Yutaro Hara, Tomonori Uruma, Yasuyuki Morishima, Yuji Hirai

Matthew J Saunders, Marco A Tovar, Dami Collier, Matthew R Baldwin, Rosario Montoya, Teresa R Valencia, Robert H Gilman, Carlton A Evans

Although active case-finding made an important contribution to tuberculosis detection among contacts, passive case-finding detected most of the tuberculosis burden. Compared with passive case-finding, active case-finding was equitable, helped to diagnose tuberculosis earlier and usually before a positive result on sputum smear microscopy, and showed a high burden of undetected tuberculosis among women.

Maryam Vahabzadeh, Ali Banagozar Mohammadi

A 28-year-old man was transferred to our hospital after he suddenly lost consciousness in the street. He had an initial diagnosis of opioid overdose. Further, because of respiratory depression, hypoxaemia, miosis, loss of consciousness, and an absence of focal neurological signs and symptoms, the patient was given progressively larger doses of naloxone until he regained consciousness and started breathing normally and spontaneously. He said he had been abusing heroin and so because of this, and the clinical presentation, he was transferred to a clinical toxicology ward for further management.

Stephanie Lheureux, Charlie Gourley, Ignace Vergote, Amit M Oza

Epithelial ovarian cancer generally presents at an advanced stage and is the most common cause of gynaecological cancer death. Treatment requires expert multidisciplinary care. Population-based screening has been ineffective, but new approaches for early diagnosis and prevention that leverage molecular genomics are in development. Initial therapy includes surgery and adjuvant therapy. Epithelial ovarian cancer is composed of distinct histological subtypes with unique genomic characteristics, which are improving the precision and effectiveness of therapy, allowing discovery of predictors of response such as mutations in breast cancer susceptibility genes BRCA1 and BRCA2, and homologous recombination deficiency for DNA damage response pathway inhibitors or resistance (cyclin E1).

Tony Kirby

Twelve years on from the so-called Berlin patient, a second patient in London, UK, appears to be in remission from HIV infection. Tony Kirby reports.

Samantha Cristine Winter, Robert Dreibelbis, Millicent Ningoma Dzombo, Francis Barchi

by Samantha Cristine Winter, Robert Dreibelbis, Millicent Ningoma Dzombo, Francis Barchi While access to safe sanitation is a global issue, there are large disparities in access. Women living in informal settlements, in particular, are disproportionately affected by lack of access to sanitation. Without adequate sanitation, these women may resort to unsafe strategies to manage their sanitation needs, but limited research has focused specifically on this issue. Qualitative and quantitative data were collected from women in the Mathare informal settlement in Nairobi, Kenya in 2016. A latent class analysis (LCA) using the quantitative data yielded five distinct sanitation profiles (SP) among women in Mathare. In-depth interviews and sanitation walks with women added further detail about the characteristics of and motivations underlying each profile. Women’s sanitation profiles in these settlements are complex. A majority of women in this study utilized an unsafe method of disposal at least once in a 24-hour period that increased their risk of direct exposure to waste and harmful pathogens.

Abstract Background Little is known about the morbidity and mortality of invasive fungal disease (IFD) at a population level. The aim of this study was to determine the incidence, trends and outcomes of IFD in all haematology-oncology patients by linking Victorian hospital data to state-based registries. Methods Episodes of IFD complicating adult haematological malignancy (HM) and haematopoietic stem cell transplantation (HSCT) patients admitted to Victorian hospitals from 1st July 2005 to 30th June 2016 were extracted from the Victorian Admitted Episodes Dataset and linked to the date of HM diagnosis from the Victorian Cancer Registry and mortality from the Victorian Death Index. Descriptive analyses and regression modelling were used. Results There were 619,702 inpatient-episodes among 32,815 HM and 1,765 HSCT-patients. IFD occurring twelve-months from HM-diagnosis was detected in 669 (2.04%) HM-patients and 111 (6.29%) HSCT-recipients, respectively. Median time to IFD-diagnosis was 3, 5, 15 and 22 months in acute myeloid leukaemia, acute lymphoblastic leukaemia, Hodgkin lymphoma and multiple myeloma, respectively. Median survival from IFD-diagnosis was 7, 7 and 3 months for invasive aspergillosis, invasive candidiasis and mucormycosis, respectively. From 2005-2016, IFD incidence decreased 0.28% per 1,000 bed-days. Fungal incidence coincided with spring peaks on time-series analysis. Conclusions Data linkage is an efficient means of evaluating the epidemiology of a rare disease, however the burden of IFD is likely underestimated, arguing for better quality hospital level surveillance data to improve management strategies.…

Abstract The Demographic and Health Surveys (DHS) Program has supported three household Malaria Indicator Surveys (MIS) in Madagascar. The results of 13 key malaria indicators from these surveys have been mapped as continuous surfaces using model-based geostatistical methods. The opportunities and limitations of these mapped outputs were discussed during a workshop in Antananarivo, Madagascar in July 2018, attended by 15 representatives from various implementation, policy and research stakeholder institutions in Madagascar. Participants evaluated the findings from the maps, using these to develop figures and narratives to support their work in the control of malaria in Madagascar.…

Yunyun Yang, Liping Li, Linjie Yuan, Xiaoying Zhou, Jianxin Duan, Hongying Xiao, Ningning Cai, Shuai Han, Xianqiang Ma, Weidong Liu, Chun-Chi Chen, Lingle Wang, Xin Li, Jiahuan Chen, Ning Kang, Jing Chen, Zhixun Shen, Satish R. Malwal, Wanli Liu, Yan Shi, Eric Oldfield, Rey-Ting Guo, Yonghui Zhang

Vγ9Vδ2 T cells sense tumor and microbial metabolites without MHC restriction. Yang et al. used a multifaceted approach to show how the highly potent microbial HMBPP binds to BTN3A1 and triggers inside-out signaling to activate Vγ9Vδ2 T cells. This study will have implications in emerging clinical applications of allogeneic Vγ9Vδ2 T cells.

