Current State of Platelet-rich Plasma in the Treatment of Rheumatic Disease: A Retrospective Review of the Literature.

INTRODUCTION: Rheumatic diseases are a spectrum of autoimmune or inflammatory diseases that cause damage to the musculoskeletal system as well as vital organs, such as the heart, lungs, kidneys, and central nervous system. METHODS: The study of rheumatic disease has made great progress in the understanding and management of these conditions in the last few decades using disease-modifying antirheumatic drugs and synthesized biological immunomodulating therapies. However, one potential treatment that has not been well investigated in rheumatic disease is platelet-rich plasma (PRP). PRP is proposed to facilitate the healing of injured tendons and ligaments through a variety of mechanisms, including mitogenesis, angiogenesis and macrophage activation via cytokine release, although its exact mechanism is unclear. RESULT: There has been a great deal of work in determining the exact preparation method and composition of PRP for regenerative purposes in orthopedic surgery, sports medicine, dentistry, cardiac surgery, pediatric surgery, gynecology, urology, plastic surgery, ophthalmology, and dermatology. Despite this, there is a paucity of research on the impact of PRP on rheumatic disease. CONCLUSION: This study aims to summarize and evaluate the current research concerning the use of PRP in rheumatic disease.

Celecoxib-tramadol co-crystal in patients with moderate-to-severe pain following bunionectomy with osteotomy: A phase 3, randomized, double-blind, factorial, active- and placebo-controlled trial.

BACKGROUND: Celecoxib-tramadol co-crystal (CTC) is a first-in-class analgesic co-crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co-crystal structure, compared with its active constituents administered alone/concomitantly. AIM: We evaluated CTC in moderate-to-severe acute postoperative pain. MATERIALS AND METHODS: This randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate-to-severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac-tramadol hydrochloride] every 12 h), tramadol (50 mg every 6 h), celecoxib (100 mg every 12 h), or placebo for 48 h. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0-48 h sum of pain intensity differences (SPID0-48) in all randomized patients. Pain intensity was assessed on a 0-10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals. RESULTS: In 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n = 184), tramadol (n = 183), celecoxib (n = 181), or placebo (n = 89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID0-48 (least-squares mean: -139.1 [95% confidence interval: -151.8, -126.5]) than tramadol (-109.1 [-121.7, -96.4]; p < 0.001), celecoxib (-103.7 [-116.4, -91.0]; p < 0.001), or placebo (-74.6 [-92.5, -56.6]; p < 0.001). Total treatment-emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug-related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths. CONCLUSION: CTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the United States.

Likelihood of hip infection with image-guided hip aspiration dry tap: a 10-year retrospective study.

OBJECTIVE: To determine the rate of infection in patients with suspected hip septic arthritis who underwent image-guided aspiration (IHA) resulting in dry-tap, diagnostic value of subsequent lavage and re-aspiration, and if pre-aspiration MRI can help prevent a dry tap. MATERIALS AND METHODS: Retrospective review between 2010 to 2020 identified native hip (NH) and total hip arthroplasty (THA) patients who had a dry-tap following aspiration for suspected infection or periprosthetic joint infection (PJI). Serology tests, lavage/re-aspiration volumes, and aspirate cell-count/culture were assessed. On pre-aspiration MRI, presence/grade of joint effusion (JE), pseudocapsule dehiscence (PD), extraarticular fluid and sinus-tract were recorded. RESULTS: Out of 215 included dry-taps, 185 (86.0%) were non-infected and 30 (13.9%) infected. In subgroup analysis, 64/71(90.1%) NH and 121/144(84.0%) THA dry-taps were non-infected. Pre-aspiration MRI of THA group with dry-tap showed significant findings; PD with extraarticular fluid (8/12, 66.7%) and sinus tract (7/12, 58.3%) were higher in the infected compared to non-infected group (5/42, 11.9% and 0/42, 0.0%) (both p < 0.001). Among THA group, polymorphonuclear-leukocytes > 80% was present in 8/9 (88.9%) of infected versus 4/28 (14.3%) non-infected group (p < 0.001). Multivariable regression showed PD (p = 0.005) and JE (p = 0.042) being significant independent predictors of PJI, similarly the elevated CRP (p = 0.044) and JE (p = 0.017). CONCLUSION: Majority of patients suspected of hip joint infection with dry-tap were non-infected. Synovial PMN% following lavage maintains high sensitivity for detection of PJI. In patients with THA, PD and subsequent extraarticular collection can be associated with dry-tap therefore, pre-aspiration MRI can help determine their presence and plan the aspiration.

