Search

Training the next generation of global health researchers is vital for sustainable research partnerships and global health equity. The Fogarty International Center (National Institutes of Health) supports postdoctoral fellows and professional/graduate students in long-term, hands-on mentored research in low- and middle-income countries (LMICs). We surveyed 627 alumni (58% from the United States, 42% from LMICs) from three sequential Fogarty-sponsored global health research training programs (response rate: N = 257, 41%). Publications in the Index Medicus were used to ascertain scholarly output. Most alumni (63%) reported remaining engaged in LMICs and/or worked in academic/research careers (70%). Since completing their Fogarty fellowship, 144 alumni (56%) had received 438 new grants as principal investigator (PI), co-/multi-PI, or site PI. The 257 responding alumni had 5,318 publications during and since their Fogarty fellowships; 2,083 (39%) listed the Fogarty trainee as the first or senior author. These global health training programs highlight the value of LMIC research experience in nurturing the global health research workforce.

This brief report describes the rapid conversion of a randomized trial of a Hatha-based yoga program for older women with urinary incontinence to a telehealth videoconference platform during the coronavirus disease 2019 (COVID-19) pandemic. Interim results demonstrate the feasibility of recruiting and retaining participants across a wide range of ages and ethnic backgrounds, but also point to potential obstacles and safety concerns arising from telehealth-based instruction. The investigators present lessons learned about the benefits and challenges of using telehealth platforms to deliver movement-based interventions and consider strategies to promote accessible and well-tolerated telehealth-based yoga programs for older and diverse populations. Clinical Trial Registration number: NCT03672461.

Background Dogs are the reservoir host of Leishmania infantum, the agent of zoonotic visceral leishmaniasis (VL), which is transmitted by the bite of phlebotomine sand flies. The sand fly Phlebotomus perniciosus is the main vector of zoonotic VL in the western Mediterranean region. Fluralaner has been shown to effectively kill this vector. The aim of this study was to evaluate the insecticidal efficacy of oral fluralaner in dogs bitten by P. perniciosus. Methods Two parallel-group, negative-controlled, randomized, masked laboratory trials with equivalent designs were performed in two different locations using two different pathogen-free laboratory-bred P. perniciosus strains for the challenge. In each trial, 12 purpose-bred beagles, initially ranked on natural attractiveness to sand flies, were randomly allocated to two groups (6 animals/group). Dogs in one group received fluralaner orally at the approved dose on day 0, and dogs in the control group were not treated. Each dog was subsequently exposed to an average of 70 unfed live sand fly females on days 1, 28, 56 and 84. Viability of blood-fed females was then evaluated for up to 96 h after exposure, and insecticidal efficacy was measured as the survival rate of flies fed on the fluralaner-treated dogs versus that of dogs in the control group. Significance was calculated for the proportion of live fed sand fly counts from treated versus control group dogs. Results Comparison of the survival proportions between treated and control groups showed that fluralaner insecticidal efficacy was highly significant in both trials (P P P Conclusion A single oral fluralaner administration to dogs under laboratory conditions results in strong and reproducible insecticidal efficacy against P. perniciosus for at least 8 weeks. Graphical Abstract

Purpose High-quality radiotherapy (RT) planning for children and young adults with primary brain tumours is essential to minimize the risk of late treatment effects. The feasibility of using automated machine-learning (ML) to aid RT planning in this population has not previously been studied. Methods and materials We developed a ML model that identifies learned relationships between image features and expected dose in a training set of 95 patients with a primary brain tumour treated with focal radiotherapy to a dose of 54 Gy in 30 fractions. This ML method was then used to create predicted dose distributions for 15 previously-treated brain tumour patients across two institutions, as a testing set. Dosimetry to target volumes and organs-at-risk (OARs) were compared between the clinically-delivered (human-generated) plans versus the ML plans. Results The ML method was able to create deliverable plans in all 15 patients in the testing set. All ML plans were generated within 30 min of initiating planning. Planning target volume coverage with 95% of the prescription dose was attained in all plans. OAR doses were similar across most structures evaluated; mean doses to brain and left temporal lobe were lower in ML plans than manual plans (mean difference to left temporal, – 2.3 Gy, p = 0.006; mean differences to brain, – 1.3 Gy, p = 0.017), whereas mean doses to right cochlea and lenses were higher in ML plans (+ 1.6–2.2 Gy, p Conclusions Use of an automated ML method to aid RT planning for children and young adults with primary brain tumours is dosimetrically feasible and can be successfully used to create high-quality 54 Gy RT plans. Further evaluation after clinical implementation is planned.

Gay, bisexual, and other men who have sex with men (MSM) and transgender women are disproportionately affected by human papillomavirus (HPV). HPV vaccination is routinely recommended for U.S. adolescents at age 11-12years, with catch-up vaccination through age 26years. We assessed HPV vaccination coverage and associated factors among young MSM and transgender women. The Vaccine Impact in Men study enrolled MSM aged 18-26years from clinics in Seattle, Chicago, and Los Angeles, during February 2016-September 2018. Participants self-reported socio-demographic information and HPV vaccination status. Among 1416 participants, 673 (47.5%) reported ≥1 HPV vaccine dose. Among vaccinated participants, median age at first dose was 19years and median age at first sex was 17years; 493 (73.3%) reported that their age at first dose was older than their age at first sex. There were significant differences in HPV vaccination coverage by city (range 33%-62%), age, race/ethnicity, and gender identity. Coverage was highest in Seattle, where younger age was the only factor associated with vaccination. Differences in coverage by city may be due to variation in vaccination practices or enrollment at study sites. Increasing both routine and catch-up vaccination will improve coverage among MSM and transgender women.

Background: Potentiating current antidepressant treatment is much needed. Based on animal studies, caffeine may augment the effects of currently available antidepressants. Objective: Here, we tested whether habitual caffeine consumption moderates the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) using intermittent theta-burst stimulation (iTBS). Methods: Forty patients with current depressive episodes were randomized to active iTBS ( n = 19) or sham treatment ( n = 21; shielded side of the coil and weak transcutaneous electrical stimulation) delivered two times per day for 10–15 weekdays. Neuronavigated stimulation was applied to the dorsomedial prefrontal cortex. Symptom improvement was measured using change in self-reported Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pretreatment habitual caffeine consumption was quantified using self-reports of number of cups of coffee and energy drinks consumed the 2 days before the treatment starts. Results: Habitual caffeine consumption was associated with symptom improvement following active iTBS ( r = 0.51, 95% confidence interval (CI): 0.08–0.78, p = 0.025) but not following sham treatment ( r = −0.02, 95% CI: −0.45 to 0.42, p = 0.938). A multiple regression analysis corroborated the findings by showing a significant caffeine consumption × treatment group interaction (β = 0.62, p = 0.043), but no main effects of treatment group (β = 0.22, p = 0.140) or caffeine consumption (β = −0.01, p = 0.948). No group differences in pretreatment symptom scores or caffeine consumption were detected ( p values > 0.86). Conclusion: Habitual caffeine consumption moderated the antidepressant effect of dorsomedial iTBS, consistent with caffeine improving antidepressant pharmacological treatments in animals. Caffeine is an antagonist of adenosine receptors and may enhance antidepressant effects through downstream dopaminergic targets.

This study investigated the implementation status, attitudes, and practices regarding maternal pertussis vaccination in delivery facilities in Kanagawa, Japan. We conducted a questionnaire survey of pertussis vaccination during pregnancy at 125 delivery service facilities, excluding midwifery clinics, in Kanagawa Prefecture from June 18 to July 20, 2020. The questionnaire comprised multiple-choice items, with single or multiple answers depending on the question. Of the 125 facilities surveyed, valid responses were obtained from 72 facilities (58%). There were 41 primary clinics with birthing facilities (57%), 16 general hospitals (not designated perinatal centers) (22%), 10 regional perinatal centers (14%), and five tertiary perinatal centers (7%). None of the facilities administered pertussis vaccination during pregnancy. Forty facilities (56%) reported knowledge of the severity of neonatal and infant pertussis infections. Twenty-three facilities (32%) reported knowledge of the prevention of pertussis infection by vaccination during pregnancy. All facilities reported willingness to consider vaccination if included in the Japanese guidelines. In Japan, the pertussis vaccination during pregnancy is not highly practiced by obstetricians; thus, it is not as popular as in other countries. Further studies are needed to promote strategies to prevent pertussis infection in the neonatal and infant periods.

To respond to potential public health impacts of social media influencing vaccine confidence, Facebook proposed that prior to proceeding to any link about Human Papillomavirus (HPV) vaccination, a pop-up will prompt the user to visit a reputable website on vaccine information. This study explored the acceptability of a pop-up Facebook message for HPV vaccine information. A national sample of U.S. adults (n = 579) was surveyed online. Most participants rated the pop-up messages as acceptable, useful, and factual. Regression results indicated that being male, seeing HPV content on social media in the past month, believing that information on social media is credible, holding positive HPV vaccination attitudes, and having shared HPV content on their own social media were associated with greater likelihood of clicking on a pop-up. While the pop-up approach may be acceptable, there are many factors that may be associated with being less likely to click on the pop-up.

Background Some studies addressed the issue of omalizumab (OML) effectiveness in children starting their first oral immunotherapy (OIT) attempt but no study investigated the possible role of OML in the setting of patients with persisting milk allergy after a failed OIT attempt. Methods Single‐center, prospective, observational study in a selected group of patients with a persisting and severe cow milk (CM) allergy associated with moderate allergic asthma, in which a previous OIT attempt had already failed. We performed an open oral food challenge (OFC) to identify patients who tolerated less than 173 mg of cow's milk protein. At the end of the recruitment, we have found four patients with a mean age of 16.25 years (8–24) who had suspended a previous OIT attempt and still reacted to an amount of CM equal or below 173 mg. Enrolled patients, after an 8‐week course of OML along with a CM avoiding diet, underwent again an open OFC with CM to re‐evaluate their threshold. Eventually, a new OIT course was started using the same OIT protocol of the previous attempt, maintaining cotreatment with OML for the first 12 months. For each patient, we documented: the threshold of CM at OFC, level of specific immunoglobulin E (IgE) and IgG4 for milk, and quality of life (QoL). Results During OIT the four patients experienced no reactions or extremely mild ones (oral itching, transient mild abdominal pain). All increased their threshold of CM in OML if compared with the baseline and maintained it long after that biologic therapy had discontinued. Specific milk proteins IgG4 levels significantly increased in all. Conclusion In this series, OML was effective in patients with severe CM allergy who had previously failed OIT, allowing milk intake without adverse reactions and improving the QoL.

Background Common mental disorders (CMD) are among the largest contributors to global maternal morbidity and mortality. Although research on perinatal mental health in India has grown in recent years, important evidence gaps remain, especially regarding CMD. Our study aims to improve understanding of CMD among perinatal and non-perinatal women of reproductive age across two settings in India: Bangalore (Karnataka) and Tanda (Himachal Pradesh). Methods The study is embedded within the Maternal and Perinatal Health Research Collaboration India (MaatHRI). This mixed-methods observational study comprises three consecutive phases: (i) focus group discussions and individual interviews to explore women’s knowledge and seek feedback on CMD screening tools; (ii) validation of CMD screening tools; and (iii) prospective cohort study to identify CMD incidence, prevalence and risk factors among perinatal and non-perinatal women. Results of the three phases will be analyzed using inductive thematic analysis, psychometric analysis and multivariable regression analysis, respectively. Conclusion Improving understanding, detection and management of CMD among women is key to improving women’s health and promoting gender equality. This study will provide evidence of CMD screening tools for perinatal and non-perinatal women in two diverse Indian settings, produce data on CMD prevalence, incidence and risk factors and enhance understanding of the specific contribution of the perinatal state to CMD.

The dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the relative numbers and gene expression of T cells. The presence of peripheral T-cell abnormalities in PD is well-documented, but less is known about their association to clinical parameters, such as age, age of onset, progression rate or severity of the disease. We took a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of PD patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay. We show that the well-pronounced decrease in relative T-cell numbers in PD blood is mostly driven by a decrease of CD8+ cytotoxic T cells and is primarily associated with the severity of the disease. In addition, we demonstrate that the expression of inflammatory genes in T cells from PD patients is also associated with disease severity. PD T cells presented with increased activation upon stimulation with phytohemagglutinin that also correlated with disease severity. In summary, our data suggest that the consequences of disease severity account for the changes in PD T cells, rather than age, age of onset, duration or the disease progression rate.

Background The ability to track individual immune cells within the central nervous system has revolutionized our understanding of the roles that microglia and monocytes play in synaptic maintenance, plasticity, and neurodegenerative diseases. However, distinguishing between similar subpopulations of mobile immune cells over time during episodes of neuronal death and tissue remodeling has proven to be challenging. Methods We recombineered a photoconvertible fluorescent protein (Dendra2; D2) downstream of the Cx3cr1 promoter commonly used to drive expression of fluorescent markers in microglia and monocytes. Like the popular Cx3cr1–GFP line (Cx3cr1+/GFP), naïve microglia in Cx3cr1–Dendra2 mice (Cx3cr1+/D2) fluoresce green and can be noninvasively imaged in vivo throughout the CNS. In addition, individual D2-expressing cells can be photoconverted, resulting in red fluorescence, and tracked unambiguously within a field of green non-photoconverted cells for several days in vivo. Results Dendra2-expressing retinal microglia were noninvasively photoconverted in both ex vivo and in vivo conditions. Local in vivo D2 photoconversion was sufficiently robust to quantify cell subpopulations by flow cytometry, and the protein was stable enough to survive tissue processing for immunohistochemistry. Simultaneous in vivo fluorescence imaging of Dendra2 and light scattering measurements (Optical Coherence Tomography, OCT) were used to assess responses of individual microglial cells to localized neuronal damage and to identify the infiltration of monocytes from the vasculature in response to large scale neurodegeneration. Conclusions The ability to noninvasively and unambiguously track D2-expressing microglia and monocytes in vivo through space and time makes the Cx3cr1–Dendra2 mouse model a powerful new tool for disentangling the roles of distinct immune cell subpopulations in neuroinflammation. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02285-x., Key points New mouse for tracking microglia and all mononuclear phagocytes both ex and in vivo within the CNS over time.Dendra2 protein is stable enough to survive tissue processing for immunohistochemistry and flow cytometry quantification.Simultaneous fluorescence imaging of Dendra2 and light scattering measurements can be used to assess the immune response to retinal damage.Chronic in vivo imaging reveals mixed populations of microglia and monocytes during retinal degeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02285-x.

Background It has been demonstrated that children who had been breastfed remain better protected against various infections, and notably respiratory tract infections, well beyond infancy. Since the role of breastfeeding to explain why children are less affected by COVID-19 has not been studied until now, the aim of this study was to determine whether any history of breastfeeding reduces the incidence rate of COVID-19 in children. Methods This was a secondary analysis of an observational study on clinical and epidemiological characteristics of pediatric COVID-19 in Majorca. A total of 691 children were recruited during the 5 months of August–December 2020. Eligible participants were children under 14 who were tested for SARS-CoV-2 in pediatric emergency services. The independent explanatory variable was any breastfeeding. Bivariate analyses were conducted through the Chi-square test, the Fisher’s Exact test or the Student’s T test. All children had the same demographic, epidemiological and clinical data collected through a study team member interview and via the participants medical records. Results Within the sample of children who visited emergency services with symptoms of potential COVID-19, we found higher prevalence of positive SARS-CoV-2 RT-PCR test results among those who were exclusively formula fed compared with those who were ever breastfed (OR 2.48; 95% CI 1.45, 3.51; P = 0.036). Conclusions The present study suggests that ever breastfeeding reduces the risk of COVID-19 among children, as documented for other infections.

Background Immunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD). Methods Dogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC Results Of the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ2 = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ2 = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ2 = 9.56, df = 2, P = 0.008), globulins (χ2 = 11.08, df = 3, P = 0.011) and gamma globulins (χ2 = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ2 = 16.7, df = 3, P = 0.001), but not in big ET-1 (χ2 = 2.04, df = 3, P = 0.563). Conclusions This study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD. Graphical abstract

Concerns were raised about HPV vaccination possibly leading to riskier sexual behavior. We assessed sexual behaviors, risk of sexually transmitted infection, and attendance to cervical cancer screening by HPV vaccinated and unvaccinated young women. In this analysis, 1475 questionnaires completed by women aged 17–29 years were included. The majority of respondents (67.9%) were vaccinated against HPV. The proportion of those vaccinated decreased with age: from 93.2% in those aged 17–19 to 72.9% in those aged 20–22, and 21.8% in 23–29-year olds. A higher proportion of unvaccinated respondents had at least one sexual intercourse under the age of 15 when compared to those vaccinated (30% vs. 23%, p

Sickle cell trait (SCT) carriers inherit one copy of the Glu6Val mutation in the hemoglobin gene and is particularly common in Black individuals (5–10%). Considering the roles of hemoglobin in immune responses and the higher risk for coronavirus disease (COVID-19) among Black individuals, we tested whether Black SCT carriers were at increased risk for COVID-19 infection and mortality according to the United Kingdom Biobank. Among Black individuals who were tested for COVID-19, we found similar infection rates among SCT carriers (14/72; 19.7%) and noncarriers (167/791; 21.1%), but higher COVID-19 mortality rates among SCT carriers (4/14; 28.6%) than among noncarriers (21/167; 12.6%) (odds ratio [OR], 3.04; 95% confidence interval [CI], 0.69–11.82; P = 0.12). Notably, SCT carriers with preexisting diabetes had significantly higher COVID-19 mortality (4/4; 100%) than those without diabetes (0/10; 0%; (OR, 90.71; 95% CI, 5.66–infinite; P = 0.0005). These findings suggest that Black SCT carriers with preexisting diabetes are at disproportionally higher risk for COVID-19 mortality. Confirmation by larger studies is warranted.

SummaryBackground. The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Method and patients. Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local–regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). Results. All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60 Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0–42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7–34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 months, p = 0.020) and eMFS (8.1 months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8 months (p Conclusion. In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm.

Summary Chronic active Epstein–Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV+ haematological clones that are lost on successful treatment.

This study aimed to show the proportion of fundus examinations in patients with diabetes who were scheduled for surgery. We retrospectively analyzed 455 consecutive patients with diabetes admitted for surgery. Just 49% had fundus examinations before hospitalization. The decision tree analysis showed that the type of family doctor was the first split associated with fundus examination; patients treated by a diabetes specialist were more likely to receive the examination. In this subgroup, glycated hemoglobin levels ≥8.0% and age ≥71 years were associated with a lower proportion of receiving the examination. In patients whose family doctor was not a diabetes specialist, glycated hemoglobin levels, We investigated the proportion of fundus examinations in patients with diabetes scheduled for surgery. Only approximately half of these patients had fundus examination. Clinical variables associated with receiving the examination were not identical between diabetes specialists and non‐specialists.

Background Anaplasma platys is a tick-borne bacterium which infects blood platelets of dogs, causing canine cyclic thrombocytopenia. The disease is distributed worldwide, particularly in the tropics and subtropics, but information on the epidemiology of A. platys infection in dogs is fragmentary in many countries, including Egypt. In this study, we investigated the prevalence and risk factors associated with A. platys infection in dogs from Egypt. Methods A conventional PCR targeting a fragment of the 16S rRNA gene of A. platys was used to screen 500 dogs from five North Egyptian governorates. DNA sequencing and phylogenetic analysis were performed for one of the positive samples. Results The overall prevalence of A. platys in the studied dogs was 6.4%. Females of the German shepherd breed without veterinary care had higher odds for A. platys positivity. High tick infestation and lack of anti-tick treatment were also identified as risk factors for A. platys infection. Phylogenetic analysis revealed that the sequence obtained herein was closely related to sequences from Egypt, South Africa and Uruguay. Conclusions This is the first large-scale epidemiological study of A. platys in Egypt, where female German shepherd dogs without veterinary care, as well as dogs with high tick infestation and without anti-tick treatment are at a higher risk of infection. Graphical abstract

The present retrospective study aimed to identify factors associated with an increased risk of acute kidney injury in Japanese patients with type 2 diabetes treated with sodium–glucose cotransporter 2 inhibitors. We identified 171,622 patients with type 2 diabetes treated with sodium–glucose cotransporter 2 inhibitors; among them, 476 (0.3%) patients developed acute kidney injury. The hazard ratio for acute kidney injury occurrence risk was analyzed using a Cox proportional hazards model adjusted for patient characteristics at baseline and use of concomitant agents. In the adjusted model, patients who developed acute kidney injury were mostly men, aged ≥65 years, had lower body mass index, had a history of heart failure and used diuretics more frequently than those who did not. These findings suggest that associated clinical risk factors should be thoroughly evaluated before administering sodium–glucose cotransporter 2 inhibitors to minimize acute kidney injury onset., BLURB FOR ETOC: AKI risk associated with SGLT2 inhibitors

Summary We aimed at molecularly dissecting the anatomical heterogeneity of small lymphocytic lymphoma (SLL), by analysing a cohort of 12 patients for whom paired DNA from a lymph node biopsy and circulating cells, as well as plasma‐circulating tumour DNA (ctDNA) was available. Notably, the analyses of the lymph node biopsy and of circulating cells complement each other since a fraction of mutations (20·4% and 36·4%, respectively) are unique to each compartment. Plasma ctDNA identified two additional unique mutations. Consistently, the different synchronous sources of tumour DNA complement each other in informing on driver gene mutations in SLL harbouring potential prognostic and/or predictive value.

SummaryParaneoplastic neurologic syndromes(PNSs) caused by immune checkpoint inhibitors(ICIs) is rare and requires clinicians to differentiate between disease progression and immune-related adverse effects(irAEs). We hereby report the case of immune-related myelitis accompanied by positive paraneoplastic autoantibodies following durvalumab treatment for extensive-stage small cell lung cancer (ES-SCLC). A 70-year-old Chinese woman with ES-SCLC was administered durvalumab with etoposid-platinum(EP) as first-line treatment. Four cycles after treatment with EP plus ICI, she developed immune-related myelitis with positive paraneoplastic autoantibodies (CV2, SOX1, ZIC4). Spinal MRI showed diffuse abnormal signal shadow in the cervicothoracic spinal cord. She was discontinued for chemotherapy, and treated with high-dose steroids, intravenous immunoglobulin and plasmapheresis, maintenance therapy with steroids resulted in a favorable neurologic outcome. This is the first report of durvalumab-related PNSs. We supposed that the development of paraneoplastic myelitis was causally related to immune activation by durvalumab. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of paraneoplastic myelitis.

Introduction Diagnosis and treatment of obstructive sleep apnea (OSA) in children is often delayed due to the high prevalence and limited physician and sleep testing resources. As a result, children may be referred to multiple specialties, such as pediatric sleep medicine and pediatric otolaryngology, resulting in long waitlists. Method We used data from our pediatric OSA clinic to identify predictors of tonsillectomy and/or adenoidectomy (AT). Before being seen in the clinic, parents completed the Pediatric Sleep Questionnaire (PSQ) and screening questionnaires for restless leg syndrome (RLS), nasal rhinitis, and gastroesophageal reflux disease (GERD). Tonsil size data were obtained from patient charts and graded using the Brodsky-five grade scale. Children completed an overnight oximetry study before being seen in the clinic, and a McGill oximetry score (MOS) was assigned based on the number and depth of oxygen desaturations. Logistic regression, controlling for otolaryngology physician, was used to identify significant predictors of AT. Three triage algorithms were subsequently generated based on the univariate and multivariate results to predict AT. Results From the OSA cohort, there were 469 eligible children (47% female, mean age = 8.19 years, SD = 3.59), with 89% of children reported snoring. Significant predictors of AT in univariate analysis included tonsil size and four PSQ questions, (1) struggles to breathe at night, (2) apneas, (3) daytime mouth breathing, and (4) AM dry mouth. The first triage algorithm, only using the four PSQ questions, had an odds ratio (OR) of 4.02 for predicting AT (sensitivity = 0.28, specificity = 0.91). Using only tonsil size, the second algorithm had an OR to predict AT of 9.11 (sensitivity = 0.72, specificity = 0.78). The third algorithm, where MOS was used to stratify risk for AT among those children with 2+ tonsils, had the same OR, sensitivity, and specificity as the tonsil-only algorithm. Conclusion Tonsil size was the strongest predictor of AT, while oximetry helped stratify individual risk for AT. We recommend that referral letters for snoring children include graded tonsil size to aid in the triage based on our findings. Children with 2+ tonsil sizes should be triaged to otolaryngology, while the remainder should be referred to a pediatric sleep specialist. Graphical abstract

Summary Autoimmune disease is a risk factor for first incident venous thromboembolism (VTE). However, data on the risk of recurrent VTE in people with autoimmune disease is sparse. We explored the risk of recurrent VTE using the RIETE registry, comparing people with autoimmune disease (n = 1305) to those without (n = 50608). Overall rates were 6.5 and 5.1 recurrent VTE/100 years for patients with autoimmune disease vs controls, respectively. After adjustment for sex and unprovoked/provoked VTE yielded an adjusted hazard ratio of 1.29 (95%CI 1.03‐1.62). The analysis was limited by short median follow up time (161 days overall), precluding definitive conclusions on recurrent VTE risks.

Summary The impact of COVID‐19 infection on pregnant women remains relatively unknown but the physiological changes of pregnancy and hypercoagulability of COVID‐19 may further increase thrombotic risk. In this retrospective multicentre observational study, we report clinical characteristics and outcomes in 36 pregnant women requiring hospitalisation for COVID‐19 compared to a propensity‐matched cohort of non‐pregnant women. Pregnant women had a lower haemoglobin and higher lymphocyte counts but no differences in other haematological or biochemical parameters on admission compared to non‐pregnant women. There was no significant difference in the duration of hospitalisation; median two days (1–77) for pregnant versus eight days (1–49) for non‐pregnant women. A higher proportion of non‐pregnant women required mechanical ventilation [11/36 (31%) vs 3/36 (8%), P = 0·03] and received thromboprophylaxis with low‐molecular‐weight heparin (LMWH) within 24 h of admission [25/36 (69%) vs 15 /36(42%), P = 0·03] compared to pregnant women. One pregnant woman required extracorporeal membrane oxygenation. The rate of thrombosis was similar in both groups (one in each group). No women developed major bleeding or died. Data suggest that although non‐pregnant women had a severe clinical course, overall outcomes were not different between women with or without pregnancy. The use of thromboprophylaxis was inconsistent, demonstrating a need for establishing evidence‐based guidance for COVID‐19 during pregnancy.

Rubella is a contagious disease caused by rubella virus leading to adverse outcomes among pregnant women including abortions, low birth weight, stillbirths and congenital rubella syndrome (CRS) in the baby. If not pregnant, the clinical manifestations are mild and self-limiting. In this hospital based cross-sectional study, 1985 blood samples were collected from females attending outpatient services of various hospitals to serologically detect Rubella infection. Rubella antibodies namely Immunoglobulin M (IgM)/Immunoglobulin G (IgG) were detected through enzyme linked immunosorbent assay (ELISA) or by identifying virus through polymerase chain reaction (PCR). From the total enrolled participants, 1951 samples were tested with age ranging from 16 to 38 years. Among the positive samples, about 60% patients had IgG antibodies as compared to less than 1% IgM and 0.40% by PCR. Out of 1951 samples, 7/849 (0.82%) and 651/1070 (60.8%) had IgM & IgG rubella antibodies respectively. The odds of having abortion was [OR-13.14 (4.94–34.97)] among anti-rubella positive and primi-gravida [OR-43.6 (5.9–322)] women. Therefore, vaccination of women against rubella before planning of pregnancy or at adolescence seems to be the need of hour to avoid the ill consequences during pregnancy as well as for the new born baby.

Summary Background There is a need to establish an effective neoadjuvant therapy for soft tissue sarcomas (STSs). We previously showed that apatinib, administered in combination with doxorubicin-based chemotherapy, improves the efficacy of treatment. This study aimed to clarify the effectiveness and safety of apatinib combined with doxorubicin and ifosfamide (AI) neoadjuvant chemotherapy for STSs. Methods This retrospective study included patients with STS who received neoadjuvant therapy and surgery between January 2016 and January 2019. The patients were divided into two treatment groups: AI + apatinib group and AI group (doxorubicin + ifosfamide). Results The study included 74 patients (AI + apatinib: 26, AI: 48) with STS. There were significant between-group differences in objective response rates (53.85% vs. 29.17%, p = 0.047) and the average change in target lesion size from baseline (-40.46 ± 40.30 vs. -16.31 ± 34.32, p = 0.008). The R0 rate (84.62% vs. 68.75%; p = 0.170) and 2-year disease-free survival (73.08% vs. 62.50%, p = 0.343) were similar across groups. Finally, the rates of neoadjuvant therapy-related adverse effects and postoperative complications were similar in both groups (p > 0.05). Conclusion Apatinib plus doxorubicin and ifosfamide regimen is safe and effective as neoadjuvant therapy for patients with STS. However, the significantly improved preoperative ORR observed after neoadjuvant therapy did not translate into a significantly improved R0 rate and 2-year DFS. Prospective, well-powered studies are warranted to determine the long-term efficacy and optimal application of these protocols.

Following a rubella outbreak in 2011, Vietnam implemented a mass measles-rubella vaccination campaign for children aged 1–14 years in 2014–2015, further expanding the target age to 16–17 years in 2016; routine vaccination was introduced in 2014. However, there was concern that a substantial proportion of women of child-bearing age were still susceptible to rubella, with the fear of congenital rubella emergence. Thus, we conducted a prospective cohort study in Nha Trang, Vietnam, from 2017–2018 to investigate pregnant women’s susceptibility to rubella infection, the incidence of congenital rubella infection, and factors associated with susceptibility. Cord blood was tested for rubella-specific immunoglobulin M (IgM) and IgG; neonatal saliva and cord blood specimens were examined for rubella-RNA. We analyzed 2013 mother-baby pairs. No baby was rubella-IgM or rubella-RNA positive. Overall, 20.4% of mothers were seronegative (95% confidence interval, 18.6%–22.1%). The seronegativity was significantly low among mothers aged

Data are needed on the acceptability of Covid-19 vaccination among young, low-income, diverse populations. To assess this, we surveyed 18-45-year-old women on their intent to be vaccinated, experiences with Covid-19, and uptake of other vaccines. Among the 342 who completed the survey, only one-third were likely to accept the Covid-19 vaccine as soon as it was available. Less than half would accept it even if recommended by their doctor. Most (69%) wanted more information on its safety and 48% wanted proof it works. Likelihood of accepting the vaccine with a doctor's recommendation was associated with fear of catching Covid-19 and exposure to social media as well as HPV and annual flu vaccination. This demonstrates it will be necessary to help vaccine-hesitant individuals overcome their concerns to reach herd immunity in the US. Physician recommendation and social media may play important roles.

Summary Background Mortality data of non-critically ill patients presenting with symptomatic atrial fibrillation to an emergency department are scarce. We aimed to analyze the short-term mortality of these patients compared with that of the general Austrian population. Design/methods This study analyzed a consecutive series of non-critically ill adults presenting to the emergency department at the Medical University of Vienna between 2012 and 2016 with complaints related to atrial fibrillation. The study outcome was mortality during the observation period. Age-specific and sex-specific mortality rates per 100 person-years were calculated and compared with the mortality rates of the Austrian population during the same period. Results In total, 1754 patients with atrial fibrillation (43.1% female) were included in the study. During a median follow-up of 25 months, 248 of these patients died. Observed mortality rates were 7.8 per 100 person-years for females (95% confidence interval, CI 6.6–9.5) and 5.9 per 100 person-years for males (95% CI 5.0–7.1). Age-adjusted and sex-adjusted mortality rates were 2.8 (95% CI 2.3–3.3) and 2.7 (95% CI 2.2–3.2) per 100 person-years, respectively. Mortality rates for the Austrian population were 1.1 per 100 person-years for both females and males. Corresponding standardized mortality ratios were 2.5 for females (95% CI 2.1–3.0) and 2.4 for males (95% CI 2.0–2.9). Conclusion The short-term mortality of patients with symptomatic atrial fibrillation presenting to the emergency department was substantially higher compared with the general Austrian population.

© The Authors., Given its myeloid-restricted expression, myeloperoxidase (MPO) is typically used for lineage assignment (myeloid vs. lymphoid) during acute leukaemia (AL) diagnostics. In the present study, a robust flow cytometric definition for MPO positivity was established based on the standardised EuroFlow protocols, the standardised Acute Leukaemia Orientation Tube and 1734 multicentre AL cases (with confirmed assay stability). The best diagnostic performance was achieved by defining MPO positivity as ≥20% of the AL cells exceeding a lymphocyte-based threshold. The methodology employed should be applicable to any form of standardised flow cytometry., The co-ordination of this study was supported by the EuroFlow Consortium. The EuroFlow Consortium received support from the FP6-2004-LIFESCIHEALTH-5 programme of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for Hemato-Oncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA).

Transovarial transmission (TOT) of dengue virus (DENV) in Aedes spp. is an important mechanism for DENV maintenance in nature and may be important in initiating outbreaks. The objective of this study was to explore the occurrence of TOT in wild Aedes albopictus populations in Cuba. Mosquito larvae were collected in Cotorro municipality, Havana, Cuba, and identified to species. Fifteen pools of Ae. albopictus each containing 30 larvae were processed for DENV detection by using conventional reverse transcription polymerase chain reaction (RT-PCR) and nested PCR. Four out of 15 pools processed were positive for DENV-3, but no other DENV serotype was detected. This is the first time TOT of DENV detected in Cuban field populations of Ae. albopictus, and this suggests that this species may be an important vector of DENV in Cuba.

This study examined whether future COVID-19 vaccine acceptance differed based on an experimental manipulation of the vaccine safety and effectiveness profile. Data come from the Detroit Metro Area Community Study, a population-based study conducted July 15–20, 2020. Participants were asked whether they would get a new COVID-19 vaccine after being randomly assigned information about the vaccine’s effectiveness (50% or 95%) and chance of fever (5% or 20%). Among 1,117 Detroiters, 51.3% would accept a COVID-19 vaccine that is 50% effective and 77.1% would accept a vaccine that is 95% effective. Women and adults ≥65 were more accepting of a vaccine; Black Detroiters were less accepting. Believing vaccines to be important, effective, and safe was associated with higher acceptance. Uptake of a COVID-19 may be limited, depending on perceived vaccine effectiveness and general attitudes toward vaccines. Public health approaches to modifying these attitudes will be especially important in the Black community.

Background Since the onset of the COVID-19 pandemic in December 2019, many countries around the world have imposed lockdown measures in order to reduce virus spread. Social isolation is known to have a significant psychological impact, potentially triggering alcohol misuse in adults. In our study, we aimed to investigate the effect of COVID-19 lockdown measures on alcohol consumption in adults in Bavaria. Methods In this cross-sectional study, we enrolled 2067 participants, with 1961 young adults (mean age 23.3 ± 4.1) and 106 mature adults (mean age 66.7 ± 9.7). Participants were asked to complete a standardized questionnaire, semi-quantitatively evaluating the alcohol drinking behaviour before and during the pandemic lockdown. Results After implementation of lockdown, the alteration of alcohol consumption was significantly different between young and mature adults (p 0 to p Conclusion The COVID-19 pandemic lockdown significantly affected alcohol drinking behaviour. Further studies exploring long-term effects on potential alcohol misuse and the relevance on public health are warranted. Trial registration The study was retrospectively registered at ClinicalTrials.gov (NCT04361877) on April 24, 2020.

Summary Splicing factor 3B subunit 1 (SF3B1) mutations define a distinct myelodysplastic syndromes (MDS) patient group with a relatively favourable disease course and high response rates to luspatercept. Few data are available on bone marrow phenotype beyond ring sideroblasts in this subgroup of patients with MDS. In the present study, we identified immunophenotypic erythroid, myelomonocyte and progenitor features associated with SF3B1 mutations. In addition, we illustrate that SF3B1‐mutation type is associated with distinct immunophenotypic features, and show the impact of co‐occurrence of a SF3B1 mutation and a deletion of chromosome 5q on bone marrow immunophenotype. These genotype–phenotype associations and phenotypic subtypes within SF3B1‐MDS provide leads that may further refine prognostication and therapeutic strategies for this particular MDS subgroup.

SummaryBackground Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC.

This open-label, single-center, Phase 3 study (NCT03546842) assessed the immunogenicity and safety of the nine-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine in Vietnamese males and females, with the aim to support 9vHPV vaccine licensure in Vietnam. Participants aged 9–26 years received three 9vHPV vaccine doses (Day 1, Month 2, Month 6). Serum samples were obtained on Day 1 (pre-vaccination) and at Month 7 (one month post-Dose 3) for the measurement of anti-HPV antibodies. Geometric mean titers (GMTs) and seroconversion percentages were obtained using the HPV-9 competitive Luminex immunoassay. Injection-site adverse events (AEs), systemic AEs, serious AEs (SAEs), and study discontinuations due to AEs were recorded. Of 201 participants enrolled, 200 (99.5%) received ≥1 vaccine dose. All participants who received the three-dose regimen (198/200, 98.5%) seroconverted for all 9vHPV vaccine types by Month 7. Robust anti-HPV GMT responses were also observed. Half of participants (50.5%) reported ≥1 AE; the majority were injection-site-related (45.0%) and mild (43.0%). There were no deaths, vaccine-related SAEs, or discontinuations due to AEs. Administration of three 9vHPV vaccine doses was highly immunogenic and resulted in acceptable seropositivity percentages for all vaccine HPV types. The 9vHPV vaccine was generally well tolerated among this study population. Region of origin: Vietnam Trial registration: clinicaltrials.gov Identifier NCT03546842

SummaryThe aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in unresectable stage, locally advanced non-small cell lung cancer (NSCLC). All consecutive patients with unresectable, locally advanced NSCLC and PD-L1 expression (≥1%) treated after October 2018 were included. Regular follow up, including physical examination, PET/CT and/or contrast-enhanced CT-Thorax/Abdomen were performed every three months after CRT. Descriptive treatment pattern analyses, including reasons of discontinuation and salvage treatment, were undertaken. Statistics were calculated from the last day of thoracic irradiation (TRT). Twenty-six patients were included. Median follow up achieved 20.6 months (range: 1.9–30.6). Durvalumab was initiated after a median of 25 (range: 13–103) days after completion of CRT. In median 14 (range: 2–24) cycles of durvalumab were applied within 6.4 (range 1–12.7) months. Six patients (23%) are still in treatment and seven (27%) have completed treatment with 24 cycles. Maintenance treatment was discontinued in 13 (50%) patients: 4 (15%) patients developed grade 3 pneumonitis according to CTCAE v5 after a median of 3.9 (range: 0.5–11.6) months and 7 (range: 2–17) cycles of durvalumab. Four (15%) patients developed grade 2 skin toxicity. One (4%) patient has discontinued treatment due to incompliance. Six and 12- month progression-free survival (PFS) rates were 82% and 62%, median PFS was not reached. No case of hyperprogression was documented. Eight (31%) patients have relapsed during maintenance treatment after a median of 4.8 (range: 2.2–11.3) months and 11 (range: 6–17) durvalumab cycles. Two patients (9%) developed a local-regional recurrence after 14 and 17 cycles of durvalumab. Extracranial distant metastases and brain metastases as first site of failure were detected in 4 (15%) and 2 (8%) patients, respectively. Three (13%) patients presented with symptomatic relapse. Our prospective study confirmed a favourable safety profile of durvalumab maintenance treatment after completion of CRT in unresectable stage, locally advanced NSCLC in a real-world setting. In a median follow-up time of 20.6 months, durvalumab was discontinued in 27% of all patients due to progressive disease. All patients with progressive disease were eligible for second-line treatment.

To clarify the association between lifestyle changes as a result of coronavirus disease 2019 containment measures and changes in metabolic and glycemic status in patients with diabetes, a cross‐sectional, single‐center, observation study was carried out. A self‐reported questionnaire was provided to ascertain the frequency of various lifestyle activities before and after the coronavirus disease 2019 containment measures in Japan. Among 463 patients, change in glycated hemoglobin was significantly associated with change in bodyweight. After stratification by age 65 years, binary logistic regression analysis showed that increased frequency of snack eating increased bodyweight (odds ratio 1.709, P = 0.007) and glycated hemoglobin (odds ratio 1.420, P = 0.025) in the younger group, whereas in the older patients, reduced walking activities resulted in weight gain (odds ratio 0.726, P = 0.010). In conclusion, changes in eating behavior and physical activity increased bodyweight and reduced glycemic control among diabetes patients, but by different processes depending on age under the coronavirus disease 2019 containment measures in Japan., We investigated lifestyle changes during the coronavirus disease 2019 containment measures, and its relationship with glycemic control and body weight change.

Background: In recent years, there has been significant research on the mental health effects of classic psychedelic use, but there is very little evidence on how classic psychedelics might influence physical health. Aims: The purpose of the present study was to investigate the associations between lifetime classic psychedelic use and markers of physical health. Methods: Using data from the National Survey on Drug Use and Health (2015-2018) with 171,766 (unweighted) adults aged 18 or above in the United States, the current study examined the associations between lifetime classic psychedelic use and three markers of physical health (self-reported overall health, body mass index, and heart condition and/or cancer in the past 12 months) while controlling for a range of covariates. Results: Respondents who reported having tried a classic psychedelic at least once in their lifetime had significantly higher odds of greater self-reported overall health and significantly lower odds of being overweight or obese versus having a normal weight. The association between lifetime classic psychedelic use and having a heart condition and/or cancer in the past 12 months approached conventional levels of significance, with lower odds of having a heart condition and/or cancer in the past 12 months for respondents who had tried a classic psychedelic at least once. Conclusion: The results of the present study suggest that classic psychedelics may be beneficial to physical health. Future research should investigate the causal effects of classic psychedelics on physical health and evaluate possible mechanisms.

Background The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient’s isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens. Methods We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT. Results We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG. Conclusion Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.

Purpose: The purpose of this study was to determine the prevalence and correlates of nonprescription hormone use among Brazilian trans women. Methods: This study is a cross-sectional survey of trans women in São Paulo, Brazil, recruited by respondent-driven sampling in 2017–2019. Results: Of 790 trans women, 36.8% were taking nonprescribed hormones. Nonprescribed hormone use was higher with younger age, lower education, homelessness, and using estrogen plus progesterone. Lower use was associated with accessing health care and having trans-specific health needs met. Conclusion: Marginalized Brazilian trans women exhibit high use of nonprescription hormones, which may have health consequences and requires further examination and research.

Background Among Dermanyssoidea, the chicken red mite (Dermanyssus gallinae) and the northern fowl mite (Ornithonyssus sylviarum) are considered to be the cause of high economic losses endured by the poultry industry in the Holarctic region, with O. sylviarum predominating in North America and D. gallinae in Europe. Both species have a short life-cycle (thereby allowing a rapid build-up of massive infestations), a wide range of hosts, synanthropic presence and the ability to bite humans. The aim of this study was to analyze dermanyssoid mite specimens, collected in two human dwellings and two racing pigeon premises in different urban areas in Hungary, with molecular–phylogenetic methods. Methods Mite species were identified morphologically. This was followed by DNA extraction and molecular–phylogenetic analyses of selected mites, based on the cytochrome c oxidase subunit I (cox1) and 28S rRNA (28S) genes. Results Mites that had invaded a home from a pigeon nest and were linked to human dermatitis were morphologically and molecularly identified as D. gallinae special lineage L1. Specimens collected at all other sampling sites were identified as O. sylviarum, including mites that had invaded a home from a house martin (Delichon urbicum) nest, as well as those which were collected from racing pigeons. House martin- or pigeon-associated O. sylviarum specimens showed the highest sequence identity and closest phylogenetic relationship with conspecific mites reported in GenBank from Israel or Canada, respectively. Conclusions Detailed morphological and molecular–phylogenetic analyses of D. gallinae lineage L1 confirmed its status as a cryptic species within D. gallinae (s.l.). Taking into account the well-documented latitudinal migratory routes of house martins between Hungary and Africa, O. sylviarum associated with this bird species most likely arrived on its host from the eastern Mediterranean region. On the other hand, mites collected from pigeons in Hungary showed cox1 genetic homogeneity with North American O. sylviarum, which can only be explained by a long-distance (west-to-east intercontinental) connection of birds and their mites as part of human activity (e.g. transportation to exhibitions or trading). In summary, this is the first molecularly confirmed and phylogenetically analyzed case of O. sylviarum infestation of birds in Hungary, implicating urban environment and involving distant parts of the country. This is also the first report of D. gallinae lineage L1 in central Europe. Graphical Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem condition associated with uncontrolled overproduction and infiltration of lymphocytes and histiocytes predominantly in liver, lymph nodes, spleen, and central nervous system. Neuroimaging findings on MRI are fairly nonspecific and classically include periventricular white matter signal abnormalities and diffuse atrophy. Focal parenchymal lesions may demonstrate post contrast ring or nodular enhancement and calcification. However, the MR imaging characteristics can be highly variable. Here, we present two cases of HLH in infants with multiple hemorrhagic lesions mostly depicted in both thalami and basal ganglia regions. Thalamic, basal ganglia, and brain stem involvement with hemorrhagic changes in HLH are rarely described in literature. Early diagnosis of HLH may be lifesaving. Awareness of the disease is necessary to investigate its characteristic findings and avoiding a delay in diagnosis.

Background The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS. Methods Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23–75 years from the Generations Study. Results The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio (E/O) at the highest risk decile :0.97 (95 % CI 0.51 − 1.86) for women younger than 50 years and 1.09 (0.66 − 1.80) for women 50 years or older. Adding reproductive/lifestyle factors and PRS to the BOADICEA model improved discrimination modestly in younger women (area under the curve (AUC) 69.7 % vs. 69.1%) and substantially in older women (AUC 64.6 % vs. 56.8%). The Tyrer-Cuzick model with PRS showed evidence of overestimation at the highest risk decile: E/O = 1.54(0.81 − 2.92) for younger and 1.73 (1.03 − 2.90) for older women. Conclusion The extended BOADICEA model identified women in a European-ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. With the increasing availability of PRS, these analyses can inform choice of risk models incorporating PRS for risk stratified breast cancer prevention among women of European ancestry.

Hip-fracture patients are vulnerable to the outcomes of COVID-19. We performed a cross-sectional survey to determine measures employed to limit nosocomial spread of COVID-19 in 23 orthopaedic trauma departments in the North-West of England. Nineteen (87%) hospitals admitted patients to a ward prior to a negative swab, and only 9 (39%) patients were barrier nursed. Hip-fracture patients were operated in non-COVID-19-free theatres in 21 (91%) hospitals. Regular screening of doctors working in trauma and elective areas for COVID-19 was undertaken in three (13%) and five (22%) hospitals, respectively. Doctors moved freely between trauma and elective areas in 22 (96%) hospitals.

Previous studies using additive genetic models failed to identify robust evidence of associations between colorectal cancer (CRC) risk variants and survival outcomes. However, additive models can be prone to false negative detection if the underlying inheritance mode is recessive. Here, we tested all currently known CRC-risk variants (n = 129) in a discovery analysis of 5675 patients from a Scottish cohort. Significant associations were then validated in 2474 CRC cases from UK Biobank. We found that the TT genotype of the intron variant rs7495132 in the CRTC3 gene was associated with clinically relevant poorer CRC-specific survival in both the discovery (HR = 1.97, 95% CI = 1.41-2.74, P = 6.1x10-5 ) and validation analysis (HR = 1.69, 95% CI = 1.03-2.79, P = 0.038). In addition, the GG genotype of rs10161980 (intronic variant of AL139383.1 lncRNA) was associated with worse overall survival in the discovery cohort (HR = 1.24, 95% CI = 1.10-1.39, P = 3.4x10-4 ) and CRC-specific survival in the validation cohort (HR = 1.26, 95% CI = 1.01-1.56, P = 0.040). Our findings show that common genetic risk factors can also influence CRC survival outcome. This article is protected by copyright. All rights reserved.

We aimed to determine mortality risk in underweight patients with diabetic nephropathy for microalbuminuria or macroalbuminuria. We analyzed mortality and death‐cause data from BioBank Japan, with baseline years 2003–2007. We analyzed mortality rates from all causes and ischemic heart disease, according to body mass index (, Comparison of mortality by body mass index categories among Japanese patients with diabetic nephropathy for microalbuminuria and macroalbuminuria. Body mass index for

Background Ticks are hematophagous arthropods which normally attach to the surface of the host’s skin. Their aberrant presence in the subcutaneous tissue of a few carnivores, predominantly foxes, has been reported. However, there have been no reports of this phenomenon in other carnivores such as mustelids or golden jackals. Our aim was to investigate the host spectrum for this aberrant localization of ticks. Methods Between 2015 and 2020, a total of 198 carcasses of 12 species of carnivore were examined by parasitological necropsy. When a subcutaneous tick was found, the nodule was removed, carefully dissected, and stored in ethanol. The morphological identification of the subcutaneous tick was carried out to species level. Results A single subcutaneous tick was found in one carcass, that of a golden jackal (Canis aureus). The tick was identified as a female Ixodes ricinus. All the other carcasses were negative for the presence of subcutaneous ticks. Conclusion To our knowledge, this is the first report of a subcutaneous tick in a golden jackal. This finding broadens the host spectrum of subcutaneous ticks, and reinforces the idea that, among carnivores, this phenomenon only occurs in canids. Graphical Abstract