Uptake of postplacental intrauterine device placement at cesarean delivery.

BACKGROUND: Several studies have investigated the effectiveness of intrauterine device placement at cesarean delivery as a contraceptive method. However, national-level use and outcomes of a postplacental intrauterine device at cesarean delivery are currently understudied in the United States. OBJECTIVE: This study aimed to examine the trends, characteristics, and outcomes of patients who received a postplacental intrauterine device at cesarean delivery. STUDY DESIGN: This retrospective cohort study used the National Inpatient Sample. The study cohort included patients who underwent cesarean delivery from October 2015 to December 2018. The exclusion criteria included hemorrhage, chorioamnionitis, uterine anomaly, hysterectomy, and permanent surgical sterilization. Eligible cases were grouped on the basis of the use of a postplacental intrauterine device at cesarean delivery. The primary outcome measures were temporal trends and characteristics associated with the use of a postplacental intrauterine device at cesarean delivery, assessed using the generalized estimating equation model in multivariable analysis. The secondary outcome measure was perioperative morbidity (leukocytosis, endometritis, myometritis, and sepsis). Propensity score matching was used to balance the baseline characteristics. RESULTS: Among 2,983,978 patients who met the inclusion criteria, 10,145 patients (0.3%) received a postplacental intrauterine device at cesarean delivery. The use of a postplacental intrauterine device increased from 0.1% in the fourth quarter of 2015 to 0.6% in the fourth quarter of 2018 (P<.001). In a multivariable analysis, the use of a postplacental intrauterine device increased by 14% every quarter-year (adjusted odds ratio, 1.14; 95% confidence interval, 1.13-1.15). In addition, (1) patient characteristics of young age, non-White race, obesity, tobacco use, lowest quartile median household income, and insured with Medicaid; (2) hospital characteristics of large bed capacity and urban teaching setting in Northeast region; and (3) pregnancy characteristics of early gestational age at cesarean delivery, hypertensive disease, previous cesarean delivery, multifetal pregnancy, grand multiparity, placenta previa, and nonelective cesarean delivery represented the independent characteristics associated with the use of a postplacental intrauterine device (all P<.05). A regression tree model identified 35 discrete patterns of the use of a postplacental intrauterine device based on 8 factors (time, race or ethnicity, primary expected payer, obesity, hospital bed capacity, hospital teaching status, hospital region, and previous cesarean delivery). There were 9 patterns, representing 8.8% of the study population, exhibiting a use rate of ≥1.0%, whereas there were 7 patterns, representing 16.0% of the study population, exhibiting no use of a postplacental intrauterine device (absolute rate difference from the highest group to the lowest group, 4.7%). In a propensity score-matched model, postplacental intrauterine device placement at cesarean delivery was not associated with increased risk of measured morbidity (any, 1.8% vs 1.7%; odds ratio, 1.06; 95% confidence interval, 0.66-1.69; P=.812), including postpartum endometritis (1.2% vs 1.0%; odds ratio, 1.19; 95% confidence interval, 0.67-2.14; P=.554). CONCLUSION: The use of a postplacental intrauterine device at cesarean delivery increased significantly in recent years in the United States.

Impact of alternative histopathology protocols in the dermatopathology laboratory: A prospective quality improvement study.

BACKGROUND: Histopathology protocols for processing dermatopathology specimens vary among laboratories. OBJECTIVE: To determine an optimal histopathology protocol to minimize cost and turnaround time (TAT) for biopsy specimens in a dermatopathology laboratory. METHODS: A prospective, 4-month study compared the mean cost and TAT of producing one versus two initial H&E slides, and zero versus three unstained slides that could be used for frequently used special or immunohistochemical (IHC) stains. RESULTS: For all cases, cost was lower for one versus two initial H&E slides, with an insignificant increase in TAT. Producing three vs zero unstained slides incurred higher cost, with no reduction in TAT. In a subset of cases in which frequently used special or IHC stains were performed, cost and TAT were optimized by producing one initial H&E and three unstained slides. CONCLUSION: A protocol of one initial H&E slide and zero unstained slides optimizes cost and TAT in our dermatopathology laboratory. Pigmented lesions and inflammatory dermatoses may benefit from the addition of unstained slides. Further study is needed to quantify this benefit and evaluate for other cases for which an alternative protocol is advantageous.

PTPN11 Mosaicism Causes a Spectrum of Pigmentary and Vascular Neurocutaneous Disorders and Predisposes to Melanoma.

Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic group and high-depth next-generation sequencing of affected tissues, we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis pigmentovascularis type III or spilorosea. Within an individual, the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to show that the same variants can cause either the pigmentary or vascular phenotypes alone, and drive melanoma development within pigmentary lesions. Protein structure modeling highlights that although variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modeling of the missense variants confirms downstream MAPK pathway overactivation and widespread disruption of human endothelial cell angiogenesis. Importantly, patients with PTPN11 mosaicism theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of nevus spilus and capillary malformation syndromes, paving the way for better clinical management.

Association of Persistent Rubella Virus With Idiopathic Skin Granulomas in Clinically Immunocompetent Adults.

Importance: Vaccine-derived and wild-type rubella virus (RuV) has been identified within granulomas in patients with inborn errors of immunity, but has not been described in granulomas of healthy adults. Objective: To determine the association between RuV and atypical granulomatous inflammation in immune-competent adults. Design, Setting, and Participants: This case series, conducted in US academic dermatology clinics from January 2019 to January 2021, investigated the presence of RuV in skin specimens using RuV immunofluorescent staining of paraffin-embedded tissue sections, real-time reverse-transcription polymerase chain reaction, whole-genome sequencing with phylogenetic analyses, and cell culture by the US Centers for Disease Control and Prevention. Rubella immunoglobulin G, immunoglobulin M enzyme-linked immunoassay, and viral neutralization assays were performed for the sera of immunocompetent individuals with treatment refractory cutaneous granulomas and histopathology demonstrating atypical palisaded and necrotizing granulomas. Clinical immune evaluation was performed. Main Outcomes and Measures: Identification, genotyping, and culture of vaccine-derived and wild-type RuV within granulomatous dermatitis of otherwise clinically immune competent adults. Results: Of the 4 total immunocompetent participants, 3 (75%) were women, and the mean (range) age was 61.5 (49.0-73.0) years. The RuV capsid protein was detected by immunohistochemistry in cutaneous granulomas. The presence of RuV RNA was confirmed by real-time reverse-transcription polymerase chain reaction in fresh-frozen skin biopsies and whole-genome sequencing. Phylogenetic analysis of the RuV sequences showed vaccine-derived RuV in 3 cases and wild-type RuV in 1. Live RuV was recovered from the affected skin in 2 participants. Immunology workup results demonstrated no primary immune deficiencies. Conclusions and Relevance: The case series study results suggest that RuV (vaccine derived and wild type) can persist for years in cutaneous granulomas in clinically immunocompetent adults and is associated with atypical (palisaded and necrotizing type) chronic cutaneous granulomas. These findings represent a potential paradigm shift in the evaluation, workup, and management of atypical granulomatous dermatitis and raises questions regarding the potential transmissibility of persistent live RuV.

Knuckle pads: an ancient disease frequently misdiagnosed because of minimal modern attention.

Knuckle pads are benign painless papules and nodules that most commonly appear on the extensor surfaces of the proximal interphalangeal joints. Knuckle pads are frequently misdiagnosed due to their location overlying joints, which can lead to costly interventions and patient discomfort for a relatively harmless condition. We describe a 44-year-old woman who presented with mildly painful nodules on multiple bilateral proximal interphalangeal joints. The patient did not have a family history of fibromatosis and the rheumatoid factor was negative. Histology showed mild epidermal hyperkeratosis, papillomatosis, and acanthosis with a deep dermal, poorly circumscribed, proliferative nodule made of spindled myofibroblasts without cytological atypia. The diagnosis of knuckle pads was established based on the clinical and morphological presentation of the nodules. Treatment with intralesional triamcinolone acetonide injection produced significant clinical improvement. Our findings highlight the challenging diagnosis of knuckle pads and the importance of increasing the familiarity of knuckle pads in modern medical practice.

Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth.

PURPOSE: Somatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1. METHODS: Affected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity. RESULTS: The phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone. CONCLUSION: Somatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway.

Reactive angioendotheliomatosis associated with antiphospholipid syndrome.

Reactive angioendotheliomatosis (RAE) is an uncommon, benign, antiproliferative condition associated with systemic diseases that may cause occlusion or inflammation of the vascular lumina. A link between antiphospholipid syndrome (APS) and RAE has been reported a few times in the literature. Herein, we present a unique case of RAE diagnosed in a patient with primary APS who was well-managed on warfarin and rituximab with no recent thrombotic events. As RAE can precede or follow a diagnosis of APS, the presence of the condition indicates a need to workup for APS and to ensure those with the condition are adequately anticoagulated. However, as demonstrated in this case, the condition can still occur in patients who are adequately anticoagulated.

Sex difference in the immunogenicity of the quadrivalent Human Papilloma Virus vaccine: Systematic review and meta-analysis.

BACKGROUND: Immunological differences between males and females in response to viral vaccines are well known. This the first review to examine them for the Human Papilloma Virus. METHODS: We conducted a systematic review and meta-analysis of the immunogenicity of the Quadrivalent Human Papilloma Virus Vaccine qHPVV. We searched Medline, Embase, and CENTRAL for trials published until September 17, 2019. Inclusion criteria were 3-doses and reporting geometric mean titers (GMTs). We performed random-effects meta-analyses and meta-regression separated by age group and sex. RESULTS: Our search yielded 1809 unique studies. 334 full texts were screened and data from 18 studies were extracted. Females had higher pooled geometric mean titers than males in all age groups. Log transformed GMTs in male children (<16) years were: against HPV6: 6·62 (95% CI 6·29-6·94; I2 = 86·0%), against HPV11: 7·07 (95% CI 6·90-7·23; I2 = 63.1%), against HPV16: 8·53 (95% CI 8·28-8·78; I2 = 73·0%), and against HPV18 7·21 (95% CI 7·08-7·34; I2 = 26·4%). In females: against HPV6 7·10 (95% CI 6·79-7·41; I2 = 96·6%), HPV11: 7·32 (95% CI 7·15-7·50; I2 = 90·6%), HPV16: 8·71 (95% CI 8·52-8·91; I2 = 90·2%), and HPV18 7·35 (95% CI 7·11-7·58; I2 = 92·7%). In the meta-regression, the sexual difference was significant for HPV6 (p = 0·022) with a similar tendency for HPV11 (p = 0·066) and HPV18 (p = 0·079). Immunogenicity was significantly higher in children (<16) than in adults (p < 0·001). CONCLUSION: Females have higher antibody titers against HPV after receiving the qHPVV than do males. The difference is bigger in low-risk HPV strains. Adjusting the doses and schedules for each sex should be explored further.

Generalized infantile myofibromatosis with visceral involvement presenting as diffuse hypopigmented macules at birth.

The initial clinical presentation of infantile myofibromatosis can vary from subtle skin changes to large tumors. Here, we describe a case of congenital generalized infantile myofibromatosis which presented with diffuse hypopigmented macules, some with subtle atrophy and telangiectasia. Further workup revealed visceral involvement which led to treatment with systemic chemotherapy. Awareness of this rare clinical presentation is crucial to expedite workup and treatment given the poor prognosis in infants with visceral involvement.

Rubella Vaccine Persistence Within Cutaneous Granulomas in Common Variable Immunodeficiency Disorder.

