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Background: Gender-affirming bilateral orchiectomy (GABO) may be completed as either a standalone procedure (sGABO) or at the same time as gender-affirming vaginoplasty (vGABO). GABO is postulated to decrease gender-affirming hormone therapy (GAHT) dosages and reduce gender dysphoria, but these phenomena are not empirically described in the medical literature. Aim: The primary aim of this study was to describe changes in GAHT dosages after sGABO and vGABO. A secondary aim was to assess sGABO patients' preoperative decision-making priorities and postoperative satisfaction. Methods: A retrospective chart review identified 204 patients who completed GABO as either a standalone procedure (64% of patients) or at the same time as vaginoplasty (36%). Patient demographic data, surgical outcomes, and pre- and postoperative GAHT dosage data were recorded. Patients completed an opinion questionnaire to assessed decision-making priorities, as well as postoperative satisfaction and changes in quality-of-life measures. Outcomes: Primary outcomes included pre- and postoperative dosages of estradiol, progesterone, and spironolactone. Secondary outcomes included sGABO patient priorities, satisfaction with sGABO, changes in quality-of-life measures between sGABO and vGABO patients, and sGABO recommendations to future patients. Results: The sGABO and vGABO patients experienced a statistically significant dosage reduction in all three GAHT assessed: estradiol, progesterone, and spironolactone (P < .05). All patients discontinued spironolactone postoperatively. Zero complications related to GABO were recorded for patients in either group. The patient questionnaire revealed that sGABO patients prioritize decreasing endogenous testosterone and reducing their GAHT as most important in their decision to undergo sGABO prior to vaginoplasty. A majority of sGABO patients reported improvement in all nine quality-of-life indices. None of the sGABO patients would recommend against sGABO to a friend who is waiting for vaginoplasty. Clinical Implications: For patients who are interested in vaginoplasty, sGABO may serve as a more immediate, low-risk, intermediary step that comes with the benefits of GABO, including significant GAHT medication reduction and gender dysphoria relief. Strengths and Limitations: This study offers a comprehensive evaluation of the impact of GABO on patients, combining empirical data with subjective patient feedback. Limitations include the retrospective design and the use of unvalidated survey questions. Conclusion: Prevaginoplasty GABO is a viable option to more immediately alleviate gender dysphoria and reduce GAHT medications for patients who are interested in gender-affirming vaginoplasty.

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Background: In the REST-ON clinical trial (NCT02720744), mean sleep latency on the Maintenance of Wakefulness Test (MWT) was significantly improved with extended-release once-nightly sodium oxybate (ON-SXB) vs placebo (P < 0.001) in participants with narcolepsy. This post hoc analysis assessed response to treatment and improvement in excessive daytime sleepiness. Methods: Participants with narcolepsy aged ≥16 years were randomized 1:1 to receive ON-SXB (4.5 g, week 1; 6 g, weeks 2-3; 7.5 g, weeks 3-8; and 9 g, weeks 9-13) or placebo. Mean sleep latency on the MWT was measured across 5 trials of ≤30 min each. Post hoc assessments included percentage of participants whose sleep latency improved ≥5, ≥10, ≥15, and ≥20 min and with a mean sleep latency of 30 min. Results: Significantly more participants receiving ON-SXB vs placebo experienced increased mean sleep latency ≥5 min (all doses P < 0.001), ≥10 min (all doses P < 0.001), ≥15 min (6 and 7.5 g, P < 0.001; 9 g, P < 0.01), and ≥20 min (6 g, P < 0.01; 7.5 g, P < 0.001; 9 g, P < 0.05). More participants receiving ON-SXB had mean sleep latency of 30 min vs placebo (6 g, 5.7 % vs 0 %, respectively [P < 0.05]; 7.5 g, 10.5 % vs 1.3 % [P < 0.05]; 9 g, 13.2 % vs 5.1 % [P = 0.143]). Conclusions: Significantly more participants who received ON-SXB experienced increased mean sleep latency ≥5 to ≥20 min; at the 2 highest doses, >10 % remained awake for the entirety of the MWT. ON-SXB offers a once-at-bedtime treatment option for adults with narcolepsy.

