Identification of human papillomavirus as a preventive strategy for cervical cancer in asymptomatic women in the Peruvian Andes

Objective: To detect the most prevalent human papillomavirus (HPV) genotypes samples of asymptomatic Peruvian women by analyzing the correlation betwe ienn c Pearvpiacnailc somlaeoaur (PAP)-stained cervical tests and PCR-sequencing. Methods: A total of 254 women attending routine gynecological examinations were included in pthaitsh ostluogdiys.t Tahned scalmaspsliefise dw ebrye tahnea Blyeztehde sbdya PsAysPt etmec.h HnPiqVu ea manpdli feicxaatmioinn ewda su nddoenre au msinicgr othsceo pprei mbeyr as specific for E1 region and positive specimens were confirmed by direct sequencing. Results: The prevalence of HPV was investigated in 254 cervical scrape samples by PCR. PAP smear showed that 94.9% cases had normal morphology and 5.1% had an inflammatory pattern; 2p0r.e5v%a lwenert eg efonuontydp teo ibne c ionrfreeclatetido nw iwthit hH PchVa, ncgoems pinri scienrgv i2c0a dl icfyfetorelongt yg.enotypes. HPV16 was the most Conclusions: Our results suggest the HPV is very frequent even in women with negative PAP, eannddo PceCrRvi csaele smasm tpol ebs.e Itdheen tbifeicsat toiopnt ioofn t htoe HdePtVe rgmeinnoety tphee inc aaussyamtipvteo magateinc tw oofm HePnV m ianyf eaclltoiown t hine nimatpulreaml henisttaotriyo no fo tfh ea pdpisroepasreia aten dp rthope hsyulbascetqicu emnet adseuvreelso pwmheicnht omf acye rhviacvael ma adliirgencatn [email protected] work has been partially supported by Universidad Peruana de Ciencias Aplicadas (UPC), Instituto de Investigación Nutricional and Instituto de Investigación de Efrnomfe rtmheed pardoegsr aImnf ecciosas, Lima, Peru. JR has a fellowship I3, of the ISCIII (Grant No. CES11/012), and LJDV from the Generalitat de Catalunya (2009SGR1208).Revisión por pare

Manejo anestésico en síndrome corazón izquierdo hipoplásico: Reporte de un caso

Background: Hypoplastic left heart syndrome may appear with clinical signs immediately at birth, being responsible for neonatal deaths within the first week of life. Clinical recognition and echocardiographic findings are key to timely diagnosis and treatment. Case report: describes the anesthetic procedure of a neonate with hemodynamic instability who required emergency surgery for bilateral pulmonary banding to maintain the balance between pulmonary and near-unit systemic flow ratio, along with mechanical ventilation maneuvers, anesthetic, inotropic and adjuvant drugs to control vascular resistance and blood flow, thus achieving hemodynamic stability of the patient, which allowed him to undergo an elective Norwood Sano procedure on the fifth day, and which was tolerated with extubation 15 days after surgery. Conclusion: The right timing of the surgical indication increases the survival of patients with hypoplastic left heart syndrome.Introducción: El síndrome corazón izquierdo hipoplásico puede presentarse con signos clínicos inmediato al nacimiento, siendo responsable de las muertes neonatales en la primera semana de vida. El reconocimiento clínico y los hallazgos ecocardiográficos son claves para un diagnóstico y tratamiento oportuno. Reporte de caso: describe el manejo anestésico de un neonato con inestabilidad hemodinámica que requirió cirugía de emergencia con banding pulmonar bilateral para mantener el equilibrio entre la relación del flujo sanguíneo pulmonar y sistémico cercano a la unidad, junto a maniobras de ventilación mecánica, medicamentos anestésicos, inotrópicos y adyuvantes con el objetivo de manipular las resistencias vasculares y el flujo sanguíneo logrando estabilidad hemodinámica del paciente que permitió al quinto día ser sometido a una cirugía electiva de Norwood Sano, tolerando procedimiento con extubación a los 15 días de la cirugía. Conclusión: el momento oportuno de la indicación quirúrgica aumenta la sobrevida de los pacientes síndrome corazón izquierdo hipoplásico

Prediction of Opioid-Induced Respiratory Depression on Inpatient Wards Using Continuous Capnography and Oximetry: An International Prospective, Observational Trial.

BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting \u3e30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. RESULTS: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17-26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P \u3c .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44-8.30; P \u3c .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P \u3c .0001) identified using continuous oximetry and capnography monitoring. CONCLUSIONS: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls