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This article compares the accuracy of two methods, the Risk of Malignancy Index (RMI) and the Ovarian-Adnexal Reporting and Data System (O-RADS), in predicting the malignancy of ovarian masses. The study analyzed data from 453 cases and found that O-RADS, based on the International Ovarian Tumor Analysis (IOTA) ADNEX model, had a better performance than RMI in preoperative assessment. O-RADS had a higher sensitivity for predicting malignancy and a higher area under the receiver-operating characteristic curve (AUC). The authors recommend implementing O-RADS into routine assessment of adnexal masses. [Extracted from the article]

Background: Patient-reported outcome measures (PROMs) have gained increased importance in assessing outcomes after reconstructive surgery. This also applies to the reconstruction of vulvoperineal defects after resection of gynecological or colorectal cancers in women. The objective of this study is to analyze the current state of PROM tool use within this patient population., Methods: By systematic literature searches in Embase, Medline, and Web of Science, English-language studies published after 1980, including randomized controlled trials, cohort studies, and case series reporting on vulvoperineal defect reconstruction, which were included if they also analyzed quality of life (QoL) and/or PROMs. The PROM tools used by each study were extracted, analyzed, and compared., Results: The primary search yielded 2576 abstracts, of which 395 articles were retrieved in full text. Of these, 50 reported on vulvoperineal defect reconstruction, among which 27 studies analyzing QoL were found. Of those, 17 met the inclusion criteria for this systematic review. After full-text screening, 14 different PROM tools and 5 individual, non-standardized questionnaires were identified. Only 22% of studies used a validated PROM tool., Conclusion: Far too few studies currently use PROM tools to assess outcomes in oncological vulvoperineal defect reconstruction. Less than half of the used PROMs are validated. No PROM was designed to specifically measure QoL in this patient population. The standardized implementation of a validated PROM tool in the clinical treatment of this patient population is an essential step to improve outcomes, enable the comparison of research, and support evidence-based treatment approaches.

Background: Patients with advanced vulvoperineal cancer require a multidisciplinary treatment approach to ensure oncological safety, timely recovery, and the highest possible quality of life (QoL). Reconstructions in this region often lead to complications, affecting approximately 30% of patients. Flap design has evolved towards perforator-based approaches to reduce functional deficits and (donor site) complications, since they allow for the preservation of relevant anatomical structures. Next to their greater surgical challenge in elevation, their superiority over non-perforator-based approaches is still debated., Methods: To compare outcomes between perforator and non-perforator flaps in female vulvoperineal reconstruction, we conducted a systematic review of English-language studies published after 1980, including randomized controlled trials, cohort studies, and case series. Data on demographics and surgical outcomes were extracted and classified using the Clavien-Dindo classification. We used a random-effects meta-analysis to derive a pooled estimate of complication frequency (%) in patients who received at least one perforator flap and in patients who received non-perforator flaps., Results: Among 2576 screened studies, 49 met our inclusion criteria, encompassing 1840 patients. The overall short-term surgical complication rate was comparable in patients receiving a perforator ( n = 276) or a non-perforator flap ( n = 1564) reconstruction ( p * > 0.05). There was a tendency towards fewer complications when using perforator flaps. The assessment of patients' QoL was scarce., Conclusions: Vulvoperineal reconstruction using perforator flaps shows promising results compared with non-perforator flaps. There is a need for the assessment of its long-term outcomes and for a systematic evaluation of patient QoL to further demonstrate its benefit for affected patients.

Platinum and taxane chemotherapy is associated with the risk of hypersensitivity reactions (HSRs), which may require switching to less effective treatments. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen. Therefore, we aimed to investigate the current management of HSRs to platinum and/or taxane chemotherapy in patients with gynecologic cancers. We conducted an online cross-sectional survey among gynecological and medical oncologists consisting of 33 questions. A total of 144 respondents completed the survey, and 133 respondents were included in the final analysis. Most participants were gynecologic oncologists (43.6%) and medical oncologists (33.8%), and 77.4% ( n = 103) were involved in chemotherapy treatment. More than 73% of participants experienced >5 HSRs to platinum and taxane per year. Premedication and a new attempt with platinum or taxane chemotherapy were used in 84.8% and 92.5% of Grade 1-2 HSRs to platinum and taxane, respectively. In contrast, desensitization was used in 49.4% and 41.8% of Grade 3-4 HSRs to platinum and taxane, respectively. Most participants strongly emphasized the need to standardize the management of platinum and taxane HSRs in gynecologic cancer. Our study showed that HSRs in gynecologic cancer are common, but management is variable and the use of desensitization is low. In addition, the need for guidance on the management of platinum- and taxane-induced HSRs in gynecologic cancer was highlighted.