Comparing the Ratio of Therapist Support to Internet Sessions in a Blended Therapy Delivered to Trauma-Exposed Veterans: Quasi-experimental Comparison Study.

BACKGROUND: Blended models of therapy, which incorporate elements of both internet and face-to-face methods, have been shown to be effective, but therapists and patients have expressed concerns that fewer face-to-face therapy sessions than self-guided internet sessions may be associated with lower therapeutic alliance, lower program completion rates, and poorer outcomes. OBJECTIVE: A multisite quasi-experimental comparison study with a noninferiority design implemented in routine clinical care was used to assess webSTAIR, a 10-module blended therapy derived from STAIR (skills training in affective and interpersonal regulation) for trauma-exposed individuals delivered with 10 weekly therapist sessions (termed Coach10) compared to 5 biweekly sessions (Coach5). It was hypothesized that Coach5 would be as good as Coach10 in a range of outcomes. METHODS: A total of 202 veterans were enrolled in the study with 101 assigned to Coach5 and 101 to Coach10. Posttraumatic stress disorder (PTSD) symptoms, depression, emotion regulation, interpersonal problems, and social functioning measures were collected pre-, mid-, and posttreatment, and at a 3-month follow-up. Noninferiority analyses were conducted on symptom outcome measures. Comparisons were made of continuous and categorical measures regarding participant and therapist activities. RESULTS: Participants reported moderate to severe levels of baseline PTSD, depression, or both. Significant reductions were obtained in all symptom measures posttreatment and at the 3-month follow up. Coach5 was not inferior to Coach10 in any outcome. Therapeutic alliance was at an equivalently high level across the 2 treatment conditions; completion rates and web usage were similar. Total session time was substantially less for the Coach5 therapists than the Coach10 therapists. Both programs were associated with a low, but equal number of therapist activities related to scheduling and crisis or motivational sessions. CONCLUSIONS: A blended model delivered with 5 sessions of therapist support was noninferior to 10 sessions in individuals with moderate to severe symptoms. Future studies identifying patient characteristics as moderators of outcomes with high versus low doses of therapist support will help create flexible, technology-based intervention programming.

PPARdelta activation induces metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes.

Pluripotent stem-cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease, but they are functionally and structurally immature. Here, we induce efficient human PSC-CM (hPSC-CM) maturation through metabolic-pathway modulations. Specifically, we find that peroxisome-proliferator-associated receptor (PPAR) signaling regulates glycolysis and fatty acid oxidation (FAO) in an isoform-specific manner. While PPARalpha (PPARa) is the most active isoform in hPSC-CMs, PPARdelta (PPARd) activation efficiently upregulates the gene regulatory networks underlying FAO, increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation, and augments FAO flux. PPARd activation further increases binucleation, enhances myofibril organization, and improves contractility. Transient lactate exposure, which is frequently used for hPSC-CM purification, induces an independent cardiac maturation program but, when combined with PPARd activation, still enhances oxidative metabolism. In summary, we investigate multiple metabolic modifications in hPSC-CMs and identify a role for PPARd signaling in inducing the metabolic switch from glycolysis to FAO in hPSC-CMs.

Ultrasound-Guided Injection Treatments Versus Surgical Neurectomy for Morton Neuroma: A Cost-Effectiveness Analysis.

BACKGROUND. Morton neuroma is a common, painful disorder of the foot with multiple treatment options of varying cost and effectiveness. OBJECTIVE. The aim of this study was to determine the most cost-effective treatment pathway for symptomatic Morton neuromas when conservative management has failed. METHODS. An incremental cost-utility analysis was performed comparing a direct to surgical neurectomy strategy with three selective injection strategies in which one or more ultrasound-guided injection therapies was tried first before surgery for patients who did not respond to treatment. The three selective injection strategies were selective steroid injection, selective alcohol injection, and selective steroid/alcohol injection in which both steroid injections and alcohol sclerosing injections were trialed successively before surgical neurectomy. The direct-to-surgery approach was compared with the three different selective injection strategies and with a no-treatment strategy in a decision-analytic model for a hypothetical group of patients with symptomatic Morton neuroma in whom conservative management had failed. Model parameters, including treatment costs, effectiveness, complication rates, and health utility states, were estimated from the literature, reimbursement databases, and expert opinion. The outcome was cost per quality-adjusted life year (QALY) with a time horizon of 3 years. A societal cost perspective was adopted with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses for key model parameters were performed. RESULTS. For the base input values, the steroid/alcohol selective injection strategy was dominant and yielded an incremental cost-effectiveness ratio of $4401.61/QALY compared with no treatment. The probabilistic sensitivity analysis supported this strategy in 74% of 10,000 simulated trials. Results were robust with low sensitivity to most input parameters. However, when the probability of successful alcohol injection treatment dropped below 40%, the steroid selective injection strategy became most cost-effective. CONCLUSION. A trial of ultrasound-guided injection therapies for Morton neuroma is a cost-effective strategy compared with proceeding directly to surgical neurectomy. CLINICAL IMPACT. Ultrasound-guided injection therapies are indicated as first-line treatment of patients with symptomatic Morton neuromas when conservative management fails.

Increasing access to care for trauma-exposed rural veterans: A mixed methods outcome evaluation of a web-based skills training program with telehealth-delivered coaching.

PURPOSE: While rural veterans with trauma exposure report high rates of posttraumatic stress disorder (PTSD), depression, and functional impairment, utilization of health services is low. This pilot study used mixed qualitative and quantitative methods to evaluate the potential benefits of a transdiagnostic web-based skills training program paired with telehealth-delivered coaching to address a range of symptoms and functional difficulties. The study directed substantial outreach efforts to women veterans who had experienced military sexual trauma given their growing representation in the Veterans Healthcare Administration (VHA) and identified need for services. METHODS: Participants were 32 trauma-exposed veterans enrolled in rural-serving VHA facilities who screened positive for either PTSD or depression. Symptoms of PTSD, depression, emotion regulation, and interpersonal problems were assessed at baseline, midpoint, posttreatment, and 3-month follow-up. Veterans completed exit interviews to identify benefits and limitations of the program. RESULTS: Intent-to-treat analyses revealed significant symptom reduction for all outcomes, with large to moderate effect sizes at 3-month follow-up. Outcomes did not differ by gender or military sexual trauma status. Veterans' rating of the therapeutic alliance was high and interview responses indicated that the presence of the coach was critical to success in the program. CONCLUSION: This remotely delivered transdiagnostic intervention provided significant benefits across a range of symptoms and functional outcomes and was viewed positively by veterans. The results indicate that further research (ie, a randomized controlled trial) is warranted. Attention to the role of the coach as a means by which to increase engagement and retention in technology-delivered interventions is warranted.

Effect of the presence of amniotic fluid for optical transabdominal fetal monitoring using Monte Carlo simulations.

About a third of babies are delivered by Cesarean section. There has been an increase in maternal deaths during labor due to complications with subsequent births after a C-section. Therefore, there is a clinical motivation to reduce the C-section rate. Current techniques are, however, inefficient at determining fetal distress leading to a high false positive rate for complications and ultimately a C-section. For the current study, Monte Carlo simulations were used to calculate the amount of signal received on a model of a pregnant mother, as well as, the percent of the signal that comes from the fetal layer. Models with and without a 1 mm amniotic fluid were compared and showed differing trends.