Common variable immunodeficiency disorder is a primary immunodeficiency disorder characterized by reduced levels of serum immunoglobulins and impaired antibody response. This condition may be associated with development of noninfectious granulomatous dermatitis of the skin which may be disfiguring and destructive. There are no published guidelines for the treatment of cutaneous granulomas in this patient population. In recent studies, rubella virus-positive cells in granulomas were localized to M2 macrophages which have an important role in wound healing and the secretion of immunoregulatory cytokines. We present a case of treatment-refractory, disfiguring common variable immunodeficiency disorder-associated granulomatous dermatitis. Immunofluorescence microscopy of the biopsy specimen confirmed the presence of rubella vaccine capsid proteins in M2 macrophages within the granuloma, a newly recognized phenomenon in this patient population. This knowledge may serve to identify future therapeutic targets or preventative strategies for granulomatous dermatitis in patients with primary immunodeficiency disorder.

Body height and waist circumference of young Swiss men as assessed by 3D laser-based photonic scans and by manual anthropometric measurements.

Overweight and obesity are considered among the major health concerns worldwide. The body mass index is a frequently used measure for overweight and obesity and is associated with common non-communicable diseases such as diabetes type II, cardiovascular diseases and certain cancers. However, the body mass index does not account for the distribution of body fat and relative fat to muscle mass. 3D laser-based photonic full body scans provide detailed information on various body circumferences, surfaces, and volumes as well as body height and weight (using an integrated scale). In the literature, body scans showed good feasibility, reliability, and validity, while also demonstrating a good correlation with health parameters linked to the metabolic syndrome. However, systematic differences between body scan derived measurements and manual measurements remain an issue. This study aimed to assess these systematic differences for body height, waist circumference, and body mass index using cross-sectional data from a homogenous sample of 52 young Swiss male volunteers. In addition to 3D laser-based photonic full body scans and correlative manual measurements, body fat distribution was assessed through bioelectrical impedance analysis. Overall, an excellent correlation was found between measurements of waist circumference and body mass index, and good correlation between body mass index and total fat mass, as well as between waist circumference and visceral fat mass as assessed by bioelectrical impedance analysis. Volunteers were shorter in height measured by body scan when compared to manual measurements. This systematic difference became smaller when volunteers stood in the scanner in a completely upright position with their feet together. Waist circumference was slightly smaller for manual measurements than for body scan derived values. This systematic difference was larger in overweight volunteers compared to leaner volunteers.

Cutaneous metastases of papillary renal cell carcinoma: A case report and review of the literature.

Papillary renal cell carcinoma (RCC) is an uncommon subtype of RCC that is typically encountered at early stages and has a high survival rate. Histopathology typically shows well-defined papillary architecture with tumor cells lining fibrovascular cores and can be further subdivided into type 1 and type 2 tumors based on cytology and genetic basis. Type 1 tumors have a single layer of basophilic cells and low nuclear atypia, while type 2 tumors have a pseudostratified layer of eosinophilic cells and high nuclear atypia. Some tumors have overlapping features of both types. We present a unique case of cutaneous metastases of papillary RCC with typical papillary architecture in the dermis and review the literature on this rare entity.

Effects of ritonavir-boosted protease inhibitors on combined oral contraceptive pharmacokinetics and pharmacodynamics in HIV-positive women.