Background: Exposure to paclitaxel and carboplatin has the risk of developing hypersensitivity reactions (HSRs), which could necessitate using less effective treatments to avoid anaphylaxis. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen; therefore, this study investigated rates and benefits of successful desensitization in patients with gynecologic cancers (GC)., Methods: We collected data from 241 patients with GC who had at least one cycle of platinum or taxane chemotherapy. The rate of HSRs and successful desensitization were evaluated, and an outcome analysis was conducted., Results: The rate of HSRs to platinum and taxane was 6.39% and 13.07%, respectively. We observed a 100% success rate of desensitization in our cohort. Patients with HSR were significantly younger (57.1 vs. 64.9 years, p = 0.030) in the taxane cohort. Importantly, the overall survival (OS) of patients with platinum and taxane HSRs who underwent desensitization was comparable to that of patients with no HSRs (platinum vs. controls; median OS 60.36 vs. 60.39 months, p = 0.31; taxane vs. controls; OS 80.29 vs. 60.00 months, p = 0.59)., Conclusion: Thus, we show that desensitization for platinum and taxane HSRs is safe and effective, resulting in an outcome that is well comparable to patients without HSR. Based on these observations, desensitization procedures might be considered as standard of care before switching to less effective treatment for patients with GC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: In the management of uterine myomas, laparoscopic surgery with morcellation enables a minimal invasive procedure. Cases of unsuspected uterine sarcoma dissemination have been reported and led to regulative restrictions. To help to distinguish preoperatively myomas from sarcomas, we assessed the value of six sonographic criteria (Basel Sarcoma Score, BSS) in a prospective outpatient cohort of consecutive patients with uterine masses., Material and Methods: We prospectively evaluated all patients presenting with myoma-like masses planned for surgery with standardized ultrasound examination. BSS including the following criteria was investigated: rapid growth in past three months, high blood flow, atypical growth, irregular lining, central necrosis and oval solitary lesion. For each criterion, a score 0/1 was given. BSS (0-6) equals the sum of all given scores. Histological diagnosis was used as reference., Results: Among 545 patients, 522 had the final diagnosis of myoma, 16 had peritoneal masses with sarcomatous components (PMSC), and seven had other malignancies. Median BSS for PMSC was 2.5 (range: 0-4) vs 0 for myomas (range: 0-3). The most common sonographic criteria leading to a false positive score in myomas were rapid growth in past three months and high blood flow. For the detection of sarcomatous masses with BSS threshold of >1, sensitivity was 93.8%, specificity 97.9%, and positive predictive value (PPV) and negative predictive value (NPV) were 57.7% and 99.8%, respectively (AUC 0.95)., Conclusion: BSS can help distinguishing between myomas and sarcomatous masses, with high NPV. Caution is required when >1 criterion is present. As a simple tool, it could easily be integrated into routine myoma sonographic examination and help develop standardized assessment of uterine masses for better preoperative triage., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Endocrine therapy is an effective treatment for low-grade serous ovarian cancer. However, the role of estrogen and progesterone receptors as biomarkers for high-grade serous ovarian cancer (HGSOC) is yet to be elucidated because not all estrogen and progesterone receptor-positive tumors benefit from anti-estrogen therapy. The degree of expression is presumed to play a vital role; however, that role is not well-defined in ovarian cancer. We aimed to determine the role of estrogen and progesterone receptor expression in primary and paired relapsed HGSOC. In this study, primary and matched relapsed tumor samples were collected from 80 patients with International Federation of Gynecology and Obstetrics Stage II-IV HGSOC. Tissue microarray was conducted and immunohistochemistry for estrogen and progesterone receptor expression was performed. Two independent pathologists performed the tissue microarray analysis with the Immunoreactive Score and Allred Total score. In the paired analysis, no significant difference in estrogen receptor expression was observed. However, progesterone receptor expression was significantly lower in patients with recurrent platinum-sensitive HGSOC. We conclude that anti-estrogen therapy targeting estrogen receptor positive HGSOC could be administered in primary and relapsed settings. The use of endocrine maintenance with an aromatase inhibitor in patients with estrogen receptor positive HGSOC needs to be further evaluated and validated in a randomized controlled trial.

Introduction: Radical abdominal surgery is part of the standard treatment for women with advanced gynaecological carcinoma. The surgery often leads to intraoperative blood loss frequently exceeding 1000 mL. Approximately 50% of women undergoing radical surgery require blood transfusions. Perioperative blood transfusions have been shown to increase the risk of postoperative complications, delayed wound healing, increased length of stay, increased postoperative morbidity and mortality. Previous studies have demonstrated an association between perioperative anaemia and surgical morbidity and mortality. By reducing transfusions and improving recovery from surgery, preoperative diagnostic and management of perioperative anaemia is a great opportunity to optimise postoperative patient outcome., Methods and Analysis: This is a single-blind, monocentre, randomised trial with four parallel groups (three therapeutic groups and one control group without treatment according to current standards of care) conducted in women undergoing radical gynaecological surgery. The primary study objective is to determine the effect of perioperative treatment with either intravenous iron, tranexamic acid or with a combination of both medicines on the reduction of intraoperative and postoperative red blood cell transfusions in gynaecological carcinoma patients. A total of N=126 women with gynaecological carcinoma will be recruited at the University Hospital Basel, Department of Gynaecology. Blood parameters will be measured at the recruitment, prior to surgery, 2 days after surgery and on the 21st-28th day after surgery. Recruitment started in August 2021., Ethics and Dissemination: The study will be performed according to the guidelines of the Declaration of Helsinki and is approved by the Ethics Committee for Northwest and Central Switzerland in Basel (EKNZ Protocol ID 2020-01194). The results of this study will be published and presented in various scientific forums., Trial Registration Number: NCT03792464., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Main aim of this study is to assess the effect of a structured, interdisciplinary, surgical, team-training protocol in robotic gynecologic surgery, with the gradual integration of an advanced nurse practitioner. Data from all robotic surgical procedures were prospectively acquired. The surgical team consisted of one experienced surgeon and two surgical fellows and the scrub nurse team from three advance nurse practitioners, specialized in robotic surgery. The training was performed in a four-phase manner over 4 years and included theoretical training, hands-on training and team-communication skills enhancement. Scrub nurses increasingly adopted an active role during surgery. For a period of 4 years, 175 patients could be included in the analysis. All of them underwent a robotic gynecologic procedure. Mean docking time decreased from 45.3 to 27.3 min (p < 0.001), mean operating time from 235 to 179 min (p = 0.0071) and costs per case from 17,891 to 14,731 Swiss Francs (p = 0.035). There were no statistically significant changes in perioperative complications and conversions to laparotomy. An interdisciplinary long-term training protocol for high specialized robotic surgery within a "fixed" team with the gradually addition of an advanced study nurse improves the efficacy of the procedure in terms of time and costs. Although the surgery is performed quicker, the same performance and quality of surgical care could be reached., (© 2021. The Author(s).)

Aim: In patients with postmenopausal hormone receptor-positive breast cancer (ER + eBC), aromatase inhibitors (AIs) are widely used for effective relapse prevention. However, AIs reduce bone density and increase bone-related events (BREs). Alongside calcium and vitamin D3 supplementation, bisphosphonates and denosumab are well-known options for improving outcomes in bone health and breast cancer prognosis. This study aimed to evaluate the practice patterns of bone health guideline-based management in real-world patients with ER + eBC., Material and Methods: In total, 68 patients with ER + eBC treated between 2009 and 2014 at the University Hospital Basel were included in this retrospective cohort study. Chart reviews were analyzed. Baseline, clinicopathological, treatment, and BRE data were extracted. Each patient was specifically reviewed for therapy adherence to the Swiss bone health guidelines (Swiss Association against Osteoporosis 2010 [SVGO])., Results: The mean patient age was 66.5 (range, 56-74) years, all post-menopausal. The most frequent tumor characteristics were tumor size of pT1-pT2 (N = 53, 77.9%) and treatment with letrozole (N = 35, 51.5%), followed by tamoxifen as a switch strategy (N = 27, 40.3%). The median treatment time with AIs was 47 (range, 30-60) months. Five patients (7.8%) experienced a fracture during or after AI treatment. Moreover, 51 (75%) patients were treated according to the SVGO recommendations., Conclusion: The fracture rate in our retrospective cohort was comparable to that in the larger phase III randomized trials. The adherence to bone health guidelines was satisfactory but still suboptimal. Clinicians should strictly adhere to the current bone health guidelines to ensure the best possible prevention of BREs and maintain bone health and cancer prognosis in patients with ER + eBC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Inc.)

Purpose: Several studies evidenced the potential of L1CAM as a prognostic marker in endometrial cancer. The aim of this study was to investigate whether L1CAM can predict lymph node metastasis and could therefore be used preoperatively to identify patients with low to high-intermediate risk endometrial cancer who would profit from a lymphadenectomy and an adjuvant treatment. To avoid unnecessary morbidity, de-escalating strategies are still required. Methods: Immunohistochemistry for L1CAM was performed on curettage or hysterectomy specimens from 212 patients diagnosed with endometrial cancer who were treated at the University Hospital Basel during 2011-2019. L1CAM expression was correlated with clinicopathological features such as histological subtype, FIGO stage, lymph node metastasis, lymphadenectomy, adjuvant treatment and outcome. Results: Using a cut off ≥10%, L1CAM was positive in 41/212 patients (19.3%) and negative in 171/212 patients (80.7%). L1CAM was associated with high-risk features such as non-endometrioid histology, high tumour grade, and high FIGO stage. There was no significant correlation between L1CAM expression and lymph node metastasis. However, patients with L1CAM positive tumours showed improved disease-specific survival if treated with adjuvant radiotherapy. Conclusion: Although L1CAM expression pointed towards aggressive tumour biology, preoperative L1CAM analysis did not add any substantial predictive information regarding lymph node metastasis in low to high-intermediate risk groups. Therefore, L1CAM status is not suitable to tailor the surgical algorithm for lymph node staging. Nevertheless, our results suggest that L1CAM could be used as a predictive biomarker to select patients who may benefit the most from adjuvant radiotherapy., (© The author(s).)

We studied HIV prevalence and genetic diversity in rural forest areas in Cameroon, where chimpanzee and gorilla populations infected with the ancestors of the different HIV-1 groups have been identified and transmitted to humans during the 20th century. A total of 2812 individuals were studied, 924 from south-central, 1116 from south-east and 772 from south-west Cameroon. Of 208 (7.4%) samples that were confirmed for HIV-1 infection all belong to HIV-1 group M. In all sites and in all age categories, HIV-1 prevalence was higher in women (160/1599 (10.0%)) as compared to men (48/1213 (4.0%)) with the highest prevalence in women aged between 25 and 34 years (>17%). For 188/208 (92.3%) HIV-1 positive individuals, a fragment of the pol gene was successfully amplified and sequenced. Phylogenetic analysis showed predominance of CRF02&#95;AG (58%), a large diversity of subtypes (A, D, F2 and G), nine different CRFs and more than 12% URFs. Interestingly, 35/188 (18.6%) HIV-1 strains form 12 recent transmission chains. The majority of the clusters are composed of two (n = 8) or three (n = 3) sequences but one cluster included ten HIV-1 strains from women living in four different villages on a major road for logging concessions in the south-east (60 km distance). In the three regions of Cameroon where the ancestors of the four HIV-1 groups have been transmitted to humans, we observed a high HIV prevalence, especially in the southeast where HIV-1 M originated. Many factors allowing rapid establishment in the human population and subsequent rapid spread to urban areas of a new retrovirus or other pathogens of zoonotic origin are now present. Our study shows clearly that some rural areas should also be considered as hot-spots for HIV infection. Prevention efforts together with growing access to HIV diagnosis and antiretroviral treatment are urgently needed in these remote areas., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Large tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer., Materials and Methods: We analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay)., Results: The analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity., Conclusion: These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.

Background: Treatment options for advanced cervical cancer are limited and patients experiencing recurrence after first-line cisplatin-based chemotherapy and bevacizumab have a poor prognosis. A recent phase II study in advanced cervical cancer has demonstrated a disease control rate of 68.4% with the immune checkpoint inhibitor nivolumab. By blocking immune checkpoints, immunotherapy puts the immune system into a state of hyper-activation that can cause immune-related adverse events. We present the clinical, pathological and molecular data of a patient with metastatic cervical cancer and progressive disease after second-line therapy. We report on the therapeutic response under third-line immunotherapy with nivolumab, the immune-related adverse events (IRAE), and their successful management., Case Presentation: We report the case of a 62-year-old woman who was diagnosed with advanced squamous cell carcinoma of the cervix with paraaortic lymph node metastases. After an initial combined radio-chemotherapy with cisplatin, she developed local and nodal (supraclavicular) recurrence. Second-line chemotherapy with 6 cycles of carboplatin, paclitaxel, and bevacizumab resulted in a partial response for 6 months. Checkpoint inhibition with nivolumab was started due to progression, leading to persistent complete remission. Immunotherapy was well tolerated for 8 months until the patient presented with an immune-related isolated vulvitis, which was successfully managed with topical corticosteroids., Conclusions: The persistent complete response after third-line treatment for relapsed chemotherapy-resistant cervical cancer presented in this case highlights the potential of immunotherapy for patients with advanced cervical cancer impressively. To our knowledge, this is the first report of an isolated immune-related vulvitis under nivolumab. This adverse event might be underdiagnosed and mistreated, however, it is of importance due to its impact on quality of life, sexual wellbeing and compliance of patients. Successful IRAE management may enable prolonged immune checkpoint inhibitor therapy. In the future, routine molecular tumour profiling is likely to aid in the stratification of cervical cancer patients for immunotherapy. Here, we provide the methylome data of a case with complete response.

Peritoneal biopsies (PB) and peritoneal washing (PW) are routine measures in abdominal staging of gynecological malignancies and are used particularly for the assessment of occult microscopic tumor spread to the peritoneal surface including the diaphragm. Cytological diaphragmatic smears (DS) have been suggested as a supplemental tool; however, they are not routinely taken and their usefulness is still unclear. The present study retrospectively evaluated whether DS provide an additional benefit over PB and PW for the detection of peritoneal malignancies in patients with gynecological cancer. The data from patients who underwent laparotomy for suspected gynecological cancer and had DS and either PB, PW or ascites were reviewed. Sensitivity and specificity, and the number upstaged patients were determined. A total of 43 patients were excluded due to benign diagnosis (those with negative DS or PW) and 2 out of the remaining had 2 carcinomas simultaneously. Among these 41 malignancies, DS were positive in 12, PW in 18 and PB in 19 cases. No case was DS-positive while negative for both PB and PW. Four cases were missed when only PB and 5 when only PW was performed. Notably, no case of peritoneal disease was identified solely on positive DS, indicating that all 23 positive cases (presence of occult peritoneal disease in 56.1%) were identified by PB and PW together (100% sensitivity; 62% specificity). In addition, none of the cases was upstaged solely on positive DS results. Taken together, these data demonstrated that DS do not present an additional benefit to PW and PB in the detection of peritoneal gynecological disease.

Background: Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology., Methods: Twelve patients with loiasis and microfilarial counts <2000 mf/mL were randomized to receive single-dose DEC (8 mg/kg) or IVM (200 µg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment., Results: Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups., Conclusions: Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology., Clinical Trials Registration: NCT01593722., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Since the mid-2000s, the immunochromatographic card test (ICT), a point-of-care test for detecting Wuchereria bancrofti circulating filarial antigens (CFAs), has been the backbone for mapping and monitoring lymphatic filariasis (LF) worldwide. Recently, there have been instances in which CFA positivity has been associated with Loa loa microfilaremia. Here, we examined the association, at both the community and individual levels, between L. loa and CFA using additional diagnostic tools (quantitative polymerase chain reaction [qPCR], Og4C3 enzyme-linked immunosorbent assay, and IgG4 antibodies to Wb123 assays) to demonstrate the relationship between L. loa microfilaremia and ICT positivity. In May 2013, peripheral blood was collected during the day from 1,812 individuals living in southern Cameroon. ICT tests were done on the spot, and positive individuals were resampled at night. Results of qPCR and Wb123 assays concurred proving the absence of W. bancrofti infection. Og4C3 assays indicate a quantitative relationship between the level of L. loa microfilaremia and that of CFA. This was confirmed by epidemiological analyses, which reveal a strong association between L. loa microfilaremia and ICT positivity, with 50% of ICT reacting to L. loa when its microfilarial density exceeds 30,000 microfilariae/mL. At the community level, the proportion of positive ICT would exceed 2% when the prevalence of L. loa microfilaremia in the total population is above 20%. This has significant implications in terms of mapping and control of LF caused by W. bancrofti in Loa-endemic areas. Cross-reactivity of ICT with L. loa has to be considered in the context of both individual and community diagnostics., (© The American Society of Tropical Medicine and Hygiene.)

The study of the interactions among parasites within their hosts is crucial to the understanding of epidemiology of disease and for the design of effective control strategies. We have conducted an assessment of infections with Loa loa, Mansonella perstans, Wuchereria bancrofti, and Plasmodium falciparum in eastern Cameroon using a highly sensitive and specific quantitative polymerase chain reaction assay using archived dried whole blood spots. The resident population (N = 1,085) was parasitized with M. perstans (76%), L. loa (39%), and P. falciparum (33%), but not with W. bancrofti Compared with single infections (40.1%), coinfection was more common (48.8%): 21.0% had L. loa-M. perstans (Ll(+)/Mp(+)/Pf(-)), 2.7% had L. loa-P. falciparum (Ll(+)/Pf(+)/Mp(-)), 15.1% had M. perstans-P. falciparum (Mp(+)/Pf(+)/Ll(-)), and 10.0% had L. loa-M. perstans-P. falciparum (Ll(+)/Mp(+)/Pf(+)). Interestingly, those with all three infections (Ll(+)/Mp(+)/Pf(+)) had significantly higher L. loa microfilaria (mf) counts than either single Ll(+) (P = 0.004) or double Ll(+)/Mp(+) (P = 0.024) infected individuals. Of those infected with L. loa, the mean estimated counts of L. loa mf varied based on location and were positively correlated with estimated intensities of M. perstans mf. Finally, at a community level, heavy L. loa infections were concentrated in a few individuals whereby they were likely the major reservoir for infection., (© The American Society of Tropical Medicine and Hygiene.)

In West and West Central Africa, multiple subtypes, circulating recombinant forms (CRF), and high proportions of unique recombinant forms (URF) are documented. The predominance of recombinants strongly suggests that dual infections occur frequently. In the present study, we adapted the multi-region hybridization assay (MHA), previously developed to identify dual infections in geographic regions where few HIV-1 variants circulate, to identify HIV-1 variants and dual infections. We designed clade-specific probes in three genomic regions (gag p17, vpu, nef) to detect eight different variants that are common in this part of Africa (A, B/D, C, F, G, CRF02&#95;AG, CRF06&#95;cpx, CRF22&#95;01A1). The assay was validated with 163 samples representing the corresponding HIV-1 variants. Depending on the genomic regions, the global sensitivity of the assay ranged from 86% to 94%, and the global specificity was between 85% and 96%. The assay was then applied on 156 antiretroviral treatment-naive patients from Cameroon. The MHA assay identified 79%, 85% and 90% of the strains in nef, gag and vpu regions, respectively. The subtype/CRF distribution and the proportion of inter-region recombinants obtained by the new MHA assay were in accordance with known subtype/CRF distribution in Cameroon. Moreover, the MHA assay identified 35 (22.4%) patients as dually infected, from which 20 were reactive in more than one region and/or with concordant multigenomic recombination pattern. Despite the high genetic diversity, we successfully developed an hybridization assay allowing identification of eight common HIV-1 variants circulating in West and West Central Africa. We documented high rates of dual infection in a low-risk population group, illustrating that the global evolution of HIV diversity is driven by dual infections. This assay could become a useful screening tool for the global surveillance and monitoring of inter-subtype/CRF dual infections in West and West Central Africa., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Altered DNA methylation patterns hold promise as cancer biomarkers. In this study we selected a panel of genes which are commonly methylated in a variety of cancers to evaluate their potential application as biomarkers for prognosis and diagnosis in high grade serous ovarian carcinoma (HGSOC); the most common and lethal subtype of ovarian cancer., Methods: The methylation patterns of 10 genes (BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR., Results: The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10-11.07), p=0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign OSE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated., Conclusions: This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the frequency and progression over time of the WHO-defined transmitted HIV-1 drug resistance mutations (DRMs) among antiretroviral treatment (ART)-naive HIV-1-infected patients in Cameroon., Design: We analyzed HIV-1 DRM data generated from 369 ART-naive individuals consecutively recruited between 1996 and 2007 in urban and rural areas in Cameroon., Methods: HIV-1 drug resistance genotyping was performed in the pol gene using plasma samples and surveillance DRMs were identified using the 2009 WHO-DRM list., Results: We observed in Yaounde, the capital city, an increasing prevalence of DRMs over time: 0.0% (none of 61 participants) in 1996-1999; 1.9% (one of 53 participants) in 2001; 4.1% (two of 49 participants) in 2002; and 12.3% (10 of 81 participants) in 2007. In the rural areas with more recently implemented ART programs, we found DRMs in six of 125 (4.8%) ART-naive individuals recruited in 2006-2007. DRMs identified in both areas included resistance mutations to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) that might impair the efficacy of available first-line and second-line treatments., Conclusion: This report showed an increase in transmitted DRMs in areas where antiretroviral drugs were introduced earlier, although other factors such as natural viral polymorphisms and acquired DRMs through exposure to antiretroviral cannot be totally excluded. Further surveillances are needed to confirm this evolution and inform public health policies on adequate actions to help limit the selection and transmission of drug-resistant HIV, while scaling up access to ART in developing countries.

To evaluate the presence of drug resistance mutations in antiretroviral-naive patients in Dakar (Senegal), cross-sectional studies were conducted since the circulation of ARVs in the country. Protease and RT genes were sequenced in 96 baseline samples from patients included in the Senegalese Initiative for Antitretroviral Access treatment between 1998 and 2001 and for 104 samples from naive, recently diagnosed patients in 2003, 2005, and 2007. Phylogenetic analysis showed a predominance of CRF02&#95;AG [128/200 (64%)] and a high genetic diversity with 10 other variants and 25 URFs. Analysis for the presence of drug resistance mutations according to the WHO SDRM 2009 list showed a prevalence of 4.16% for nucleoside inhibitors and 1.04% for protease inhibitors at the start of the structured Senegalese ART initiative and 1.9% for protease inhibitors at the time of scaling up. The prevalence in untreated patients remains low and stable, below 5% after 10 years of ARV circulation.

In this study, HIV strains circulating among military personnel were characterized, in Malabo, the capital city of Equatorial Guinea. One sample was found to be HIV-2 group A while a high degree of genetic diversity was recorded in the pol region of 41 HIV-1-positive samples. CRF02&#95;AG accounted for 53.7% of the strains, and 11 different variants were obtained in the remaining 19 samples: subtype G (n = 3), A3 (n = 2), C (n = 2), CRF26&#95;A5U (n = 2), F2 (n = 1), CRF06 (n = 1), CRF09 (n = 1), CRF11 (n = 1), CRF22 (n = 1), and divergent subtype A (n = 1) and F (n = 1). One strain could not be classified and three were unique recombinants. Analysis of antiretroviral drug resistance mutations revealed two patients each harboring one major mutation, M46I in protease and D67N in reverse transcriptase sequences, respectively. The high genetic diversity and emerging ARV resistance mutations call for frequent surveys and appropriate monitoring of ARV considering the increasing access to ARV in the country.

A cross-sectional study, performed at a routine human immunodeficiency virus (HIV)/AIDS clinic in Cameroon that uses the World Health Organization public health approach, showed low rates of virological failure and drug resistance at 12 and 24 months after initiation of antiretroviral therapy. Importantly, the cross-sectional study also showed that the World Health Organization recommendation for second-line treatment would be effective in almost all patients with HIV drug resistance mutations.

The development and validation of dried sample spots as a method of specimen collection are urgently needed in developing countries for monitoring of human immunodeficiency virus (HIV) infection. Our aim was to test some crucial steps in the use of dried spots, i.e., viral recovery and storage over time. Moreover, we investigated whether dried plasma and blood spots (DPS and DBS, respectively) give comparable viral load (VL) results. Four manual RNA extraction methods from commercial HIV type 1 (HIV-1) VL assays--a QIAamp minikit (Qiagen), the Abbott Molecular sample preparation system, the Nuclisens assay (bioMarieux), and High Pure viral nucleic acid kit (Roche Applied Science)--were compared for VL quantification and PCR amplification for genotypic drug resistance testing on dried spots from spiked plasma and residual samples from HIV-1 patients (n = 47; median VL, 4.13 log(10) copies/ml). RNA recovery from DPS was efficient using Nuclisens extraction (median difference, 0.03 log(10) copies/ml) and slightly underestimated using the Abbott Molecular sample preparation system (median difference, 0.35 log(10) copies/ml). PCR amplification results were in concordance. Measurements from DBS overestimated VL for plasma, with VL results showing <3.7 log(10) copies/ml. VL was stable for up to 3 months in spiked DPS stored at 20 degrees C but for only 1 month at 37 degrees C. A faster decline was observed in PCR efficiency: DPS could be stored for 1 week at 37 degrees C and for 1 month at 20 degrees C. In conclusion, the RNA extraction method is an important factor in obtaining reliable RNA quantification and PCR amplification of HIV-1 on DPS/DBS. DBS could be used as an alternative for DPS depending on HIV RNA cutoffs for virological failure. VL measurements remain stable over a longer period than do PCR amplification results.

Objective: Venous thromboembolism (VTE) is a leading cause of maternal morbidity and mortality in pregnancy and the puerperium. To reduce the incidence of VTE, it is helpful to understand the haemostatic changes during pregnancy and to recognise thrombophilic states. According to the individual risk profile a prophylactic or therapeutic anticoagulation needs to be considered., Methods: A narrative, non-systematic overview of articles published in English, German or French over the past three decades with an emphasis on manuscripts from 2003 to 2008., Results: Heparins are the main agents used for anticoagulation during pregnancy. Low-molecular-weight heparins have more advantages than unfractionated heparin and should be preferred. Vitamin-K antagonists are not recommended in this condition as first-line treatment because of the risk for embryopathy and fetal bleeding, but they can be given under certain conditions. Subgroups of patients, such as women with prosthetic heart valves, require special attention. Adverse pregnancy outcomes due to hereditary thrombophilia are new indications for use of anticoagulants during pregnancy., Conclusions: National and international guidelines on prevention and treatment of thromboembolism are helpful in applying the proper regimen in pregnant women.

Estrogen receptor (ER) alpha and beta and aromatase are expressed in various cell-types and compartments of the penis, including the epidermis of glans penis. Here, we hypothesize that estrogen helps maintain the viability and integrity of glans penis and test the hypothesis by treating lesioned glans penis with either 17beta-estradiol or vehicle only. Estrogen was found to facilitate wound healing and increase vascular endothelial growth factor (VEGF) immunoreactivity compared to control, as revealed by scanning electron microscopy, histology, and immunohistochemistry. We conclude that estrogen plays a role in maintaining glans penis integrity, in part, by facilitating penile healing, possibly via up-regulating VEGF levels.

To document the actual genetic diversity of HIV-1 strains in the Republic of Congo, 114 HIV-1 positives persons were sampled in 2003 and 2004 after their informed consent. They were attending the teaching hospital, the reference health center in Makelekele, Brazzaville and the regional hospital centers in Pointe-Noire, Gamboma and Ouesso. A total of 104 samples were genetically characterized by direct sequencing of the p24 gag region and 80 were also subtyped in the V3-V5 env region. The genetic subtype distribution of the Congolese strains showed the predominance of subtype A (36.5% and 32.5% in gag and env, respectively) and G (30.8% and 21.25%), whereas subtype D strains represented 12.5% and 15%. Subtypes C, F, H, J, K and the CRFs-01, -02, -05 -06, and also the recently characterized CRF18 were seen at lower rates. Finally, 4.8% (gag) and 6.25% (env) of the strains could not be classified. Moreover, a high intra-subtype diversity was observed in our study. Among 70 strains which have been characterized in the two genomic regions, 14 (20%) appeared to be unique recombinants. These data show a high genetic variability in the Republic of Congo, where all the subtypes have been documented together with certain subsubtypes and several CRFs.