Ziad Al Nabhani, Sophie Dulauroy, Rute Marques, Clara Cousu, Shahed Al Bounny, François Déjardin, Tim Sparwasser, Marion Bérard, Nadine Cerf-Bensussan, Gérard Eberl

Al Nabhani et al. find that the changes in the intestinal microbiota at weaning induced a vigorous immune response—a “weaning reaction”—that is programmed in time. The weaning reaction is associated with the induction of regulatory T cells, and its perturbation results in increased susceptibility to immunopathologies later in life.

Kim W, No J, Lee D, et al.

AbstractBackgroundEndemic outbreaks of hantaviruses pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS) in humans. Using comparative genomic analyses of partial and nearly complete sequences of HTNV from humans and rodents, we are able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequence; finer granularity of rodent sampling reflects more precisely the circulation of strains.MethodsA total of five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during the hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex PCR-based NGS (Next-Generation Sequencing) to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated by the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents.ResultsThe phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens with the HTNV circulating in rodents at suspected sites of patient infections.ConclusionsThis study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing to the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will enable identification of infectious sources, disease risk assessment and preparedness against vector-borne viruses.

Li, Shengnan; Wang, Shu; Priyanka, Priyanka; Kellum, John A.

Objectives: Acute kidney injury is a common complication of major surgery. However, acute kidney injury occurring within the first 48 hours after surgery (early acute kidney injury) and therefore likely related to the surgery itself is possibly different from acute kidney injury occurring after 48 hours (late acute kidney injury). The aim of this study was to describe the epidemiology and identify differences in risk factors and outcomes between early and late acute kidney injury following major surgery. Design: Retrospective cohort study. Setting: Academic Medical Center. Patients: Patients admitted to ICU following noncardiac major surgery. Interventions: None. Measurements and Main Results: We analyzed data from 3,499 patients and defined acute kidney injury according to full Kidney Disease: Improving Global Outcomes criteria and classified as early (48 hr or less) or late (> 48 hr to 7 d) based on time from surgery. Separate multivariable logistic regression models were fit to identify risk factors of early acute kidney injury compared with no acute kidney injury and risk factors of late acute kidney injury compared with no acute kidney injury. Overall 41.7% (1,459/3,499) developed early acute kidney injury versus 14.4% (504/3,499) late acute kidney injury. Most acute kidney injury occurred within 48 hours following surgery and 12 hours was the peak interval. Risk factors for early acute kidney injury included increased age, body mass index, decreased estimated glomerular filtration rate, and anemia, whereas late acute kidney injury cases were closely associated with postoperative factors, like sepsis, mechanical ventilation, positive fluid balance, blood transfusions and exposure to diuretics, vasopressors, and nonsteroidal anti-inflammatory drugs. After adjusting for age, body mass index, estimated glomerular filtration rate, comorbidities, surgery type, both early acute kidney injury (odds ratio [95% CI], 1.84 [1.50–2.27]) and late acute kidney injury (odds ratio [95% CI], 1.42 [1.09–1.85]) were associated with higher 1-year mortality compared with patients without acute kidney injury. We found similar results in a validation cohort of 10,723 patients admitted between 2008 and 2014. Conclusions: Most surgery-related acute kidney injury occurred within 48 hours of surgery. Acute kidney injury occurring within the first 48 hours was associated with underlying health, whereas acute kidney injury occurring after 48 hours was related to postoperative complications or drugs. Design of clinical and experimental interventions for acute kidney injury in this population should consider these differences. The data reported here have been supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government. The content is solely the responsibility of the authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Drs. Wang and Kellum received support for article research from the National Institutes of Health (R01 DK083961-121860). Dr. Priyanka has disclosed that she does not have any potential conflicts of interest. Supported, in part, by institutional grant R01 DK083961-121860 from the National Institutes of Health to Dr. Kellum. For information regarding this article, E-mail: kellumja@upmc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Giulia Tarquini, Giusi Zaina, Paolo Ermacora, Francesca De Amicis, Barbara Franco-Orozco, Nazia Loi, Marta Martini, Gian Luca Bianchi, Laura Pagliari, Giuseppe Firrao, Emanuele de Paoli, Rita Musetti

by Giulia Tarquini, Giusi Zaina, Paolo Ermacora, Francesca De Amicis, Barbara Franco-Orozco, Nazia Loi, Marta Martini, Gian Luca Bianchi, Laura Pagliari, Giuseppe Firrao, Emanuele de Paoli, Rita Musetti The Grapevine Pinot Gris disease (GPG-d) is a novel disease characterized by symptoms such as leaf mottling and deformation, which has been recently reported in grapevines, and mostly in Pinot gris. Plants show obvious symptoms at the beginning of the growing season, while during summer symptom recovery frequently occurs, manifesting as symptomless leaves. A new Trichovirus, named Grapevine Pinot gris virus (GPGV), which belongs to the family Betaflexiviridae was found in association with infected plants. The detection of the virus in asymptomatic grapevines raised doubts about disease aetiology. Therefore, the primary target of this work was to set up a reliable system for the study of the disease in controlled conditions, avoiding interfering factor(s) that could affect symptom development. To this end, two clones of the virus, pRI::GPGV-vir and pRI::GPGV-lat, were generated from total RNA collected from one symptomatic and one asymptomatic Pinot gris grapevine, respectively. The clones, which encompassed the entire genome of the virus, were used in Agrobacterium-mediated inoculation of Vitis vinifera and Nicotiana benthamiana plants. All inoculated plants developed symptoms regardless of their inoculum source, demonstrating a correlation between the presence of GPGV and symptomatic manifestations. Four months post inoculum, the grapevines inoculated with the pRI::GPGV-lat clone developed asymptomatic leaves that were still positive to GPGV detection. Three to four weeks later (i.e. ca. 5 months post inoculum), the same phenomenon was observed in the grapevines inoculated with pRI::GPGV-vir. This observation perfectly matches symptom progression in infected field-grown grapevines, suggesting a possible role for plant antiviral mechanisms, such as RNA silencing, in the recovery process.