OBJECTIVE: To assess the pharmacokinetics of combined oral contraceptive (COC) components and prevalence of ovulation in HIV-positive women using ritonavir-containing antiretroviral regimens compared to those using regimens previously found not to interact with COCs or not using any antiretrovirals. STUDY DESIGN: We conducted a prospective cohort pharmacokinetic pilot study comparing the pharmacokinetics of levonorgestrel (LNG) and ethinyl estradiol (EE) in HIV-positive women taking ritonavir-containing antiretroviral regimens to those in women using non-ritonavir-containing regimens or no antiretrovirals. Participants received COCs containing LNG/EE 150/30 mcg for 21 days. Beginning day 21, we collected serial blood samples over 72 h. The primary outcome was area under the curve (AUC) of LNG, with secondary outcomes including other LNG pharmacokinetic measures, EE pharmacokinetics and ovulation as measured by serum progesterone. RESULTS: Pharmacokinetic parameters of LNG showed a trend toward increased exposure in women on ritonavir. LNG AUClast increased by 32.6% (312±60.9 vs. 243±82.6 ng/mL*h, p=.033, n=5) in women taking ritonavir compared to the control group (n=10). The Cmax (9.68±1.81 vs. 7.62±2.29 ng/mL) and Cmin (4.97±1.15 vs. 3.70±1.29 ng/mL) were also higher in the ritonavir arm. After excluding the inconsistent users (n=2), CL of LNG was reduced in the ritonavir arm (p=.032). EE pharmacokinetic profiles were not different between groups. The progesterone concentrations were similar in women of both groups, and none were consistent with ovulation during the treatment cycle. CONCLUSION: Women on ritonavir showed an approximately 30% increase in LNG exposure but no difference in EE exposure. IMPLICATIONS: The current data suggest that ritonavir does not have a clinically significant impact on oral contraceptive pharmacokinetics.

Pulmonary arterial pressure at rest and during exercise in chronic mountain sickness: a meta-analysis.

Up to 10% of the more than 140 million high-altitude dwellers worldwide suffer from chronic mountain sickness (CMS). Patients suffering from this debilitating problem often display increased pulmonary arterial pressure (PAP), which may contribute to exercise intolerance and right heart failure. However, there is little information on the usual PAP in these patients.We systematically reviewed and meta-analysed all data published in English or Spanish until June 2018 on echocardiographic estimations of PAP at rest and during mild exercise in CMS patients.Nine studies comprising 287 participants fulfilled the inclusion criteria. At rest, the point estimate from meta-analysis of the mean systolic PAP was 27.9 mmHg (95% CI 26.3-29.6 mmHg). These values are 11% (+2.7 mmHg) higher than those previously meta-analysed in apparently healthy high-altitude dwellers. During mild exercise (50 W) the difference in mean systolic PAP between patients and high-altitude dwellers was markedly more accentuated (48.3 versus 36.3 mmHg) than at rest.These findings indicate that in patients with CMS PAP is moderately increased at rest, but markedly increased during mild exercise, which will be common with activities of daily living.

Clustering of sociodemographic and lifestyle factors among adults with excess weight in a multilingual country.

OBJECTIVE: The aim of this study was to identify and cluster potential sociodemographic and lifestyle determinants of excess weight (body mass index ≥ 25 kg/m2) in Switzerland. METHODS: Participants of the cross-sectional National Nutrition Survey menuCH (2014-2015, n = 2057) were categorized according to body mass index. Logistic regressions were conducted with sociodemographic (age, language region, education, household income, household status) and lifestyle factors (smoking, self-rated health status, physical activity, energy intake, Alternate Healthy Eating Index) to identify determinants of excess weight. Factorial analysis and clustering were applied to identify patterns among individuals with excess weight (n = 891). RESULTS: Poor or very poor self-rated health status and low levels of physical activity were associated with increased odds for obesity in men (odds ratio [OR] = 5.39 [95% confidence interval = 5.30-5.48], OR = 2.51 [2.14-2.95], respectively) and women (OR = 12.40 [11.59-13.26], OR = 4.83 [3.04-7.67], respectively). In both sexes, the Alternate Healthy Eating Index score was inversely associated with the probability of having obesity. Cluster analysis identified four distinct patterns: "young living with parents" (14.6%), "men with high educational level" (41.5%), "women living alone" (34.9%), and "low educational level and Italian language region" (9.0%). CONCLUSIONS: We identified four discrete subgroups of individuals with excess weight who differed by sociodemographic and lifestyle factors. Such subgroups may prove useful for targeted public health interventions.

Retention in care of HIV-infected children from HIV test to start of antiretroviral therapy: systematic review.

BACKGROUND: In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined. METHODS: We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate. RESULTS: Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years. CONCLUSION: Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.

Chlamydia control activities in Europe: cross-sectional survey.

BACKGROUND: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. METHODS: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. RESULTS: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). CONCLUSION: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes.