social NetworkingABSTRACT
An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.
Subject(s)
Early Detection of Cancer/standards , Mass Screening/standards , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Cytodiagnosis , Early Detection of Cancer/methods , Female , Humans , Mass Screening/methods , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Vaginal Smears , Uterine Cervical Dysplasia/virologyABSTRACT
RATIONALE: Oxygen isotope ratios (δ18 O values) of fish otoliths (ear bones) are valuable geochemical tracers of water conditions and thermal life history. Delta Smelt (Hypomesus transpacificus) are osmerid forage fish endemic to the San Francisco Estuary, California, USA, that are on the verge of extinction. These fish exhibit a complex life history that allows them to survive in a dynamic estuarine environment; however, a rapidly warming climate threatens this thermally sensitive species. Here we quantify the accuracy and precision of using δ18 O values in otoliths to reconstruct the thermal life histories of Delta Smelt. METHODS: Delta Smelt were reared for 360 days using three different water sources with different ambient δ18 Owater values (-8.75, -5.28, and -4.06) and different water temperatures (16.4°C, 16.7°C, 18.7°C, and 20.5°C). Samples were collected after 170 days (n = 28) and 360 days (n = 14) post-hatch. In situ δ18 O values were measured from the core of the otolith to the dorsal edge using secondary ion mass spectrometry (SIMS) to reconstruct temporally resolved thermal life histories. RESULTS: The δ18 Ootolith values for Delta Smelt varied as a linear inverse function of water temperature: 1000 ln α = 18.39 (±0.43, 1SE)(103 TK-1 ) - 34.56 (±1.49, 1SE) and δ18 Ootolith(VPDB) - δ18 Owater (VPDB) = 31.34(±0.09, 1SE) - 0.19(±0.01, 1SE) × T ° C. When the ambient δ18 Owater value is known, this species-specific temperature-dependent oxygen isotope fractionation model facilitated the accurate (0.25°C) and precise (±0.37°C, 2σ) reconstruction of the water temperature experienced by the fish. In contrast, the use of existing general fractionation equations resulted in inaccurate temperature reconstructions. CONCLUSIONS: The species-specific δ18 Ootolith fractionation equation allowed for accurate and precise reconstructions of water temperatures experienced by Delta Smelt. Characterization of ambient δ18 Owater values remains a critical next step for reconstructing thermal life histories of wild Delta Smelt. This tool will provide new insights into habitat utilization, potential thermal refugia, and resilience to future warming for this critically endangered fish.
Subject(s)
Osmeriformes , Otolithic Membrane/chemistry , Oxygen Isotopes/analysis , Animals , Calibration , California , Climate , Ecosystem , Endangered Species/statistics & numerical data , Spectrometry, Mass, Secondary Ion/methods , Spectrometry, Mass, Secondary Ion/standards , TemperatureABSTRACT
BACKGROUND: Black women with endometrial cancer are more likely to die of their disease compared with white women with endometrial cancer. These survival disparities persist even when disproportionately worse tumor characteristics among black women are accounted. Receipt of less complete adjuvant treatment among black patients with endometrial cancer could contribute to this disparity. OBJECTIVE: We assessed the hypothesis that black women with endometrial cancer are less likely than their white counterparts to receive adjuvant treatment within subgroups defined by tumor characteristics in the NRG Oncology/Gynecology Oncology Group 210 Study. STUDY DESIGN: Our analysis included 615 black and 4283 white women with endometrial cancer who underwent hysterectomy. Women completed a questionnaire that assessed race and endometrial cancer risk factors. Tumor characteristics were available from pathology reports and central review. We categorized women as low-, intermediate-, or high-risk based on the European Society for Medical Oncology definition. Adjuvant treatment was documented during postoperative visits and was categorized as no adjuvant treatment (54.3%), radiotherapy only (16.5%), chemotherapy only (15.2%), and radiotherapy plus chemotherapy (14.0%). We used polytomous logistic regression to estimate odds ratios and 95% confidence intervals for multivariable-adjusted associations between race and adjuvant treatment in the overall study population and stratified by tumor subtype, stage, or European Society for Medical Oncology risk category. RESULTS: Overall, black women were more likely to have received chemotherapy only (odds ratio, 1.40; 95% confidence interval, 1.04-1.86) or radiotherapy plus chemotherapy (odds ratio, 2.01; 95% confidence interval, 1.54-2.62) compared with white women in multivariable-adjusted models. No racial difference in the receipt of radiotherapy only was observed. In tumor subtype-stratified models, black women had higher odds of receiving radiotherapy plus chemotherapy than white women when diagnosed with low-grade endometrioid (odds ratio, 2.04; 95% confidence interval, 1.06-3.93) or serous tumors (odds ratio, 1.81; 95% confidence interval, 1.07-3.08). Race was not associated with adjuvant treatment among women who had been diagnosed with other tumor subtypes. In stage-stratified models, we observed no racial differences in the receipt of adjuvant treatment. In models that were stratified by European Society for Medical Oncology risk group, black women with high-risk cancer were more likely to receive radiotherapy plus chemotherapy compared with white women (odds ratio, 1.41; 95% confidence interval, 1.03-1.94). CONCLUSION: Contrary to our hypothesis, we observed higher odds of specific adjuvant treatment regimens among black women as compared with white women within specific subgroups of endometrial cancer characteristics.