Anaerobic infections with Clostridium perfringens (CP) occur rarely but are associated with considerable maternal mortality. We report the case of a patient who developed uterine gas gangrene postpartum and discuss the management of this infection. A 28-year-old patient, GII, PII with history of Caesarean in 2002, delivered a healthy girl per vacuum extraction. Postpartally she presented with an acute abdomen and a laparotomy was performed. The uterotomy suture was intact but a parametrane tear had to be resutured. 36 hours later the patient's condition worsened quickly. Cellulitis was diagnosed and after receiving the results of the wound swabs (CP positive) from the uterus and haematoma, tazobactam and clindamycin were administered. Her condition continued to deteriorate and gaseous gangrene was seen with unilateral extension to the abdomen reaching as far as the axilla cranially and to the thigh caudally. Due to the extensive infection it was necessary to perform a hysterectomy, necrosis removal and splitting of the fascia followed by several debridements and leaving the wound open in order to avoid anaerobic conditions. The patient was discharged after 21 days. She developed a post-traumatic syndrome with severe depression. Clostridium perfringens is ubiquitous and is found vaginally in ca. 1 - 10 % of healthy women and usually does not cause a serious infection. Under the right conditions it can cause an endometritis leading to sepsis. Early recognition and interdisciplinary treatment are of extreme importance. In this case the surgical treatment through hysterectomy combined with targeted antibiotic therapy, ultimately saved the patient's life.

On the basis of partial env and gag subtyping, we documented that the majority of HIV-1 strains circulating in Niger were CRF02-AG (54.3%) or CRF06-cpx (18.1%) and that 9% of the samples were possible recombinants between CRF02 and CRF06. To determine in more detail the precise structure of these viruses we sequenced the full-length genomes for three such strains (97NE-003, 00NE-036, and 00NE-095). From the bootscan and phylogenetic tree analysis it is evident that the new viruses are the result of recombination events between CRF02-AG and CRF06-cpx strains. Importantly, each virus had a different complex recombinant structure with multiple breakpoints, leading to viruses with complex mosaic patterns.

A total of 110 HIV-1-positive samples obtained in 1997 (n = 44) and 2000 (n = 66) were genetically characterized in the V3-V5 envelope region and the p24 gag region. The majority of the strains were CRF02-AG (54.3%) or CRF06-cpx (18.1%) in env and gag. More than 9% of the samples were recombinants between CRF02 and CRF06; 9 were CRF06 in env but CRF02 in gag, and for one sample the opposite was seen. Overall for 23 (20.9%) samples, the subtype designation was different between env and gag, and in 20 of these 23 samples a CRF was involved in the recombination event. No significant differences were seen between subtype distributions in 1997 and 2000, except that the proportion of recombinants increased from 13.6% in 1997 to 27.2% in 2000.

We report a case of noma having occurred in an adult female patient with HIV. The strain was characterized as HIV-1 group M subtype G. In order to explore the interactions between HIV/AIDS and this disease, we purpose systematic HIV screening for any case of noma, especially for adult patients.

Phylogenetic analysis of numerous strains of HIV-1 isolated from diverse geographic origins has revealed three distinct groups of HIV-1: groups M, N, and O. Within group M, subtypes, sub-subtypes and circulating recombinant forms (CRFs) exist. Recently, two near-full-length genomes of similar complex mosaic viruses containing fragments of subtypes A, G, I, and J were described in patients from Burkina Faso (BFP-90) and Mali (95ML-84). Here, we report on the characterization of two additional full-length genome sequences with similar mosaic structure in epidemiologically unlinked individuals from Senegal (97SE-1078) and Mali (95ML-127). Phylogenetic and recombinant analysis confirmed that the previously described strains, BFP-90 and 95ML-84, were indeed a new CRF of HIV-1, which we can now designate as CRF06-cpx. This new CRF fits the complex (cpx) designation, because four different subtypes (A, G, K, and J) were involved in the mosaic genome structure. The fragment in the pol gene, which was initially characterized as unknown in the BFP-90 strain and subsequently as subtype I in the 95ML-84 strain, is now, with the recent description of the new K subtype, clearly identified as subtype K. CRF06-cpx circulates in Senegal, Mali, Burkina Faso, Ivory Coast, and Nigeria, although the exact prevalence remains to be determined. Importantly, this new variant has also been documented on other continents (Europe [France] and Australia), showing that these viruses are spreading not only locally but globally.