Maternal overweight and obesity and its associated factors and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected black South African pregnant women.

AIM: This study aimed to investigate various variables between maternal overweight and/or obesity versus normal-weight pregnant black South African women living with and without human immunodeficiency virus (HIV). METHODS: A cross-sectional study design was employed. A total of 200 pregnant women were enrolled in the study, categorized according to body mass index (BMI) (kg/m2 ) into two groups: (1) overweight/obese (≥25 kg/m2 ) (n = 97); and (2) nonoverweight/nonobese (<25 kg/m2 ) (n = 103), where 90 were HIV-infected and 110 were HIV-uninfected. The differences between the maternal BMI categories were assessed using Fisher's exact t-test and the χ2 test. Simple and multiple logistic regression analyses were used to determine factors associated with maternal overweight and obesity. RESULTS: Multiple logistic regression analysis showed that maternal age (odds ratio [OR]: 1.061; 95% confidence interval [CI] 1.008-1.117; p = 0.023) and gestational age (OR: 1.121; 95% CI 1.005-1.251; p = 0.041) were significantly associated with maternal overweight/obesity in both HIV-infected and HIV-uninfected. For maternal health outcomes, multiple logistic regression analysis showed that hypertensive disorders (OR: 0.273; 95% CI 0.124-0.601; p = 0.001) and anemia (OR: 2.420; 95% CI 1.283-4.563; p = 0.006) were significantly associated with maternal overweight/obesity in both HIV-infected and HIV-uninfected. The overweight/obese HIV-infected participants (OR: 0.233; 95% CI 0.075-0.717; p = 0.011) had increased odds for developing hypertensive disorders compared to HIV-uninfected overweight/obese participants (OR: 0.471; 95% CI 0.172-1.291; p = 0.143). CONCLUSIONS: Maternal overweight/obesity in both HIV-infected and HIV-uninfected pregnant black South African women was significantly associated with maternal age, gestational age, HPT disorders, and anemia. Maternal overweight/obesity decreased the odds for anemia, but increased the odds for the development of HPT disorders, especially in the HIV-infected pregnant women.

A multi-institutional phase 2 trial of stereotactic body radiotherapy in the treatment of bone metastases in pediatric and young adult patients with sarcoma.

BACKGROUND: Metastasectomy is standard of care for pediatric patients with metastatic sarcoma with limited disease. For patients with unresectable disease, stereotactic body radiotherapy (SBRT) may serve as an alternative. Herein, the authors report the results of a prospective, multi-institutional phase 2 trial of SBRT in children and young adults with metastatic sarcoma. METHODS: Patients aged >3 years and ≤40 years with unresected, osseous metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone were eligible. Patients received SBRT to a dose of 40 Gray (Gy) in 5 fractions. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Fourteen patients with a median age of 17 years (range, 4-25 years) were treated to 37 distinct metastatic lesions. With a median follow-up of 6.8 months (30.5 months in surviving patients), the Kaplan-Meier patient-specific and lesion-specific LC rates at 6 months were 89% and 95%, respectively. The median PFS was 6 months and the median OS was 24 months. In a post hoc analysis, PFS (median, 9.3 months vs 3.7 months; log-rank P = .03) and OS (median not reached vs 12.7 months; log-rank P = .02) were improved when all known sites of metastatic disease were consolidated with SBRT compared with partial consolidation. SBRT was well tolerated, with 2 patients experiencing grade 3 toxicities. CONCLUSIONS: SBRT achieved high rates of LC in pediatric patients with inoperable metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone. These results suggest that the ability to achieve total consolidation of metastatic disease with SBRT is associated with improved PFS and OS.

Radiation therapy for gynecologic malignancies during the COVID-19 pandemic: International expert consensus recommendations.

OBJECTIVE: To develop expert consensus recommendations regarding radiation therapy for gynecologic malignancies during the COVID-19 pandemic. METHODS: An international committee of ten experts in gynecologic radiation oncology convened to provide consensus recommendations for patients with gynecologic malignancies referred for radiation therapy. Treatment priority groups were established. A review of the relevant literature was performed and different clinical scenarios were categorized into three priority groups. For each stage and clinical scenario in cervical, endometrial, vulvar, vaginal and ovarian cancer, specific recommendations regarding dose, technique, and timing were provided by the panel. RESULTS: Expert review and discussion generated consensus recommendations to guide radiation oncologists treating gynecologic malignancies during the COVID-19 pandemic. Priority scales for cervical, endometrial, vulvar, vaginal, and ovarian cancers are presented. Both radical and palliative treatments are discussed. Management of COVID-19 positive patients is considered. Hypofractionated radiation therapy should be used when feasible and recommendations regarding radiation dose, timing, and technique have been provided for external beam and brachytherapy treatments. Concurrent chemotherapy may be limited in some countries, and consideration of radiation alone is recommended. CONCLUSIONS: The expert consensus recommendations provide guidance for delivering radiation therapy during the COVID-19 pandemic. Specific recommendations have been provided for common clinical scenarios encountered in gynecologic radiation oncology with a focus on strategies to reduce patient and staff exposure to COVID-19.