Subject(s)
Black or African American/statistics & numerical data , Chemotherapy, Adjuvant/statistics & numerical data , Endometrial Neoplasms/therapy , Radiotherapy, Adjuvant/statistics & numerical data , White People/statistics & numerical data , Aged , Combined Modality Therapy/statistics & numerical data , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Healthcare Disparities/ethnology , Humans , Middle Aged , Neoplasm Staging , Odds RatioABSTRACT
OBJECTIVE: The aim of the study was to estimate the excess cost of guideline nonadherent cervical cancer screening in women beyond the recommended screening ages or posthysterectomy in a single healthcare system. MATERIALS AND METHODS: All Pap tests performed between September 1, 2012, and August 31, 2014, in women younger than 21 years, older than 65 years, or after hysterectomy, were coded as guideline adherent or nonadherent per the 2012 America Society of Colposcopy and Clinical Pathology guidelines. We assumed management of abnormal results per the 2013 America Society of Colposcopy and Clinical Pathology management guidelines. Costs were obtained from a literature review and Center for Medicare and Medicaid Services data and applied to nonadherent screening and subsequent diagnostic tests. RESULTS: During this period, 1,398 guideline nonadherent Pap tests were performed (257 in women <21 years, 536 in women >65 years, and 605 after hysterectomy), with 88 abnormal results: 35 (13.5%) in women younger than 21 years, 14 (2.6%) in women older than 65 years, and 39 (6.5%) in women after hysterectomy. The excess cost for initial screening, diagnostic tests, and follow-up was US $35,337 for 2 years in women younger than 21 years, US $54,378 for 5 years in women older than 65 years, and US $77,340 for 5 years in women after hysterectomy, resulting in a total excess cost of US $166,100 for 5 years. Of the 1,398 women who underwent guideline nonadherent screening, there were only 2 (0.1%) diagnoses of high-grade dysplasia (VaIN3). CONCLUSIONS: Guideline nonadherent cervical cancer screening in women beyond the recommended screening ages and posthysterectomy resulted in costs exceeding US $160,000 for screening, diagnostic tests, and follow-up with minimal improvement in detection of high-grade dysplasia.
Subject(s)
Mass Screening/economics , Uterine Cervical Neoplasms/diagnosis , Adult , Age Factors , Aged , Female , Humans , Hysterectomy , Middle Aged , Papanicolaou Test , Uterine Cervical Neoplasms/surgery , Young AdultABSTRACT
INTRODUCTION: Optimal pain control after major surgery contributes to a patient's recovery and satisfaction. The use of liposomal bupivacaine in subcostal transversus abdominis plane (TAP) blocks for postoperative pain control after robot assisted abdominal surgery has yet to be studied. METHODS: We conducted a prospective randomized controlled observer-blinded study comparing bilateral subcostal TAP blocks with bupivacaine to bilateral subcostal TAP blocks with liposomal bupivacaine. These were performed prior to the patient undergoing robot assisted hysterectomy. The patients' pain scores, opioid use, side effects, and satisfaction were followed for 72h after injection. RESULTS: Total opioid use in the first 72h after injection was significantly decreased in the group that received liposomal bupivacaine compared to bupivacaine. Patients in the liposomal bupivacaine group had significantly lower maximal pain scores at all time periods studied as well as decreased incidence of nausea/vomiting. There was a trend toward decreased length of stay in the liposomal bupivacaine group. CONCLUSION: Subcostal TAP blocks with liposomal bupivacaine decreased the total opioid requirement for the first 72h after robot assisted hysterectomy when compared to subcostal TAP blocks with bupivacaine.
Subject(s)
Abdominal Muscles/surgery , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Hysterectomy/methods , Nerve Block/methods , Ultrasonography, Interventional/methods , Female , Humans , Liposomes/administration & dosage , Middle Aged , Pain, Postoperative/prevention & control , Prospective Studies , Robotic Surgical Procedures/methodsABSTRACT
BACKGROUND: Few studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial. METHODS: Prior to surgery, participants completed a questionnaire assessing risk factors for gynecologic cancers. Pathology data were derived from clinical reports and central review. We used the Fine and Gray subdistribution hazards model to estimate subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations between etiologic factors and cause-specific subhazards in the presence of competing risks. These models were stratified by tumor subtype and adjusted for stage and socioeconomic status indicators. RESULTS: Median follow-up was 60months after enrollment (range: 1day-118months). Among 4609 participants, a total of 854 deaths occurred, of which, 582 deaths were attributed to endometrial carcinoma. Among low-grade endometrioid cases, endometrial carcinoma-specific subhazards were significantly associated with age at diagnosis (HR=1.04, 95% CI=1.01-1.06 per year, P-trend) and BMI (class II obesity vs. normal BMI: HR=2.29, 95% CI=1.06-4.98, P-trend=0.01). Among high-grade endometrioid cases, endometrial carcinoma-specific subhazards were associated with age at diagnosis (HR=1.05, 95% CI=1.02-1.07 per year, P-trend<0.001). Among non-endometrioid cases, endometrial carcinoma-specific subhazards were associated with parity relative to nulliparity among serous (HR=0.55, 95% CI=0.36-0.82) and carcinosarcoma cases (HR=2.01, 95% CI=1.00-4.05). DISCUSSION: Several endometrial carcinoma risk factors are associated with prognosis, which occurs in a tumor-subtype specific context. If confirmed, these results would suggest that factors beyond histopathologic features and stage are related to prognosis. ClinicalTrials.gov Identifier: NCT00340808.
Subject(s)
Endometrial Neoplasms/etiology , Endometrial Neoplasms/mortality , Age Factors , Carcinoma, Endometrioid/etiology , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , Female , Humans , Obesity/complications , Obesity/epidemiologyABSTRACT
OBJECTIVE: The goal of this pilot study was to evaluate adherence to the 2012 cervical cancer screening guidelines among health care providers in a large health maintenance organization. STUDY DESIGN: A cross-sectional survey evaluating knowledge, reported practices, and views of the 2012 cervical cancer screening guidelines was distributed to 325 health care providers within HealthPartners. The survey was divided into 3 sections: (1) provider demographics; (2) knowledge of the 2012 age-specific cancer screening guidelines; and (3) provider practice. Comparisons based on appropriate knowledge and practice of the guidelines were made using Fisher exact tests. RESULTS: The response rate was 42%. Of 124 respondents, 15 (12.1%) reported they were not aware of the 2012 guideline changes. Only 7 (5.7%) respondents answered all the knowledge questions correctly. A majority of respondents reported correct screening practices in the 21-29 year patient age group (65.8%) and in the >65 year patient age group (74.3%). Correct screening intervals in the 30-65 year patient age group varied by modality, with 89.3% correctly screening every 3 years with Pap smear alone, but only 57.4% correctly screening every 5 years with Pap smear + human papillomavirus cotesting. The most frequently cited reasons for not adhering were lack of knowledge of the guidelines and patient demand for a different screening interval. CONCLUSION: Adherence to the 2012 cervical cancer screening guidelines is poor due, in part, to a lack of knowledge of the guidelines. Efforts should focus on improved provider and patient education, and methods that facilitate adherence to the guidelines such as electronic health record order sets.
Subject(s)
Early Detection of Cancer/standards , Guideline Adherence/statistics & numerical data , Uterine Cervical Neoplasms/diagnosis , Adult , Aged , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Pilot Projects , United States , Young AdultABSTRACT
OBJECTIVE: We sought to determine the effect of a subcostal transversus abdominis plane (TAP) block with liposomal bupivacaine on postoperative maximal pain score and length of hospital stay among women undergoing robotic-assisted hysterectomy. METHODS: This was a retrospective study comparing patients before and after consistent implementation of TAP blocks with liposomal bupivacaine during robotic-assisted hysterectomies at a single academic institution. Analysis compared patient demographic and operative characteristics by TAP block use, along with outcomes of interest, including postoperative pain and length of hospital stay. RESULTS: There was a statistically significant decrease in maximal numerical rating scale pain scores, presence of nausea and vomiting, and length of hospital stay in those who had a TAP block with liposomal bupivacaine compared with those who did not receive a TAP block. These differences remained even after adjustment for potential confounders. CONCLUSIONS: In this retrospective study, liposomal bupivacaine used in a TAP block was a useful method to provide postoperative pain control in patients undergoing robotic-assisted hysterectomy and was associated with lower postoperative maximal pain scores and length of hospital stay.
Subject(s)
Abdominal Muscles/surgery , Bupivacaine/administration & dosage , Hysterectomy/adverse effects , Nerve Block/methods , Pain, Postoperative/prevention & control , Robotics , Ultrasonography, Interventional , Abdominal Muscles/diagnostic imaging , Anesthetics, Local/administration & dosage , Female , Follow-Up Studies , Humans , Laparoscopy , Length of Stay , Liposomes , Middle Aged , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Endometrial stromal sarcoma (ESS) is a rareform of endometrial cancer, comprising < 0.2% of all uterine malignancies and 10% of all uterine sarcomas. To date, the English-language literature contains 6 reports of extrauterine ESS arising primarily in the vagina. We describe the seventh such case, and the first case in which the origin is at the introitus of the vagina. CASE: A 43-year-old, nulligravid, Caucasian woman presented for an annual gynecologic examination and was found to have an asymptomatic 5 x 5-mm, rubbery, soft tissue mass at the 5 o'clock position of the vaginal introitus. As has been reported in several cases of low-grade ESS, this case originated at a site of endometriosis. CONCLUSION: Based on our experience as well as a thorough review of the literature, it appears that early stage low-grade ESS arising in the vagina can be treated effectively with surgical resection followed by close observation for recurrence.