Efficacy of a high-intensity home stretching device and traditional physical therapy in non-operative management of adhesive capsulitis - a prospective, randomized control trial.

BACKGROUND: Historically, in-person physical therapy serves as a foundational component of nonoperative treatment of adhesive capsulitis (AC). This study compares the effectiveness of an at-home high-intensity stretch (HIS) device to traditional physical therapy (PT) and to PT in combination with the HIS device. We hypothesize that the HIS device will be as effective as PT alone or as combination therapy in the first-line treatment of AC and use of the HIS device will exhibit improvement at higher rate. METHODS: Thirty-four patients with idiopathic adhesive capsulitis and a minimum of 12 months follow-up were included in this study. Patients were randomized into one of the three groups: HIS device, PT alone, or HIS device + PT. Passive range of motion (ROM), American Shoulder and Elbow Surgeons (ASES), and Simple Shoulder Test (SST) scores were measured. Additionally, patient satisfaction, compliance and complications were recorded. Paired t-test, ANOVA and Chi-squared tests were used in analysis. RESULTS: Final ROM in all planes improved for all groups compared to baseline (p < 0.001), with only HIS device group able to restore > 95% of contralateral ROM in all planes at final follow-up. Patients with PT alone were on average slowest to improve ROM from baseline, at 3 months, 6 months, and 1 year in all planes except internal rotation. ASES and SST scores improved for all groups when compared to baseline (p < 0.001). Use of HIS-device resulted in greater improvement in SST and ASES Total scores compared to PT alone (p = 0.045, and p = 0.048, respectively). CONCLUSIONS: Use of an at-home high-intensity stretching device for conservative treatment of idiopathic adhesive capsulitis improves outcomes in ROM and in ASES and SST scores both when used as an adjunct to physical therapy and when used alone. TRIAL REGISTRATION: The study protocol was registered at www. CLINICALTRIALS: gov (20/05/2022, NCT05384093).

The S1 subunits of SARS-CoV-2 variants differentially trigger the IL-6 signaling pathway in human brain endothelial cells and downstream impact on microglia activation.

Objectives: Cerebrovascular complications are prevalent in COVID-19 infection and post-COVID conditions; therefore, interactions of SARS-CoV-2 with cerebral microvascular cells became an emerging concern. Methods: We examined the inflammatory responses of human brain microvascular endothelial cells (HBMEC), the main structural element of the blood-brain barrier (BBB), following exposure to the S1 subunit of the spike protein of different SARS-CoV-2 variants. Specifically, we used the S1 subunit derived from the D614 variant of SARS-CoV-2, which started widely circulating in March of 2020, and from the Delta variant, which started widely circulating in early 2021. We then further examined the impact of the HBMEC secretome, produced in response to the S1 exposure, on microglial proinflammatory responses. Results: Treatment with S1 derived from the D614 variant and from the Delta variant resulted in differential alterations of the IL-6 signaling pathway. Moreover, the HBMEC secretome obtained after exposure to the S1 subunit of the D614 variant activated STAT3 in microglial cells, indicating that proinflammatory signals from endothelial cells can propagate to other cells of the neurovascular unit. Overall, these results indicate the potential for different SARS-CoV-2 variants to induce unique cellular signatures and warrant individualized treatment strategies. The findings from this study also bring further awareness to proinflammatory responses involving brain microvasculature in COVID-19 and demonstrate how the surrounding microglia react to each unique variant derived response.

MicroRNA193a: An Emerging Mediator of Glomerular Diseases.

MicroRNAs (miRNAs) are noncoding small RNAs that regulate the protein expression of coding messenger RNAs. They are used as biomarkers to aid in diagnosing, prognosticating, and surveillance of diseases, especially solid cancers. MiR-193a was shown to be directly pathogenic in an experimental mouse model of focal segmental glomerulosclerosis (FSGS) during the last decade. Its specific binding and downregulation of Wilm's tumor-1 (WT-1), a transcription factor regulating podocyte phenotype, is documented. Also, miR-193a is a regulator switch causing the transdifferentiation of glomerular parietal epithelial cells to a podocyte phenotype in in vitro study. Interaction between miR-193a and apolipoprotein 1 (APOL1) mRNA in glomeruli (filtration units of kidneys) is potentially involved in the pathogenesis of common glomerular diseases. Since the last decade, there has been an increasing interest in the role of miR-193a in glomerular diseases, including diabetic nephropathy and membranous nephropathy, besides FSGS. Considering the lack of biomarkers to manage FSGS and diabetic nephropathy clinically, it is worthwhile to invest in evaluating miR-193a in the pathogenesis of these diseases. What causes the upregulation of miR-193a in FSGS and how the mechanism is different in different glomerular disorders still need to be elucidated. This narrative review highlights the pathogenic mechanisms of miR-193a elevation in various glomerular diseases and its potential use in clinical management.