Observer-independent assessment of psoriasis-affected area using machine learning.

BACKGROUND: Assessment of psoriasis severity is strongly observer-dependent, and objective assessment tools are largely missing. The increasing number of patients receiving highly expensive therapies that are reimbursed only for moderate-to-severe psoriasis motivates the development of higher quality assessment tools. OBJECTIVE: To establish an accurate and objective psoriasis assessment method based on segmenting images by machine learning technology. METHODS: In this retrospective, non-interventional, single-centred, interdisciplinary study of diagnostic accuracy, 259 standardized photographs of Caucasian patients were assessed and typical psoriatic lesions were labelled. Two hundred and three of those were used to train and validate an assessment algorithm which was then tested on the remaining 56 photographs. The results of the algorithm assessment were compared with manually marked area, as well as with the affected area determined by trained dermatologists. RESULTS: Algorithm assessment achieved accuracy of more than 90% in 77% of the images and differed on average 5.9% from manually marked areas. The difference between algorithm-predicted and photograph-based estimated areas by physicians was 8.1% on average. CONCLUSION: The study shows the potential of the evaluated technology. In contrast to the Psoriasis Area and Severity Index (PASI), it allows for objective evaluation and should therefore be developed further as an alternative method to human assessment.

Plasmodium cynomolgi as Cause of Malaria in Tourist to Southeast Asia, 2018.

We report human infection with simian Plasmodium cynomolgi in a tourist from Denmark who had visited forested areas in peninsular Malaysia and Thailand in August and September 2018. Because P. cynomolgi may go unnoticed by standard malaria diagnostics, this malaria species may be more common in humans than was previously thought.

Phase I study of emactuzumab single agent or in combination with paclitaxel in patients with advanced/metastatic solid tumors reveals depletion of immunosuppressive M2-like macrophages.

BACKGROUND: Emactuzumab is a monoclonal antibody against the colony-stimulating factor-1 receptor and targets tumor-associated macrophages (TAMs). This study assessed the safety, clinical activity, pharmacokinetics (PK) and pharmacodynamics (PD) of emactuzumab, as monotherapy and in combination with paclitaxel, in patients with advanced solid tumors. PATIENTS AND METHODS: This open-label, phase Ia/b study comprised two parts (dose escalation and dose expansion), each containing two arms (emactuzumab, every 2 or 3 weeks, as monotherapy or in combination with paclitaxel 80 mg/m2 weekly). The dose-escalation part explored the maximum tolerated dose and optimal biological dose (OBD). The dose-expansion part extended the safety assessment and investigated the objective response rate. A PK/PD analysis of serial blood, skin and tumor biopsies was used to explore proof of mechanism and confirm the OBD. RESULTS: No maximum tolerated dose was reached in either study arm, and the safety profile of emactuzumab alone and in combination does not appear to preclude its use. No patients receiving emactuzumab monotherapy showed an objective response; the objective response rate for emactuzumab in combination with paclitaxel was 7% across all doses. Skin macrophages rather than peripheral blood monocytes or circulating colony-stimulating factor-1 were identified as an optimal surrogate PD marker to select the OBD. Emactuzumab treatment alone and in combination with paclitaxel resulted in a plateau of immunosuppressive TAM reduction at the OBD of 1000 mg administered every 2 weeks. CONCLUSIONS: Emactuzumab showed specific reduction of immunosuppressive TAMs at the OBD in both treatment arms but did not result in clinically relevant antitumor activity alone or in combination with paclitaxel. (ClinicalTrials.gov Identifier: NCT01494688).

Development and evaluation of molecular tools for detecting and differentiating intestinal amoebae in healthy individuals.

