Thickened endometrium in asymptomatic postmenopausal women - determining an optimum threshold for prediction of atypical hyperplasia and cancer

There is a lack of consensus about the significance and the management of an incidental finding of endometrial thickness (ET) > 4 mm on transvaginal ultrasound scans in postmenopausal women without postmenopausal bleeding (PMB). The data of 1995 consecutive women attending PMB clinic were collected prospectively; of them 81 (4.1%) were referred because of ET >4 mm without PMB. The prevalence of endometrial atypical hyperplasia and cancer was 4/81 (4.9%), and polyp was 20/81 (24.7%). On using a receiver operator characteristic curve, the diagnosis of endometrial atypical hyperplasia and cancer using the ET threshold of ≥10 mm had a sensitivity of 100% (95% CI = 40–100%), a specificity of 60% (95% CI = 48–71%) with AUC = 0.8 (95% CI = 0.66–0.93), p = .04. For the 35 women with an ET ≥10 mm, the prevalence of endometrial atypical hyperplasia and cancer was 4/35 (11.4%) and benign endometrial polyps was 16/35 (45.7%). The use of ≥10 mm ET threshold to prompt investigations did not miss any case of endometrial atypical hyperplasia or cancer.Impact Statement What is already known on this subject? Unlike women with PMB in whom an endometrial thickness (ET) ≤ 4 mm is considered as low risk for endometrial hyperplasia and cancer, in postmenopausal women without PMB, the threshold that separates normal from a pathologically thickened endometrium has not been standardised. A decision-analysis study in a hypothetical cohort found that ET threshold of 11 mm yields a similar separation as ≤4 mm in those with PMB. What the results of this study add? The study uses prospectively collected data from consecutive patients using a standardised format, thus minimising bias from incomplete data. This study is the third prospective series in the literature to address the dilemma of the management of asymptomatic postmenopausal women with an incidental finding of a thickened endometrium. It showed that the prevalence of endometrial atypical hyperplasia and cancer is high enough to justify investigation and for the clinical problem not to be trivialised. All cases of endometrial atypical hyperplasia and cancer had ET of ≥10 mm. What are the implications of these findings for clinical practice and/or future research? Our data strengthen the current body of literature to help the development of clinical practice guidelines about the management work-up. However, a well-designed multi-centre large prospective study is required to confirm the findings since most studies in the literature are either retrospective or small

Lassa Fever Infection among Healthcare Workers during the 2018 Outbreak in Nigeria

Introduction: Healthcare workers (HCWs) are potentially exposed to infection during viral hemorrhagic fever outbreaks. In the wake of 2018, Nigeria experienced an unprecedented surge in cases of Lassa fever (LF), which affected HCWs. To guide infection prevention and control (IPC) strategies in similar settings, we characterize HCWs' infection and describe the gaps in IPC standards and practices during the outbreak. Methods: Data was collected using a structured questionnaire, interview, and review of case notes of 21 HCW with laboratory-confirmed Lassa fever who were treated at the Irrua Specialist Teaching Hospital (ISTH) Irrua and the Alex-Ekwemen Federal Teaching Hospital, Abakaliki (AEFETHA), between 1st January and 27th May 2018. Information collected was the patients' socio-demographic characteristics, date of potential exposure and onset of illness, nature, and type of exposure, clinical features, outcome, use of personal protective equipment (PPE), and personnel IPC training and were analyzed using descriptive statistics with Microsoft Excel. Results: The study included 21 HCWs, and 12 (57.14%) were doctors. The case fatality rate was 23%. Nearly two-thirds (62%) of the HCWs could describe a likely procedure leading to their exposure and infection. Among 13 HCWs, 85% had multiple blood and body fluids exposure, while 15% had needle stick injury or scalpel cut. About one-fifth of the participants had received some IPC training. Conclusion: Limited IPC adherence and inappropriate risk assessment were identified as factors leading to Lassa fever exposure and infection among HCWs. There is an urgent need to provide IPC training for all HCWs and to ensure an adequate supply of IPC materials to all healthcare facilities as part of emergency preparedness, especially in LF endemic areas

Is routine adnexal scanning for postmenopausal bleeding of value? Observational study of 2101 women

Our objective is to assess the merits of adnexal scanning during the investigation of women with postmenopausal bleeding (PMB) in terms of adnexal cancer diagnosis. This observational study was designed utilising an institutional PMB database in a teaching hospital, analysing a sample of 2101 consecutive women with PMB seen between 16th February 2012 and 12th August 2014 looking at the prevalence of cancer in adnexal masses identified on Trans-vaginal ultrasound scanning (TVS) in these PMB women. This study suggests that routine adnexal scanning in women with PMB may provide no benefit. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications. Most of the women who underwent surgery presented with palpable masses. Those with negative clinical examination had either benign masses which may have remained inconsequential or non-suspicious scan findings. A well-designed randomised controlled trial is needed to confirm the findings.Impact statement Trans-vaginal ultrasound scanning (TVS) is the standard first line investigation for women presenting with postmenopausal bleeding (PMB) primarily to assess the endometrial thickness. This has led to a widespread practice of opportunistic adnexal scanning, which generated a debate amongst gynaecologists about the value of such practice. This observational study, assessing the merits of routine adnexal scanning in these women in terms of adnexal cancer diagnosis, suggests that this practice may provide no benefit to women with isolated self-limiting PMB and unremarkable bimanual examination. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications when insignificant adnexal masses are identified on the scan. A well-designed randomised controlled trial is needed to elucidate if clinical examination in combination with endometrial scanning only is more effective and cost-effective than clinical examination followed by systematic pelvic scanning to detect cases of ovarian cancer in women with PMB

Identifying Barriers Faced by Applicants without a Home Residency Program when Matching into Plastic Surgery

BACKGROUND Applying into plastic surgery is competitive. Lacking a home residency program (HRP) is another barrier. Our goal is to characterize challenges faced by plastic surgery (PS) applicants without HRPs and identify solutions. METHODS Surveys were designed for current integrated PS residents and applicants in the 2022 Match without HRPs. Surveys were distributed electronically. Only U.S. allopathic graduate responses were included. RESULTS Of 182 individuals surveyed, 74 responded (39%, 33-residents, 41-applicants). Sixty-six percent reported feeling disadvantaged due to lacking an HRP. 76% of applicants successfully matched. Of these, 48% felt they required academic time off (research year) vs 10% of unmatched applicants. 97% of matched applicants identified a mentor vs 40% of unmatched applicants (p<0.05). Matched applicants identified mentors through research (29%) and cold calling/emailing (25%). Matched vs unmatched applicants utilized the following resources: senior students (74vs10%), (p<0.05) and social media (52vs10%), (p<0.05). Among residents, sixteen had PS divisions (48%). Thirty-six percent with divisions felt they had opportunities to explore PS, compared to 12% without divisions. Residents without divisions felt disadvantaged in finding research (94vs65%, p<0.05), delayed in deciding on PS (50vs28%), and obtaining mentors (44vs35%) and letters of recommendation (LOR) (31vs24%). CONCLUSIONS PS residents and applicants without HRPs reported feeling disadvantaged when matching. The data suggest access to departments or divisions assists in matching. We identified external outreach and research were successful strategies to obtain mentorship. To increase awareness for unaffiliated applicants, we should increase networking opportunities during local, regional, and national meetings

Epidemiologic and Clinical Features of Lassa Fever Outbreak in Nigeria, January 1–May 6, 2018

Lassa fever (LF) is endemic to Nigeria, where the disease causes substantial rates of illness and death. In this article, we report an analysis of the epidemiologic and clinical aspects of the LF outbreak that occurred in Nigeria during January 1–May 6, 2018. A total of 1,893 cases were reported; 423 were laboratory-confirmed cases, among which 106 deaths were recorded (case-fatality rate 25.1%). Among all confirmed cases, 37 occurred in healthcare workers. The secondary attack rate among 5,001 contacts was 0.56%. Most (80.6%) confirmed cases were reported from 3 states (Edo, Ondo, and Ebonyi). Fatal outcomes were significantly associated with being elderly; no administration of ribavirin; and the presence of a cough, hemorrhaging, and unconsciousness. The findings in this study should lead to further LF research and provide guidance to those preparing to respond to future outbreaks

Development and evaluation of antibody-capture immunoassays for detection of Lassa virus nucleoprotein-specific immunoglobulin M and G

<div><p>Background</p><p>The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Therefore, we aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using recombinant Lassa virus nucleoprotein (NP) as antigen.</p><p>Methodology/Principal findings</p><p>The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and the IgG ELISA is based on capturing IgG antibody–antigen complexes using rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic (Ghana and Germany) areas. Using the IFA as reference method, we observed 91.5–94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to hospital in an endemic area revealed a clinical sensitivity for the stand-alone IgM ELISA of 31% (95% CI 25–37) and for combined IgM/IgG detection of 26% (95% CI 21–32) compared to RT-PCR. The specificity of IgM and IgG ELISA was estimated at 96% (95% CI 93–98) and 100% (95% CI 99–100), respectively, in non-Lassa fever patients from non-endemic areas. In patients who seroconverted during follow-up, Lassa virus-specific IgM and IgG developed simultaneously rather than sequentially. Consistent with this finding, isolated IgM reactivity, i.e. IgM in the absence of IgG, had no diagnostic value.</p><p>Conclusions/Significance</p><p>The ELISAs are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they are of value in diagnosing patients at later stage. The IgG ELISA may be useful for epidemiological studies and clinical trials due its high specificity, and the higher throughput rate and easier operation compared to IFA.</p></div

Sample-to-cut-off (S/CO) values for 880 sera tested in IgM ELISA, RF-based IgG ELISA, and CD32-based IgG ELISA and comparison with IFA results.

<p>The S/CO values obtained with the ELISA are shown as histograms according to sample origin, type of ELISA, and IFA results. The cut-offs for the ELISAs are indicated by vertical dotted lines. The number of samples with OD < CO and OD > CO is indicated in left and right corner, respectively, of each diagram.</p

Clinical performance characteristics of the IgM ELISA as stand-alone test and in combination with the IgG ELISA depending on prevalence of Lassa fever and pre-existing IgG among all patients tested.

<p>The calculations are based on the data shown in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006361#pntd.0006361.t003" target="_blank">Table 3</a>. PPV and NPV of the stand-alone IgM ELISA depend only on the Lassa fever prevalence in diagnostics. However, PPV, NPV, sensitivity, and positive likelihood ratio for combined detection of IgM and IgG (i.e. a positive test result means that both IgM and IgG is positive) depend on the prevalence of Lassa fever as well as the prevalence of pre-existing IgG among all patients tested. To simplify calculation, we assumed a ratio of 1:3 between prevalence of Lassa fever and pre-existing IgG, which roughly corresponds to the setting in Nigeria where the study was performed.</p

Phylogeography of Lassa Virus in Nigeria

ABSTRACT Lassa virus is genetically diverse with several lineages circulating in West Africa. This study aimed at describing the sequence variability of Lassa virus across Nigeria and inferring its spatiotemporal evolution. We sequenced and isolated 77 Lassa virus strains from 16 Nigerian states. The final data set, including previous works, comprised metadata and sequences of 219 unique strains sampled between 1969 and 2018 in 22 states. Most of this data originated from Lassa fever patients diagnosed at Irrua Specialist Teaching Hospital, Edo State, Nigeria. The majority of sequences clustered with the main Nigerian lineages II and III, while a few sequences formed a new cluster related to Lassa virus strains from Hylomyscus pamfi .Within lineages II and III, seven and five sublineages, respectively, were distinguishable. Phylogeographic analysis suggests an origin of lineage II in the southeastern part of the country around Ebonyi State and a main vector of dispersal toward the west across the Niger River, through Anambra, Kogi, Delta, and Edo into Ondo State. The frontline of virus dispersal appears to be in Ondo. Minor vectors are directed northeast toward Taraba and Adamawa and south toward Imo and Rivers. Lineage III might have spread from northern Plateau State into Kaduna, Nasarawa, Federal Capital Territory, and Bauchi. One sublineage moved south and crossed the Benue River into Benue State. This study provides a geographic mapping of lineages and phylogenetic clusters in Nigeria at a higher resolution. In addition, we estimated the direction and time frame of virus dispersal in the country. IMPORTANCE Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality rate of approximately 30% in Africa. Previous studies disclosed a geographical pattern in the distribution of Lassa virus strains and a westward movement of the virus across West Africa during evolution. Our study provides a deeper understanding of the geography of genetic lineages and sublineages of the virus in Nigeria. In addition, we modeled how the virus spread in the country. This knowledge allows us to predict into which geographical areas the virus might spread in the future and prioritize areas for Lassa fever surveillance. Our study not only aimed to generate Lassa virus sequences from across Nigeria but also to isolate and conserve the respective viruses for future research. Both isolates and sequences are important for the development and evaluation of medical countermeasures to treat and prevent Lassa fever, such as diagnostics, therapeutics, and vaccines.info:eu-repo/semantics/publishe