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We examined reporting agreement of oral, vaginal, and anal sex in adolescents and young adults living with perinatally-acquired HIV and those perinatally HIV-exposed and uninfected in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) and AMP Up studies. Agreement between fixed constructs (e.g., age at first sex) and prevalence of logical inconsistencies (e.g., reclaimed virginity status) over time were assessed. Internal consistency was also examined using an attention check question and questions regarding condom use in the prior three months. Those who reported having anal sex in adolescence had a higher proportion of inconsistent responses compared to vaginal and oral sex measures. At their most recent survey, 84% of young adults correctly answered an attention check question and 74% agreed within the survey on condom use in the prior three months. In bivariate analyses, HIV status was not associated with responding inconsistently. Increased time between surveys, male sex, and younger age at first survey were associated with multiple measures of inconsistency over time, while lower cognitive scores, having less than a high school diploma, and negatively answering post-survey acceptability questions were associated with incorrectly answering an attention check question.

Negative pressure wound treatment (NPWT) is very useful for the treatment of chronic or deep wounds and in the setting of skin grafting. Due to the need for adhesive dressings, this treatment is rarely attempted in patients with skin fragility secondary to hereditary epidermolysis bullosa (EB). We present a neonate with EB simplex, severe generalized in a critical clinical state where NPWT was successfully applied and describe the measures taken to avoid any further skin damage. This case is of clinical importance to physicians and health care staff treating patients with this rare disease where additional therapeutic measures for the treatment of chronic wounds are scarce.

This is the fourth American Society of Colposcopy and Cervical Pathology (ASCCP)-sponsored consensus guidelines for management of cervical cancer screening abnormalities, after the original consensus conferences in 20011 and subsequent updates in 20062 and 2012.3 An interim guidance publication providing management recommendations for primary HPV screening was released in 2015.4 This document updates and replaces all previous guidance. The key difference between 2019 guidelines and previous versions is the change from primarily test results–based algorithms (e.g., “Colposcopy is recommended for patients with HPV-positive atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL],” etc.) to primarily “risk-based” guidelines (e.g., “Colposcopy is recommended for any combination of history and current test results yielding a 4.0% or greater probability of finding CIN 3+,” etc.). See Box 1 for essential changes. Tables of risk estimates for possible combinations of current screening test results and screening history (including unknown history) have been generated from a prospective longitudinal cohort of more than 1.5 million patients followed for more than a decade at Kaiser Permanente Northern California (KPNC). All KPNC estimates of risk underlying guideline decisions are detailed in the accompanying article by Egemen et al.5 The applicability of these risk estimates to other United States regions and populations has been confirmed in other data sets from screening programs and clinical trials.6 Many patients, especially those with minor abnormalities, can be managed by identifying their risk level using Tables 1A to 5B in Egemen et al5 and linking it to a recommended clinical action (return to routine screening, surveillance with repeat testing at 1- or 3-year intervals, colposcopy, or treatment). To facilitate use of these tables, the same information will be accessible via smartphone app (for purchase) and web (no cost) through http://www.asccp.org. Decision aids may facilitate use of the tables.7 Common abnormalities are managed using risk estimates outlined in Section E, and rare abnormalities are managed via the result-specific consensus recommendations outlined in Sections G-K. Box 1. Essential Changes From Prior Management Guidelines 1) Recommendations are based on risk, not results. Recommendations of colposcopy, treatment, or surveillance will be based on a patient's risk of CIN 3+ determined by a combination of current results and history (including unknown history). The same current test results may yield different management recommendations depending on the history of recent past test results. 2) Colposcopy can be deferred for certain patients. Repeat HPV testing or cotesting at 1 year is recommended for patients with minor screening abnormalities indicating HPV infection with low risk of underlying CIN 3+ (e.g., low-grade cytologic abnormalities after a documented negative screening HPV test or cotest). At the 1-year follow-up test, referral to colposcopy is recommended if results remain abnormal. 3) Guidance for expedited treatment is expanded (i.e., treatment without colposcopic biopsy). Expedited treatment was an option for patients with HSIL cytology in the 2012 guidelines; this guidance is now better defined. For nonpregnant patients 25 years or older, expedited treatment, defined as treatment without preceding colposcopic biopsy demonstrating CIN 2+, is preferred when the immediate risk of CIN 3+ is ≥60%, and is acceptable for those with risks between 25% and 60%. Expedited treatment is preferred for nonpregnant patients 25 years or older with high-grade squamous intraepithelial lesion (HSIL) cytology and concurrent positive testing for HPV genotype 16 (HPV 16) (i.e., HPV 16–positive HSIL cytology) and never or rarely screened patients with HPV-positive HSIL regardless of HPV genotype. Shared decision-making should be used when considering expedited treatment, especially for patients with concerns about the potential impact of treatment on pregnancy outcomes. 4) Excisional treatment is preferred to ablative treatment for histologic HSIL (CIN 2 or CIN 3) in the United States. Excision is recommended for adenocarcinoma in situ (AIS). 5) Observation is preferred to treatment for CIN 1. Treatment remains acceptable for patients with repeat diagnoses of CIN 1 persisting 2 years or more. 6) Histopathology reports based on Lower Anogenital Squamous Terminology (LAST)/World Health Organization (WHO) recommendations for reporting histologic HSIL should include CIN 2 or CIN 3 qualifiers, i.e., HSIL(CIN 2) and HSIL (CIN 3). 7) All positive HPV tests, regardless of genotype, should have additional reflex triage testing performed from the same laboratory specimen (e.g., reflex cytology). Additional testing from the same laboratory specimen is recommended because the findings may inform colposcopy practice. For example, those with HSIL cytology and concurrent positive testing for HPV genotype 16 qualify for expedited treatment. HPV 16 or 18 infections have the highest risk for CIN 3 and occult cancer, so additional evaluation (e.g., colposcopy with biopsy) is necessary even when cytology results are negative. If HPV 16 and 18 testing is positive, and additional laboratory testing of the same sample is not feasible, the patient should proceed directly to colposcopy. 8) Continued surveillance with HPV testing or cotesting at 3-year intervals for at least 25 years is recommended after treatment of histologic HSIL, CIN 2, CIN 3, or AIS. Continued surveillance at 3-year intervals beyond 25 years is acceptable for as long as the patient's life expectancy and ability to be screened are not significantly compromised by serious health issues. The 2012 guidelines recommended return to 5-year screening intervals and did not specify when screening should cease. New evidence indicates that risk remains elevated for at least 25 years, with no evidence that treated patients ever return to risk levels compatible with 5-year intervals. Surveillance with cytology alone is acceptable only if testing with HPV or cotesting is not feasible. Cytology is less sensitive than HPV testing for detection of precancer and is therefore recommended more often. Cytology is recommended at 6-month intervals when HPV testing or cotesting is recommended annually. Cytology is recommended annually when 3-year intervals are recommended for HPV or cotesting. 9) Human papilloma virus assays that are Food and Drug Administration (FDA)-approved for screening should be used for management according to their regulatory approval in the United States. (Note: all HPV testing in this document refers to testing for high-risk HPV types only). For all management indications, HPV mRNA and HPV DNA tests without FDA approval for primary screening alone should only be used as a cotest with cytology, unless sufficient, exceptionally rigorous data are available to support primary HPV testing in management. The minimum amount of data required to generate a recommendation will include the patient's age and current test results, as we recognize that previous screening history is often not known. Increased precision of management guidance will be possible if information is available on test results within the past 5 years and previous precancer treatment within the past 25 years.3 Current results and past history are designed to generate the patient's risk estimate from data tables.5 Risk estimates are available for the following clinical situations: abnormal screening test results with unknown history, abnormal screening test results with medical record documentation of a preceding negative HPV test or cotest, surveillance of previous abnormal screening test results that did not require immediate colposcopic referral (e.g., follow-up after an HPV-positive cytology negative result), colposcopy/biopsy results, and follow-up surveillance tests after colposcopy or after treatment for, or resolution of, high-grade abnormalities (e.g., CIN 2+). The recognition that persistent HPV infection is necessary for developing precancer and cancer (defined as CIN 3+, which includes diagnoses of CIN 3, AIS, and cancer) underlies the 2019 guideline update. Prospective longitudinal data indicate that when a new abnormal screening test result follows a negative HPV test or cotest within the past 5 years, the estimated risk of CIN 3+ is reduced by approximately 50%.8 A negative cytology result within 3 years of a new abnormal screening test, however, does not confer a similar reduction in risk.9 The 2019 guidelines also recognize that a colposcopic examination performed according to accepted standards (e.g., using the KPNC colposcopy protocol or the ASCCP Colposcopy Standards10) confirming low-grade or normal histology reduces a patient's estimated risk of having precancer/cancer in the next 2 years.11 This allows patients with an HPV-positive ASC-US or LSIL result at their 1-year follow-up visit after a colposcopy confirming normal- or low-grade histology to return for repeat HPV or cotesting in 1 more year, rather than immediately return to colposcopy. Thus, incorporating a patient's history of previous HPV tests and colposcopy/biopsy results will permit detection and treatment of CIN 3+ while avoiding unnecessary interventions for patients with new HPV infections who are at lower risk.12

Nowadays, solid organ transplantation (SOT) is an established treatment for patients with end-organ dysfunction, which dramatically improves the quality-of-life. Vascularized composite allotransplants (VCAs) including hand and face have been reported worldwide over the last 20 years. However, VCAs, differently to SOT, are life-enhancing instead of life-saving and are not routinely performed due to the risk of immune rejection and the adverse effects of immunosuppression. Over the past decade, although considerable improvements in short-term outcomes after allotransplantation have been registered, these results have not been translated into major progress in long-term allograft acceptance and patient survival. Recently active researches in the field of biomarker discovery have been conducted to develop individualized therapies for allograft recipients. MicroRNAs (miRNAs) are a small noncoding RNAs functioning as critical regulators of gene and protein expression by RNA interference. They have been connected in numerous biological processes and diseases. Due to their immunomodulatory functions, miRNAs have been amended as potential diagnostic and prognostic biomarker for the detection of rejection in allotransplantation. Due to their specific circulating expression profile, they could act as noninvasive predictive tools for rejection that may help clinicians in an early adjustment of the immunosuppression protocol during acute rejections episodes. Indeed, specific anti-sense oligonucleotides suppressing miRNAs expressed in rejection could reduce the rejection rate in allografts and decrease the use of immunosuppressants. We present a literature review of the immunomodulatory properties and characteristics of miRNAs. We will summarize the current knowledge on miRNAs as potential biomarkers for allograft rejection and possible application in allotransplantation monitoring. Finally, we will discuss the advances in preclinical miRNA-based therapies for immunosuppression.

Purpose Current cervical cancer screening guidelines recommend 3-year screening intervals, in contrast to the previous recommendation of annual screening, to prevent over screening and overtreatment. We evaluated the impact of viewing a tablet-based educational tool prior to seeing a clinician on young women’s knowledge and understanding of cervical cancer screening, HPV vaccination follow-up of abnormal pap smears, and comfort in communicating with their providers. Methods This cross-sectional study was part of a cluster-randomized study of fourteen primary care clinics from January 2015 to December 2016. We developed the cervical cancer education tool in English and Spanish using a community-based approach that included formative work and cognitive interviewing. Clinics were randomized to use the intervention (tablet-based patient education tool) or to participate as a control group. We administered surveys to a convenience sample of 229 English- or Spanish-speaking women aged 19 to 35 years in these clinics. We used descriptive analyses and logistic regression models with cluster-robust standard errors to compare differences among the two groups. Results Compared to women seen in control clinics, women seen in intervention clinics demonstrated greater knowledge regarding human papilloma virus (HPV (p = 0.004) and understanding (p p = 0.053). Women in the intervention group felt that the tool helped them understand that an abnormal Pap smear does not require immediate treatment (61.5%). Conclusion Innovative online patient education that is offered prior to patients’ interaction with their clinicians can improve their knowledge about cervical cancer prevention and treatment.

Introduction This study sought to determine whether a provider mobile phone application, used with or without a patient educational tool accessed on a computer tablet, would promote adherence to guidelines for cervical cancer screening and management of abnormal cytology in young women. Methods The study was conducted as a prospective cohort study in which 14 Family Planning, Access, Care, and Treatment provider clinics were randomized to 1 of 2 arms: (1) provider mobile phone application only or (2) provider mobile phone application plus patient educational tool. The provider mobile phone application gave information to providers regarding cervical cancer screening and management of abnormal cytology. The patient educational tool accessed on a computer tablet was a patient-centered educational tool. Each arm was compared with clinic control groups (no intervention) in a 2:1 ratio (control:intervention). Claims data were used to calculate and compare 18-month cytology (Pap) and colposcopy rates before the intervention and during the 18 months using the Poisson mixed-effect regression model. A sensitivity analysis examined the differences in the rate of change between each arm and controls. The study took place between July 2015 and December 2016, and analysis was performed in 2019. Results The clinics randomized to the provider mobile phone application plus patient educational tool arm and their control group achieved similar 18-month Pap rates (0.52, 95% CI=0.37, 0.74 and 0.68, 95% CI=0.53, 0.86, respectively) as well as the provider mobile phone application arm and their control group (0.44, 95% CI=0.33, 0.58 and 0.41, 95% CI=0.34, 0.51; p-values >0.1). In the sensitivity analysis, the difference in the rate of change in Pap rates for the provider mobile phone application plus patient educational tool arm and their control group before and during the intervention was −0.22 and −0.09, respectively (p=0.02), but no differences were seen between the provider mobile phone application arm and their control group. No significant changes were observed for colposcopy rates. Conclusions Providing clinicians and patients with information on guidelines had no demonstrable effect on 18-month Pap and colposcopy rates in the regression model; however, results from the sensitivity analysis for the patient educational tool were encouraging. Trial registration This study is registered at www.clinicaltrials.gov NCT02270021.

BACKGROUND AND OBJECTIVES:We recently reported the short-term results of this trial revealing that higher-calorie refeeding (HCR) restored medical stability earlier, with no increase in safety events and significant savings associated with shorter length of stay, in comparison with lower-calorie refeeding (LCR) in hospitalized adolescents with anorexia nervosa. Here, we report the 1-year outcomes, including rates of clinical remission and rehospitalizations.METHODS:In this multicenter, randomized controlled trial, eligible patients admitted for medical instability to 2 tertiary care eating disorder programs were randomly assigned to HCR (2000 kcals per day, increasing by 200 kcals per day) or LCR (1400 kcals per day, increasing by 200 kcals every other day) within 24 hours of admission and followed-up at 10 days and 1, 3, 6, and 12 months post discharge. Clinical remission at 12 months post discharge was defined as weight restoration (≥95% median BMI) plus psychological recovery. With generalized linear mixed effect models, we examined differences in clinical remission over time.RESULTS:Of 120 enrollees, 111 were included in modified intent-to-treat analyses, 60 received HCR, and 51 received LCR. Clinical remission rates changed over time in both groups, with no evidence of significant group differences (P = .42). Medical rehospitalization rates within 1-year post discharge (32.8% [19 of 58] vs 35.4% [17 of 48], P = .84), number of rehospitalizations (2.4 [SD: 2.2] vs 2.0 [SD: 1.6]; P = .52), and total number of days rehospitalized (6.0 [SD: 14.8] vs 5.1 [SD: 10.3] days; P = .81) did not differ by HCR versus LCR.CONCLUSIONS:The finding that clinical remission and medical rehospitalization did not differ over 1-year, in conjunction with the end-of-treatment outcomes, support the superior efficacy of HCR as compared with LCR.

Catherine Milne and colleagues present the findings of their review, ccna2@juno.com

Background Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. Methods This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9–11 year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL® 9) over 24 months, with a deferred booster dose at 24 months and an optional booster at 30 months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30 months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. Discussion Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm. Trial registration ClinicalTrials.gov Identifier: NCT02568566. Registered on October 6, 2015. Electronic supplementary material The online version of this article (10.1186/s12885-019-5444-4) contains supplementary material, which is available to authorized users.

Objectives This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth. Methods We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART. Results Among 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older. Conclusion Our study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.

Toll-like receptors (TLRs) are innate immune defenders thought to be critical for the clearance of human papillomavirus (HPV) infections hence preventing the development of HPV-associated high-grade cervical intra-epithelial neoplasia (CIN2 or 3), a potential cervical cancer precursor. However, the role of TLRs in the regression of established cervical lesions, such as CIN2, is hindered by a lack of prospective design studies. Using SYBR green real-time PCR assays, we have examined the gene expression of TLR2, TLR3, TLR7, TLR8 and TLR9, in cytobrush collected endocervical cells of 63 women diagnosed with CIN2 at study entry (baseline) and followed over a 3-year period. Wilcoxon rank-sum test was used to examine the association between TLR expression levels, measured at baseline, and CIN2 outcome (regression vs. persistence/progression) over time. HPV genotyping was performed using Roche Linear Array Assay detecting 37 HPV types. Women with CIN2 regression showed significantly higher baseline levels of TLR2 (p = 0.006) and TLR7 (p = 0.007), as well as a non-significant trend for a higher TLR8 expression (p = 0.053) compared to women with CIN2 persistence/progression. Six women with CIN2 regression, who presented with an HR-HPV DNA-negative CIN2 lesion at study entry, had significantly higher baseline levels of TLR2 (p = 0.005), TLR7 (p = 0.013) and TLR8 (p = 0.012), compared to women with CIN2 persistence/progression, suggesting their role in clearance of HPV prior to clearance of the lesion. Our results confirm a key role of TLRs in regression of CIN2 and support the potential use of TLR-agonists for treatment of these lesions.

When should young women begin cervical cancer screening? Dr. Moscicki states that we should continue to initiate screening before the age of 25 years in the US. The reasons include a lower rate of HPV vaccination among the current generation of young adult women and increases in invasive cervical cancer cases in countries that have raised the screening age to 25 years. She further cites specific shortcomings of the US healthcare system that can contribute to underscreening among young women, including fragmented healthcare, lack of health insurance, and a rapidly declining rate of pelvic examinations for cervical cancer screening among this age group, despite current guidelines that continue to recommend screening. She posits that although cervical cancer is rare among women aged 21 to 24 years, promoting screening in this age group acts as a safety net to prevent cancers among women aged 25 to 29 years.

Aim We sought to improve retention of neonatal resuscitation skills by modifying step 3 through additional functional verbalisation in Peyton's four-step approach (P4S). Methods Newborn life support (NLS) training was performed in a simulation-based setting. In contrast to the traditional approach, students taught with the modified approach were requested to explain every step of their performance in Peyton's step 3. A total of 123 students were allocated into both experimental groups. Students were then assessed by megacode on day four (initial assessment) and 6 months (follow-up assessment). Results Both groups showed similar scorings in the initial, follow-up assessment and in mean change. On initial megacode, time to start with initial inflation and post-resuscitation care was significantly faster in the control group. All showed a significant loss of performance irrespective of modification in step 3 in the follow-up assessment. Only time until start with post-resuscitation care shows a significant group difference in mean change between initial and follow-up with increasing time in the control and decreasing time span in intervention group. Conclusion Both methods showed equal levels of knowledge acquisition and long-term decline in NLS performances. Verbalisation in step 3 influenced speed of applied NLS performance.

This study examined associations of self-regulatory behavior and cognitive functioning with substance use (SU) to inform interventions for youth with perinatal HIV infection (YPHIV) or exposure but uninfected (YPHEU). Youth aged 7-15 years (YPHIV, n = 390; YPHEU, n = 211) were followed longitudinally with cognitive testing and behavioral questionnaires including self-report of alcohol, marijuana, tobacco, and other SU. Cox proportional hazards analyses were used to examine correlates of initiating each substance for those without prior use at baseline and generalized estimating equation analyses were used to address associations of cognitive/behavioral measurements with SU prevalence for the entire sample. Lower self-reported self-regulation skills, but higher cognitive functioning abilities, were associated with initiation and prevalent use of alcohol and marijuana regardless of HIV status. Our findings suggest SU screening tools and self-regulation interventions developed for general adolescent populations should be implemented for those with PHIV, who may be at heightened risk for SU-related health consequences.En este estudio se examina el vínculo del comportamiento autorregulado y la función cognoscitiva con el consumo de sustancias para argumentar intervenciones para los jóvenes con infección perinatal por el VIH (JIPVIH) y los jóvenes con exposición perinatal sin infección por el VIH (JEPSIVIH). Se hizo un seguimiento longitudinal de jóvenes de 7 a 15 años de edad (JIPVIH, n = 390; JEPSIVIH, n = 211) por medio de pruebas cognoscitivas y cuestionarios sobre el comportamiento, incluyendo el autoinforme de consumo de alcohol, marihuana, tabaco y otras sustancias. Se usaron los análisis Cox de riesgos proporcionales para examinar factores correlacionados con el inicio del consumo de cada sustancia por personas no consumidoras en el punto de referencia inicial. Asimismo, se usaron análisis de ecuaciones de estimación generalizadas para examinar la asociación entre la prevalencia del consumo de sustancias y las medidas cognoscitivas y las medidas conductuales para toda la muestra. Habilidades de autorregulación disminuidas, según autoinforme, pero capacidades superiores de función cognoscitiva, fueron vinculadas con el inicio y consumo frecuente de alcohol y marihuana, independientemente de la condición de VIH. Nuestros hallazgos sugieren que herramientas para detectar el consumo de sustancias e intervenciones de autorregulación creadas para la población general de adolescentes se deberían implementar para los JIPVIH que podrían correr mayores riesgos de sufrir consecuencias en la salud relacionadas con el consumo de sustancias.

Hand and face transplants are becoming increasingly common, recording progressively more penile, uterus, abdominal wall, and allotransplantation cases reported worldwide. Despite current protocols allow long-term survival of the allografts, the ultimate goal of donor-specific tolerance has not been achieved yet. In fact, the harmful adverse effects related to the lifelong administration of immunosuppressive agents are the main drawbacks for vascularized composite allotransplantations. Research is very active in investigating alternative methods to induce greater tolerance while minimizing toxicity. Adipose-derived stem cells (ASCs) represent promising cell therapies for immunomodulation in preclinical and clinical settings. Their clinical appeal is due to their easy harvest in large quantities through a noninvasive and well-accepted approach; they may well promote donor-specific tolerance and potentially reduce immunosuppression. Several experimental studies exist, but lacking review articles reporting current evidence. This work proposes a literature review on the immunomodulatory role of ASCs in vascularized composite allotransplantations. In vitro and in vivo evidence will be summarized. The role that cell passaging and upstream progenitors - the so-called spheroid ASCs - may play in modulating the immune response will also be discussed. Finally, this article will summarize current knowledge on biodistribution, migration, and homing of injected stem cells. This review may well provide useful information for preclinical and clinical studies, aiming at a breakthrough for donor-specific tolerance.

Background Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. Methods We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. Results Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment. Conclusions Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.

With the advent of combined antiretroviral therapies, the face of HIV infection has changed dramatically from a disease with almost certain mortality from serious comorbidities, to a manageable chronic condition with an extended lifespan. In this paper we present the more recent investigations into the epidemiology, microbiology, and pathogenesis of periodontal diseases in patients with HIV, and the effects of combined antiretroviral therapies on the incidence and progression of these diseases both in adults and perinatally infected children. In addition, comparisons and potential interactions between the HIV-associated microbiome, host responses, and pathogenesis in the oral cavity with the gastrointestinal tract and other areas of the body are presented. Also, the effects of HIV and combined antiretroviral therapies on comorbidities such as hyposalivation, dementia, and osteoporosis on periodontal disease progression are discussed.

Over the last two decades studies of the natural history of human papillomavirus (HPV) have elucidated the transient nature of most HPV infections and underscored the importance of HPV persistence in the development of invasive cancers associated with HPV. Studies also demonstrated the benign nature of cervical intraepithelial neoplasia (CIN 1) and the importance of CIN 3 as the critical precancerous lesion requiring detection and treatment in order to prevent progression to invasive cancers. Cofactors associated with cervical cancer include smoking cigarettes, prolonged oral contraceptive use, chlamydia infections, and multiparity. However, these contributions of these cofactors remain miniscule compared to the role of high risk HPV persistence.

Zusammenfassung. Hintergrund: Die atopische Dermatitis (AD) ist eine chronische, rezidivierende Hauterkrankung. Jedes fünfte bis sechste Kind ist in der westlichen Zivilisation davon betroffen. Die Folgen der Erkrankung können gravierend sein: Chronische Entzündung der Haut und plagender Juckreiz verbunden mit Schlafstörungen. Für den Erfolg der Therapie ist die Edukation der Eltern von betroffenen Kindern zentral. Ziel: Entwicklung und Evaluation von evidenzbasierten Edukationsvideos für Eltern von einem Kleinkind mit AD. Methode: In den Videos wurde die Methode Storytelling eingesetzt. Ziel von Storytelling ist, Informationen durch den Einsatz von Geschichten einfach zu vermitteln. Anschließend an die Entwicklung wurden die Videos hinsichtlich der Verständlichkeit, der Wichtigkeit sowie der Nützlichkeit der Inhalte von einem multi-professionellem Team sowie von Familien mit betroffenen Kindern evaluiert. Ergebnisse: Es entstanden insgesamt sechs Videos, welche Themen wie Ursachen der AD, Symptome, Hautpflege, Behandlung sowie Leben mit AD beinhalteten. Storytelling wurde umgesetzt indem zwei Familien mit betroffenen Kindern von ihren Erfahrungen mit der Erkrankung erzählten. Fachinformationen wurden durch Spezialistinnen vermittelt. Die Evaluation ergab, dass die Informationen in den Videos einfach verständlich und relevant sind. Schlussfolgerungen: Mit evidenzbasierten Videos kann die Edukation auf innovative, kreative und moderne Art und Weise gefördert werden. Storytelling ist eine nutzerfreundliche Methode um komplexe Informationen einfach und verständlich zu vermitteln.

BACKGROUND: Lower weight has historically been equated with more severe illness in anorexia nervosa (AN). Reliance on admission weight to guide clinical concern is challenged by the rise in patients with atypical anorexia nervosa (AAN) requiring hospitalization at normal weight. METHODS: We examined weight history and illness severity in 12- to 24-year-olds with AN (n = 66) and AAN (n = 50) in a randomized clinical trial, the Study of Refeeding to Optimize Inpatient Gains (www.clinicaltrials.gov; NCT02488109). Amount of weight loss was the difference between the highest historical percentage median BMI and admission; rate was the amount divided by duration (months). Unpaired t tests compared AAN and AN; multiple variable regressions examined associations between weight history variables and markers of illness severity at admission. Stepwise regression examined the explanatory value of weight and menstrual history on selected markers. RESULTS: Participants were 16.5 ± 2.6 years old, and 91% were of female sex. Groups did not differ by weight history or admission heart rate (HR). Eating Disorder Examination Questionnaire global scores were higher in AAN (mean 3.80 [SD 1.66] vs mean 3.00 [SD 1.66]; P = .02). Independent of admission weight, lower HR (β = −0.492 [confidence interval (CI) −0.883 to −0.100]; P = .01) was associated with faster loss; lower serum phosphorus was associated with a greater amount (β = −0.005 [CI −0.010 to 0.000]; P = .04) and longer duration (β = −0.011 [CI −0.017 to 0.005]; P = .001). Weight and menstrual history explained 28% of the variance in HR and 36% of the variance in serum phosphorus. CONCLUSIONS: Weight history was independently associated with markers of malnutrition in inpatients with restrictive eating disorders across a range of body weights and should be considered when assessing illness severity on hospital admission.

Zusammenfassung. Hintergrund: Vulväre Neoplasien sind gynäkologische Erkrankungen mit zum Teil einschneidenden Folgen für die Betroffenen. Neben physischen Komplikationen leiden die Frauen häufig unter psychischen Problemen. Die mit Scham besetzte Krankheit führt zu einer Verminderung der Lebensqualität und beeinträchtigt das Sozialleben. Es ist wenig bekannt darüber, was diese Frauen an sozialer Unterstützung erhalten. Ziel: Das Ziel dieser qualitativen Studie war, zu beschreiben, wie betroffene Frauen die Unterstützung durch das soziale Umfeld in der Zeit von der Diagnose bis sechs Monate postoperativ erleben bzw. vermissen. Methode: In der vorliegenden Sekundäranalyse wurde ein qualitatives Design gewählt. Es wurden 20 transkribierte Interviews aus der WOMAN-PRO-Studie mittels qualitativer Inhaltsanalyse nach Mayring ausgewertet. Ergebnisse: Die Analyse ergab vier Hauptkategorien: Eine schlimme Krankheit haben zeigt, wie die Frauen die Diagnose als Schock erlebten, mit welchen Tabuthemen sowie Schuldfragen sie sich auseinandersetzen mussten. Stark ausgeprägt war die Kategorie Sich allein fühlen, bedingt durch Nicht-Sprechen, Nicht-Hinschauen und Nicht-Handeln. In Selber anpacken wird beschrieben, welche Strategien den Frauen halfen, aus dem Alleinsein herauszufinden. In Hilfe erfahren wird deutlich, dass diejenigen Frauen, die von sich aus mit dem sozialen Umfeld in Kontakt traten, in der Regel soziale Unterstützung erhielten. Schlussfolgerungen: Diese Patientinnen haben einen hohen Bedarf an umfassenden Informationen sowie an emotionaler und praktischer Unterstützung durch das private Umfeld und besonders auch durch die Gesundheitsfachleute. Eine definierte Bezugs- und Vertrauensperson während des ganzen Behandlungsprozesses ist zu empfehlen.