Amoebae are single-celled parasites frequently colonizing human gut. However, few molecular tools are available for accurate identification. Here, we evaluated a panel of polymerase chain reactions (PCRs) targeting Entamoeba histolytica, Entamoeba dispar, Entamoeba coli, Entamoeba hartmanni, Entamoeba polecki, Endolimax nana and Iodamoeba bütschlii. Thirty-six faecal samples (18 containing at least one amoeba species by microscopy and 18 microscopy negative for amoebae) were tested. Real-time PCRs were used for detection and differentiation of E. histolytica and E. dispar. Conventional PCR with Sanger sequencing were applied for detection and differentiation of E. coli, E. hartmanni, E. polecki, E. nana and I. bütschlii. All microscopy results were confirmed by DNA-based methods. However, more samples were positive for single and mixed amoebic species by DNA-based assays than by microscopy (22 vs 18 and 7 vs 1, respectively). DNA sequencing allowed identification of E. coli subtypes (ST1 and ST2), showed low intra-specific variation within E. hartmanni, identified two phylogenetically distinct groups within E. nana, and identified Iodamoeba at the ribosomal lineage level. Taking into account the high intra-genetic diversity within some of the species at the small subunit (SSU) rRNA gene level, amplification of SSU rRNA genes with subsequent sequencing represents a useful method for detecting, differentiating and subtyping intestinal amoebae.

Dientamoeba fragilis, a Commensal in Children in Danish Day Care Centers.

Dientamoeba fragilis is an intestinal protozoan of debated clinical significance. Here, we present cross-sectional and longitudinal observations on D. fragilis in children aged 0 to 6 years from a 1-year multi-day-care-center cohort study set in Copenhagen, Denmark. The inclusion period for the cohort was 2009 through 2012. Stool samples collected from the children were accompanied by questionnaires completed by the parents or guardians of the children. Using real-time PCR, D. fragilis was detected in the first stool sample from 97 of 142 (68.3%) children. We evaluated the associations between seven plausible risk factors (age, sex, having siblings, having domestic animals at home, having had infant colic, recent history of intake of antibiotics, and recent history of travel abroad) as well as six reported symptoms (lack of appetite, nausea, vomiting, abdominal pain, weight loss, and diarrhea) and testing positive for D. fragilis The final multivariable model identified being >3 years old and having a history of recent travel abroad as risk factors for testing positive for D. fragilis Moreover, univariable analyses indicated that having siblings was a risk factor. There was no statistical association between a recent history of gastrointestinal symptoms and testing positive for D. fragilis Among the 108 children who were represented by ≥2 samples and thus included in the longitudinal analysis, 32 tested negative on the first sample and positive later, and the last sample from each of the 108 children was positive. The results are in support of D. fragilis being a common enteric commensal in this population.

Biomechanical Analysis of Latarjet Screw Fixation: Comparison of Screw Types and Fixation Methods.

PURPOSE: To compare the initial fixation stability, failure strength, and mode of failure of 5 different screw types and fixation methods commonly used for the classic Latarjet procedure. METHODS: Thirty-five fresh-frozen cadaveric shoulder specimens were allocated into 5 groups. A 25% anteroinferior glenoid defect was created, and a classic Latarjet coracoid transfer procedure was performed. All grafts were fixed with 2 screws, differing by screw type and/or fixation method. The groups included partially threaded solid 4.0-mm cancellous screws with bicortical fixation, partially threaded solid 4.0-mm cancellous screws with unicortical fixation, fully threaded solid 3.5-mm cortical screws with bicortical fixation, partially threaded cannulated 4.0-mm cancellous screws with bicortical fixation, and partially threaded cannulated 4.0-mm captured screws with bicortical fixation. All screws were stainless steel. Outcomes included cyclic creep and secant stiffness during cyclic loading, as well as load and work to failure during the failure test. Intergroup comparisons were made by a 1-way analysis of variance. RESULTS: There were no significant differences among different screw types or fixation methods in cyclic creep or secant stiffness after cyclic loading or in load to failure or work to failure during the failure test. Post-failure radiographs showed evidence of screw bending in only 1 specimen that underwent the Latarjet procedure with partially threaded solid cancellous screws with bicortical fixation. The mode of failure for all specimens analyzed was screw cutout. CONCLUSIONS: In this biomechanical study, screw type and fixation method did not significantly influence biomechanical performance in a classic Latarjet procedure. When performing this procedure, surgeons may continue to select the screw type and method of fixation (unicortical or bicortical) based on preference; however, further studies are required to determine the optimal method of treatment. CLINICAL RELEVANCE: Surgeons may choose the screw type and fixation method based on preference when performing the Latarjet procedure.

Prevalence and genotype distribution of Pneumocystis jirovecii in Cuban infants and toddlers with whooping cough.

This study describes the prevalence and genotype distribution of Pneumocystis jirovecii obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163 young Cuban children with WC who were admitted to the respiratory care units at two pediatric centers were studied. The prevalence of the organism was determined by a quantitative PCR (qPCR) assay targeting the P. jirovecii mitochondrial large subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP) analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected P. jirovecii DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed the presence of three different genotypes in the population. Genotype 2 was most common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed-genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR products revealed four genotypes, 18% of which were associated with resistance to sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95% confidence interval {CI}, 1.79 to 6.87]; P = 0.000) and exposure to tobacco smoke (PR, 1.82 [95% CI, 1.14 to 2.92]; P = 0.009) were statistically associated with being colonized by P. jirovecii. The prevalence of P. jirovecii in infants and toddlers with WC and the genotyping results provide evidence that this population represents a potential reservoir and transmission source of P. jirovecii.

Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases.

OBJECTIVES: Triazole resistance in Aspergillus fumigatus has been increasing. We explored the A. fumigatus azole resistance profiles in bronchoalveolar lavage (BAL) fluid samples from Danish patients examined for aspergillosis. METHODS: A total of 94 BAL samples from 87 patients were evaluated by galactomannan (GM) test and A. fumigatus CYP51A profiling by PCR. RESULTS: Aspergillus spp. were isolated from 27/48 (56.3%) cultured samples, including 23 A. fumigatus with one resistant strain (4.3%). Samples were classified into GM-positive (≥3.0), GM-intermediate (0.5 to <3.0) and GM-negative (<0.5) groups, where the CYP51A PCR was positive in 81.8% (36/44), 56.3% (18/32) and 38.9% (7/18) of samples, respectively. Nine CYP51A PCR-positive samples (9/61, 14.8%) were found to have mutations resulting in amino acid substitutions. M220V was detected from a sample culture positive for susceptible A. fumigatus and P216L was found in a culture-negative BAL sample. Conversely, no mutation was found in one sample culture positive for azole-resistant A. fumigatus. The tandem repeat/L98H mutation was not detected. CONCLUSIONS: Our study shows that azole resistance in A. fumigatus can be cryptic and may go undiagnosed. The combination of improved culture/susceptibility tests and the direct molecular detection of resistance markers will facilitate prompt institution of appropriate antifungal therapy.

First molecular documented case of a rarely reported parasite: Plasmodium knowlesi infection in Denmark in a traveller returning from Malaysian Borneo.

Plasmodium knowlesi has been reported as an emerging infection throughout the Southeast Asian region, especially in the Malaysian state of Sabah, where it accounts for the majority of the malaria cases reported. This is in contrast to Europe, where imported P. knowlesi is a rarely reported infection. We present a case of P. knowlesi infection in a Danish woman returning from a short trip to Malaysian Borneo. Microscopy of blood smears revealed 0.8% infected erythrocytes, but due to the atypical morphological presentation, a conclusive species identification was made by molecular methods. Plasmodium knowlesi is a potentially fatal infection and taking the increasing travel activity into consideration after the coronavirus disease 2019 (COVID-19) pandemic, P. knowlesi should be a differential diagnosis in patients with travel-associated illness returning from highly endemic Southeast Asian areas.

Improving providers' survival estimates and selection of prognosis- and guidelines-appropriate treatment for patients with symptomatic bone metastases: Development of the Bone Metastases Ensemble Trees for Survival Decision Support Platform.

RATIONALE, AIMS AND OBJECTIVES: In the management of symptomatic bone metastases, current practice guidelines do not provide clear methodology for selecting palliative radiotherapy (RT) regimens based on specific patient and disease features. Decision support aids may offer an effective means for translating the complex data needed to render individualised treatment decisions, yet no such tools are available for use in this setting. Thus, we describe the development of the Bone Metastases Ensemble Trees for Survival-Decision Support Platform (BMETS-DSP), which aims to optimise selection of evidence-based, individualised palliative RT regimens. METHOD: The Ottawa Decision Support Framework was used as the theoretical basis for development of BMETS-DSP. First, we utilised stakeholder input and review of the literature to assess determinants underlying the provider decision. Based on this assessment and iterative stakeholder feedback, we developed the web-based, provider-facing BMETS-DSP. Consistent with the underlying theoretical framework, our design also included assessment of decision quality using the International Patient Decision Aids Standards (IPDAS) certification checklist. RESULTS: Stakeholder input and review of 54 evidence-based publications identified the following determinants of the provider decision: estimated prognosis, characteristics of the target symptomatic lesion and the primary cancer type, consideration of alternative interventions, access to patient-specific recommendations, and patient preferences. Based on these determinants, we developed the BMETS-DSP that (1) collects patient-specific data, (2) displays an individualised predicted survival curve, and (3) provides case-specific, evidence-based recommendations regarding RT, open surgery, systemic therapy, and hospice referral to aid in the decision-making process. The finalised tool met IPDAS quality requirements. Preliminary results of a pilot assessment suggest impact of clinical outcomes. CONCLUSIONS: We describe the successful development of a provider-facing decision support platform to aid in the provision of palliative RT in better alignment with patient and disease features. Impact of the BMETS-DSP on decision outcomes will be further assessed in a randomised, controlled study.

Evaluation of the Clinical Utility of the Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP): A Case-Based Pilot Assessment.

PURPOSE: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment. METHODS: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05. RESULTS: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy. CONCLUSION: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform.

Impact of angiotensin system inhibitors on esophageal cancer survival.

INTRODUCTION: Angiotensin system inhibitors are associated with improved prognosis in patients with gastrointestinal and hepatobiliary cancers. Data suggest that renin-angiotensin system signaling stimulates the tumor's immune microenvironment to impact overall survival. The goal of this study is to investigate the role of angiotensin system inhibitor use on the overall survival and disease-free survival of esophageal cancer patients. METHODS: Retrospective review of esophagectomy patients with esophageal adenocarcinoma and squamous cell cancer at a single institution tertiary care center from 2007 to 2018 was performed. Outcomes include overall survival and disease-free survival. Patient characteristics were compared with t test and χ2 test. Survival was analyzed with Kaplan-Meier and Cox proportional-hazards regression. RESULTS: One hundred seventy-one patients were identified and 123 underwent esophagectomy for cancer. No significant differences in patient demographics were found between angiotensin system inhibitor users and non-angiotensin system inhibitor users except for the rates of hypertension (40% vs 94%, P < .01) and diabetes (16% vs 47%, P < .01). Distributions of tumor neoadjuvant therapy, adjuvant therapy, pathology, staging, margins, and surgical approach were similar. Postoperatively, there was no difference in major adverse cardiovascular events or infection rates. This study did not find any differences in overall survival and disease-free survival between angiotensin system inhibitor users and non-angiotensin system inhibitor users. CONCLUSION: Angiotensin system inhibitors have been shown to improve survival and decrease relative risk for several types of cancers; however, our data do not support the same effect on esophageal cancer patients undergoing curative intent surgery. Further research is needed to investigate potential nuances in angiotensin system inhibitor dose, chronicity of use, esophageal pathology, and applicability to nonsurgical candidates.

External Validation of the Bone Metastases Ensemble Trees for Survival (BMETS) Machine Learning Model to Predict Survival in Patients With Symptomatic Bone Metastases.

PURPOSE: The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data sets are unknown. PATIENTS AND METHODS: Patients treated with palliative radiation therapy for SBM from May 2013 to May 2016 at two hospital-based community radiation oncology clinics were included, and medical records were retrospectively reviewed to collect model covariates and survival time. The Kaplan-Meier method was used to estimate overall survival from consultation to death or last follow-up. Model discrimination was estimated using time-dependent area under the curve (tAUC), which was calculated using survival predictions from BMETS based on the initial training data set. RESULTS: A total of 216 sites of SBM were treated in 182 patients. Most common histologies were breast (27%), lung (23%), and prostate (23%). Compared with the BMETS training set, the external validation population was older (mean age, 67 v 62 years; P < .001), had more primary breast (27% v 19%; P = .03) and prostate cancer (20% v 12%; P = .01), and survived longer (median, 10.7 v 6.4 months). When the BMETS model was applied to the external data set, tAUC values at 3, 6, and 12 months were 0.82, 0.77, and 0.77, respectively. When refit with data from the combined training and external validation sets, tAUC remained > 0.79. CONCLUSION: BMETS maintained high discriminative ability when applied to an external validation set and when refit with new data, supporting its generalizability, stability, and the feasibility of dynamic modeling.

Eradication of Blastocystis carriage with antimicrobials: reality or delusion?

Metronidazole constitutes a mainstay in the antimicrobial therapy of intestinal protozoa, and is also traditionally considered first-line therapy in cases where there is a requirement to treat Blastocystis, a common protist of disputable clinical significance. Many compounds have been used in attempts to eradicate the parasite, and an accumulating body of data indicates that successful antimicrobial eradication of Blastocystis is far from straightforward. This review focuses on some issues that prevent us from reaching a clear understanding of how to eradicate Blastocystis based on chemotherapeutic intervention, by focusing on conflicting reports on the efficacy of metronidazole and other compounds and study design and data limitations. The review provides a comprehensive overview of antimicrobials used to target Blastocystis, and discusses issues pertaining to drug resistance, treatment failure, and reinfection. Finally, key methodological and molecular diagnostic tools that will assist in the generation of data required to improve current knowledge are identified and discussed.

Identification and delineation of members of the Entamoeba complex by pyrosequencing.

A method using a single-round PCR coupled to pyrosequencing was developed for the detection and differentiation of members of the Entamoeba complex. The technique was evaluated using DNA isolated directly from faecal specimens and compared with a duplex real-time PCR targeting Entamoeba histolytica and Entamoeba dispar, and a conventional single-round PCR for the detection of Entamoeba moshkovskii. Tetranucleate cysts from 102 faecal specimens from Swedish, Danish and Dutch patients test-positive for the Entamoeba complex by coproscopic examination were identified to species using each of the three methods. Although none of the patients were confirmed to be positive for E. moshkovskii, E. histolytica and E. dispar were identified in 17 and 86 of the samples, respectively, one of the samples containing both species. There was concordance in results between pyrosequencing and the two other methods used. This study showed that PCR and pyrosequencing could be used for the rapid and high throughput identification of Entamoeba species.

Aiming for 100% Local Control in Locally Advanced Cervical Cancer: The Role of Complex Brachytherapy Applicators and Intraprocedural Imaging.

The use of brachytherapy for the treatment of gynecologic malignancies, particularly cervical cancer, has a long and rich history that is nearly as long as the history of radiation oncology itself. From the first gynecologic brachytherapy treatments in the early 20th century to the modern era, significant transformation has occurred driven largely by advancements in technology. The development of high-dose rate sources, remote afterloaders, novel applicators, and 3-dimensional image guidance has led to improved local control, and thus improved survival, solidifying the role of brachytherapy as an integral component in the treatment of locally advanced cervical cancer. Current research efforts examining novel magnetic resonance imaging sequences, active magnetic resonance tracking, and the application of hydrogel aim to further improve local control and reduce treatment toxicity.

Developing an Improved Statistical Approach for Survival Estimation in Bone Metastases Management: The Bone Metastases Ensemble Trees for Survival (BMETS) Model.

PURPOSE: To determine whether a machine learning approach optimizes survival estimation for patients with symptomatic bone metastases (SBM), we developed the Bone Metastases Ensemble Trees for Survival (BMETS) to predict survival using 27 prognostic covariates. To establish its relative clinical utility, we compared BMETS with 2 simpler Cox regression models used in this setting. METHODS AND MATERIALS: For 492 bone sites in 397 patients evaluated for palliative radiation therapy (RT) for SBM from January 2007 to January 2013, data for 27 clinical variables were collected. These covariates and the primary outcome of time from consultation to death were used to build BMETS using random survival forests. We then performed Cox regressions as per 2 validated models: Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Model performance was assessed using cross-validation procedures and measured by time-dependent area under the curve (tAUC) for all 3 models. For temporal validation, a separate data set comprised of 104 bone sites treated in 85 patients in 2018 was used to estimate tAUC from BMETS. RESULTS: Median survival was 6.4 months. Variable importance was greatest for performance status, blood cell counts, recent systemic therapy type, and receipt of concurrent nonbone palliative RT. tAUC at 3, 6, and 12 months was 0.83, 0.81, and 0.81, respectively, suggesting excellent discrimination of BMETS across postconsultation time points. BMETS outperformed simpler models at each time, with respective tAUC at each time of 0.78, 0.76, and 0.74 for the C-3 model and 0.80, 0.78, and 0.77 for the W-2 model. For the temporal validation set, respective tAUC was similarly high at 0.86, 0.82, and 0.78. CONCLUSIONS: For patients with SBM, BMETS improved survival predictions versus simpler traditional models. Model performance was maintained when applied to a temporal validation set. To facilitate clinical use, we developed a web platform for data entry and display of BMETS-predicted survival probabilities.