A 316MP, 120FPS, High Dynamic Range CMOS Image Sensor for Next Generation Immersive Displays.

We present a 2D-stitched, 316MP, 120FPS, high dynamic range CMOS image sensor with 92 CML output ports operating at a cumulative date rate of 515 Gbit/s. The total die size is 9.92 cm × 8.31 cm and the chip is fabricated in a 65 nm, 4 metal BSI process with an overall power consumption of 23 W. A 4.3 µm dual-gain pixel has a high and low conversion gain full well of 6600e- and 41,000e-, respectively, with a total high gain temporal noise of 1.8e- achieving a composite dynamic range of 87 dB.

Convalescent Plasma Therapy in Late-State, Severe COVID-19 Infection.

OBJECTIVES: Current evidence favors plasma to be effective against coronavirus disease 2019 (COVID-19) in critically ill patients in the early stages of infection. We investigated the safety and efficacy of convalescent plasma in specifically late-stage (designated as after 2 weeks of hospital admission) severe COVID-19 infection. We also conducted a literature review on the late-stage use of plasma in COVID-19. METHODS: This case series examined eight COVID-19 patients admitted to the intensive care unit (ICU) who met criteria for severe or life-threatening complications. Each patient received one dose (200 mL) of plasma. Clinical information was gathered in intervals of 1 day pretransfusion and 1 hour, 3 days, and 7 days posttransfusion. The primary outcome was effectiveness of plasma transfusion, measured by clinical improvement, laboratory parameters, and all-cause mortality. RESULTS: Eight ICU patients received plasma late in the course of COVID-19 infection, on average at 16.13 days postadmission. On the day before transfusion, the averaged initial Sequential Organ Failure Assessment (SOFA) score, PaO2:FiO2 ratio, Glasgow Coma Scale (GCS), and lymphocyte count were 6.5, 228.03, 8.63, and 1.19, respectively. Three days after plasma treatment, the group averages for the SOFA score (4.86), PaO2:FiO2 ratio (302.73), GCS (9.29), and lymphocyte count (1.75) improved. Although the mean GCS improved to 10.14 by posttransfusion day 7, the other means marginally worsened with an SOFA score of 5.43, a PaO2:FiO2 ratio of 280.44, and a lymphocyte count of 1.71. Clinical improvement was noted in six patients who were discharged from the ICU. CONCLUSIONS: This case series provides evidence that convalescent plasma may be safe and effective in late-stage, severe COVID-19 infection. Results showed clinical improvement posttransfusion as well as decreased all-cause mortality in comparison to pretransfusion predicted mortality. Randomized controlled trials are needed to conclusively determine benefits, dosage, and timing of treatment.

The Effect of COVID-19 on Adolescents' Mental Health, Social Lives, and Academic Achievement.

The aim of this study was to discover the effects of COVID-19 on the mental health, academic life, social life of students and discover their interrelationships at a boarding school in New Jersey, USA. A majority of participants reported that COVID-19 had a negative effect on their mental health and social lives, felt well informed about COVID-19 cases on campus, and were unconcerned about getting COVID-19 at school. Given the correlations and differences observed, it is likely that some groups of adolescents may be at greater risk of impacted mental health as a result of the COVID-19 pandemic. .

Subacute Cardiac Tamponade in a COVID-19 Patient Despite Negative Testing.

COVID-19 infection has been documented to cause a wide range of symptoms including cardiac complications. We present a case of subacute cardiac tamponade in a patient infected with COVID-19 in the absence of respiratory symptoms; we also review the current literature on this rare sequela. Our patient is a 67-year-old man who presented to the hospital due to intermittent chest pain for three weeks. COVID-19 polymerase chain reaction (PCR) testing was negative two times. He had an outpatient echocardiogram that showed a moderate pericardial effusion about a week prior to the hospital presentation. On admission, a repeat echocardiogram showed a large pericardial effusion with tamponade physiology. Pericardiocentesis did not reveal a clear etiology of the hemorrhagic effusion but four days later, the patient was found to be positive for COVID-19 infection without any clear respiratory illness. Given the absence of other etiology and negative workup, cardiac tamponade was attributed to pericardial inflammation from this virus and our patient improved with colchicine and steroids. We, therefore, advise providers to consider COVID-19 as a cause of hemorrhagic, cryptogenic cardiac tamponade despite negative COVID-19 testing. We also review 42 additional reported cases of cardiac tamponade in patients infected with COVID-19. COVID-19 can cause cardiac tamponade even in the absence of pulmonary disease. This case and literature review highlight tamponade as a rare complication of COVID-19 and should be considered in the differential of any acute deterioration in this patient population.

MRI evaluation of soft tissue tumors: comparison of a fast, isotropic, 3D T2-weighted fat-saturated sequence with a conventional 2D T2-weighted fat-saturated sequence for tumor characteristics, resolution, and acquisition time.

OBJECTIVES: To test whether a 4-fold accelerated 3D T2-weighted (T2) CAIPIRINHA SPACE TSE sequence with isotropic voxel size is equivalent to conventional 2DT2 TSE for the evaluation of intrinsic and perilesional soft tissue tumors (STT) characteristics. METHODS: For 108 patients with histologically-proven STTs, MRI, including 3DT2 (CAIPIRINHA SPACE TSE) and 2DT2 (TSE) sequences, was performed. Two radiologists evaluated each sequence for quality (diagnostic, non-diagnostic), tumor characteristics (heterogeneity, signal intensity, margin), and the presence or absence of cortical involvement, marrow edema, and perilesional edema (PLE); tumor size and PLE extent were measured. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios and acquisition times for 2DT2 in two planes and 3DT2 sequences were reported. Descriptive statistics and inter-method agreement were reported. RESULTS: Image quality was diagnostic for all sequences (100% [108/108]). No difference was observed between 3DT2 and 2DT2 tumor characteristics (p < 0.05). There was no difference in mean tumor size (3DT2: 2.9 ± 2.5 cm, 2DT2: 2.8 ± 2.6 cm, p = 0.4) or PLE extent (3DT2:0.5 ± 1.2 cm, 2DT2:0.5 ± 1.0 cm, p = 0.9) between the sequences. There was no difference in the SNR of tumors, marrow, and fat between the sequences, whereas the SNR of muscle was higher (p < 0.05) on 3DT2 than 2DT2. CNR measures on 3DT2 were similar to 2DT2 (p > 0.1). The average acquisition time was shorter for 3DT2 compared with 2DT2 (343 ± 127 s vs 475 ± 162 s, respectively). CONCLUSION: Isotropic 3DT2 MRI offers higher spatial resolution, faster acquisition times, and equivalent assessments of STT characteristics compared to conventional 2DT2 MRI in two planes. 3DT2 is interchangeable with a 2DT2 sequence in tumor protocols. KEY POINTS: • Isotropic 3DT2 CAIPIRINHA SPACE TSE offers higher spatial resolution than 2DT2 TSE and is equivalent to 2DT2 TSE for assessments of soft tissue tumor intrinsic and perilesional characteristics. • Multiplanar reformats of 3DT2 CAIPIRINHA SPACE TSE can substitute for 2DT2 TSE acquired in multiple planes, thereby reducing the acquisition time of MRI tumor protocols. • 3DT2 CAIPIRINHA SPACE TSE and 2DT2 TSE had similar CNR of tissues.

Sphingomonas Paucimobilis Pneumonia Complicated by Empyema in an Immunocompetent Patient: A Case Report and Concise Review of Literature.

Sphingomonas paucimobilis is an aerobic, Gram-negative bacterium that is found widely in the environment and on hospital equipment. Although this organism usually causes infection in immunocompromised patients, it may cause pulmonary disease in immunocompetent patients, in rare cases. We report a case of Sphingomonas paucimobilis pneumonia complicated by empyema in an immunocompetent patient. We present a case of a 59-year-old female who was admitted for a congestive heart failure exacerbation and pneumonia. After imaging confirmed pneumonia and pleural effusion, monotherapy with levofloxacin was started. Thoracentesis revealed empyema caused by Sphingomonas paucimobilis. Despite chest tube placement, thoracoscopy with decortication was required due to continued clinical deterioration. After surgical intervention and an adjusted antibiotic regimen of cefepime, the patient clinically improved and was discharged. Upon follow-up, she had recovered completely with no residual disease. Alongside a concise review of the literature, our study highlights the importance of this infection in immunocompetent patients and advises providers to identify causes of aspiration when Sphingomonas paucimobilis empyema is diagnosed.

Cause of In-Hospital Death After Weaning from Venoarterial-Extracorporeal Membrane Oxygenation.

PURPOSE: A survival gap between weaning from venoarterial-extracorporeal membrane oxygenation (VA-ECMO) and the hospital discharge has been consistently reported. The aim of this study is to investigate the clinical features of patients who underwent successful VA-ECMO decannulation at our institution and to identify the major contributors responsible for adverse outcomes. METHODS: We retrospectively reviewed all patients supported with VA-ECMO in our institution between January 2013 and June 2020. Only patients that survived VA-ECMO and underwent successful decannulation were included and dichotomized based on survival to hospital discharge: non-survivors versus survivors. The primary study outcome was the cause of death after successful VA-ECMO decannulation. RESULTS: Of the 262 adult patients who underwent VA-ECMO decannulation, 72 (27.5%) patients did not survive to hospital discharge. Non-survivors were older (62 vs. 54 years, p < 0.001) and suffering from many pre-existing comorbidities. Pneumonia and sepsis were the most frequent infectious complication and almost twice as likely in non-survivors. Major causes of death were: cardiovascular (31.9%), infections (25.0%) and neurological (20.8%). The survival curve demonstrated that 51.4% of our patients died within 8 days after decannulation. Multivariate analysis identified older age, central venous cannulation, pulmonary bleeding and infection, dialysis after VA-ECMO, sepsis, and ischemic stroke (OR = 7.86, 95% CI: 2.76-2.43, p < 0.001) as factors significantly predisposing to patients' death. CONCLUSION: In our study, one-third of patients decannulated off VA-ECMO did not survive to hospital discharge due to end-stage heart failure, infections or neurological injury. The first 8 post-decannulation days were recognized as a critical period where thorough strategies to prevent acquired infections and cautious support of end-organ function should be warranted. Future large-scale trials are needed to confirm our results.

Enhanced Recovery After Surgery in Patients Implanted with Left Ventricular Assist Device.

INTRODUCTION: We sought to develop and implement a comprehensive enhanced recovery after surgery (ERAS) protocol for patients implanted with a left ventricular assist device (LVAD). METHODS AND RESULTS: In this article, we describe our approach to the development and phased implementation of the protocol. Additionally, we reviewed prospectively collected data for patients who underwent LVAD implantation at our institution from February 2019 to August 2020. To compare early outcomes in our patients before and after protocol implementation, we dichotomized patients into two 6-month cohorts (the pre-ERAS and ERAS cohorts) separated from each other by 6 months to allow for staff adoption of the protocol. Of the 115 LVAD implants, 38 patients were implanted in the pre-ERAS period and 46 patients in the ERAS period. Preoperatively, the patients` characteristics were similar between the cohorts. Postoperatively, we observed a decrease in bleeding (chest tube output of 1006 vs 647.5 mL, P < .001) and blood transfusions (fresh frozen plasma 31.6% vs 6.7%, P = .04; platelets 42.1% vs 8.7%, P = .001). Opioid prescription at discharge were 5-fold lower with the ERAS approach (P < .01). Furthermore, the number of patients discharged to a rehabilitation facility decreased significantly (20.0% vs 2.4%, P = .02). The index hospitalization length of stay and survival were similar between the groups. CONCLUSIONS: ERAS for patients undergoing LVAD implantation is a novel, evidence-based, interdisciplinary approach to care with multiple potential benefits. In this article, we describe the details of the protocol and early positive changes in clinical outcomes. Further studies are needed to evaluate benefits of an ERAS protocol in an LVAD population.Lay Summary: Enhanced recovery after surgery (ERAS) is the implementation of standardized clinical pathways that ensures the use of best practices and decreased variation in perioperative care. Multidisciplinary teams work together on ERAS, thereby enhancing communication among health care silos. ERAS has been used for more than 30 years by other surgical services and has been shown to lead to a decreased length of stay, fewer complications, lower mortality, fewer readmissions, greater job satisfaction, and lower costs. Our goal was to translate these benefits to the perioperative care of complex patients with a left ventricular assist device. Early results suggest that this goal is possible; we have observed a decrease in transfusions, discharge on opioids, and discharge to a rehabilitation facility.

Long-term renal function after venoarterial extracorporeal membrane oxygenation.

BACKGROUND: The utilization of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a life-supporting therapy has increased exponentially over the last decade. As more patients receive and survive ECMO, there are a number of unanswered clinical questions about their long-term prognosis and organ function including the need for long-term dialysis. METHODS: We aimed to utilize over 208 patient-years of follow-up data from our large institutional cohort of VA-ECMO patients to determine the incidence of requiring VA-ECMO support on the need for renal replacement therapy after discharge (LT-dialysis). This retrospective review included all adult VA-ECMO patients at our institution from January 2014 to October 2018 (N = 283). RESULTS: Out of the 99 (35%) survivors, 88 (89%) did not require LT-dialysis of any duration after discharge from the index hospitalization. Patients who required VA-ECMO for decompensated cardiogenic shock were more likely to need LT-dialysis (p = .034), and those who required renal replacement therapy during VA-ECMO (N = 27) also had a higher incidence of LT-dialysis (33%). CONCLUSION: Overall, these data suggest there is a low incidence of long-term dialysis dependence among survivors of VA-ECMO support. Worries about the potential long-term detrimental effect of VA-ECMO should not preclude patients from receiving this life-saving support.

Defecation versus pre- and post-defecation Valsalva maneuvers for dynamic MR assessment of pelvic floor dysfunction.

PURPOSE: To compare prevalence and severity of multi-compartment pelvic floor dysfunction between supine magnetic resonance defecography with defecation (MRD) and supine dynamic MRI during Valsalva, both with and without rectal distention. METHODS: This was an IRB-approved, HIPAA-compliant retrospective review of consecutive patients referred for MR Defecography. MRD protocol included imaging at rest, during pre-defecation Valsalva (Pre-DV), defecation (Def), and post-defecation Valsalva (Post-DV). The Post-DV images were performed after complete evacuation either during the defecation acquisition or, in cases where patient was unable to defecate during the examination, in a conventional toilet. Size of cystocele, vaginal prolapse, anorectal (AR) descent, and enterocele were measured on all acquisitions relative to the pubococcygeal line. Rectocele size was recorded in anteroposterior dimension. The presence or absence of rectal intussusception (RI) was documented. The prevalence, absolute size, and grades of prolapse, rectocele, and RI were compared between the acquisitions using pair-wise ANOVA, Friedman, Dunn pair-wise, and Cochran-Mantel-Haenszel tests. RESULTS: 30 patients were included in the final analysis. Higher prevalence of cystocele, vaginal prolapse, enterocele, AR descent grade 2 or higher, rectocele grade 2 or higher, and RI were seen on Def compared to Post-DV and Pre-DV. Cystocele, vaginal prolapse, enterocele, AR descent, and rectocele sizes were significantly larger on Def compared to Post-DV by 0.7-1.95 cm (p ≤ 0.007). Prolapse in all compartments and rectocele size were significantly larger on Def compared to Pre-DV (p < 0.0001). Cystocele, vaginal prolapse, and enterocele sizes were significantly larger on Post-DV compared to Pre-DV (p < 0.0001). There were significant differences in grading of all types of prolapse and rectocele between the various acquisitions of MRD (p < 0.0001). Cystocele, AR descent, and rectocele grades were significantly higher on Def compared to Post-DV (p range ≤ 0.0002). Grading of all types of prolapse and rectocele was significantly higher on Def compared to Pre-DV (p < 0.0001). Cystocele, vaginal prolapse, and enterocele grades were all significantly higher on Post-DV compared to Pre-DV (p ≤ 0.0007). CONCLUSION: Defecation images during supine MRD elicit higher prevalence and size of prolapse of all pelvic compartments in comparison to both pre- and post-defecation Valsalva images. Post-defecation Valsalva images show larger size of anterior and middle compartment prolapse than pre-defecation Valsalva images. Functional evaluation of pelvic floor dysfunction with MRI should include image acquisition during defecation. If Valsalva images are acquired, these should be performed after the defecation acquisition and without rectal distention.

Venoarterial-Extracorporeal Membrane Oxygenation Without Routine Systemic Anticoagulation Decreases Adverse Events.

BACKGROUND: Despite limited evidence, systemic anticoagulation is the current standard of care for patients supported on venoarterial-extracorporeal membrane oxygenation (VA-ECMO). We hypothesized that not anticoagulating patients on VA-ECMO would decrease complications. METHODS: We retrospectively reviewed adult patients supported on VA-ECMO at our institution. Patients were stratified based on anticoagulation strategy. The primary outcome was a composite of hemorrhagic and thrombotic complications. Secondary outcomes included blood product use, incidence of heparin-induced thrombocytopenia (HIT), hospital length of stay, and in-hospital mortality. RESULTS: From May 2011 through January 2018, there were 203 eligible patients supported on VA-ECMO, 35% (75 patients) were not anticoagulated. Overall complication rates were significantly lower for the no anticoagulation group (57% versus 76%; P = .007) including a trend toward fewer hemorrhagic complications (53% versus 63%; P = .178) without increased risk of thrombosis (13% versus 21%; P = .147). The anticoagulated group required more transfusions of packed red blood cells (12.8 versus 1.09; P = .002) and platelets (3.0 versus 1.3; P = .009) and showed a higher incidence of HIT (8% versus 0%; P = .015). No difference was found in overall mortality (72% versus 62%; P = .165). CONCLUSIONS: The absence of routine systemic anticoagulation for patients supported on VA-ECMO is not associated with higher mortality, pump failure, or thrombotic complications. Patients had a lower requirement for blood product transfusions, and there was no incidence of HIT. Patients supported on VA-ECMO without other indications for anticoagulation can be treated without systemic anticoagulation during their VA-ECMO course.

Supine magnetic resonance defecography for evaluation of anterior compartment prolapse: Comparison with upright voiding cystourethrogram.

PURPOSE: To compare utility of supine Magnetic Resonance Defecography (MRD) with upright Voiding Cystourethrogram (VCUG) for evaluation of cystocele and urethral hypermobility (UHM). METHODS: This was an IRB-approved, HIPAA-compliant, retrospective study of 51 consecutive patients with symptomatic pelvic organ prolapse (POP) and lower urinary tract symptoms who underwent both upright VCUG and supine MRD. Cystocele height was defined in centimeters with reference to the inferior edge of the pubic bone on VCUG and the pubococcygeal line on MRD. Urethral angle at rest (UAR) and during straining (UAS) was measured in degrees between the urethral axis and a vertical line at the external meatus. Pairedt-test and simple linear regression were applied to compare VCUG and MRD data sets. p < 0.05 was considered significant. RESULTS: The mean cystocele extent was 1.58 cm lower (more inferior to the reference point) (95% CI for the mean difference: 1.21, 1.94;p < 0.0001) on MRD (-2.73 ± 1.99 cm) than on VCUG (-1.16 ± 1.75 cm). Mean UAS on MRD (72.29 ± 26.45) was 31.8 degrees higher compared to that on VCUG (40.45 ± 21.41), (95% CI for mean difference in UAS: 37.57, 26.11; p < 0.0001). Mean UAS-UAR on MRD (74.30 ± 28.50) was 58.6 degrees higher compared to that on VCUG (15.70 ± 11.27) (95% CI for mean difference in UAS-UAR 65.94, 51.26; p < 0.0001). Cystocele size was upgraded in 22 (43.3%) patients on MRD compared to VCUG. Five (9.8%) patients demonstrated UHM on VCUG; 48 (94.1%) patients demonstrated UHM on MRD. The differences between VCUG and MRD scores persisted across the range of VCUG measurements. Cystocele size was significantly larger in POP (+) patients than in POP (-) patients on MRD (p = 0.005) but not on VCUG (p = 0.06). CONCLUSIONS: Supine MRD demonstrates significantly higher prevalence and degree of cystocele and UHM than upright VCUG, and alters the grade of bladder prolapse in a significant portion of the patient population. Cystocele size on MRD correlates with clinical presence of prolapse symptoms.

The impact of a pulmonary embolism response team on the efficiency of patient care in the emergency department.

The concept of a pulmonary embolism response team (PERT) is multidisciplinary, with the hope that it may positively impact patient care, hospital efficiency, and outcomes in the treatment of patients with intermediate and high risk pulmonary embolism (PE). Clinical characteristics of a baseline population of patients presenting with submassive and massive PE to URMC between 2014 and 2016 were examined (n = 159). We compared this baseline population before implementation of a PERT to a similar population of patients at 3-month periods, and then as a group at 18 months after PERT implementation (n = 146). Outcomes include management strategies and efficiency of the emergency department (ED) in diagnosing, treating, and dispositioning patients. Before PERT, patients with submassive and massive PE were managed fairly conservatively: heparin alone (85%), or additional advanced therapies (15%). Following PERT, submassive and massive PE were managed as follows: heparin alone (68%), or additional advanced therapies (32%). Efficiency of the ED in managing high risk PE significantly improved after PERT compared with before PERT; where triage to diagnosis time was reduced (384 vs. 212 min, 45% decrease, p = 0.0001), diagnosis to heparin time was reduced (182 vs. 76 min, 58% decrease, p = 0.0001), and the time from triage to disposition was reduced (392 vs. 290 min, 26% decrease, p < 0.0001). Our analysis showed that following PERT implementation, patients with intermediate and high risk acute PE received more aggressive and advanced treatment modalities and received significantly expedited care in the ED.

Incidence of Posteromedial Meniscocapsular Separation and the Biomechanical Implications on the Anterior Cruciate Ligament.

PURPOSE: To report the incidence of posterior medial meniscocapsular junction (PMCJ) separation in patients with anterior cruciate ligament (ACL) injury and to evaluate its biomechanical effect on the ACL. METHODS: Three hundred thirty-seven consecutive patients undergoing isolated primary ACL reconstruction were retrospectively analyzed for PMCJ lesion. Forty-four patients were identified with PMCJ lesion and studied. Eight cadaver knees underwent biomechanical testing to determine anterior tibial displacement and anteromedial bundle ACL strain in the intact, PMCJ lesion, and PMCJ repair states at 0°, 30°, 60°, and 90° of flexion. Mixed-effects linear regression with Bonferroni correction was used for statistical analysis. RESULTS: PMCJ tear incidence with ACL disruption was 13.1%. Specimen with PMCJ tears had statistically increased anterior tibial translation at 30° (1.2 mm; P < 0.01) and statistically increased ACL strain at 30° (24%; P < 0.01) and 90° (50%; P < 0.01). With PMCJ repair, translation reduced (P > 0.05) by 12%, 18%, and 10% at 0°, 30°, and 90° of flexion, respectively. PMCJ repair reduced (P < 0.05) ACL strain by 40%, 39%, 43%, and 31% at 0°, 30°, 60°, and 90° of flexion, respectively. CONCLUSIONS: A PMCJ lesion was observed in 13% of ACL injuries. This injury contributes to increased ACL strain, and PMCJ repair markedly reduces ACL strain to preinjury levels.

Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis.

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a fatal disease with no available disease-modifying therapies. While pathogenic TTR mutations (TTRm) destabilize TTR tetramers, the T119M variant stabilizes TTRm and prevents disease. A comparison of potency for leading TTR stabilizers in clinic and structural features important for effective TTR stabilization is lacking. Here, we found that molecular interactions reflected in better binding enthalpy may be critical for development of TTR stabilizers with improved potency and selectivity. Our studies provide mechanistic insights into the unique binding mode of the TTR stabilizer, AG10, which could be attributed to mimicking the stabilizing T119M variant. Because of the lack of animal models for ATTR-CM, we developed an in vivo system in dogs which proved appropriate for assessing the pharmacokinetics-pharmacodynamics profile of TTR stabilizers. In addition to stabilizing TTR, we hypothesize that optimizing the binding enthalpy could have implications for designing therapeutic agents for other amyloid diseases.

Is Edema at the Posterior Medial Tibial Plateau Indicative of a Ramp Lesion? An Examination of 307 Patients With Anterior Cruciate Ligament Reconstruction and Medial Meniscal Tears.

BACKGROUND: Medial meniscal tears are commonly seen during anterior cruciate ligament reconstruction (ACLR). A subset of these injuries includes posterior meniscocapsular junction or "ramp" tears. One criterion that may correlate with a ramp lesion is the presence of posterior medial tibial plateau (PMTP) edema. PURPOSE: To compare patients with ramp lesions to patients with nonramp (meniscal body) medial meniscal tears and correlate PMTP edema on preoperative magnetic resonance imaging (MRI) to the incidence of ramp tears. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: From 2006 to 2016, a total of 852 patients underwent ACLR and had operative reports available for review. Age, sex, laterality, mechanism of injury (contact/noncontact), sport, revision procedure, multiligament injury, time to MRI, and time to surgery were recorded. Preoperative MRI scans were reviewed for PMTP edema using axial, coronal, and sagittal T2 and proton-density sequences. Differences between groups were analyzed using a 2-sample t test and chi-square test. Univariate and multivariate logistic regression models examined correlations with tear type. RESULTS: Overall, 307 patients had medial meniscal tears identified during ACLR (127 ramp lesions, 180 meniscal body lesions). The ramp group was 7.5 years younger than the meniscal body group (P < .01). The groups were not different regarding sex, contact injury, revision surgery, laterality, or multiligament injury. Patients with delayed ACLR were significantly more likely to have a meniscal body tear than a ramp lesion (odds ratio, 3.3 [95% CI, 1.9-5.6]; P < .01). The sensitivity of PMTP edema for a ramp tear was 66.3%, and 54.5% of patients with ACLR and a medial meniscal tear had PMTP edema. Patients with PMTP edema were significantly more likely to have a ramp tear than a meniscal body tear (odds ratio, 2.1 [95% CI, 1.1-4.1]; P < .03). CONCLUSION: The overall incidence of ramp tears in patients undergoing ACLR was 14.9%, and these tears were more prevalent in younger patients. Meniscal body tears were significantly more likely than ramp tears with delayed ACLR. In patients undergoing ACLR with an associated medial meniscal tear, the presence of PMTP edema demonstrated significantly greater odds for ramp lesions compared with meniscal body tears.

Synthetic MRI of the Knee: Phantom Validation and Comparison with Conventional MRI.

Purpose To test the hypothesis that synthetic MRI of the knee generates accurate and repeatable quantitative maps and produces morphologic MR images with similar quality and detection rates of structural abnormalities than does conventional MRI. Materials and Methods Data were collected prospectively between January 2017 and April 2018 and were retrospectively analyzed. An International Society for Magnetic Resonance in Medicine-National Institute of Standards and Technology phantom was used to determine the accuracy of T1, T2, and proton density (PD) quantification. Statistical models were applied for correction. Fifty-four participants (24 men, 30 women; mean age, 40 years; range, 18-62 years) underwent synthetic and conventional 3-T MRI twice on the same day. Fifteen of 54 participants (28%) repeated the protocol within 9 days. The intra- and interday agreements of quantitative cartilage measurements were assessed. Contrast-to-noise (CNR) ratios, image quality, and structural abnormalities were assessed on corresponding synthetic and conventional images. Statistical analyses included the Wilcoxon test, χ2 test, and Cohen Kappa. P values less than or equal to .01 were considered to indicate a statistically significant difference. Results Synthetic MRI quantification of T1, T2, and PD values had an overall model-corrected error margin of 0.8%. The synthetic MRI interday repeatability of articular cartilage quantification had native and model-corrected error margins of 3.3% and 3.5%, respectively. The cartilage-to-fluid CNR and menisci-to-fluid CNR was higher on synthetic than conventional MR images (P ≤ .001, respectively). Synthetic MRI improved short-tau inversion recovery fat suppression (P ˂ .01). Intermethod agreements of structural abnormalities were good (kappa, 0.621-0.739). Conclusion Synthetic MRI of the knee is accurate for T1, T2, and proton density quantification, and simultaneously generated morphologic MR images have detection rates of structural abnormalities similar to those of conventional MR images, with similar acquisition time. © RSNA, 2018.