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The article examines whether canonical signal transducer SMAD1 is an important downstream mediator of BMPR2 signaling in the pathogenesis of pulmonary arterial hypertension (PAH). It was revealed that the sensitivity of SMAD2 phosphorylation by transforming growth factor-beta1 was improved in the Bmpr2-deficient cells. Furthermore, the inhibitory effect of transforming growth factor-beta1-mediated SMAD2 phosphorylation by BMP4 was hindered in the Bmpr2-deficient cells.

BACKGROUND: The torn hamstring is a common athletic injury. The purpose of the present study was to review the clinical presentation of this injury, the diagnostic imaging findings, the surgical technique of reattachment, and the likely clinical outcome of surgery for the treatment of avulsion of the proximal hamstring origin. METHODS: Seventy-two consecutive reconstructions in seventy-one patients with avulsion of the proximal hamstring origin were performed at a single center. The mean age at the time of the operation was 40.2 years. The mean duration of follow-up was twenty-four months, and all patients with a minimum duration of follow-up of six months were included. There were no exclusions. Patients were independently reviewed, and the mean postoperative isotonic hamstring strength was compared with that on the uninjured side. RESULTS: Waterskiing was the most frequent cause of injury (twenty-one cases). The mean time between the injury and the operation was twelve months. The most common pathological finding was a complete avulsion of the proximal hamstring origin (sixty-three cases; 87.5%), with a mean retraction of 7 cm (range, 0 to 20 cm). The mean postoperative isotonic hamstring strength measured 84% (range, 43% to 122%) and the mean postoperative hamstring endurance measured 89% (range, 26% to 161%) when compared with the values on the contralateral side. CONCLUSIONS: It is important to distinguish proximal hamstring origin avulsions (for which we recommend early surgical repair) from the majority of hamstring muscle injuries (which respond well to nonoperative treatment). The present study suggests that, in cases of complete avulsion with hamstring retraction, a delay in surgical repair renders the repair more technically challenging, may increase the likelihood of sciatic nerve involvement, increases the need for postoperative bracing, and reduces postoperative outcome in terms of hamstring strength and endurance. Once the nature of the injury has been established, the surgical treatment of hamstring origin avulsions has predictable and satisfactory results. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: The torn hamstring is a common athletic injury. The purpose of the present study was to review the clinical presentation of this injury, the diagnostic imaging findings, the surgical technique of reattachment, and the likely clinical outcome of surgery for the treatment of avulsion of the proximal hamstring origin. Methods: Seventy-two consecutive reconstructions in seventy-one patients with avulsion of the proximal hamstring origin were performed at a single center. The mean age at the time of the operation was 40.2 years. The mean duration of follow-up was twenty-four months, and all patients with a minimum duration of follow-up of six months were included. There were no exclusions. Patients were independently reviewed, and the mean postoperative isotonic hamstring strength was compared with that on the uninjured side. Results: Waterskiing was the most frequent cause of injury (twenty-one cases). The mean time between the injury and the operation was twelve months. The most common pathological finding was a complete avulsion of the proximal hamstring origin (sixty-three cases; 87.5%), with a mean retraction of 7 cm (range, 0 to 20 cm). The mean postoperative isotonic hamstring strength measured 84% (range, 43% to 122%) and the mean postoperative hamstring endurance measured 89% (range, 26% to 161%) when compared with the values on the contralateral side. Conclusions: It is important to distinguish proximal hamstring origin avulsions (for which we recommend early surgical repair) from the majority of hamstring muscle injuries (which respond well to nonoperative treatment). The present study suggests that, in cases of complete avulsion with hamstring retraction, a delay in surgical repair renders the repair more technically challenging, may increase the likelihood of sciatic nerve involvement, increases the need for postoperative bracing, and reduces postoperative outcome in terms of hamstring strength and endurance. Once the nature of the injury has been established, the surgical treatment of hamstring origin avulsions has predictable and satisfactory results. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

A fifty-nine-year-old woman with seropositive rheumatoid arthritis and osteoporosis underwent an elective total hip replacement with use of a cemented Muller prosthesis. Aseptic loosening of the stem occurred three years later, at which time the patient underwent revision of the stem with a long-stem cemented implant. Seven years later, the patient sustained an atraumatic unstable periprosthetic fracture of the shaft of the femur at the distal end of the prosthesis. In this article authors describes an alternative management option for this complex femoral reconstruction that includes the use of a long-stemmed hydroxyapatite-coated implant with distal interlocking screw fixation.

Background: Depression is a pervasive symptom in patients with gynecological cancer undergoing chemotherapy., Objectives: Purposes were to identify subgroups of patients with distinct depression profiles and evaluate for differences in demographic and clinical characteristics, severity of common symptoms, and quality of life (QOL) outcomes among these subgroups., Methods: Patients with gynecological cancer (n = 231) completed the Center for Epidemiologic Studies-Depression Scale 6 times over 2 cycles of chemotherapy. All of the other measures were completed prior to the second or third cycle of chemotherapy. Latent profile analysis was done to identify the distinct depression profiles. Differences were evaluated using parametric and nonparametric tests., Results: Three distinct profiles were identified: low (60.1%), high (35.1%), and very high (4.8%). Compared with low class, the other 2 classes had lower functional status and were more likely to self-report a diagnosis of depression. Patients in the 2 worse profiles reported a higher comorbidity burden, higher levels of trait and state anxiety, sleep disturbance, and fatigue, as well as lower levels of cognitive function and poorer QOL. State and trait anxiety, evening fatigue, and sleep disturbance scores exhibit a "dose-response effect" (ie, as the depression profile worsened, the severity of these symptoms increased)., Conclusions: Almost 40% of our sample experienced high or very high levels of depression across 2 cycles of chemotherapy., Implications for Practice: Clinicians can use the identified risk factors to identify high patients risk and provide tailored psychological interventions aimed to decrease symptom burden and prevent decrements in QOL., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Home-time is an emerging, patient-centered outcome that represents the amount of time a patient spends alive and outside of health care facility settings, comprising of hospitals, skilled nursing facilities, and acute rehabilitation centers. Studies evaluating home-time in the context of heart failure are limited, and the impact of quality improvement interventions on home-time has not been studied., Methods: Medicare beneficiaries aged 65 years or older who were hospitalized for heart failure in the Get With the Guidelines-Heart Failure registry between 2019 and 2021 were included. Postdischarge home-time, mortality, and readmission rates at 30 days and 1 year were calculated with the goal of establishing baseline metrics before the initiation of IMPLEMENT-HF, a multicenter quality improvement program aimed at improving heart failure management., Results: Overall, 66 019 patients were included across 437 sites. Median 30-day and 1-year home-time were 30 (18-30) and 333 (139-362) days, respectively. Only 22.1% of patients experienced 100% home-time in the year after discharge. Older patients spent significantly less time at home, with a median 1-year home-time of 302 (86-359) compared with 345 (211-365) days in patients over 85 and those between 65 and 74 years old, respectively ( P <0.001). Black patients also experienced the least amount of home-time with only 328 (151-360) days at 1-year follow-up. Rates of heart failure readmission and all-cause mortality 1-year post-discharge were high at 29.8% and 37.0%, respectively., Conclusions: In this contemporary multicenter cohort, patients hospitalized with heart failure spent a median of 91.2% of their time in the year after discharge alive and at home, largely driven by high mortality rates. These findings serve as a preimplementation baseline for IMPLEMENT-HF, which will evaluate the impact of targeted heart failure initiatives on home-time and other clinical outcomes., Competing Interests: Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, the American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards or as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Lilly, Lexicon, Merck, Novo Nordisk, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Butler has consulted for Abbott, American Regent, Amgen, Applied Therapeutics, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Lexicon, Lilly, LivaNova, Janssen, Medtronic, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pharmacosmos, Pharmain, Pfizer, Prolaio, Regeneron, Renibus, Roche, Salamandra, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Lewis has received grants from the American Heart Association and Merck and has consulted for AstraZeneca, Intellia, and Merck. Dr Fonarow has consulted for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer.

The number of health technology-based intervention studies has grown significantly. However, issues in the recruitment and retention for such studies, especially of Asian Americans, have rarely been discussed. The purpose of this paper was to discuss issues in the recruitment and retention of a specific group of Asian Americans-Korean American midlife women with depressive symptoms-into a technology-based intervention study using computers and mobile devices with a measurement device and to provide directions for future participant recruitment and retention in technology-based intervention studies. The written memos of research team members and the written records of research team meetings were analyzed using a content analysis. The issues in the recruitment and retention process included (1) low recruitment and retention rates; (2) the perceived long intervention period; (3) strict inclusion/exclusion criteria; (4) concerns related to the use of a measurement device; and (5) the perceived adequacy of monetary incentives. Based on the issues identified in the study, several suggestions are made for future recruitment and retention of racial/ethnic minorities in technology-based intervention studies (eg, appropriate intervention period, innovative and creative motivation strategies, acceptable measurement scales and devices, and adequate monetary reimbursement)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aims to determine if a novel imaging protocol (ultralow-dose dynamic expiratory computed tomography [CT] with repeated imaging) identifies tracheomalacia (TM) more reliably than traditional dynamic tracheal CT., Methods: We performed a retrospective evaluation of 184 consecutive ultralow-dose dynamic CTs for TM during 2017. The protocol obtains images during 1 inspiration and 2 forced expirations. Tracheal narrowing during both expirations (airway narrowing [percentage] during first dynamic expiration CT [DE1], airway narrowing [percentage] during second dynamic expiration CT [DE2]) was reported as a percentage of inspiratory area. We identified maximum narrowing of each patient's sequence (maximum narrowing [percentage] on either dynamic expiration CT [DEmax] = greatest narrowing of DE1 or DE2) and compared DE1, DE2, and DEmax in individual studies and between patients. Outcomes included frequency of TM, tracheal narrowing, and severity. Reliability was assessed by comparing tracheal area narrowing and TM grade., Results: There was significantly more airway narrowing using 2 expiratory image acquisitions. Average DEmax tracheal area was 12% narrower than DE1 alone and 21% worse than DE2 alone (both P < 0.001). Using DEmax, TM was diagnosed 35% more often than DE1 alone and 31% more often than DE2 alone ( P < 0.001). DEmax identified more severe distribution of TM compared with DE1 or DE2 alone ( P < 0.001). Reliability between DE1 and DE2 was good for tracheal narrowing and moderate for TM grade. The mean effective radiation dose was 2.41 millisievert (mSv) for routine inspiration CT and 0.07 mSv for each dynamic expiration CT (total effective radiation, 2.55 mSv)., Conclusions: Dynamic expiration CT with 2 expiratory image acquisitions enhanced evaluation of TM, minimally increased radiation dose, and should be considered as a noninvasive screening option., Competing Interests: S.L.C. and B.C.B. have received funding from Siemens Healthineers and Society of Thoracic Radiology. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. No conflicts of interest were declared for the remaining authors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Sirolimus (mammalian target of rapamycin inhibitor) is a potent immunosuppressive agent, used in patients receiving hematopoietic stem cell transplant (HSCT) for Graft vs Host disease prophylaxis. Compared to calcineurin inhibitors, sirolimus has no neurotoxicity or nephrotoxicity, but sirolimus causes dose-dependent thrombocytopenia, leukopenia, delayed wound healing, hyperlipidemia, and hypertriglyceridemia. Here we report a case of acute pancreatitis and diabetic ketoacidosis in a patient with sickle cell disease post haploidentical family donor HSCT which was managed conservatively without plasmapheresis. Based on our review of the literature, this is the first reported case of developing acute pancreatitis as an adverse effect of sirolimus-induced hypertriglyceridemia leading to diabetic ketoacidosis in a recipient of HSCT., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: HIV induces immunologic dysfunction in T cells of infected individuals. However, the impact of aging on T cell phenotypes in HIV-infected individuals receiving antiretroviral therapy (ART) has not been fully delineated. We evaluated the relationship between aging and the expression of immune activation and exhaustion markers on CD8 + T cells of age-matched HIV-infected and -uninfected male participants., Design: Levels of immune activation and exhaustion markers on peripheral blood CD8 + T cells of HIV-infected and -uninfected participants were examined., Methods: 110 HIV-infected aviremic male participants receiving ART and 146 HIV-uninfected male participants were studied. The levels of TIGIT, PD-1, CD38, and CD226 on CD8 + T cells of the study participants were determined by flow cytometry., Results: The level of TIGIT on CD8 + T cells was higher in aviremic HIV-infected compared to uninfected participants ( P  < 0.0001). In contrast, no significant differences were found in the levels of PD-1 and CD38 on CD8 + T cells between the two groups. Statistically significant correlations were observed between age and the levels of TIGIT + and CD38 + CD8 + T cells in both groups; however, no correlation was found between age and the level of PD-1 + CD8 + T cells in HIV-infected participants. Age-stratification of HIV-infected and -uninfected groups did not show any significant differences in the level of PD-1 expression on CD8 + T cells., Conclusions: The findings of our study highlight the role of aging in the expression of immune markers on CD8 + T cells and have important implications for therapies that target immune checkpoints in HIV-infected individuals., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nonalcoholic steatohepatitis (NASH) continues to increase in frequency as an indication for liver transplantation (LT). Data on long-term outcomes for these patients are limited. We aimed to compare long-term patient and graft survival in patients undergoing LT for NASH in the United States to other indications., Methods: We analyzed data from the Scientific Registry of Transplant Recipients of adult patients who underwent primary deceased-donor LT from January 1, 2005, to December 31, 2019., Results: NASH has increased as an indication for LT by 4.5-fold, from 5.2% in 2005 to 23.4% in 2019. Patient (61.2%) and graft survival (59.2%) at 10 y are significantly poorer for NASH than for all other indications other than alcohol. Patients transplanted for NASH have higher body mass index (32.2 versus 27.6) and greater frequency of diabetes (13% versus 11.6%) than any other indication ( P < 0.001). Portal vein thrombosis, location in intensive care unit, dialysis, and pre-LT diabetes ( P < 0.001 for all) are independently predictive of patient death and graft loss. Body mass index is not predictive. NASH patients undergoing simultaneous liver kidney have markedly worse 10-y patient and graft survival than liver-only (52.3% versus 62.1%). Graft loss was attributed to recurrence of NASH in <1% of patients., Conclusions: LT for NASH is associated with relatively poor long-term patient and graft survival when compared with patients transplanted for other indications, NASH patients undergoing simultaneous liver kidney have the worst long-term outcomes., Competing Interests: S.P. received research/grant funding from Intercept, Target PharmaSolutions, and Genfit. M.C. has consulted for Gilead, AbbVie, Bristol Myers, AMRA, Terns, Madrigal, Novartis, Lipocene, Metacrine, NGM Bio, and Intercept. The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This is a descriptive study to characterize rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric solid organ transplant (SOT) recipients during the early days of the pandemic. We hypothesized that asymptomatic infection may represent a large proportion of SARS-CoV-2 infection in pediatric SOT recipients., Methods: We queried Organ Transplant Tracking Record (OTTR) for all pediatric SOT recipients followed at our center and reviewed medical records to identify patients tested for SARS-CoV-2 between March 15, 2020 and June 30, 2021. Patients were tested by polymerase chain reaction (PCR): prior to planned procedures or because of symptoms; OR: tested by measurement of IgG to spike protein with their routine labs q 2-monthly. A positive PCR was called acute infection. A positive IgG with negative PCR was called convalescence. For immunologic studies, blood was obtained when the PCR or IgG was positive. Statistical comparisons were made between (1) acute infection versus convalescence; (2) acute infection versus SOT recipients without infection (called healthy controls); (3) liver transplant (LT) versus small bowel (SB)/multivisceral transplant (MVT); (4) positive versus negative test result., Results: Of 257 LT recipients, 99 were tested: 6 were PCR positive, 13 were antibody positive. Of 150 SB/MVT recipients, 55 were tested: 4 were PCR positive, 6 were antibody positive. Of 8 simultaneous liver, kidney transplant recipients, 3 were tested: 1 was PCR positive. Symptoms when present were mostly mild. Patients with a positive test result were younger (6.3 vs 10.0 years; P = 0.017). We observed a rapid decline in viral load within 96 hours without a change in immunosuppression. Antibody lasted >8 months beyond the time it was monitored. Acute infection was associated with increased CD4 and CD8 T EM cell frequency ( P = 0.04, P = 0.03, respectively), decreased interferon (IFN)-γ production from T-cells (2.8% vs 11.3%; P = 0.006), and decreased CD8 TEMRA frequency (4.56% vs 11.70%; P = 0.006)., Conclusions: Early in the pandemic, COVID-19 disease was mostly mild in pediatric SOT recipients with no rejection, patient death, or graft loss observed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Objectives: A prominent theory proposes that neuroplastic recruitment of perilesional tissue supports aphasia recovery, especially when language-capable cortex is spared by smaller lesions. This theory has rarely been tested directly and findings have been inconclusive. We tested the perilesional plasticity hypothesis using 2 fMRI tasks in 2 groups of patients with previous aphasia diagnosis., Methods: Two cohorts totaling 82 patients with chronic left-hemisphere stroke with previous aphasia diagnosis and 82 control participants underwent fMRI using either a naming task or a reliable semantic decision task. Individualized perilesional tissue was defined by dilating anatomical lesions and language regions were defined using meta-analyses. Mixed modeling examined differences in activity between groups. Relationships with lesion size and aphasia severity were examined., Results: Patients exhibited reduced activity in perilesional language tissue relative to controls in both tasks. Although a few cortical regions exhibited greater activity irrespective of distance from the lesion, or only when distant from the lesion, no regions exhibited increased activity only when near the lesion. Larger lesions were associated with reduced language activity irrespective of distance from the lesion. Using the reliable fMRI task, reduced language activity was related to aphasia severity independent of lesion size., Discussion: We found no evidence for neuroplastic recruitment of perilesional tissue in aphasia beyond its typical role in language. Rather, our findings are consistent with alternative hypotheses that changes in left-hemisphere activation during recovery relate to normalization of language network dysfunction and possibly recruitment of alternate cortical processors. These findings clarify left-hemisphere neuroplastic mechanisms supporting language recovery after stroke., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objectives: Women living with HIV (WLWH) have a greater risk of anal cancer than women without HIV; however, there are limited studies that examine awareness of anal cancer risk among WLWH and "high-risk" HIV-negative women. This study examines risk factors for anal cancer, perceptions of risk for anal cancer, and perceptions of anal cancer screening among a cohort of WLWH and high-risk HIV-negative women., Materials and Methods: From the Atlanta, GA, and Bronx, NY, sites of the Women's Interagency HIV Study, 155 WLWH and HIV-negative women were enrolled and the Champion Health Belief Model Scale questionnaire measuring risk perceptions to anal cancer was administered to each participant., Results: The WLWH perceived anal cancer to be less serious and perceived facing fewer barriers to anal cancer screening than HIV-negative women (both p = .01). Older women (≥50 years) felt that they had less barriers to anal cancer screening (p = .047). Moreover, women who had less than a high school education felt more susceptible to anal cancer (p = .001), as did women who reported a history of anal intercourse (p = .017)., Conclusions: Despite being at an increased risk for anal cancer, perceptions of susceptibility to anal cancer and seriousness of anal cancer were low among WLWH. These findings highlight opportunities for provider and patient educational interventions to improve awareness of anal cancer risk among WLWH., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Abstract: This case report details the efficacy of in-clinic customized scleral lens trial with self-preserved antibiotic eye drop in the liquid reservoir, in promoting fast healing of persistent corneal epithelial defect (PED). A 57-year-old man with a PED following injury, not responding to conventional treatment, underwent an in-clinic therapeutic trial of prosthetic replacement of ocular surface ecosystem device, to promote epithelial healing. After device wear with antibiotic eye drop in the liquid reservoir for 8 hrs during the day on five consecutive days and pressure patching at night with antibiotic eye ointment, there was complete resolution of the PED. Prosthetic replacement of ocular surface ecosystem scleral lenses are an effective treatment modality for PED. In-clinic daytime lens wear with night time pressure patching is a cost-effective option. Expert supervision avoids patient learning curve issues. Corneal re-epithelization happens because of the moisture and protection of the fragile healing epithelium afforded by these high DK lenses., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Contact Lens Association of Ophthalmologists.)

The development of ascites in patients with cirrhosis can cause numerous complications including abdominal discomfort, pain, respiratory distress, decreased mobility, diminished quality of life, and contributes to an increased mortality. Symptom self-monitoring that incorporates evidence-based treatments has been effective when used by patients with noncirrhotic chronic diseases. Guided by the theory of Self-Care of Chronic Illness, a self-monitoring guide was adapted from an existing validated tool. In the context of a pilot quality initiative, staff nurses educated patients with ascites and their caregivers, with the adapted symptom self-monitoring guide using a standardized process. Clinicians were surveyed regarding their satisfaction with the patient education pre- and post-implementation. Results indicated improved clinician satisfaction with the education provided to patients and their caregivers during the clinic visit. Implementation of self-monitoring may improve clinician and patient satisfaction and clinic workflows. Additional evaluation of the self-monitoring guide and its effect on patient satisfaction, impact on hospital admissions, and outpatient paracentesis is warranted., Competing Interests: Melanie Samardzija, PhD, APRN, FNP-BC, is a member of the advisory boards at Gilead and Intercept and speaker for Gilead and AbbVie. Sonali Paul, MD, MS has received research grant funding from Intercept, GENFIT, and TARGET PharmaSolutions. For the remaining authors, no conflicts of interest were declared., (Copyright © 2021 Society of Gastroenterology Nurses and Associates.)

Competing Interests: The authors have no conflicts of interest to declare.

Inflammation is an important pathophysiological process after an acute stroke (AS). Pro- and anti-inflammatory molecules (cytokines and interleukins) are the key players during this mechanism. Emerging evidence indicate that these molecules can serve as biomarkers of stroke progression and outcome and as novel therapeutics agents. The aim of this study is to explore the temporal changes in these molecules and validate them as biomarker of AS progression and neurological outcome.The "Cytokine Registry In Stroke Patients (CRISP)" is a prospective cohort study of 600 AS patients presenting to the tertiary hospital with-in 24 h of the onset of symptoms. Plasma cytokines and interleukins will be collected at admission and 24 h after and will be measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the difference in their variation among different gender, race and ethnicity and their association with various neurological outcomes. The primary exposures are biological sex (male, female) and race/ethnicity. Confounding variables include age, vascular risk factors, infarct size, stroke onset to presentation time, and identified stroke etiologies. Matched controls will be used for the comparison and evaluation of the difference among gender and race/ethnicities.CRISP is a prospective observational study that investigates the role and relationship of molecular biomarkers identifying specific and relevant targets pertinent for monitoring the progression and outcome in AS patients.Trial Registration: The study is registered on ClinicalTrial.gov: https://clinicaltrials.gov/ (NCT03297827).

Background: Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels)., Methods: This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody., Results: Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays., Conclusions: Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.

Objective, noninvasive, clinical assessment of patients with heart failure can be made using biomarker measurements, including natriuretic peptides, cardiac troponins, soluble suppression of tumorigenicity 2, and galectin-3. The aim of this review is to provide clinicians with guidance on the use of heart failure biomarkers in clinical practice. The authors provide a didactic narrative based on current literature, an exemplary case study, and their clinical experience.

Background: Early steps of HIV infection are mediated by the binding of the envelope to mucosal receptors as α4β7 and the C-type lectins DC-SIGN and langerin. Previously Env-specific B-cell responses have been reported in highly exposed seronegative individuals (HESN)., Method: Here, we studied gp120-specific antibodies ability to block HIV interaction with α4β7, DC-SIGN and/or langerinin HESN. New cell-based assays were developed to analyze whether antibodies that can alter gp120 binding to α4β7, DC-SIGN and/or langerin are induced in HESN. A mucosal blocking score (MBS) was defined based on the ability of antibodies to interfere with gp120/α4β7, gp120/DC-SIGN, and gp120/langerin binding. A new MBS was evaluated in a cohort of 86 HESN individuals and compared with HIV+ patients or HIV- unexposed healthy individuals., Results: Antibodies reducing gp120 binding to both α4β7 and DC-SIGN were present in HESN serum but also in mucosal secretions, whereas antibodies from HIV+ patients facilitated gp120 binding to DC-SIGN. Any correlation was observed between MBS and the capacity of antibodies to neutralize infection of α4β7 CD4+ T cells with primary isolates., Conclusions: MBS is significantly associated with protection in HESN and might reflect altered HIV spreading to mucosal-associated lymphoid tissues.

Background: SB2, an infliximab (IFX) biosimilar to the reference infliximab (R.I.) product (Remicade), received approval in the European Union for all IFX indications. Many decision algorithms based on the measurement of IFX trough levels and antibodies to infliximab are being increasingly used to optimize IFX treatment. The aim of our study was to evaluate whether the biosimilar SB2 could be efficiently monitored using the LISA-TRACKER IFX and anti-IFX assays developed by Theradiag (Croissy Beaubourg, France)., Methods: Standard curves of R.I. and SB2 were compared, and then accuracy of the LISA-TRACKER IFX assay in detecting the spiked concentration of SB2 was measured. Levels of IFX from SB2 spiked samples and R.I. clinical samples were calculated. Intra-run and inter-run imprecision were also measured with SB2 spiked samples. The ability of polyclonal antibodies directed against R.I. to block the detection of SB2 using the LISA-TRACKER IFX assay and the capacity of SB2 to block the detection of anti-R.I. antibodies using the LISA-TRACKER anti-IFX assay were tested., Results: Twelve patients treated with SB2 including 2 patients with SB2-specific antibodies were measured with the LISA-TRACKER anti-IFX assay. We demonstrated that the LISA-TRACKER assay is suitable for the quantification of SB2 in human serum samples. The percentage of recovery was between 82% and 113%. High intra-run and inter-run imprecisions were obtained with the LISA-TRACKER infliximab assay for the quantification of SB2 (SD ranged from 3.3% to 17.9%). The SB2-blocking capacity of R.I. polyclonal antibodies in spiked samples was demonstrated with inhibition between 80% and 97%. SB2 trough levels and anti-SB2 antibodies have also been confirmed in SB2-treated patients., Conclusions: LISA-TRACKER IFX and anti-IFX assays are suitable for the monitoring of patients treated with SB2.

: Most new HIV infections occur via sexual routes. The induction of protective anti-HIV antibodies in genital mucosa is an important step toward reducing HIV transmission. Mucosal anti-HIV antibodies may play a dual role by either protecting against HIV transmission or facilitating it. Protective properties against HIV of mucosal IgGs and IgAs exhibiting neutralizing or antibody-dependent cell-mediated cytotoxicity activities have been described in highly exposed seronegative individuals. Conversely, some IgGs may facilitate the crossing of HIV free-particles through epithelial barriers by transcytosis. Hence knowledge of the mechanisms underlying anti-HIV antibody production in the genital tract and their exact role in sexual transmission may help to develop appropriate preventive strategies based on passive immunization or mucosal vaccination approaches. Our review focuses on the characteristics of the humoral immune responses against HIV in the male genital tract and related prevention strategies.

Background: Readmission and length of stay (LOS) are increasingly accepted as quality measures for surgical care. Centers for Medicare & Medicaid Services will soon assess penalties for excessive readmissions after coronary artery bypass graft (CABG) surgery and hip and knee replacements., Objective: To determine and compare population level changes in LOS and relationship with 30-day readmission over time for patients undergoing CABG and hip and knee replacements. Secondary objective was to determine relationship between LOS and discharge disposition as well as mortality., Research Design: Observational cohort study of patients undergoing CABG and hip and knee replacements in New York and California. Temporal trends in LOS, discharge disposition, 30-day readmission, and mortality were examined. Generalized linear-mixed models, accounting for hospital clustering, were used to assess differences in outcomes., Subjects: Patients undergoing CABG and hip and knee replacements in New York and California between 2005 and 2011., Measures: Trends in LOS, discharge disposition, 30-day readmission and mortality, and risk-adjusted odds of all-cause 30-day readmission., Results: We identified 206,784, 336,271, and 416,391 patients who underwent CABG, hip, and knee replacements, respectively, in New York State and California between 2005 and 2011. The risks of readmission within 30 days decreased over time in both states. LOS decreased by 1 day after hip and knee surgery and remained unchanged after CABG. Adjusted analysis confirmed these trends. In secondary analyses patients in New York had higher overall odds of 30-day readmission compared with patients in California., Conclusions: We found no evidence of inverse relationship between LOS and readmission over time. In hip and knee replacement there is strong evidence that both LOS and readmission have been reduced simultaneously.