Benoit Lemarie, Morgan Matt, Laurene Deconinck, Christian Perronne, Aurélien Dinh, Benjamin Davido

Abstract Background The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir. Methods This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL 

Abstract Background Erysipelothrix rhusiopathiae is a zoonotic pathogen that causes erysipeloid and is most frequently associated with exposure to domestic swine. Infection of native and prosthetic joints is a rarely reported manifestation. Case presentation We describe a case of E. rhusiopathiae prosthetic joint infection in a woman with a history of exposure to wild animals in the Canadian Arctic. Patient management involved a 1-stage surgical revision exchange with an antibiotic impregnated cement spacer and 6 weeks of intravenous penicillin G followed by 6 weeks of oral amoxicillin. Ten previously reported cases of E. rhusiopathiae joint infection are reviewed. Recent increases in mortality due to infection with this organism among host animal populations in the Canadian Arctic have generated concern regarding a potential increase in human infections. However, whole genome sequencing (WGS) of the organism was unable to identify a zoonotic origin for this case. Conclusions Consideration should be given to E. rhusiopathiae as a cause of joint infections if the appropriate epidemiologic and host risk factors exist. Expanded use of WGS in other potential animal hosts and environmental sources may provide important epidemiologic information in determining the source of human infections.…

Abstract Background Diarrhoea remains an important cause of childhood mortality in Nigeria, with Rotavirus and Cryptosporidium reported to have the highest contribution. However, high use of antibiotics for treatment of paediatric diarrhoea has been observed, although World Health Organization guidelines discourage the use of antibiotics for treating acute diarrhoea. Here we investigated more closely management and treatment practices for acute paediatric diarrhoea, both in home and healthcare settings. Methods Children under 5 years of age (n = 199) presenting at healthcare centres in Abakaliki, Nigeria with acute watery diarrhoea were included in the study. Background information on the children was collected by questionnaire, including home treatments, and clinical information including symptoms and treatment were provided by the healthcare centres. Analysis of faecal samples from the children indicated that over 90% had Rotavirus infection and over 6% Cryptosporidium infection. Data were compiled in a spreadsheet and analysed for associations between variables and use of antibiotics using logistic regression analysis. Results Although most children were treated supportively (oral rehydration solution and intravenous fluids at home and in healthcare settings, respectively) over 15% were given anti-diarrhoea drugs at home and over 85% were also prescribed antibiotics at the healthcare centre, mostly ciproflaxin, but also metronidazole and gentamycin. The only variable positively associated with antibiotic prescription was diarrhoea more than three times per 24 h at admission. Conclusions It is clear that young children presenting with acute watery diarrhoea to healthcare centres in Abakaliki are likely to be prescribed antibiotics, despite there being no obvious reason that this treatment is appropriate. Our study results support the need for institution-based antimicrobial stewardship being implemented in Nigeria.…

Abstract Background Malaria control in Panama is problematic due to the high diversity of morphologically similar Anopheles mosquito species, which makes identification of vectors of human Plasmodium challenging. Strategies by Panamanian health authorities to bring malaria under control targeting Anopheles vectors could be ineffective if they tackle a misidentified species. Methods A rapid mass spectrometry identification procedure was developed to accurately and timely sort out field-collected Neotropical Anopheles mosquitoes into vector and non-vector species. Matrix-assisted laser desorption/ionization (MALDI) mass spectra of highly-abundant proteins were generated from laboratory-reared mosquitoes using different extraction protocols, body parts, and sexes to minimize the amount of material from specimen vouchers needed and optimize the protocol for taxonomic identification. Subsequently, the mass spectra of field-collected Neotropical Anopheles mosquito species were classified using a combination of custom-made unsupervised (i.e., Principal component analysis—PCA) and supervised (i.e., Linear discriminant analysis—LDA) classification algorithms. Results Regardless of the protocol used or the mosquito species and sex, the legs contained the least intra-specific variability with enough well-preserved proteins to differentiate among distinct biological species, consistent with previous literature. After minimizing the amount of material needed from the voucher, one leg was enough to produce reliable spectra between specimens. Further, both PCA and LDA were able to classify up to 12 mosquito species, from different subgenera and seven geographically spread localities across Panama using mass spectra from one leg pair. LDA demonstrated high discriminatory power and consistency, with validation and cross-validation positive identification rates above 93% at the species level. Conclusion The selected sample processing procedure can be used to identify field-collected Anopheles species, including vectors of Plasmodium, in a short period of time, with a minimal amount of tissue and without the need of an expert mosquito taxonomist. This strategy to analyse protein spectra overcomes the drawbacks of working without a reference library to classify unknown samples. Finally, this MALDI approach can aid ongoing malaria eradication efforts in Panama and other countries with large number of mosquito’s species by improving vector surveillance in epidemic-prone sites such as indigenous Comarcas.…

Tara McGinty, Aoife G. Cotter, Caroline A. Sabin, Alan Macken, Eoin Kavanagh, Juliet Compston, Gerard Sheehan, John Lambert, Patrick W. G. Mallon, on behalf of the HIV UPBEAT ( U nderstanding the P athology of B one Dis ea ses in HIV-infec t ed Subjects) Study Group

by Tara McGinty, Aoife G. Cotter, Caroline A. Sabin, Alan Macken, Eoin Kavanagh, Juliet Compston, Gerard Sheehan, John Lambert, Patrick W. G. Mallon, on behalf of the HIV UPBEAT ( U nderstanding the P athology of B one Dis ea ses in HIV-infec t ed Subjects) Study Group Introduction Increased prevalence of low bone mineral density (BMD) and increased fracture incidence are observed in persons living with HIV (PLWH). The trabecular bone score (TBS) is a novel index of bone microarchitecture which improves fracture prediction independent of BMD. Methods The HIV UPBEAT study is a single centre, prospective cohort study that enrolled subjects with and without HIV from similar sociodemographic backgrounds for annual assessments of bone health. TBS was derived from lumbar spine (LS) dual-energy X-ray absorptiometry images. Univariate and multivariable linear regression was used to assess relationships between baseline TBS, BMD, sociodemographic and clinical factors. Results 463 subjects (201 HIV positive) were included; PLWH were younger and more likely male, of non-African ethnicity and current smokers. HIV was associated with a mean reduction of 0.037 [-0.060, -0.013] (p = 0.002) in TBS. Lower TBS was also associated with male gender, non-African ethnicity, current smoking status and lower LS BMD. HIV remained associated with lower TBS after adjustment for LS BMD, age, gender and ethnicity. However, adjustment for current smoking significantly attenuated the association between HIV and TBS, with further adjustment for higher bone turnover markers largely explaining any residual association. Among the sub-group of PLWH, exposure to protease inhibitors and lower nadir CD4+ T-cell counts were both predictors of lower TBS. Conclusions PLWH have lower TBS independent of LS BMD. However, this is largely explained by higher current smoking rates and higher bone turnover in those with HIV. Exposure to PI, but not tenofovir disproxil fumarate, also contributed to lower TBS in those with HIV.…

Eckel RH.

Nutrition research, in contrast with randomized clinical trials that compare a drug with placebo, is more difficult for many reasons, including complexities in data gathering and changes in human behavior over time. In this issue of JAMA, Zhong and colleagues report new insights about a controversial topic, the association of egg consumption and dietary cholesterol with cardiovascular disease (CVD) incidence and all-cause mortality. Clearly, the topic of this study is important to clinicians, patients, and the public at large because the association of egg consumption and dietary cholesterol with CVD, although debated for decades, has more recently been thought to be less important. Compared with the meta-analyses and reviews previously published, this report is far more comprehensive, with enough data to make a strong statement that eggs and overall dietary cholesterol intake remain important in affecting the risk of CVD and more so the risk of all-cause mortality.

Abstract Objectives To investigate the proportion of asymptomatic infection among blood donors in a region endemic for Leishmania; and to ascertain epidemiological and genetic factors associated with this condition. Methods We studied 1260 blood donors in the Province of Granada in the Southern Spain. After obtaining informed consent in each participant, a poll about habits, housing and contact with animals were carried out. Blood samples were obtained for determining antileishmanial antibodies and a PCR assay. HLA typing was performed in a randomly sample among the donors with positive serology. Results We have found that L. infantum antibodies were present in 7.9% of blood donors and DNA in blood was detected in 2.5% of donors. There was no concordance between both determinations, except in one patient. Taking into consideration both techniques, 129 participants were considered to have asymptomatic Leishmania infection. No participant in this study developed clinical leishmaniasis during a follow-up period of 2 years. HLA were typed in 51 donors. Asymptomatic Leishmania infection might be associated with certain HLA antigens. A multivariate analysis was done with the variables obtained through the participants’ interview. The contact with livestock (goats, pigs, and sheep), but not dogs, either at home or in the environment, was significantly and independently associated with asymptomatic leishmania infection. Conclusions Asymptomatic leishmanial infection among blood donors is frequent in the Granada Province, south of Spain. The presence of livestock in this region is related to this infection, perhaps influencing vector density of this disease. Some HLA genes might be associated with asymptomatic leishmanial state.…

William Calero-Cáceres, Mao Ye, José Luis Balcázar

Although antibiotic resistance represents a significant and growing public health concern, the contribution of bacteriophages (phages) to the mobilization of antibiotic resistance genes (ARGs) in the environment has not been extensively studied. Recent studies, however, suggest that phages play an important role in the acquisition, maintenance, and spread of ARGs than previously expected. This Opinion article offers an update on the contribution of phages to environmental antibiotic resistance. A better understanding of the mechanisms and factors that promote antibiotic resistance may significantly contribute to the implementation of control strategies.

Martin EJ.

In this narrative medicine essay, a palliative care physician’s experience—holding the hand of a man who was flung to a curb after miscalculating a light change as he dashed across the street causing him to be struck by truck—cured her of fainting at the sight of pain, which enabled her to choose a career in palliative care.

Swanstrom J, Nivarthi U, Patel B, et al.

AbstractBackgroundDengue virus is an emerging mosquito-borne flavivirus responsible for considerable morbidity and mortality worldwide. The US National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research has developed live-attenuated vaccines to each of the four serotypes of Dengue virus (DEV1-DEN4). While overall levels of DENV neutralizing antibodies (nAbs) in people have been correlated with protection, these correlations vary depending on DENV serotype, pre-vaccination immune status, age and study site. By combining both the level and molecular specificity of nAbs to each serotype, it may be possible to develop more robust correlates that predict long-term outcome.MethodsUsing depletions and recombinant chimeric epitope transplant DENVs, we evaluate the molecular specificity and mapped specific epitopes and antigenic regions targeted by vaccine induced nAbs in volunteers who received the NIH monovalent vaccines against each DENV serotype.ResultsAfter monovalent vaccination, subjects developed high levels of nAbs that mainly targeted epitopes that are unique (type-specific) to each DENV serotype. The DENV1, 2 and 4 monovalent vaccines induced type-specific nAbs directed to quaternary structure envelope (E) epitopes known to be targets of strongly nAbs induced by wild type DENV infections.DiscussionOur results reported here on the molecular specificity of NIH vaccine induced antibodies enable new strategies, beyond the absolute levels of nAbs, for determining correlates and mechanisms of protective immunity.

Sancar F.

In a recent letter, the FDA encouraged health care professionals to learn more about the association between all breast implants—regardless of filling or texture—and anaplastic large cell lymphoma (ALCL), a type of non-Hodgkin lymphoma.

Asa Oxner, Kullatham Kongpakpaisarn, Stephanie Hudey, Andrew Myers, John Martin Sesay, John Bawel Thomas, Fodei Daboh, Alpha Kabba, Admire Fillie, Aminata Tina Kainessie, Tamba S. Abdulai, Eric Elliott

A comprehensive, patient-centric HIV clinic can result in high rates of case detection for tuberculosis and recognition of immunological ART failure.

Evangelia-Theophano Piperaki, Leonidas S. Tzouvelekis, Vivi Miriagou, George L. Daikos

Carbapenem-resistant Acinetobacter baumannii (CRAB) has gained global notoriety as a critically important nosocomial pathogen. It mostly affects debilitated patients causing pneumonia and bloodstream infections with high mortality rates. Difficulties in treating CRAB infections stem from a formidable resistance profile that leaves available a few antibiotics of uncertain efficacy such as colistin and tigecycline. Despite the relentless attempts to improve therapeutic approaches (as depicted in colistin-oriented randomized clinical trials and the numerous observational studies), progress is still limited.

Agarwal, Sachin; Presciutti, Alex; Cornelius, Talea; Birk, Jeffrey; Roh, David J.; Park, Soojin; Claassen, Jan; Elkind, Mitchell S. V.; Edmondson, Donald

Objectives: To compare 1-year all-cause mortality and major adverse cardiovascular events in cardiac arrest survivors with and without posttraumatic stress disorder symptomatology at hospital discharge. Design: Prospective, observational cohort. Setting: ICUs at a tertiary-care center. Patients: Adults with return of spontaneous circulation after in-hospital or out-of-hospital cardiac arrest between September 2015 and September 2017. A consecutive sample of survivors with sufficient mental status to self-report cardiac arrest and subsequent hospitalization–induced posttraumatic stress disorder symptoms (cardiac arrest–induced posttraumatic stress symptomatology) at hospital discharge were included. Interventions: None. Measurements and Main Results: The combined primary endpoint was all-cause mortality or major adverse cardiovascular event—hospitalization for nonfatal myocardial infarction, unstable angina, congestive heart failure, emergency coronary revascularization, or urgent implantable cardio-defibrillators/permanent pacemaker placements within 12 months of discharge. An in-person posttraumatic stress disorder symptomatology was assessed at hospital discharge via the Posttraumatic Stress Disorder Checklist-Specific scale; a suggested diagnostic cutoff of 36 for specialized medical settings was adopted. Outcomes for patients meeting (vs not meeting) this cutoff were compared using Cox-hazard regression models. Of 114 included patients, 36 (31.6%) screened positive for cardiac arrest–induced posttraumatic stress symptomatology at discharge (median 21 d post cardiac arrest; interquartile range, 11–36). During the follow-up period (median = 12.4 mo; interquartile range, 10.2–13.5 mo), 10 (8.8%) died and 29 (25.4%) experienced a recurrent major adverse cardiovascular event: rehospitalizations due to myocardial infarction (n = 4; 13.8%), unstable angina (n = 8; 27.6%), congestive heart failure exacerbations (n = 4; 13.8%), emergency revascularizations (n = 5, 17.2%), and urgent implantable cardio-defibrillator/permanent pacemaker placements (n = 8; 27.6%). Cardiac arrest–induced posttraumatic stress symptomatology was associated with all-cause mortality/major adverse cardiovascular event in univariate (hazard ratio, 3.19; 95% CI, 1.7–6.0) and in models adjusted for age, sex, comorbidities, preexisting psychiatric condition, and nonshockable initial rhythm (hazard ratio, 3.1; 95% CI, 1.6–6.0). Conclusions: Posttraumatic stress disorder symptomatology is common after cardiac arrest, and cardiac arrest–induced posttraumatic stress symptomatology was associated with significantly higher risk of death and cardiovascular events. Further studies are needed to better understand the underlying mechanisms. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by the institutional funds provided to Dr. Agarwal. Dr. Park received grant support from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (K01ES026833). Dr. Edmondson received grant support from the National Heart, Lung, and Blood Institute, NIH, Bethesda, MD (HL117832) . The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: sa2512@columbia.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Singh A, Whisenant TE, Peiris AN.

This JAMA Patient Page describes why and how cardiac catheter ablation is used to correct atrial fibrillation and other heart rhythm abnormalities.

Blomström-Lundqvist C, Gizurarson S, Schwieler J, et al.

This randomized trial compares the effects of pulmonary vein isolation using radiofrequency ablation vs antiarrhythmic medication on self-reported quality of life at 1 year in patients with atrial fibrillation and previous medication failure.

Shakiba, N., Fahmy, A., Jayakumaran, G., McGibbon, S., David, L., Trcka, D., Elbaz, J., Puri, M. C., Nagy, A., van der Kooy, D., Goyal, S., Wrana, J. L., Zandstra, P. W.

The ability to generate induced pluripotent stem cells from differentiated cell types has enabled researchers to engineer cell states. Although studies have identifed molecular networks that reprogram cells to pluripotency, the cellular dynamics of these processes remain poorly understood. Here, by combining cellular barcoding, mathematical modelling, and lineage tracing approaches, we demonstrate that reprogramming dynamics in heterogeneous populations are driven by dominant "elite" clones. Clones arise a priori from a population of poised mouse embryonic fibroblasts (MEFs) derived from Wnt1-expressing cells that may represent a neural crest population. This work highlights the importance of cellular dynamics in fate programming outcomes and uncovers cell competition as a mechanism by which cells with context-specific eliteness emerge to occupy and dominate the reprogramming niche.…

Biard, Lucie; Darmon, Michaël; Lemiale, Virginie; Mokart, Djamel; Chevret, Sylvie; Azoulay, Elie; Resche-Rigon, Matthieu

Objectives: We aimed to investigate center effects on hospital mortality of ICU patients with hematologic malignancies and to explore interactions between center and patients characteristics. Design: Multicenter prospective cohort. Setting: Seventeen ICUs across France and Belgium. Patients: One-thousand eleven patients with hematologic malignancies hospitalized in ICUs. Interventions: Reanalysis of the original data using state-of-the-art statistical methods with permutation procedures for testing multiple random effects. Measurements and Main Results: Average crude mortality was 39% and varied from 11% to 58% across centers. There was a significant center effect on the mean hospital mortality, after adjustment on individual prognostic factors (p < 0.001; median adjusted odds ratio for center effect 1.57 [interquartile range, 1.24–2.18]). There was also a quantitative interaction between center and the effect of the Sequential Organ Failure Assessment score: higher scores were associated with higher mortality (odds ratio for 1 point = 1.24 on average; 95% CI, 1.15–1.33) but with a magnitude that depended on center (p = 0.028). Conclusions: Between-center heterogeneity in hospital mortality was confirmed after adjustment for individual prognostic factors. It was partially explained by center experience in treating oncology patients. Interestingly, center effect was similar in magnitude to that of known mortality risk factors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by institutional grant number Programme Hospitalier de Recherche Clinique Appel Offre Ministériel AOM 08235 from the French Ministry of Health. Dr. Azoulay’s institution received funding from Gilead, Merck Sharp & Dohme, Astellas, Fisher and Paykel, and Jazz Pharmaceuticals, and he received funding from Gilead, Alexion, Ablynx, and Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: lucie.biard@univ-paris-diderot.fr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background We assessed the utility of a multi-target, real-time PCR assay for Bordetella pertussis detection and diagnosis in patients with severe respiratory illness (SRI), influenza-like illness (ILI), and asymptomatic controls. Methods Real-time PCR detection of IS481, pIS1001, hIS1001 and ptxS1 was performed on nasopharyngeal specimens (SRI, ILI and controls) and induced sputum (SRI) collected from June 2012 to May 2016 through respiratory illness surveillance. Using PCR cycle threshold (Ct) value cut-offs, IS481 positive cases were classified as confirmed (Ct 

Kim J, Davis M, Farchione T.

To the Editor In a Viewpoint, Drs Sisti and Joffe expressed concern that interventions to reduce suicide have not been well studied in clinical trials and proposed inclusion of actively suicidal individuals in trials. The US Food and Drug Administration (FDA) provides regulatory advice on clinical trials for psychiatric drug development. We wish to comment on several issues in the article.

Sisti DA, Joffe S.

In Reply We are gratified to know that the FDA is developing guidance that supports inclusion of individuals with suicidal ideation or behavior associated with serious mental illnesses, including schizophrenia and bipolar disorder, in clinical trials. We agree that trial participants with acute suicidal ideation or behavior, including those in the control groups of clinical trials evaluating suicidal ideation or behavior as an end point, be provided with standard-of-care (including emergency) interventions or with investigational approaches hypothesized to be as good as or better than the standard of care. However, mandating participant exclusion when suicidal ideation or behavior passes a predetermined threshold is a step backward: drawing conclusions about new treatments for the population most at risk would be impossible.

Basu A, Maciejewski ML.

This JAMA Guide to Statistics and Methods reviews considerations that go into investigators’ choice of time over which to define and measure the benefits and costs of interventions in risk-benefit and cost-effectiveness analyses.

Nicolle L, Gupta K, Bradley S, et al.

AbstractAsymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.

Kuehn BM.

This Medical News story discusses initiatives aimed at improving recovery from life-threatening illnesses after release from the intensive care unit.

Josué Díaz-Delgado, Kátia R. Groch, Eva Sierra, Simona Sacchini, Daniele Zucca, Óscar Quesada-Canales, Manuel Arbelo, Antonio Fernández, Elitieri Santos, Joana Ikeda, Rafael Carvalho, Alexandre F. Azevedo, Jose Lailson-Brito Jr, Leonardo Flach, Rodrigo Ressio, Cristina T. Kanamura, Marcelo Sansone, Cíntia Favero, Brian F. Porter, Cinzia Centelleghe, Sandro Mazzariol, Ludovica Di Renzo, Gabriella Di Francesco, Giovanni Di Guardo, José Luiz Catão-Dias

by Josué Díaz-Delgado, Kátia R. Groch, Eva Sierra, Simona Sacchini, Daniele Zucca, Óscar Quesada-Canales, Manuel Arbelo, Antonio Fernández, Elitieri Santos, Joana Ikeda, Rafael Carvalho, Alexandre F. Azevedo, Jose Lailson-Brito Jr, Leonardo Flach, Rodrigo Ressio, Cristina T. Kanamura, Marcelo Sansone, Cíntia Favero, Brian F. Porter, Cinzia Centelleghe, Sandro Mazzariol, Ludovica Di Renzo, Gabriella Di Francesco, Giovanni Di Guardo, José Luiz Catão-Dias Cetacean morbillivirus (CeMV) is a major natural cause of morbidity and mortality in cetaceans worldwide and results in epidemic and endemic fatalities. The pathogenesis of CeMV has not been fully elucidated, and questions remain regarding tissue tropism and the mechanisms of immunosuppression. We compared the histopathologic and viral immunohistochemical features in molecularly confirmed CeMV-infected Guiana dolphins (Sotalia guianensis) from the Southwestern Atlantic (Brazil) and striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) from the Northeast-Central Atlantic (Canary Islands, Spain) and the Western Mediterranean Sea (Italy). Major emphasis was placed on the central nervous system (CNS), including neuroanatomical distribution of lesions, and the lymphoid system and lung were also examined. Eleven Guiana dolphins, 13 striped dolphins, and 3 bottlenose dolphins were selected by defined criteria. CeMV infections showed a remarkable neurotropism in striped dolphins and bottlenose dolphins, while this was a rare feature in CeMV-infected Guiana dolphins. Neuroanatomical distribution of lesions in dolphins stranded in the Canary Islands revealed a consistent involvement of the cerebrum, thalamus, and cerebellum, followed by caudal brainstem and spinal cord. In most cases, Guiana dolphins had more severe lung lesions. The lymphoid system was involved in all three species, with consistent lymphoid depletion. Multinucleate giant cells/syncytia and characteristic viral inclusion bodies were variably observed in these organs. Overall, there was widespread lymphohistiocytic, epithelial, and neuronal/neuroglial viral antigen immunolabeling with some individual, host species, and CeMV strain differences. Preexisting and opportunistic infections were common, particularly endoparasitism, followed by bacterial, fungal, and viral infections. These results contribute to understanding CeMV infections in susceptible cetacean hosts in relation to factors such as CeMV strains and geographic locations, thereby establishing the basis for future neuro- and immunopathological comparative investigations.

Prada, Gabriel; Vespa, Paul M.

No abstract available…

The original version of this article unfortunately contained a mistake. Arnaldo Caruso was not listed among the authors.…

The PLOS ONE Staff

by The PLOS ONE Staff …

Abstract Background Intestinal parasites still pose major public health problems in developing countries like Ethiopia. Local epidemiological data is indispensable in order to design and monitor prevention and control strategies. Therefore the present study aimed to assess the prevalence of intestinal parasitic infections and associated factors among students at Birbir town, Southern Ethiopia. Methods A school-based cross-sectional study was conducted from March to May 2018. Three hundred fifty-one students, who were selected by stratified followed by systematic random sampling, participated in the study. Socio-demographic information was collected using a structured questionnaire. Anthropometric measurements of height and weight were taken at the time of interview. Stool samples were collected and processed by direct wet mount and formol-ether concentration techniques for microscopic detection of intestinal parasites. Data was analyzed using SPSS version 20. Results Among 351 (180 male and 171 female) children participated, 135 (38.5%) and 216 (61.5%) were within the age groups of 5–9 and 10–14 respectively. Ninety five (27.1%; 95%CI: 22.2–31.9) of them were tested positive for intestinal parasites. Helminths and protozoa account 21.1 and 7.1% prevalences respectively. Seventy eight children were infected with a single parasite species while 17 were positive for double or triple infections. A. lumbricoides (31, 8.8%) was the most frequently detected parasite followed by T. trichiura (20, 5.7%) and hookworms (19, 5.4%). Age group of 10–14 years (AOR = 2.51; 95%CI: 1.41–4.45, p = 0.002) and absence of hand washing habit after toilet (AOR = 4.49; 95%CI: 2.00–10.1, p = 0.001) were significantly associated with intestinal parasitic infection. Conclusions The prevalence of intestinal parasitic infection among school age children is still unacceptably high. Age group of 10–14 year old and not having habit of hand washing after toilet were significantly associated with intestinal parasitic infection. The ongoing school based deworming should be strengthened and be integrated with school health programs.…

Abstract Background Large-scale surveillance of mosquito populations is crucial to assess the intensity of vector-borne disease transmission and the impact of control interventions. However, there is a lack of accurate, cost-effective and high-throughput tools for mass-screening of vectors. Methods A total of 750 Anopheles gambiae (Keele strain) mosquitoes were fed Plasmodium falciparum NF54 gametocytes through standard membrane feeding assay (SMFA) and afterwards maintained in insectary conditions to allow for oocyst (8 days) and sporozoite development (14 days). Thereupon, each mosquito was scanned using near infra-red spectroscopy (NIRS) and processed by quantitative polymerase chain reaction (qPCR) to determine the presence of infection and infection load. The spectra collected were randomly assigned to either a training dataset, used to develop calibrations for predicting oocyst- or sporozoite-infection through partial least square regressions (PLS); or to a test dataset, used for validating the calibration’s prediction accuracy. Results NIRS detected oocyst- and sporozoite-stage P. falciparum infections with 88% and 95% accuracy, respectively. This study demonstrates proof-of-concept that NIRS is capable of rapidly identifying laboratory strains of human malaria infection in African mosquito vectors. Conclusions Accurate, low-cost, reagent-free screening of mosquito populations enabled by NIRS could revolutionize surveillance and elimination strategies for the most important human malaria parasite in its primary African vector species. Further research is needed to evaluate how the method performs in the field following adjustments in the training datasets to include data from wild-caught infected and uninfected mosquitoes.…

Abstract Background The need for a rapid, molecular test to diagnose tuberculosis (TB) has prompted exploration of TB-LAMP (Eiken; Tokyo, Japan) for use in resource-limited settings. We conducted a systematic review to assess the accuracy of TB-LAMP as a diagnostic test for pulmonary TB. Methods We analyzed individual-level data for eligible patients from all studies of TB-LAMP conducted between Jan 2012 and October 2015 to compare the diagnostic accuracy of TB-LAMP with that of smear microscopy and Xpert MTB/RIF® using 3 reference standards of varying stringency. Pooled sensitivity and specificity and pooled differences in sensitivity and specificity were estimated using random effects meta-analysis. Study quality was evaluated using QUADAS-2. Results Four thousand seven hundred sixty individuals across 13 studies met eligibility criteria. Methodological quality was judged to be low for all studies. TB-LAMP had higher sensitivity than sputum smear microscopy (pooled sensitivity difference + 13·2, 95% CI 4·5–21·9%) and similar sensitivity to Xpert MTB/RIF (pooled sensitivity difference − 2·5, 95% CI -8·0 to + 2·9) using the most stringent reference standard available. Specificity of TB-LAMP was similar to that of sputum smear microscopy (pooled specificity difference − 1·8, 95% CI -3·8 to + 0·2) and Xpert MTB/RIF (pooled specificity difference 0·5, 95% CI -0·9 to + 1·8). Conclusions From the perspective of diagnostic accuracy, TB-LAMP may be considered as an alternative test for sputum smear microscopy. Additional factors such as cost, feasibility, and acceptability in settings that continue to rely on sputum smear microscopy should be considered when deciding to adopt this technology. Xpert MTB/RIF should continue to be preferred in settings where resource and infrastructure requirements are adequate and where HIV co-infection or drug-resistance is of concern.…

Mushtaq Ahmad, Wanis H. Ibrahim, Sabi Al Sarafandi, Khezar S. Shahzada, Shakeel Ahmed, Irfan Ul Haq, Tasleem Raza, Mansoor Ali Hameed, Merlin Thomas, Hisham Ab ib Swehli, Hisham A. Sattar

Zhong VW, Van Horn L, Cornelis MC, et al.

This pooled cohort study reports that consumption of an additional 300 mg of dietary cholesterol per day or an additional half egg per day is significantly associated with higher risk of incident cardiovascular disease (CVD) events and all-cause mortality.

Kaewpreedee, Prathanporn; Boonrat, Potchara; Tansiri, Yada; rowland-Jones, Sarah L.; Hansasuta, Pokrath

Objectives: CD8+ T-cells recognize HLA-peptide complex through the T-cell receptor (TCR). Whilst amino acid variation in TCR variable chains often affects antigen specificity, dimorphism in the beta chain constant region (TRBC1 and TRBC2) is not thought to affect T-cell function. A recent study suggested that adoptive transfer of TRBC1-specific CAR-T cells provided an option for T-cell leukemia therapy that preserved T-cell immunity in the TRBC2 subset. This raises an important question as to whether TRBC1+T cells are qualitatively different from TRBC2+T cells. Design: Cross-sectional study. Methods: Sixty-six antiretroviral therapy-naïve HIV-infected individuals, including 19 viraemic controllers and 47 non-controllers, were enrolled. Peripheral blood mononuclear cells were isolated for T-cell functional assays, tetramer analyses, TRBC1 staining and immunophenotyping. Results: Viraemic controllers had a higher proportion of circulating TRBC1+T cells than non-controllers, raising the possibility that TRBC1+T cells might be associated with HIV control. TRBC1+T cells also showed more functional T-cell responses against both HIV and cytomegalovirus (p …

Takahashi J, Cher A, Sheeder J, et al.

This study examines whether Catholic hospitals disclose their religious identity and health care practices based on the church’s teachings on their websites.

Fabrizio De Massis, Katiuscia Zilli, Guido Di Donato, Roberta Nuvoloni, Sandro Pelini, Lorena Sacchini, Nicola D’Alterio, Elisabetta Di Giannatale

by Fabrizio De Massis, Katiuscia Zilli, Guido Di Donato, Roberta Nuvoloni, Sandro Pelini, Lorena Sacchini, Nicola D’Alterio, Elisabetta Di Giannatale Brucellosis is a major public health problem still prevalent as a neglected endemic zoonosis requiring proactive attention in many communities worldwide. The present study involved analysis of Brucella field strains submitted for typing to the Italian National Reference Laboratory for Brucellosis from 2007 to 2015. Strains were identified at the species and biovar levels by classic and molecular techniques according to the World Organisation for Animal Health Manual. In total, 5,784 strains were typed: 3,089 Brucella abortus (53.4%), 2,497 B. melitensis (43.2%), 10 B. ovis (0.2%), 181 B. suis (3.1%), and 7 B. ceti (0.1%). The 2,981 strains from cattle were typed as B. abortus biovars 1, 3, and 6 (90.1%) and B. melitensis biovar 3 (9.9%). The 318 strains from water buffalo were typed as B. abortus biovars 1, 3 (95.9%) and B. melitensis biovar 3 (4.1%). The 2,279 strains from sheep and goats were typed as B. abortus biovars 1 and 3 (4.3%); B. melitensis biovars 1, 3, (95.3%); and B. ovis (0.4%). The 173 strains from wild boar were typed as B. suis biovar 2 (98.3%) and B. melitensis biovar 3 (1.7%). The 11 strains from pigs were typed as B. suis biovar 2. The 13 strains from humans were typed as B. melitensis biovar 3. The two strains from horses were typed as B. abortus biovar 1, while the seven strains from dolphins were typed as B. ceti. This additional knowledge on the epidemiology of brucellosis in Italy may be useful to formulate policies and strategies for the control and eradication of the disease in animal populations. The animal species affected, biovars typed, geographical origins, and spatial distributions of isolates are herein analyzed and discussed.