Human Papillomavirus (HPV) is the most common sexually transmitted infection in the USA, with over 14 million people acquiring HPV each year. HPV is also the cause of most anogenital cancers. About 90% of HPV infections spontaneously resolve over 3 years. However, about 10% remain as persistent infection defined as repeatedly detected in cervical samples. As HPV is controlled by local and systemic immune responses, individuals with immunosuppression are at risk for cervical cancer. It is hypothesized that immunosuppressed individuals are more likely to have HPV persistence, which is necessary for malignant transformation. Accordingly, women with rheumatic diseases such as SLE and RA are likely vulnerable to HPV infection and the progression of cervical disease. The HPV vaccine, given as a series of vaccinations, is safe and effective that can prevent HPV infection and cervical cancer. There is no contraindication to HPV vaccination for women to age 26 with rheumatic disease, as it is not live. As in the general population, timing is key for the efficacy of the HPV vaccine as the goal is to vaccinate prior to sexual debut and exposure to HPV. There are no formal recommendations for cervical cancer screening in women with rheumatic disease but recommendations for the HIV-positive population can be adopted, meaning to screen with a Pap test annually for three consecutive years and if all normal, to extend the interval to every 3 years with the option of co-testing with HPV at 30 years and older.

Hand hygiene (HH) is the most important measure to prevent nosocomial infections. HH compliance in companion animal clinics has been reported to be poor. The present study compared an online application with the WHO evaluation form to assess the WHO five moments of HH in a Swiss companion animal clinic. In 202 hand swabs from 87 staff members, total viable count (TVC) before and after patient contact was evaluated and the swabs were tested for selected antimicrobial resistant microorganisms of public health importance. HH compliance (95% confidence interval) was 36.6% (33.8–39.5%) and was similar when assessed with the two evaluation tools. HH differed between hospital areas (p = 0.0035) and HH indications (p < 0.0001). Gloves were worn in 22.0% (18.0–26.6%) of HH observations and were indicated in 37.2% (27.3–48.3%) of these observations. Mean TVC before patient contact was lower (0.52 log CFU/cm2) than after patient contact (1.02 log CFU/cm2) but was similar before patient contact on gloved and ungloved hands. Three hand swabs (1.5% (0.4–4.3%)) were positive for methicillin-resistant Staphylococcus aureus. Gloving should not be regarded as a substitute for HH. Overall, HH in companion animal medicine should urgently be fostered.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

Aims To compare the prevalence and severity of periodontal diseases between 180 perinatally HIV-infected (PHIV) and 118 perinatally HIV-exposed and uninfected (PHEU) youth in a cross-sectional study conducted at 11 clinical sites in the United States and Puerto Rico from the Adolescent Master Protocol (AMP) study of the Pediatric HIV/AIDS cohort study (PHACS) network. Methods Several analyses were conducted, employing the current CDC/AAP classification for periodontitis and incorporating a definition of gingivitis based on a bleeding on probing threshold, and analyses based on more detailed whole mouth, intraoral regionally, site-based, and tooth-based criteria of bleeding on probing, plaque levels, pockets depths and clinical attachment levels. Results After adjusting for plaque control habits, and behavioral and sociodemographic factors, there were no significant differences in periodontal diseases between the PHIV and PHEU youth using any of these criteria. For PHIV youth, there was no significant association between parameters of periodontal disease and current HIV status. Conclusions While no significant differences in periodontal parameters were noted between the PHIV and PHEU youth, the influence of antiretroviral therapy on merits further exploration in this cohort in a longitudinal study. This article is protected by copyright. All rights reserved.

Lifetime number of sex partners, marital status, and history of sexually transmitted disease were associated with human papillomavirus (HPV) acquisition among women without prior exposure to HPV infection, with no observed differences in risk determinants patterns for HPV infections by length of follow-up. Supplemental digital content is available in the text., Background Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV. Methods Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000–September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time. Results On short-term follow-up (0–27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64–34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37–3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19–3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0–76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08–1.78) and black women (RR, 1.64; 95% CI, 1.04–2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43–0.98). Conclusions We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

Summary Background Small studies reported poor post-partum outcomes among young women living with perinatal HIV infection who are now ageing into adulthood and becoming pregnant. For targeted clinical intervention, we sought to identify women in this population at risk of poor post-partum virological control. Methods We abstracted data on pregnancy history for women living with perinatal HIV infection in the Pediatric HIV/AIDS Cohort Study-AMP Up protocol, a prospective study of young adults living with perinatal HIV from 14 sites in the USA. Linear models with generalised estimating equations described trends in HIV viral load through 1 year post-pregnancy by pregnancy outcome. We used group-based trajectory modelling to identify viral load trajectory groups in the first post-partum year after livebirths. We then compared sociodemographic and clinical factors across identified groups. We defined viraemia as 400 copies per mL or more. Findings Between April 15, 2014, and Oct 1, 2017, we enrolled 323 women, of whom 234 had perinatal HIV infection, and reported age at sexual debut and history of heterosexual vaginal intercourse. Of the 172 pregnancies recorded in these women, 147 (85%, 104 livebirths and 43 spontaneous or elective abortions) were eligible for post-pregnancy viral load trajectory analyses (ie, had at least two viral loads in the year after end of pregnancy). Viral load increased by 0·7 log10 copies per mL (95% CI 0·5 to 1·0) in the first 12 weeks post partum after 104 livebirths, and subsequently stabilised from 13 weeks to 1 year post partum (slope −0·01 log10 copies per mL, 95% CI −0·3 to 0·3). By comparison, the average viral load trajectory after 43 spontaneous or elective abortions remained at less than 400 copies per mL. We identified three distinct groups of viral load trajectories after 104 livebirths, classified as reflecting sustained suppression (31 [30%]), rebound viraemia (55 [53%]), and persistent viraemia (18 [17%]). Women with sustained post-partum suppression were older at conception (22·9 years, IQR 19·4–25·9) than those with rebound viraemia (20·4 years, 18·8–22·2), or persistent post-partum viraemia (19·0 years, 17·7–20·5). Pre-conception viraemia and immune suppression were also strong risk factors for post-partum viraemia. Interpretation Despite success achieving viral load suppression during pregnancy, women living with perinatal HIV infection have a high risk of post-partum viraemia. Younger age at conception, pre-conception viraemia, and pre-conception immune suppression could identify women in this population most likely to benefit from post-partum adherence interventions. Funding National Institutes of Health.

The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-term risk of cervical neoplasia and cancer and the need for more intense screening, surveillance, and management. Although guidance for CC screening among HIV-infected women (see Table 1) has been supported by evidence from retrospective and prospective studies, recommendations for CC screening among non-HIV immunosuppressed women remains limited because quality evidence is lacking. Moreover, CC screening guidelines for HIV-infected women have changed because better treatments evolved and resulted in longer life expectancy.The objective of this report was to summarize current knowledge of CC, squamous intraepithelial lesions, and human papillomavirus (HPV) infection in non-HIV immunocompromised women to determine best practices for CC surveillance in this population and provide recommendations for screening. We evaluated those with solid organ transplant, hematopoietic stem cell transplant, and a number of autoimmune diseases.A panel of health care professionals involved in CC research and care was assembled to review and discuss existing literature on the subject and come to conclusions about screening based on available evidence and expert opinion. Literature searches were performed using key words such as CC, cervical dysplasia/squamous intraepithelial lesion, HPV, and type of immunosuppression resulting in an initial group of 346 articles. Additional publications were identified from review of citations in these articles. All generated abstracts were reviewed to identify relevant articles. Articles published within 10 years were considered priority for review. Reviews of the literature were summarized with relevant statistical comparisons. Recommendations for screening generated from each group were largely based on expert opinion. Adherence to screening, health benefits and risks, and available clinical expertise were all considered in formulating the recommendations to the degree that information was available.Solid Organ Transplant: Evidence specific for renal, heart/lung, liver, and pancreas transplants show a consistent increase in risk of cervical neoplasia and invasive CC, demonstrating the importance of long-term surveillance and treatment. Reports demonstrate continued risk long after transplantation, emphasizing the need for screening throughout a woman's lifetime.Hematopoietic Stem Cell Transplant: Although there is some evidence for an increase in CC in large cohort studies of these patients, conflicting results may reflect that many patients did not survive long enough to evaluate the incidence of slow-growing or delayed-onset cancers. Furthermore, history of cervical screening or previous hysterectomy was not included in registry study analysis, possibly leading to underestimation of CC incidence rates.Genital or chronic graft versus host disease is associated with an increase in high-grade cervical neoplasia and posttransplant HPV positivity.Inflammatory Bowel Disease: There is no strong evidence to support that inflammatory bowel disease alone increases cervical neoplasia or cancer risk. In contrast, immunosuppressant therapy does seem to increase the risk, although results of observational studies are conflicting regarding which type of immunosuppressant medication increases risk. Moreover, misclassification of cases may underestimate CC risk in this population. Recently published preventive care guidelines for women with inflammatory bowel disease taking immunosuppressive therapy recommend a need for continued long-term CC screening.Systemic Lupus Erythematosus and Rheumatoid Arthritis: The risk of cervical high-grade neoplasia and cancer was higher among women with systemic lupus erythematosus than those with rheumatoid arthritis (RA), although studies were limited by size, inclusion of women with low-grade neoplasia in main outcomes, and variability of disease severity or exposure to immunosuppressants. In studies designed to look specifically at immunosuppressant use, however, there did seem to be an increase in risk, identified mostly in women with RA. Although the strength of the evidence is limited, the increase in risk is consistent across studies.Type 1 DM: There is a paucity of evidence-based reports associating type 1 DM with an increased risk of cervical neoplasia and cancer.The panel proposed that CC screening guidelines for non-HIV immunocompromised women follow either the (1) guidelines for the general population or (2) current center for disease control guidelines for HIV-infected women. The following are the summaries for each group reviewed, and more details are noted in accompanying table:Solid Organ Transplant: The transplant population reflects a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance.Hematopoietic Stem Cell Transplant: These women have a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening. A new diagnosis of genital or chronic graft versus host disease in a woman post-stem cell transplant results in a greater risk of CC than in the general population and should result in more intensive screening and surveillance.Inflammatory Bowel Disease: Women with inflammatory bowel disease being treated with immunosuppressive drugs are at greater risk of cervical neoplasia and cancer than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance. Those women with inflammatory bowel disease not on immunosuppressive therapy are not at an increased risk and should follow screening guidelines for the general population.Systemic Lupus Erythematosus and Rheumatoid Arthritis: All women with systemic lupus erythematosus, whether on immunosuppressant therapy or not and those women with RA on immunosuppressant therapy have a greater risk of cervical neoplasia and cancer than the general population and should follow CC screening guidelines for HIV-infected women. Women with RA not on immunosuppressant therapy should follow CC screening guidelines for the general population.Type 1 Diabetes Mellitus: Because of a lack of evidence of increased risk of cervical neoplasia and cancer among women with type 1 DM, these women should follow the screening guidelines for the general population.

Ernährungsteams sind Einrichtungen in Krankenhäusern, die sowohl für den fachgerechten Einsatz von enteralen und parenteralen stationären Ernährungstherapien als auch für die Beratung zur ambulanten Ernährung zuständig sind. Im vorliegenden Beitrag wird näher auf die Organisation, die Zusammensetzung, die Aufgaben und Herausforderungen eines klinischen Ernährungsteams betreffend Patienten-Outcome und Kosten eingegangen., Many patients are malnourished at hospital admission. This condition further worsens improve during the hospitalisation. Malnutrition itself prolongs the length of hospital stay and the rehabilitation time, increases complication rates, morbidity, and mortality. Prompt reaction is needed to prevent these negative consequences, to maximise the success of therapy and to offer patients a better quality of life and a maintained autonomy. The early recognition of a poor nutritional status is therefore indispensable to initiate an efficient and timely nutritional therapy, according to individual needs. Multidisciplinary knowledge is needed to avoid potential complications as well as clearly defined responsibilities and structured processes. Thus, inter- and multiprofessional efforts clinical nutrition support teams have been created since the 70ies, mainly in the larger hospitals, to manage nutritional therapies. The main task of a clinical nutrition support team is to detect the risk for malnutrition, to prevent malnutrition by targeted measures and, when appropriate, to adequately treat it quickest possible. In the following, we will provide more details about organisation, composition, tasks, challenges of clinical nutrition support teams as wells as efficacy regarding patients’ outcome and briefly about costs.

Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer., International Agency for Research on Cancer

AIM: To examine oral biomarkers that have been associated with periodontal disease progression in HIV infected adults in perinatally HIV-infected and HIV-exposed but uninfected youth. MATERIAL AND METHODS: This was a cross-sectional, multi-center substudy of youth participating in the Oral Health Pediatric HIV/AIDS Cohort study. Gingival crevicular fluid repository samples from participants with and without periodontal disease (using Gingival Index and Bleeding on Probing parameters on dental examination) were tested for concentration levels of inflammatory biomarkers. Associations were assessed using Wilcoxon test and Spearman correlation. RESULTS: For perinatal HIV youth (n=129), the biobiomarkers consistently elevated (p

Importance The standard of care for refeeding inpatients with anorexia nervosa, starting with low calories and advancing cautiously, is associated with slow weight gain and protracted hospital stay. Limited data suggest that higher-calorie refeeding improves these outcomes with no increased risk of refeeding syndrome. Objective To compare the short-term efficacy, safety, and cost of lower-calorie vs higher-calorie refeeding for malnourished adolescents and young adults with anorexia nervosa. Design, setting, and participants In this multicenter randomized clinical trial with prospective follow-up conducted at 2 inpatient eating disorder programs at large tertiary care hospitals, 120 adolescents and young adults aged 12 to 24 years hospitalized with anorexia nervosa or atypical anorexia nervosa and 60% or more of median body mass index were enrolled from February 8, 2016, to March 7, 2019. The primary analysis was a modified intent-to-treat approach. Interventions Higher-calorie refeeding, beginning at 2000 kcal/d and increasing by 200 kcal/d vs lower-calorie refeeding, beginning at 1400 k/cal and increasing by 200 kcal every other day. Main outcomes and measures Main outcomes were end-of-treatment outcomes; the primary end point of this trial will be clinical remission over 12 months. Short-term efficacy was defined a priori as time to restore medical stability in the hospital, measured by the following 6 indices: 24-hour heart rate of 45 beats/min or more, systolic blood pressure of 90 mm Hg or more, temperature of 35.6 °C or more, orthostatic increase in heart rate of 35 beats/min or less, orthostatic decrease in systolic blood pressure of 20 mm Hg or less, and 75% or more of median body mass index for age and sex. The prespecified safety outcome was incidence of electrolyte abnormalities; cost efficacy was defined as savings associated with length of stay. Results Because 9 participants withdrew prior to treatment, the modified intention-to-treat analyses included 111 participants (93%; 101 females [91%]; mean [SD] age, 16.4 [2.5] years). Higher-calorie refeeding restored medical stability significantly earlier than lower-calorie refeeding (hazard ratio, 1.67 [95% CI, 1.10-2.53]; P = .01). Electrolyte abnormalities and other adverse events did not differ by group. Hospital stay was 4.0 days shorter (95% CI, -6.1 to -1.9 days) among the group receiving higher-calorie refeeding, which was associated with a savings of $19 056 (95% CI, -$28 819 to -$9293) in hospital charges per participant. Conclusions and relevance In the first randomized clinical trial in the US to compare refeeding approaches in patients with anorexia nervosa and atypical anorexia nervosa, higher-calorie refeeding demonstrated short-term efficacy with no increase in safety events during hospitalization. Trial registration ClinicalTrials.gov Identifier: NCT02488109.

Background: Several studies have demonstrated the presence of the Borrelia burgdorferi (Bb) genome in the myocardium of patients with dilated cardiomyopathy (DCM). To further support a causal relationship between the presence of Bb in the heart muscle and the development of DCM, demonstration of the absence of Bb in the myocardium of subjects with normal left ventricular (LV) systolic function is needed. Aim: To determine the prevalence of Bb by polymerase chain reaction (PCR) and electron microscopy (EM) in individuals with normal LV systolic function and no history suggestive of myocarditis. Methods: We investigated 50 patients (67 ± 9 years, 15 women) with normal LV ejection fraction (EF) ≥ 50% undergoing cardiac surgery. During surgery, four samples from the right atrial appendage were obtained and subsequently examined by PCR and EM for the presence of Bb, and by immunohistochemistry to detect inflammatory cells. Serological testing of antibodies against Bb was also performed. Results: Neither PCR nor EM detected Bb in any of the subjects. Immunohistological examination revealed myocardial inflammation in 2 individuals (4%). Serological analysis by enzyme-linked immunosorbent assay demonstrated IgM antibodies against Bb in 4% and IgG antibodies in 12% of the study cohort; Western blot revealed IgM as well as IgG positivity in 14% of patients. Conclusions: The absence of Bb in the myocardium of individuals who undergo cardiac surgery and have normal LV systolic function supports the idea of Bb pathogenicity in the development of DCM.

This diagnostic study compares the efficiency and effectiveness of 6 triage testing scenarios for screening women with high-risk human papillomavirus (HPV) for referral for colposcopy., Key Points Question What combination of human papillomavirus 16 (HPV-16) and HPV-18 genotyping with liquid-based cytological (LBC) testing is associated with the best performance for triaging women with HPV to detect cervical intraepithelial neoplasia ? Findings This diagnostic study included 36 212 participants in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage study and found that a combined triage strategy of HPV-16/HPV-18 genotyping with reflex LBC was associated with an increase in the relative sensitivity to detect cervical intraepithelial neoplasia grade 2 or higher compared with LBC testing alone. Meaning The combination of HPV-16/HPV-18 genotyping with reflex LBC may offer a reliable strategy for discriminating women at greater risk of cervical cancer, avoiding unnecessary anxiety and diagnostic procedures in primary cervical cancer screening among women with high-risk HPV., Importance Triage tests enhance the efficiency cervical cancer screening based on human papillomavirus (HPV), but the best approach for maximizing programmatic effectiveness is still uncertain, particularly in a real-world scenario. Objective To compare the clinical performance of 6 triage strategies based on liquid-based cytology (LBC) and HPV-16 and HPV-18 genotyping individually or in combination as sequential triage tests to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher among women with high-risk HPV. Design, Setting, and Participants This diagnostic study of routine cervical cancer screening was conducted at 100 primary health centers in Tlaxcala, Mexico. Women aged 30 to 64 years were recruited from August 1, 2013, to February 24, 2016, as part of the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage study. Six triage scenarios for referral to colposcopy were examined: (1) LBC testing that found atypical squamous cells of undetermined significance (ASC-US) or worse, (2) positive results in HPV-16 genotyping, (3) positive results in HPV-18 genotyping, (4) positive results in HPV-16/HPV-18 genotyping, (5) positive results in HPV-16 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse, and (6) positive results in HPV-16/HPV-18 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse. Data were analyzed from October 2017 to August 2018. Exposures Liquid-based cytological testing with simultaneous HPV-16 and HPV-18 genotyping. Women whose HPV genotyping results were positive for HPV-16 or HPV-18 or whose LBC results found ASC-US or worse and a random set of negative and normal results were referred to colposcopy with histologic analysis used for disease confirmation. Main Outcomes and Measures Clinical performance of each test strategy for detection of CIN grade 2 or higher. Secondary outcomes included resource utilization of each triage scenario, measured by the number of tests performed, the referral rate for colposcopy, and the numbers of colposcopies per CIN grade 2 or higher detected. Results A total of 36 212 women (median [interquartile range] age, 40 [35-47] years) were screened, and 4051 women (11.2%) had high-risk HPV. Of these women, 1109 (24.6%) were found to have HPV-16, HPV-18, or ASC-US or worse. Further histologic testing detected CIN grade 2 or higher in 110 of 788 women (14.0%) who underwent follow-up colposcopy. Sensitivity and specificity for 3 main triage strategies were 42.9% and 74.0% for LBC; 58.3% and 54.4% for HPV-16/HPV-18 genotyping; and 86.6% and 34.0% for HPV-16/HPV-18 genotyping with reflex LBC. The referral rate to colposcopy was 29% for HPV-16/HPV-18 with reflex LBC, which was 2-fold higher than the referral rate of 12% for LBC. Conclusions and Relevance Triage of women with high-risk HPV with HPV-16/HPV-18 genotyping with reflex LBC was significantly associated with improvement in detection of CIN grade 2 or higher compared with LBC alone. The benefit of disease prevented may outweigh the cost of increasing requirements for colposcopy services in settings with limited adherence to follow-up after a positive screening result.

Background Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) evaluates the motor spinal cord and identifies subclinical myelopathies. We used galvanic-VEMP to compare spinal cord function in individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) from asymptomatic status to HTLV-1-associated myelopathy (HAM). Methodology/Principal findings This cross-sectional study with 122 individuals included 26 HTLV-1-asymptomatic carriers, 26 individuals with possible HAM, 25 individuals with HAM, and 45 HTLV-1-seronegative individuals (controls). The groups were similar regarding gender, age, and height. Galvanic stimuli (duration: 400 ms; intensity: 2 mA) were applied bilaterally to the mastoid processes and VEMP was recorded from the gastrocnemius muscle. The electromyographic parameters investigated were the latency and amplitude of the short-latency (SL) and medium-latency (ML) responses. While SL and ML amplitudes were similar between groups, SL and ML latencies were delayed in the HTLV-1 groups compared to the control group (p

Background Microbially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth. We compared oral microbiome levels and associations with caries or periodontitis in 154 PHIV and 100 PHEU youth. Results Species richness and alpha diversity differed little between PHIV and PHEU youth. Group differences in average counts met the significance threshold for six taxa; two Corynebacterium species were lower in PHIV and met thresholds for noteworthiness. Several known periodontitis-associated organisms (Prevotella nigrescens, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Filifactor alocis) exhibited expected associations with periodontitis in PHEU youth, associations not observed in PHIV youth. In both groups, odds of caries increased with counts of taxa in four genera, Streptococcus, Scardovia, Bifidobacterium, and Lactobacillus. Conclusions The microbiomes of PHIV and PHEU youth were similar, although PHIV youth seemed to have fewer “health”-associated taxa such as Corynebacterium species. These results are consistent with the hypothesis that HIV infection, or its treatment, may contribute to oral dysbiosis. Electronic supplementary material The online version of this article (10.1186/s40168-018-0484-6) contains supplementary material, which is available to authorized users.

Guidelines recommend 3-year cervical cancer screening intervals to avoid unnecessary invasive procedures; however, regular testing remains critical. We evaluated trends in cervical cancer screening among low-income women receiving family planning-related services and their association with patient and provider characteristics.Using claims and enrollment data from California's publicly funded family planning program, we identified 540,026 women with a clinician visit at 216 sites between 2011 and 2015. We calculated guideline adherent cervical cancer testing rates for 6-month periods among women aged 21 to 24, 25 to 29, and 30 to 64 years. We also calculated guideline adherent chlamydia testing for women aged 21 to 24 years.Having a 3-year cervical cancer screening test declined for all age groups. The odds of cervical cancer screening declined for women aged 21 to 24 years by an estimated 11% every 6 months (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.89-0.90), a significantly greater decline than for the other age groups. Among women aged 21 to 29 years, the decrease was significantly larger for Latina (ratio of ORs = 0.95, 95% CI = 0.95-0.96) and Spanish-speaking (ratio of ORs = 0.95, 95% CI = 0.95-0.96) women compared with non-Latina and non-Spanish-speaking women. A smaller decline was seen for chlamydia screening.Changes in screening interval guidelines are associated with overall decreased screening. This trend was strongest among women aged 21 to 24 years, even as they continued to be screened appropriately for chlamydia, suggesting many missed opportunities. Efforts to reduce unnecessary cervical cancer screening should be monitored to maintain appropriate screening rates to avoid advanced-stage diagnoses and higher health care costs.

Zusammenfassung Hintergrund Die krankheitsassoziierte Mangelernährung (KAM) ist in Krankenhäusern ein häufiges Problem mit medizinischen und ökonomischen Folgen. Die vorliegende Vier-Jahres-Analyse soll zeigen, ob die Aufwände für die Ernährungstherapien der mangelernährten Patienten durch den Mehrertrag, der durch die Kodierung der KAM im SwissDRG-System erreicht wird, gedeckt werden. Material und Methodik In dieser Datenerhebung (2013 – 2016) wurden alle stationären Patienten mit einer E4-Diagnose im Universitätsspital Bern analysiert. Betrachtet wurden die E-Diagnose, Hauptdiagnose, Spitalaufenthaltsdauer, Alter, Art der Ernährungstherapie, Mehrertrag und Kosten, welche durch die ernährungstherapeutischen Behandlungen generiert wurden. Der Aufwand für die Ernährungsberatung, daas Pflegefachpersonal und die Ernährungstherapien wurde hochgerechnet. Zudem wurden die Patienten aufgrund ihrer Hauptdiagnose in 12 Gruppen eingeteilt (beruhend auf der WHO ICD-10-Klassifikation). Ergebnisse Von den stationären Patienten (n = 169 515) wurden insgesamt 5442 Fälle (3,2 %) in den betrachteten 4 Jahren mit einer KAM kodiert. Davon waren 462 Fälle (8,5 %) erlösrelevant. Von den 5442 Patienten erhielten 3211 (59 %) orale Trinknahrungen, 1578 (29 %) eine enterale Ernährung per Sonde und 653 (12 %) eine parenterale Ernährung. Die Kodierung der KAM ergab einen Mehrertrag von insgesamt CHF 3 494 081 und einen Aufwand von hochgerechnet CHF 2 803 432. Am häufigsten wurden onkologische Patienten mit einer KAM kodiert (n = 1708; 31,4 %), gefolgt von Patienten mit Krankheiten des Verdauungssystems (n = 671; 12,3 %) und des Kreislaufsystems (n = 609; 11,2 %). Schlussfolgerung Diese Analyse zeigt, dass der Mehrertrag durch die Kodierung der KAM im SwissDRG-System den finanziellen Aufwand für die Ernährungstherapien deckt. Die konsequente und frühzeitige Erfassung, Behandlung und Kodierung der KAM führt zu einer hohen Behandlungsqualität und -sicherheit für die Patienten und ist kostendeckend für das Krankenhaus.

Pressure ulcers (PUs) are a common and highly relevant professional care issues in hospitals. They are associated with psychological and physical suffering, increased morbidity and mortality rate and higher costs for health care worldwide (Baharestani, Black, Carville, et al., 2009a; Gorecki, Brown, Nelson, et al., 2009; Allman, Laperde, Noel, et al., 1999; Anthony, Reynolds, and Russell, 2004). PU development can be attributed to multiple factors that are fairly well-studied in adults and elderly people (Whittington and Briones, 2004; Horn, Bender, Ferguson, et al., 2004; de Laat, Schoonhoven, Pickkers, et al., 2006; Baharestani et al., 2009a). Through large-scale, nationwide epidemiological studies, the prevalence of PUs in medical care institutions for adults is now known and well documented.

In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.

ObjectivesThe American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential harms, and developing an official terminology.MethodsA systematic literature review was performed. A national survey of American Society for Colposcopy and Cervical Pathology members provided input on current terminology use. The 2011 International Federation for Cervical Pathology and Colposcopy terminology was used as a template and modified to fit colposcopic practice in the United States. For areas without data, expert consensus guided the recommendation. Draft recommendations were posted online for public comment and presented at an open session of the 2017 International Federation for Cervical Pathology and Colposcopy World Congress for further comment. All comments were considered for the final version.ResultsColposcopy is used in the evaluation of abnormal or inconclusive cervical cancer screening tests. Colposcopy aids the identification of cervical precancers that can be treated, and it allows for conservative management of abnormalities unlikely to progress. The potential harms of colposcopy include pain, psychological distress, and adverse effects of the procedure. A comprehensive colposcopy examination should include documentation of cervix visibility, squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), lesion(s) visibility, size and location of lesions, vascular changes, other features of lesion(s), and colposcopic impression. Minimum criteria for reporting include squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), and colposcopic impression.ConclusionsA recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.

Adams-Oliver syndrome (AOS) is a rare malformation syndrome characterized by the presence of two anomalies: aplasia cutis congenita of the scalp and transverse terminal limb defects. Many affected individuals also have additional malformations, including a variety of intracranial anomalies such as periventricular calcification in keeping with cerebrovascular microbleeds, impaired neuronal migration, epilepsy, and microcephaly. Cardiac malformations can be present, as can vascular dysfunction in the forms of cutis marmorata telangiectasia congenita, pulmonary vein stenoses, and abnormal hepatic microvasculature. Elucidated genetic causes include four genes in different pathways, leading to a model of AOS as a multi-pathway disorder. We identified an infant with mild aplasia cutis congenita and terminal transverse limb defects, developmental delay and a severe, diffuse angiopathy with incomplete microvascularization. Whole-genome sequencing documented two rare truncating variants in DOCK6, a gene associated with a type of autosomal recessive AOS that recurrently features periventricular calcification and impaired neurodevelopment. We highlight an unexpectedly high frequency of likely deleterious mutations in this gene in the general population, relative to the rarity of the disease, and discuss possible explanations for this discrepancy.