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BACKGROUND: After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to < 5 SmfD with little or no eye involvement, DEC + ivermectin + albendazole treatment a few months after ivermectin was proposed. In 2018, the US FDA approved moxidectin for treatment of O. volvulus infection. The Phase 3 study evaluated SmfD, microfilariae in the anterior chamber (mfAC) and adverse events (AEs) in ivermectin-naïve individuals with ≥ 10 SmfD after 8 mg moxidectin (n = 978) or 150 µg/kg ivermectin (n = 494) treatment. METHODS: We analyzed the data from 1463 participants with both eyes evaluated using six (0, 1-5, 6-10, 11-20, 21-40, > 40) mfAC and three pre-treatment (< 20, 20 to < 50, ≥ 50) and post-treatment (0, > 0-5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs. RESULTS: Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096-2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27-5.749 and 1.619, 95% CI 0.80-3.280, respectively). CONCLUSIONS: The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals.

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Molecular mechanisms driving the escalation of pyrethroid resistance in the major malaria mosquitoes of Central Africa remain largely uncharacterized, hindering effective management strategies. Here, resistance intensity and the molecular mechanisms driving it were investigated in a population of Anopheles coluzzii from northern Cameroon. High levels of pyrethroid and organochloride resistance were observed in An. coluzzii population, with no mortality for 1× permethrin; only 11% and 33% mortalities for 5× and 10× permethrin diagnostic concentrations, and <2% mortalities for deltamethrin and DDT, respectively. Moderate bendiocarb resistance (88% mortality) and full susceptibility to malathion were observed. Synergist bioassays with piperonyl butoxide recovered permethrin susceptibility, with mortalities increasing to 53.39%, and 87.30% for 5× and 10× permethrin, respectively, implicating P450 monooxygenases. Synergist bioassays with diethyl maleate (DEM) recovered permethrin and DDT susceptibilities (mortalities increasing to 34.75% and 14.88%, respectively), implicating glutathione S-transferases. RNA-seq-based genome-wide transcriptional analyses supported by quantitative PCR identified glutathione S-transferase, GSTe2 (RNA-seqFC = 2.93 and qRT-PCRFC = 8.4, p < 0.0043) and CYP450, CYP6Z2 (RNA-seqFC = 2.39 and qRT-PCRFC = 11.7, p < 0.0177) as the most overexpressed detoxification genes in the pyrethroid-resistant mosquitoes, compared to mosquitoes of the susceptible Ngousso colony. Other overexpressed genes include P450s, CYP6M2 (FC = 1.68, p < 0.0114), CYP4G16 (FC = 2.02, p < 0.0005), and CYP4G17 (FC = 1.86, p < 0.0276). While high frequency of the 1014F kdr mutation (50%) and low frequencies of 1014S (6.61%) and 1575Y (10.29%) were observed, no ace-1 mutation was detected in bendiocarb-resistant populations, suggesting the preeminent role of metabolic mechanism. Overexpression of metabolic resistance genes (including GSTe2 and CYP6Z2 known to confer resistance to multiple insecticides) in An. coluzzii from the Sudan Savannah of Cameroon highlights the need for alternative management strategies to reduce malaria burden in northern Cameroon.

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OBJECTIVES: The COVID-19 pandemic had a profound and pervasive impact on the health of chronic care patients and disrupted care systems worldwide. Our research aimed to assess the impact of the pandemic on chronic care provision and provide recommendations for improving care provision, based on patient experiences. DESIGN: Qualitative semi-structured interviews were held among patients with chronic obstructive pulmonary disease (COPD) or heart failure. SETTING AND PARTICIPANTS: Using stratified sampling, 23 patients with COPD, heart failure, or both were recruited to participate in semi-structured interviews. In the summer of 2021, online interviews were conducted. METHODS: An iterative process was adopted to analyze the data. Going back and forth through the data and our analytical structure, we first coded the data, and subsequently developed categories, themes, and aggregate dimensions. The data were synthesized in a data structure and a data table, which were analyzed using an interpretative approach. RESULTS: We found 3 dimensions through which care might be improved: (1) proactive and adaptive health care organization and use of innovative technologies, (2) assistance in maintaining patient resilience and coping strategies, and (3) health care built on outreaching and person-centered care enabling identification of individual patient needs. Experiences of impaired accessibility to care, altered and unmet care demands and patient needs, and the negative impact of national containment strategies on patient resilience support the need for improvement in these dimensions. CONCLUSIONS AND IMPLICATIONS: The in-depth insight gained on the impact of the pandemic on chronic care provision was used to propose recommendations for improving care, supported by not only the what and how but also the why developments require additional efforts made by policymakers and change agents, augmented by structural use and development of innovations. Health care organizations should be enabled to rapidly respond to changing internal and external environments, develop and implement innovations, and match care to patient needs.

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BACKGROUND: Transgender men (TM) seeking gender-affirming phalloplasty and transgender women (TW) seeking vaginoplasty and desiring insertive intercourse must consider penis size. Evidence has shown that, at least among cisgender men (CM), penile dimensions tend to be poorly estimated. In transgender patients desiring gender-affirming surgery, inaccuracy in estimation of penis dimensions may lead to unnecessary morbidity: for TW, trauma to the neovagina; for TM with excess girth, an inability to insert. Studies on the accuracy with which transgender and cisgender patients estimate penis size are limited. AIM: To assess the degree of accuracy with which CM and CW, as well as TM and TW, visually estimate the size of the human penis, including length, width, and girth. METHODS: There were 142 participants included (25 TM, 47 TW, 30 CM, and 40 CW; net mean ± SD age, 36.6 ± 11.2 years). Participants were shown these models and asked to estimate length, width, and midshaft girth by visual inspection of 6 realistic models of a penis and scrotum of varying lengths and widths. We evaluated the accuracy of the visual measurements by comparing mean perceived dimensions with the actual dimensions of each model. OUTCOMES: We used a multivariate model of all 3 bias dimensions to test for differences in average bias among gender groups (CM, CW, TM, and TW). RESULTS: TM significantly overestimated length across the longest models. TW significantly overestimated length in the longer 3 models. All groups except for TM significantly underestimated girth in at least 1 model. No groups significantly underestimated width. CM, CW, and TM significantly overestimated width in all 6 models. CLINICAL IMPLICATIONS: When transgender patients use numbers to express penis size (either in neophallus or vaginal depth based on perceived partner size), the result is likely to be larger than expected. Use of realistic penis models as a decision-making tool may help manage patient expectations and surgery decision making preoperatively and improve postoperative patient satisfaction and safety. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first study to assess visual estimation in penis size in TM and CM, as well as TW and CW. The penile models in our study were shown side by side and in the flaccid state despite having dimensions more consistent with an erect penis, which may have influenced estimations across all dimensions. CONCLUSION: Men and women (cisgender and transgender) tend to significantly overestimate penis length and width.

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Objective: The objectives of this study are to evaluate the prevalence and incidence of Narcolepsy type 1 and type 2 and to determine the prevalence of narcolepsy diagnosis criteria in the US general population. Methods: This longitudinal study was conducted in the adult US general population in two occasions. The initial interviews included 15 states (Arizona, California, Colorado, Florida, Idaho, Missouri, New York, North Carolina, North Dakota, Oregon, Pennsylvania, South Dakota, Texas, Washington, and Wyoming). The follow-up interviews, was done three years later in eight of these states. Of the 19,136 contacted individuals, 15,929 completed the initial interview and 10,931 completed the follow-up. Participants were interviewed using the Sleep-EVAL system, an artificial intelligence tool. Narcolepsy Type 1 (with cataplexy) and Narcolepsy Type 2 (without cataplexy) were defined according to the ICSD-3 classification. Symptoms of narcolepsy were assessed by frequency per week and duration. Medical visits and diagnoses were also collected. Results: Participants were aged between 18 and 102 years of age (mean 45.8 ± 17.9 years), 51.3 % were women. The prevalence of narcolepsy with cataplexy was 12.6 per 100,000 individuals (95 % C.I., 0 to 30) and narcolepsy without cataplexy was 25.1 per 100,000. The incidence per year was 2.6 per 100,000 individuals (95 % C.I., 0 to 11). Conclusions: Narcolepsy is a rare condition affecting 37.7/100,000 individuals (126,191 individuals in the current US population). Our US general population prevalence is in line with rates found in community-based studies but lower than what is reported in claim database studies.

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Background: Reconstructive urologists often place both a urethral and suprapubic catheter intraoperatively to prevent extravasation of undrained urine across anastomosis sutures. As no consensus exists on which catheter drains the bladder more completely, many surgeons leave one catheter to gravity drainage and cap the other postoperatively. We sought to identify differences in catheter urine outflow during dual bladder drainage with suprapubic and urethral catheters in postoperative urology patients. Methods: Urine output (UOP) from transgender men who underwent Stage II Phalloplasty with urethral lengthening was retrospectively reviewed. Both 16 French urethral and suprapubic catheters were placed to gravity drainage postoperatively. Urine output from each catheter was recorded separately, twice daily. Mixed model regression modeling tested for differences in urine output by time of day (day/night) and activity status (Bedrest: Postop Day 0-2, Ambulatory: Postop Day 3+). Results: The aggregate number of 12-hour shift urine output observations was 250 (125 for urethral and 125 for suprapubic catheters) across 14 inpatients. Suprapubic catheters had a mean 410 ml higher output than urethral catheters per 12-hour shift (p=0.002; 95% CI: 185, 636 ml). During daytime, Suprapubic catheters demonstrated higher UOP than urethral catheters per 12-hour shift (Estimated Difference: 464 ml; p=0.002; 95% CI: 211, 718 ml). During nighttime, a similar phenomenon was observed (Estimated Difference: 356 ml; p=0.009; 95% CI: 104, 606 ml). When comparing mean UOP from each catheter during the Bedrest Phase, suprapubic catheters averaged an estimated 295 ml higher UOP compared to urethral catheters per 12-hour shift with a trend toward statistical significance (p=0.052; 95% CI -3, 594 ml). During the Ambulatory Phase, mean suprapubic catheter UOP was an estimated 472 ml higher than urethral catheters per 12-hour shift (p=0.009; 95% CI 142, 802 ml). Conclusions: Simultaneous bladder drainage with urethral and suprapubic catheters shows greater drainage from the suprapubic catheter (35% vs 65%). When using two catheters, both can be placed to gravity to maximize bladder drainage as the suprapubic catheter can drain residual urine not adequately drained by the urethral catheter.

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BACKGROUND: Artificial intelligence (AI) applications have become increasingly relevant across a broad spectrum of settings in medical imaging. Due to the large amount of imaging data that is generated in oncological hybrid imaging, AI applications are desirable for lesion detection and characterization in primary staging, therapy monitoring, and recurrence detection. Given the rapid developments in machine learning (ML) and deep learning (DL) methods, the role of AI will have significant impact on the imaging workflow and will eventually improve clinical decision making and outcomes. METHODS AND RESULTS: The first part of this narrative review discusses current research with an introduction to artificial intelligence in oncological hybrid imaging and key concepts in data science. The second part reviews relevant examples with a focus on applications in oncology as well as discussion of challenges and current limitations. CONCLUSION: AI applications have the potential to leverage the diagnostic data stream with high efficiency and depth to facilitate automated lesion detection, characterization, and therapy monitoring to ultimately improve quality and efficiency throughout the medical imaging workflow. The goal is to generate reproducible, structured, quantitative diagnostic data for evidence-based therapy guidance in oncology. However, significant challenges remain regarding application development, benchmarking, and clinical implementation. KEY POINTS: · Hybrid imaging generates a large amount of multimodality medical imaging data with high complexity and depth.. · Advanced tools are required to enable fast and cost-efficient processing along the whole radiology value chain.. · AI applications promise to facilitate the assessment of oncological disease in hybrid imaging with high quality and efficiency for lesion detection, characterization, and response assessment. The goal is to generate reproducible, structured, quantitative diagnostic data for evidence-based oncological therapy guidance.. · Selected applications in three oncological entities (lung, prostate, and neuroendocrine tumors) demonstrate how AI algorithms may impact imaging-based tasks in hybrid imaging and potentially guide clinical decision making..

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Current CT oral contrast agents improve the conspicuity and confidence for bowel and peritoneal findings in many clinical scenarios, particularly for outpatient and oncologic abdominopelvic imaging. Yet, existing positive and neutral oral contrast agents may diminish the detectability of certain radiologic findings, frequently in the same scans in which the oral contrast agent improves the detectability of other findings. With ongoing improvements in CT technology, particularly multi-energy CT, opportunities are opening for new types of oral contrast agents to further improve anatomic delineation and disease detection using CT. The CT signal of new dark oral contrast agents and of new high-Z oral contrast agents promise to combine the strengths of both positive and neutral oral CT contrast agents by providing distinct CT appearances in comparison with bodily tissues, iodinated IV contrast agents, and other classes of new CT contrast agents. High-Z oral contrast agents will unlock previously inaccessible capabilities of multi-energy CT, particularly photon-counting detector CT, for differentiating simultaneously administered IV and oral contrast agents; this technique will allow generation of rich 3D, intuitive, perfectly co-registered, high-resolution image sets with individual contrast-agent "colors" that provide compelling clarity for intertwined intraabdominal anatomy and disease processes.

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Few transgender-specific cancer screening recommendations exist. This review aims to cover current guidelines and practice patterns of cancer screening in transgender patients and, where evidence-based data are lacking, to draw from cisgender screening guidelines to suggest best practices for transgender patients based on anatomic inventory. Sufficient evidence does not exist to determine the long-term effects of gender-affirming hormone therapy on cancer risk. In the future, cancer screening and prevention should be focused on anatomic inventory and high-risk behaviors.

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Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia, respectively. Local invasion, concurrent disorders, and metastases prevent surgical removal, which is the most effective treatment to date. Given the current lack of effective medical treatment, there is a need for novel therapeutic strategies. To identify druggable pathways driving PPGL development, we performed RNA sequencing on PPGLs (n = 19) and normal adrenal medullas (NAMs; n = 10) of dogs. Principal component analysis (PCA) revealed that PPGLs clearly clustered apart from NAMs. In total, 4,218 genes were differentially expressed between PPGLs and NAMs. Of these, 232 had a log2 fold change of >3 or < -3, of which 149 were upregulated in PPGLs, and 83 were downregulated. Compared with NAMs, PPGLs had increased expression of genes related to the cell cycle, tumor development, progression and metastasis, hypoxia and angiogenesis, and the Wnt signaling pathway, and decreased expression of genes related to adrenal steroidogenesis. Our data revealed several overexpressed genes that could provide targets for novel therapeutics, such as Ret Proto-Oncogene (RET), Dopamine Receptor D2 (DRD2), and Secreted Frizzled Related Protein 2 (SFRP2). Based on the PCA, PPGLs were classified into 2 groups, of which group 1 had significantly higher Ki67 scores (p = 0.035) and shorter survival times (p = 0.04) than group 2. Increased expression of 1 of the differentially expressed genes between group 1 and 2, pleiotrophin (PTN), appeared to correlate with a more aggressive tumor phenotype. This study has shed light on the transcriptomic profile of canine PPGL, yielding new insights into the pathogenesis of these tumors in dogs, and revealed potential novel targets for therapy. In addition, we identified 2 transcriptionally distinct groups of PPGLs that had significantly different survival times.

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BACKGROUND: Shallow-depth vaginoplasty (SDV), also referred to as vaginoplasty without creation of a vaginal canal, is an understudied alternative to full-depth vaginoplasty (FDV), or vaginoplasty with creation of a vaginal canal. SDV is associated with fewer short- and long-term risks and shorter recovery, and does not require a lifelong commitment to vaginal dilation and douching. AIM: To describe a surgical technique for SDV that creates a dimpled introitus, together with clinical outcomes, decision-making prioritization, and satisfaction data. We hypothesize that SDV patients prioritize comparable appearance and sexual function to FDV over shorter-term risk factors, and experience high satisfaction. METHODS: We describe (1) a surgical technique for SDV; (2) the proportion of patients who underwent SDV vs. FDV, with SDV complication rates; and (3) the results of an anonymous, electronic questionnaire administered via Qualtrics that assessed SDV patient demographics, terminology preferences, prioritization of decision-guiding factors for choosing SDV over FDV, and postoperative satisfaction across various domains. OUTCOMES: A total of 110 patients underwent primary feminizing genital gender-affirming surgery at a single institution between April 2017 and July 2022: 35 (32%) of 110 underwent SDV and 75 (68%) underwent FDV. The 35 SDV patients were invited to answer the study questionnaire, of which 29 (83%) completed it (mean age 51.9 ± 16.7 years, mean body mass index 27.3 ± 5.3 kg/m2). RESULTS: All but one survey respondent met one or more of the following characteristics: (1) ≥40 years of age, (2) exclusively feminine-identifying sexual partners, and/or (3) significant aversion to performing long-term vaginal dilation and douching. Ranking of 8 decision-guiding factors revealed prioritization of long-term over short-term outcomes. Postoperatively, patients reported high satisfaction across all 3 domains. When asked if they had to choose between SDV and FDV over again, 86% reported that they would choose SDV. While 14% would choose FDV, all but one reported new interest in receptive vaginal intercourse due to finding masculine-identifying partners post-SDV surgery. A total of 27% of SDV patients experienced complications that required additional surgeries; 82% of complications were related to urinary spraying. CLINICAL IMPLICATIONS: SDV is a lower-risk alternative to FDV and is associated with reduced postoperative maintenance and high postoperative satisfaction. STRENGTHS AND LIMITATIONS: This study describes the clinical outcomes of the largest documented cohort of patients to undergo SDV to date. Limitations include recall bias due to the retrospective survey and use of nonvalidated questions attributed to the paucity of validated gender-affirming surgery questionnaires. CONCLUSION: SDV's appeal to a large subset of patients (32% in this study), low complication rate, high satisfaction, and low decisional regret suggests that this surgical option should be offered to all patients seeking feminizing genital gender-affirming surgery.

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Feline lymphoma is currently less commonly associated with retrovirus infections as the feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). This is thought to have caused a shift in the distribution of anatomical subtypes and eventually have led to poorer treatment outcomes. The aim of this study was to evaluate whether this change was also notable in the Netherlands, a country historically known for its low prevalence of FeLV and FIV, and to determine its consequences on treatment response. A 10-year cohort of 174 cats with large cell lymphoma (110 treated) were included and compared to historical data from previously published reports in the Netherlands. Of the 90 cats screened, only one tested positive for FeLV and three for FIV. The most current cohort had an increased age (median 8.7 years) and fever Siamese cats (6.3%) compared to previous reports, with alimentary (24.5%) and nasopharyngeal lymphoma (22.7%) being the most common subtypes. Sixty-six of the one hundred and ten cats (60%) went into complete remission, (CR) resulting in a median disease-free period (DFP) of 763 days, with nasopharyngeal and mediastinal having the longest DFP. The median overall survival time was 274 days with an estimated 1-year survival of 41.3% and a 2-year survival of 34.6%, respectively. Patient characteristics of cats with malignant lymphoma in the Netherlands have changed over the years, but this cannot be explained by differences in FeLV/FIV prevalence. Although the overall response rate to therapy did not change over time, for some lymphoma subtypes, longer DFPs were observed compared to 30 years ago.

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Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA. This article is part of the theme issue 'Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

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BACKGROUND: Pseudoprogression (PsPD) is a rare response pattern to immune checkpoint inhibitor (ICI) therapy in oncology. This study aims to reveal imaging features of PsPD, and their association to other relevant findings. METHODS: Patients with PsPD who had at least three consecutive cross-sectional imaging studies at our comprehensive cancer center were retrospectively analyzed. Treatment response was assessed according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). PsPD was defined as the occurrence of immune unconfirmed progressive disease (iUPD) without follow-up confirmation. Target lesions (TL), non-target lesions (NTL), new lesions (NL) were analyzed over time. Tumor markers and immune-related adverse events (irAE) were correlated. RESULTS: Thirty-two patients were included (mean age: 66.7 ± 13.6 years, 21.9% female) with mean baseline STL of 69.7 mm ± 55.6 mm. PsPD was observed in twenty-six patients (81.3%) at FU1, and no cases occurred after FU4. Patients with iUPD exhibited the following: TL increase in twelve patients, (37.5%), NTL increase in seven patients (21.9%), NL appearance in six patients (18.8%), and combinations thereof in four patients (12.5%). The mean and maximum increase for first iUPD in sum of TL was 19.8 and 96.8 mm (+ 700.8%). The mean and maximum decrease in sum of TL between iUPD and consecutive follow-up was - 19.1 mm and - 114.8 mm (-60.9%) respectively. The mean and maximum sum of new TL at first iUPD timepoint were 7.6 and 82.0 mm respectively. In two patients (10.5%), tumor-specific serologic markers were elevated at first iUPD, while the rest were stable or decreased among the other PsPD cases (89.5%). In fourteen patients (43.8%), irAE were observed. CONCLUSIONS: PsPD occurred most frequently at FU1 after initiation of ICI treatment. The two most prevalent reasons for PsPD were TL und NTL progression, with an increase in TL diameter commonly below + 100%. In few cases, PsPD was observed even if tumor markers were rising compared to baseline. Our findings also suggest a correlation between PsPD and irAE. These findings may guide decision-making of ICI continuation in suspected PsPD.