A Three-Year Analysis of the Impact of a Student-Run Gynecology Clinic on Access to Reproductive Health Care for Uninsured Women in East Harlem.

The East Harlem Health Outreach Partnership (EHHOP) is a medical student-run and attending-supervised clinic that provides primary care to predominantly Spanish-speaking, uninsured patients living in East Harlem, New York. In 2010, the clinic launched a Women's Health Clinic (WHC), to offer comprehensive gynecologic and reproductive healthcare under the guidance of faculty gynecologists. In this cross-sectional study, we analyzed WHC data from January 2018 to March 2021. Over this period, 59 individual patients were seen over 39 clinical sessions through a total of 164 clinical encounters staffed by 43 medical students and 19 faculty preceptors from the Department of Obstetrics and Gynecology at Mount Sinai. The most common reasons for referral to the EHHOP WHC were abnormal uterine bleeding, contraception counseling, and management of abnormal Pap smears; the most common procedures performed were Pap smears, long-acting reversible contraception placements and removals, and colposcopies. We discuss the critical role that student-run, physician-supervised reproductive health clinics play in reducing disparities in gynecologic care for uninsured women.

A Resource Building Virtual Care Programme: improving symptoms and social functioning among female and male rural veterans.

Background: Veterans have higher rates of PTSD and depression compared to the general population and experience substantial functional impairment. Impairment in social functioning has been a significant concern among Veterans, particularly rural Veterans, who have limited access to mental health care and are at risk for social isolation. Objective: A mixed-method study was implemented to evaluate the feasibility and effectiveness of webSTAIR, a web-based skills training programme, paired with home-based telehealth sessions. It was hypothesized that the programme would lead not only to reductions in PTSD and depression but also to improvements in social functioning. Method: Participants were 80 trauma-exposed Veterans enrolled in rural-serving VHA facilities with clinically elevated symptoms of either PTSD or depression. The study directed substantial outreach efforts to rural women Veterans and those who have experienced military sexual trauma (MST). Results: Significant improvements were obtained with PTSD and depression symptoms as well as in social functioning, emotion regulation, and interpersonal problems at post-treatment and 3-month follow-up. Ratings of therapeutic alliance were high as were reports of overall satisfaction in the programme. There were no differences by gender or MST status in symptom outcomes or satisfaction. Conclusions: The results support the feasibility and effectiveness of this integrated telehealth web-based skills training programme for both male and female Veterans as well as for those with and without MST. The focus on resource building and improved functioning make this programme of particular interest. Further testing is warranted.

Antecedentes: Los veteranos tienen tasas más altas de TEPT y depresión en comparación con la población general y experimentan un deterioro funcional sustancial. El deterioro del funcionamiento social ha sido una preocupación importante entre los Veteranos, particularmente los Veteranos rurales, que tienen acceso limitado a la atención de salud mental y están en riesgo de aislamiento social, lo que contribuye significativamente a problemas de salud.Objetivo: Se implementó un estudio de método mixto para evaluar la viabilidad y efectividad de webSTAIR, un programmea de capacitación en habilidades basado en la web, combinado con sesiones de telesalud en el hogar. Se planteó la hipótesis de que el programmea conduciría no solo a reducciones en el trastorno de estrés postraumático y la depresión, sino también a mejoras en el funcionamiento social.Método: Los participantes fueron 80 Veteranos expuestos a traumas inscritos en el sistema VHA de servicio rural, con síntomas clínicamente elevados de TEPT o depresión. El estudio dirigió importantes esfuerzos de divulgación a las mujeres rurales Veteranas y aquellas que han experimentado un trauma sexual militar (TSM).Resultados: Se obtuvieron mejoras significativas con el TEPT y los síntomas de depresión, así como en el funcionamiento social, la regulación de las emociones y los problemas interpersonales en el postratamiento y en el seguimiento a los 3 meses. Las puntuaciones de la alianza terapéutica fueron altas, al igual que los informes de satisfacción general en el programmea. No hubo diferencias por sexo o estado de TSM en los resultados de los síntomas o la satisfacción.Conclusiones: Los resultados respaldan la viabilidad y efectividad de este programmea integrado de capacitación en habilidades de telesalud basado en la web para veteranos masculinos y femeninos, así como para aquellos con y sin MST. El enfoque en el desarrollo de recursos y la mejora del funcionamiento hace que este programmea sea de especial interés. Se requieren nuevos estudios.

Imaging-based patient-reported outcomes (PROs) database: How we do it.

Patient-reported outcomes (PROs) provide an essential understanding of the impact a condition or treatment has on a patient, while complementing other, more traditional outcomes information like survival and time to symptom resolution. PROs have become increasingly important in medicine with the push toward patient-centered care. The creation of a PROs database within an institution or practice provides a way to collect, understand, and use this kind of patient feedback to inform quality improvement and develop the evidence base for medical decision-making and on a larger scale could potentially help determine national standards of care and treatment guidelines. This paper provides a first-hand account of our experience setting up an imaging-based PROs database at our institution and is organized into steps the reader can follow for creating a PROs database of their own. Given the limited use of PROs within both diagnostic and interventional radiology, we hope our paper stimulates a new interest among radiologists who may have never considered outcomes work in the past.

Increased staple loading pressures and reduced staple heights in laparoscopic sleeve gastrectomy reduce intraoperative bleeding.

BACKGROUND: In laparoscopic sleeve gastrectomy, tissue thickness and closed staple height of the staple cartridge determine the pressure applied to the tissue. Prior studies have suggested 8 g/mm2 to be ideal to minimize leaks or bleeding. METHODS: We evaluated the relationship between staple loading pressure applied to gastric tissue and bleeding rate prospectively with a novel tissue measuring device and video-recorded operative findings for 116 patients undergoing laparoscopic sleeve gastrectomy performed by 2 surgeons at a single institution. Stapling protocol 1 was used for 64 cases, defined as standard practice, typically using green-blue-blue-blue Ethicon staple cartridges. Stapling protocol 2 was defined as blue-blue-white-white or gold-blue-white-white. RESULTS: Tissue thickness measurements from 39 cases and staple load selection showed that surgeons preferred a median staple loading pressure of 15 g/mm2. Tissue thickness measurements at 15 g/mm2 had a mean of 1.86 mm at the antrum, 1.71 mm at the body, and 1.15 mm at the fundus, all significantly thinner than tissue thickness at 8 g/mm2. For each 10 g/mm2 increase in minimum pressure and maximum pressure value within each cartridge zone, there was a reduction in bleeding rate by 59.8% and 38.7%, respectively. Compared with stapling protocol 1, stapling protocol 2 had a lower intraoperative bleeding rate (90.2% vs 70.7%; P < .0001), usage of preventive hemostatic techniques (100% vs 10%; P < .0001), and hemostatic treatments (66% vs 46%; P = .04). In the 30-day postoperative period, there was 1 bleed in stapling protocol 1; there were no leaks. CONCLUSION: Our data suggest using shorter closed staple heights to exert higher staple loading pressures decreases intraoperative bleeding rates in laparoscopic sleeve gastrectomy.

Lung Adenocarcinoma Presenting as Multiple Thromboembolic Events: A Case Report and Review of the Literature.

Patients with malignancy may present with significant thromboembolic complications including deep vein thrombosis (DVT), pulmonary embolism, arterial thrombosis, nonbacterial thrombotic endocarditis, and stroke due to abnormal coagulation cascades. Although these events are typically recognized later in the disease process, complications of a hypercoagulable state can rarely present as the first manifestation of an occult malignancy. We report a case of a young male who was ultimately found to have an aggressive form of lung adenocarcinoma after the initial presentation of multiple thromboembolic events. DVT and stroke as an initial presentation of an active lung adenocarcinoma in a young patient is extremely rare as patients presenting in a hypercoagulable state usually are older. Though testing for a hypercoagulable state is not recommended for the first unprovoked DVT, clinicians should be prompted to screen for malignancy in the setting of cryptogenic strokes, especially in younger patients with no prior risk factors.

Collagenous Gastritis: An Unusual Presentation With Tubular Shaped Stomach.

Collagenous gastritis is a rare histopathologic entity that causes marked subepithelial collagen deposition in the gastric mucosa. Clinical presentation is diverse, considering only less than 100 cases have been reported. However, we report a unique case of isolated collagenous gastritis in a 71-year-old female who presented with a 6-month history of dyspepsia and 27 kg weight loss. Her endoscopic findings revealed a tubular shaped stomach with diffuse gastric mucosal atrophy, findings that differ with previous case reports of a cobblestone pattern. Treatment remains unclear.

Evaluation of multiple sclerosis disability outcome measures using pooled clinical trial data.

OBJECTIVE: We report analyses of a pooled database by the Multiple Sclerosis Outcome Assessments Consortium to evaluate 4 proposed components of a multidimensional test battery. METHODS: Standardized data on 12,776 participants, comprising demographics, multiple sclerosis disease characteristics, Expanded Disability Status Scale (EDSS) score, performance measures, and Short Form-36 Physical Component Summary (SF-36 PCS), were pooled from control and treatment arms of 14 clinical trials. Analyses of Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT) included measurement properties; construct, convergent, and known group validity; and longitudinal performance of the measures individually and when combined into a multidimensional test battery relative to the EDSS and SF-36 to determine sensitivity and clinical meaningfulness. RESULTS: The performance measures had excellent test-retest reliability and showed expected differences between subgroups based on disease duration and EDSS level. Progression rates in detecting time to 3-month confirmed worsening were lower for T25FW and 9HPT compared to EDSS, while progression rates for LCLA and SDMT were similar to EDSS. When the 4 measures were analyzed as a multidimensional measure rather than as individual measures, progression on any one performance measure was more sensitive than the EDSS. Worsening on the performance measures analyzed individually or as a multidimensional test battery was associated with clinically meaningful SF-36 PCS score worsening, supporting clinical meaningfulness of designated performance test score worsening. CONCLUSION: These results support the use of the 4 proposed performance measures, individually or combined into a multidimensional test battery as study outcome measures.

Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides.

Arthropod-borne viruses represent a significant public health threat worldwide, yet there are few antiviral therapies or prophylaxes targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy-acceptable antiviral compounds is to repurpose well-known and widely used FDA-approved drugs. In this study, we addressed the antiviral role of atovaquone, an FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides, indicating that atovaquone functions through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner, providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women and children.IMPORTANCE The ability to protect vulnerable populations such as pregnant women and children from Zika virus and other arbovirus infections is essential to preventing the devastating complications induced by these viruses. One class of antiviral therapies may lie in known pregnancy-acceptable drugs that have the potential to mitigate arbovirus infections and disease, yet this has not been explored in detail. In this study, we show that the common antiparasitic drug atovaquone inhibits arbovirus replication through intracellular nucleotide depletion and can impair ZIKV infection in an ex vivo human placental explant model. Our study provides a novel function for atovaquone and highlights that the rediscovery of pregnancy-acceptable drugs with potential antiviral effects can be the key to better addressing the immediate need for treating viral infections and preventing potential birth complications and future disease.

Dengue Virus Immunity Increases Zika Virus-Induced Damage during Pregnancy.

Zika virus (ZIKV) has recently been associated with birth defects and pregnancy loss after maternal infection. Because dengue virus (DENV) and ZIKV co-circulate, understanding the role of antibody-dependent enhancement in the context of pregnancy is critical. Here, we showed that the presence of DENV-specific antibodies in ZIKV-infected pregnant mice significantly increased placental damage, fetal growth restriction, and fetal resorption. This was associated with enhanced viral replication in the placenta that coincided with an increased frequency of infected trophoblasts. ZIKV-infected human placental tissues also showed increased replication in the presence of DENV antibodies, which was reversed by FcγR blocking antibodies. Furthermore, ZIKV-mediated fetal pathogenesis was enhanced in mice in the presence of a DENV-reactive monoclonal antibody, but not in the presence of the LALA variant, indicating a dependence on FcγR engagement. Our data suggest a possible mechanism for the recent increase in severe pregnancy outcomes after ZIKV infection in DENV-endemic areas.

Sensitivity of prenatal ultrasound for detection of trisomy 18.

Objectives: To evaluate the sensitivity of prenatal ultrasound (US) for trisomy (T18) diagnosis and describe US findings in a large tertiary care institution in the USA. Materials and methods: This was a retrospective cohort of all T18 cases diagnosed at our institution from October 2004 to October 2014 based on prenatal or postnatal genetic diagnostic testing. We included all women with a fetus affected by T18 who had a comprehensive US by a maternal-fetal medicine specialist performed at our institution. US findings were reviewed, classified by organ system, and categorized as an anomaly or soft marker. Chi-square or t-test was used for statistical analysis. Results: We included 128 cases of T18 with confirmed cytogenetic analysis -110 (86%) of which were diagnosed prenatally or suspected by cell-free DNA and confirmed postnatally, and 18 of which underwent neonatal blood sampling alone. One hundred and twenty-one (95%) had at least one abnormal US finding. Anomalies were more frequently identified on US at ≥20 weeks as compared with <20 weeks (93% versus 76%; p = .004). The mean number of findings detected per fetus was 5.1 ± 3.0. Fetuses diagnosed by postnatal sampling alone had a similar number of US exams performed and number of abnormal findings compared to those diagnosed prenatally. Conclusion: Ninety-five percent of fetuses with T18 had at least one abnormal US finding. This sensitivity of is higher than reported in most prior studies, but is not 100%, and should be considered when counseling women regarding prenatal diagnosis of T18. Rationale: Historical detection rates for abnormal sonographic findings in trisomy 18 fetuses range from 70% to 100%. These studies are limited by small sample sizes. This is a contemporary study of ultrasound findings in a large group of women with confirmed trisomy 18 by prenatal or postnatal genetic diagnosis. We provide expansive detail on soft markers and anomalies broken down by organ-system and gestational age.

Symbol Digit Modalities Test: A valid clinical trial endpoint for measuring cognition in multiple sclerosis.

BACKGROUND: The need for more robust outcomes in multiple sclerosis (MS) clinical trials has been a main priority of the field for decades. Dissatisfaction with existing measures has led to several consensus meetings and initiatives over the past few decades in hopes of defining and gaining acceptance of measures that are valid, reliable, sensitive to change and progression, and most importantly, relevant to those living with MS. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed for this purpose. OBJECTIVE: The objective of this paper is to describe the results of the MSOAC plan to obtain qualification for a cognitive performance measure that meets these requirements. METHODS: Using data from 14 MS disease-modifying registration trials, we completed a comprehensive examination of the psychometric qualities of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) with the goal of compiling evidence to support the utilization of one of these measures in future clinical trials. RESULTS AND CONCLUSION: Consistent with the published literature, the SDMT proved superior to the PASAT. The SDMT should be considered the measure of choice for MS trials in assessing cognitive processing speed.

Use of Copper Intrauterine Device in Transgender Male Adolescents.

Transgender men need contraception if engaging in intercourse with a cis-gender male partner. The copper IUD is an effective, non-hormonal contraceptive well suited for trans-males even while utilizing gender affirming hormone therapy. A gender-neutral medical facility with well-trained and sensitive staff is the ideal setting to provide such contraceptive care.