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To investigate the feasibility and tolerability of ultrasound and microbubbles (USMB)-enhanced chemotherapy delivery for head and neck cancer, we performed a veterinary trial in feline companion animals with oral squamous cell carcinomas. Six cats were treated with a combination of bleomycin and USMB therapy three times, using the Pulse Wave Doppler mode on a clinical ultrasound system and EMA/FDA approved microbubbles. They were evaluated for adverse events, quality of life, tumour response and survival. Furthermore, tumour perfusion was monitored before and after USMB therapy using contrast-enhanced ultrasound (CEUS). USMB treatments were feasible and well tolerated. Among 5 cats treated with optimized US settings, 3 had stable disease at first, but showed disease progression 5 or 11 weeks after first treatment. One cat had progressive disease one week after the first treatment session, maintaining a stable disease thereafter. Eventually, all cats except one showed progressive disease, but each survived longer than the median overall survival time of 44 days reported in literature. CEUS performed immediately before and after USMB therapy suggested an increase in tumour perfusion based on an increase in median area under the curve (AUC) in 6 out of 12 evaluated treatment sessions. In this small hypothesis-generating study, USMB plus chemotherapy was feasible and well-tolerated in a feline companion animal model and showed potential for enhancing tumour perfusion in order to increase drug delivery. This could be a forward step toward clinical translation of USMB therapy to human patients with a clinical need for locally enhanced treatment.

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BACKGROUND AND OBJECTIVES: Bedside chest radiographs (CXRs) are challenging to interpret but important for monitoring cardiothoracic disease and invasive therapy devices in critical care and emergency medicine. Taking surrounding anatomy into account is likely to improve the diagnostic accuracy of artificial intelligence and bring its performance closer to that of a radiologist. Therefore, we aimed to develop a deep convolutional neural network for efficient automatic anatomy segmentation of bedside CXRs. METHODS: To improve the efficiency of the segmentation process, we introduced a "human-in-the-loop" segmentation workflow with an active learning approach, looking at five major anatomical structures in the chest (heart, lungs, mediastinum, trachea, and clavicles). This allowed us to decrease the time needed for segmentation by 32% and select the most complex cases to utilize human expert annotators efficiently. After annotation of 2,000 CXRs from different Level 1 medical centers at Charité - University Hospital Berlin, there was no relevant improvement in model performance, and the annotation process was stopped. A 5-layer U-ResNet was trained for 150 epochs using a combined soft Dice similarity coefficient (DSC) and cross-entropy as a loss function. DSC, Jaccard index (JI), Hausdorff distance (HD) in mm, and average symmetric surface distance (ASSD) in mm were used to assess model performance. External validation was performed using an independent external test dataset from Aachen University Hospital (n = 20). RESULTS: The final training, validation, and testing dataset consisted of 1900/50/50 segmentation masks for each anatomical structure. Our model achieved a mean DSC/JI/HD/ASSD of 0.93/0.88/32.1/5.8 for the lung, 0.92/0.86/21.65/4.85 for the mediastinum, 0.91/0.84/11.83/1.35 for the clavicles, 0.9/0.85/9.6/2.19 for the trachea, and 0.88/0.8/31.74/8.73 for the heart. Validation using the external dataset showed an overall robust performance of our algorithm. CONCLUSIONS: Using an efficient computer-aided segmentation method with active learning, our anatomy-based model achieves comparable performance to state-of-the-art approaches. Instead of only segmenting the non-overlapping portions of the organs, as previous studies did, a closer approximation to actual anatomy is achieved by segmenting along the natural anatomical borders. This novel anatomy approach could be useful for developing pathology models for accurate and quantifiable diagnosis.

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