Two-tailed Student Research Articles

Electrocardiographic features in SCN5A mutation-positive patients with Brugada and early repolarization syndromes: a systematic review and meta-analysis

BackgroundEarly repolarization syndrome (ERS) and Brugada syndrome (BrS) are both J-wave syndromes. Both can involve mutations in the SCN5A gene but may exhibit distinct electrocardiographic (ECG) differences. The aim of this systematic review and meta-analysis is to investigate possible differences in ECG markers between SCN5A-positive patients with ERS and BrS.MethodsPubMed and Embase were searched from their inception to 20 October 2021 for human studies containing the search terms “SCN5A” and “variant” and “early repolarization” or “Brugada”, with no language restrictions. Continuous variables were expressed as mean±standard deviation. PR interval, QRS duration, QTc and heart rate from the included studies were pooled to calculate a mean for each variable amongst BrS and ERS patients. A two-tailed Student’s t test was then performed to for comparisons.ResultsA total of 328 studies were identified. After full-text screening, 12 studies met our inclusion criteria and were included in this present study. One hundred and four ERS patients (mean age 30.86±14.45) and 2000 BrS patients (mean age 36.17±11.39) were studied. Our meta-analysis found that ERS patients had shorter QRS duration (90.40±9.97 vs. 114.79±20.10, P = 0.0001) and shorter corrected QT intervals (QTc) with borderline significance (393.63±40.04 vs. 416.82±37.43, P = 0.052). By contrast, no significant differences in baseline heart rate (65.15±18.78 vs. 76.06±18.78, P = 0.068) or PR intervals (197.40±34.69 vs. 191.88±35.08, P = 0.621) were observed between ERS and BrS patients.ConclusionBrS patients with positive SCN5A mutations exhibited prolonged QRS, indicating conduction abnormalities, whereas ERS patients with positive SCN5A mutations showed normal QRS. By contrast, whilst QTc intervals were longer in BrS than in ERS SCN5A positive patients, they were within normal limits. Further studies are needed to examine the implications of these findings for arrhythmic risk stratification.

Paper 29: Return to Sport Testing vs Time-Based Clearance in Posterior Shoulder Instability

Objectives:Recurrent pain, instability and loss of function are challenging complications that can occur after arthroscopic treatment of posterior shoulder instability and SLAP tears in athletes. Many surgeons allow return to sport after a designated arbitrary postoperative time point. Recent evidence has demonstrated that a majority of athletes have residual strength and functional limitations at 6 months postoperatively – the time at which most time-based protocols allow full return to sport. Recent data has also been presented that patients undergoing arthroscopic Bankart repair who are required to meet objective return to sport testing criteria have a 4x lower rate of recurrent anterior instability than those who return based on time elapsed since surgery. Considering these findings, the purpose of this study is to investigate the use of a similar objective return to sport testing protocol on recurrence rates following arthroscopic surgery for posterior shoulder instability and SLAP tears. We hypothesized that patients who meet objective return to sport criteria would have a lower rate of reoperation and recurrence of symptoms compared to those who did not undergo the testing and were cleared to return based on time from surgery.Methods:Consecutive patients (Group 1) who underwent arthroscopic posterior shoulder stabilization surgery with or without SLAP repair by a single surgeon from 2016 to 2019, had a minimum of 1 year follow up, and completed functional and strength testing to evaluate readiness for return to sport were included in this retrospective case-controlled study. These patients were compared to a control group of historical consecutive cases (Group 2) from 2012-2016 who did not undergo return to sports testing and were cleared for sports after a minimum of 6 months following surgery. Failure was defined as recurrent symptoms of pain or instability requiring reoperation. Exclusion criteria were: patients undergoing isolated anterior stabilization procedures with or without concomitant SLAP tears, multidirectional instability, and open procedures. Chi-square, Fisher exact tests and two-tailed Students T-test were performed. Statistical significance was set at p<0.05.Results:There were 33 patients in Group 1 who underwent return to sport testing, and 91 patients in Group 2, the historical control. There were no differences between groups regarding sex (p=0.46), hand dominance (p=0.16), side affected (p= 0.69). The average age of Group 1 (20.8 +/- 4 yrs) was significantly younger than Group 2 (31.5 +/- 9.1 yrs, p< 0.00001). Patients who underwent return to sport criteria-based testing protocol had a rate of recurrent symptoms of pain or instability of 12.1% compared to 18.6% for those who did not (p= 0.43). Similarly, there were no reoperations for in Group 1, while three patients in group 2 (3.3%) underwent revision surgery for recurrent symptoms. This difference, however, did not reach statistical significance (p= 0.5633).Conclusions:In our cohort of young patients undergoing arthroscopic surgery for posterior shoulder instability, we detected no significant difference in reoperation rate and recurrence of symptoms between athletes who underwent objective return to sport testing and those who were released to sport on a time-based protocol. This may be related to an overall lower rate of reoperation in patients undergoing arthroscopic posterior stabilization or SLAP repairs in general compared to those undergoing arthroscopic anterior stabilization and differences in tolerance and presentation of recurrent posterior instability/SLAP tears versus anterior instability. It is possible that criteria-based return to sport testing prior to clearance to return to sport may be less critical for improving failure rates following arthroscopic posterior stabilization and SLAP repair than for anterior stabilization. Alternatively, given low reoperation rates overall, future studies investigating the role of return to sport testing after arthroscopic surgery for posterior shoulder instability and SLAP repairs may need to include more patients in order to detect differences related to the testing protocol. This study provides a basis upon which further studies, involving larger patient populations, may be conducted to elucidate any impact on functional scores and recurrence rates that may be associated with return-to-sport protocols based on functional testing rather than time since surgery.

Does the “Delta Variant” affect the nonlinear dynamic characteristics of SARS-CoV-2 transmission?

In this paper, we analyzed the difference of nonlinear dynamic characteristics of SARS-CoV-2 transmission caused by ‘Delta Variant’. We selected the daily new diagnostic data of SARS-CoV-2 from 15 countries. Four different kinds of complexity metrics such as Kolmogorov complexity, Higuchi's Hurst exponent, Shannon entropy, and multifractal degrees were selected to explore the features of information content, persistence, randomness, multifractal complexity. Afterwards, Student's t-tests were performed to assess the presence of differences of these nonlinear dynamic characteristics for periods before and after “Delta Variant” appearance. The results of two-tailed Student's t-test showed that for all the nonlinear dynamic characteristics, the null hypothesis of equality of mean values were strongly rejected for the two periods. In addition, by one-tailed Student's t-test, we concluded that time series in “Delta period” exhibit higher value of Kolmogorov complexity and Shannon entropy, indicating a higher level of information content and randomness. On the other hand, the Higuchi's Hurst exponent in “Delta period” was lower, which showed the weaker persistent in this period. Moreover, the multifractal specturm width after “Delta” emergence were reduced, representing a more stable multifractality. The sources for the formation of multifractal features are also investigated.

S136-operationalizing an enhanced recovery protocol after bariatric surgery: single institutional pilot experience forging data-driven standard work.

BackgroundEnhanced recovery protocols (ERPs) after metabolic and bariatric surgery (MBS) may help decrease length of stay (LOS) and postoperative nausea/vomiting but implementation is often fraught with challenges. The primary aim of this pilot study was to standardize a MBS ERP with a real-time data support dashboard and checklist and assess impact on global and individual element compliance. The secondary aim was to evaluate 30 day outcomes including LOS, hospital readmissions, and re-operations.Methods and proceduresAn ERP, paper checklist, and virtual dashboard aligned on MBS patient care elements for pre-, intra-, and post-operative phases of care were developed and sequentially deployed. The dashboard includes surgical volumes, operative times, ERP compliance, and 30 day outcomes over a rolling 18 month period. Overall and individual element ERP compliance and outcomes were compared pre- and post-implementation via two-tailed Student’s t-tests.ResultsOverall, 471 patients were identified (pre-implementation: 193; post-implementation: 278). Baseline monthly average compliance rates for all patient care elements were 1.7%, 3.7%, and 6.2% for pre-, intra-, and post-operative phases, respectively. Following ERP integration with dashboard and checklist, the intra-operative phase achieved the highest overall monthly average compliance at 31.3% (P < 0.01). Following the intervention, pre-operative acetaminophen administration had the highest monthly mean compliance at ≥ 99.1%. Overall TAP block use increased 3.2-fold from a baseline mean rate of 25.4–80.8% post-implementation (P < 0.01). A significant decrease in average intra-operative monthly morphine milligram equivalents use was noted with a 56% drop pre- vs. post-implementation. Average LOS decreased from 2.0 to 1.7 days post-implementation with no impact on post-operative outcomes.ConclusionImplementation of a checklist and dashboard facilitated ERP integration and adoption of process measures with many improvements in compliance but no impact on 30 day outcomes. Further research is required to understand how clinical support tools can impact ERP adoption among MBS patients.

The beneficial effects of square dance on musculoskeletal system in early postmenopausal Chinese women: a cross-sectional study

BackgroundThis study was set to investigate the correlation between square dance and musculoskeletal system of early postmenopausal Chinese women.MethodsChinese postmenopausal women, who had been without menstruation for 1–10 years from the onset of menopause were recruited from community centers for this study. A standardized structured face-to-face interview was performed to collect demographic information, life styles, personal medical history, diet and menstrual status. Subjects who had been practicing regular square dance without participated in other sports activities for more than 2 years and over 4 h per week (usually more than 45 min per time and more than 5 times per week) were assigned to square dance group. Those postmenopausal women who had not participated in regular exercises (no more than 0.5 h per week) were recruited as the sedentary control group. Bone mineral density (BMD) of spine, total hip and femoral neck was measured by using dual-energy X-ray absorptiometry. Lower limb muscle strength was measured for the non-dominant leg, body flexibility was measured by a simple trunk bend-and-reach test, and body balance was evaluated using a single-stance test for the non-dominant leg. Independent two-tailed Student’s t-test was used for data analysis.Results152 subjects from community centers were selected for this study and divided into square dance group (n = 74) and control group (n = 78). The square dance subjects had higher lumbar spine BMD (p = 0.01) and total hip BMD (p = 0.02) than control subjects, but there was no significant difference of femoral neck BMD (p = 0.48) between these two groups. Functional testing indicated that square dance subjects had higher lower limb muscle strength (p < 0.01) and longer single-stance time (p = 0.02) than the control subjects, but there was no significant difference in trunk bend-and-reach (p = 0.12) between these two groups.ConclusionOur results show that postmenopausal Chinese women can get beneficial effects, like higher BMD, stronger lower limb muscle and improved body balance ability on musculoskeletal system by participating in square dance regularly.

Correlation Analysis between Tibial Tuberosity-Trochlear Groove Distance and Other Patellar Stability Parameters in Young and Middle-aged Populations.

ObjectiveThe exact mechanism of patellofemoral instability has not been clearly clarified. The current study aims to explore the correlation between the tibial tuberosity‐trochlear groove (TT‐TG) distance and other patellar stability parameters.MethodsA total of 60 individuals aged 18 to 40 years who underwent knee computed tomography (CT) examination between September 2014 and December 2017 were retrospectively recruited. Five reference sites were selected on the femoral trochlear articular surface in every CT image. The TT‐TG distance and the trochlear groove angles (TGA) at the five reference sites were measured. The patellar ligament length (PLL), patellar length (PL), medial patellar retinaculum length (MPRL) and lateral patellar retinaculum length (LPRL) were quantitatively analyzed. The TT‐TG distances on different knee sides or in different sexes were compared. The relationships between the TT‐TG distance and TGA, PLL/PL, MPRL, and LPRL were analyzed by Spearman's method. Comparison analysis among patellar stability parameters was analyzed using ANOVA or two‐tailed Student's t test.ResultsVariance analysis revealed no significant differences in the TT‐TG distances among the five positions of the femoral trochlea (F = 0.67, P = 0.62) but significant differences among the five femoral TGAs at the five reference sites (F = 380.37, P < 0.01). Notably, an increasing tendency of the TT‐TG distance was observed in the sexes (male, range 16.61–19.68 mm; female, range 14.37–17.38 mm) and knee sides (left knee, range 14.37–18.43 mm; right knee, range 15.80–19.68 mm). The TGA at site 1 of the femoral trochlear cartilage was the largest, with an angle of 151.97° ± 10.4°, and then gradually decreased to the smallest when the cartilage disappeared at site 5, with an angle of 92.05° ± 10.01°. Interestingly, there was a positive relationship between the TT‐TG distance at site 1 and TGA in the right knees of males (r = 0.490, P = 0.033) as well as LPRL in the left knees of males (r = −0.420; P = 0.046). There were no correlations between the TT‐TG distance and the other patellar stability parameters, including TGA, PLL/PL, MPRL, and LPRL.ConclusionAmong young and middle‐aged populations, patella surgeries should be carefully determined based on the comprehensive consideration of these patellar stability parameters rather than the TT‐TG distance alone. Differences in sex and knee side should also be considered.

Abstract 1477: Circulating miR-125a-3p and miR-451a may be liquid biopsy biomarkers for the diagnosis of breast cancer

Abstract Background: Breast cancer is the most prevalent female cancer. Emerging evidence suggests that the unique serum miRNAs can assist in the early detection and diagnosis of breast cancer. Cell-free circulating miRNAs (about 22 nucleotides) are potential diagnostic tools and minimally invasive biomarkers for breast cancer detection. This study aimed to identify specific microRNAs in the serum of patients with breast cancer, which may serve as promising diagnostic and prognostic biomarkers and therapeutic targets. Material and methods: Next-generation sequencing and quantitative real-time PCR (qRT-PCR) array analyses of microRNAs in sera from different subtypes of breast cancer patients and normal female individuals were performed. The differentially expressed microRNAs were verified in serum samples from 100 breast cancer patients. The predictive values of the selected microRNAs were statistically analyzed, determined by the correlation between microRNA expression and tumor parameters. Datasets were graphed using GraphPad Prism Software 8.0. and analysis was done using one-way ANOVA with unpaired two-tailed Student’s t-test. Result: High serum levels of miR-125a-3p and miR-451a were found to be associated with breast cancer tumor subtype, size, and lymph node metastasis. Further functional in vitro experiments and enrichment analysis showed that overexpression and knockdown of miR-451 might significantly affect tumorigenic signaling pathways in TNBC cells. Conclusion: Altogether, our data suggested that serum levels of microRNAs miR-125a-3p and miR-451a can potentially serve as liquid biopsy biomarkers in breast cancer. Citation Format: Hassan Yousefi, Steven C. Eastlack, Jordyn T Fong, Samuel C. Okpechi, Jovanny Zabaleta, Lyndsey R. Buckner, Donnalee N Trapani, Erin Sims, Alison McDaniel McDaniel, Heather Scuderi, Meredith A. Lakey, John T. Cole, Suresh K. Alahari. Circulating miR-125a-3p and miR-451a may be liquid biopsy biomarkers for the diagnosis of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1477.

Short-term anthracyclines-induced cardiotoxicity in breast cancer patients.

e18703 Background: Anthracycline-containing regimens are effective treatment of early breast cancer; however, they can induce irreversible myocardial damage, leading to significant morbidity and mortality. The main aim of this study was to describe and evaluate early anthracycline cardiotoxicity. Methods: This was a prospective study including breast cancer patients who where candidates for adjuvant anthracycline-based chemotherapy. Patients were assessed at baseline with history, physical exam, standard 12-lead electrocardiography (ECG) and 2D echocardiography, and then shortly after completion of anthracycline-based chemotherapy. We reported the ECG parameters, LVEF calculated using Simpson's biplane method and global longitudinal strain (GLS). Cardiotoxicity was defined as a decline ≥ 5% in LVEF accompanied or not by clinical manifestations of heart failure, or a decline ≥ 10% in GLS. Statistical analysis was performed using SPSS version 26. For comparisons, we used two-tailed Student's t-test. Associations between risk factors and cardiotoxicity were assessed using linear and logistic regression; a p value &lt; 0.05 was considered significant. Results: 171 patients with stage I (10.3%), stage II (81%) or stage III (8.7%) invasive ductal breast carcinoma, with a mean age of 48,1 ± 10 years. Obesity was found in 59 patients and 92 were overweight. Among comorbidities, hypertension was present in 11.7%, diabetes mellitus in 5.2%, and dyslipidemia in 4.6%. The most common concomitant medications were β-blockers in 6.4%, followed by angiotensin II receptor blockers in 5.2%, Statins in 4.6%, biguanides in 5.2%. Cardiac function was assessed 12 ± 7 days before and 19 ± 8 days post chemotherapy. 94 patients received Doxorubicin with a cumulative dose of 240 mg/m2, and 77 received Epirubicin with a cumulative dose of 300 mg/m2. Subclinical Cardiotoxicity was observed in 9 patients (5.2%), defined as a decline ≥ 5% in LVEF and in one patient (0.5%) defined by GLS decline ≥ 10%. This patient had the lowest post-therapy LVEF (40.2%) of the cohort. LVEF and GLS although reduced significantly after treatment, remained within the normal range. (LVEF: 62.8 ± 3% vs. 58 ± 6%, p = 0.03), (GLS: -19.0 ± 2.4% vs. -17.1 ± 1.0%, p = 0.01). Patients receiving Doxorubicin had lower LVEF compared to Epirubicin after therapy (57.1 ± 2% vs. 61.4 ± 2%, p = 0.03). Additionally, we found significant ECG changes in Heart Rate (72.6 ± 11,6 vs. 85.2 ± 14.4 bpm, p = 0.013) and QTc (410.1 ± 24.9 vs. 427.7 ± 26.5 ms, p = 0.032). Cardiotoxicity was not associated with any cardiovascular risk factors. Doxorubicin use was the only risk factor, confirmed on multivariate analysis (p = 0,02). Conclusions: Anthracycline-based chemotherapy has detrimental subclinical effect on electrical activity and left ventricle systolic function in the short term after adjuvant chemotherapy. We did not observe any significant effect of risk factors, it is therefore important to monitor all patients.

Mangosteen Inhibits Growth and Survival of Cervical Cancer Cells.

Cervical cancer is the most common cancer of the female reproductive system. Late-stage cervical cancer treatment has been largely unsuccessful, and urgent anti-cancer therapy is needed. Mangosteen, a tropical fruit, has been studied and found to be rich in xanthones, known anti-cancer compounds. This study was designed to investigate the effect of mangosteen extract (ME) on SiHa cervical cancer cells and to explore the underlying molecular mechanisms. Clonogenic survival assay, Quick Cell Proliferation Assay, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, and caspase-3 activity kits were used to investigate the in vitro role of ME treatment in SiHa cervical cancer cell growth. We further investigated the possible molecular mechanisms using RT-PCR. Statistical analysis was done with unpaired two-tailed Student's t-test and significance at p-value <0.05; each experiment was repeated three times. Our study found that the growth and proliferation of SiHa cervical cancer cells was inhibited by ME. ME also induced apoptosis in SiHa cervical cancer cells. The anti-proliferative effect of ME on cervical cancer cells was associated with statistically significant (p<0.05) down-regulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin E. The pro-apoptotic effect of ME was associated with statistically significant (p<0.05) down-regulation of the anti-apoptotic molecules flice-like inhibitory protein (FLIP) and survivin. ME impedes the growth and survival of SiHa cervical cancer cells by down-regulating cyclin B, cyclin D, cyclin E as well as FLIP and survivin. ME may be a promising strategy for targeted cancer immunotherapy development.

Impaired expression of BCAT1 relates to muscle atrophy of mouse model of sarcopenia

BackgroundThe underlying mechanism of muscle atrophy in sarcopenia is still not fully understood; branched chain aminotransferase 1(BCAT1) isocitrate dehydrogenase-1 encodes an evolutionarily conserved cytoplasmic aminotransferase for glutamate and branched-chain amino acids (BCAAs), thus constituting a regulatory component of cytoplasmic amino and keto acid metabolism. In human gliomas carrying wild-type isocitrate dehydrogenase-1, BCAT1 promotes cell proliferation through amino acid catabolism. Hence, the goals of this study were to unravel the potential role of BCAT1 expression in muscle atrophy and to explore the mechanisms underlying this process.MethodsWe first measured Bcat1 expression by RT-qPCR and western blotting in murine and cellular models of muscle atrophy. To understand how the Bcat1-driven changes sustained muscle cell growth, we analyzed reactive oxygen species (ROS) levels and activation of the mTORC1/S6K1 pathway in muscle cells. Furthermore, we performed Cell Counting Kit-8(CCK8) assays and fluorescence staining to evaluate growth rate of cells and ROS levels. Finally, we verified that depletion of Bcat1 impairs the growth rate of muscle cells and increases ROS levels, indicating that muscle atrophy resulted from the downregulation of the mTORC1/S6K1 pathway. Data were analyzed by two-tailed unpaired Student’s t-test or Mann-Whitney U test for two groups to determine statistical significance. Statistical analyses were performed using GraphPad Prism version 6.0 and SPSS 16.0 software.ResultsBcat1 expression level in skeletal muscles was lower in murine and cellular models of sarcopenia than in the control groups. Bcat1 knockdown not only suppressed the growth of muscle cells but also increased the production of ROS. Impaired cell growth and increased ROS production was rescued by co-introduction of an shRNA-resistant Bcat1 cDNA or addition of the mTORC1 stimulator MYH1485. Muscle cells with Bcat1 knockdown featured lower mTORC1 and S6K1 phosphorylation (pS6K1) than NT muscle cells. Addition of either shRNA-resistant Bcat1 cDNA or MYH1485 rescued the suppression of cell growth, increase in ROS production, and decrease in pS6K1.ConclusionsThe branched chain amino acids catabolic enzyme BCAT1 is essential for the growth of muscle cells. BCAT1 expression contributes to sustained growth of muscle cells by activating mTOR signaling and reducing ROS production.

Management of severe spasticity with and without dystonia with intrathecal baclofen in the pediatric population: a cross-sectional study.

To investigate the differences in delivery mode, daily dose, and catheter tip location in pediatric patients using intrathecal baclofen (ITB) pumps with spasticity plus dystonia versus spasticity alone. A single-center, cross-sectional study was performed by collecting retrospective data from electronic medical records. Demographic and diagnostic information was obtained, comparing patients with spasticity with or without dystonia. The data were analyzed for group differences using a two-tailed Student's t-test. Categorical data were analyzed for group differences using Pearson's χ2 test. A total of 137 patients met the criteria. The majority (114) had spasticity plus dystonia whereas only 23 were documented as spasticity alone. Simple continuous dosing was the most common delivery mode, but flex dosing was used more than twice as frequently with spasticity plus dystonia compared with spasticity alone (42% vs 17%). Patients with spasticity plus dystonia also had more rostral catheter tip locations. While it has been discussed anecdotally, this study confirms the supposition that patients with spasticity plus dystonia have increased dose requirements when compared with those with spasticity alone. Although there are no clear standards of care when managing these patients, they are often on higher daily dosages, are more likely to require flexed dosing method, and have higher catheter placements. Still, there are few studies that demonstrate improvements in dystonia with the use of ITB. In general, these patients would benefit from the development of universal standardizations as well as the confirmation that this is an appropriate treatment.

Revision Pharyngoplasty in Cleft Palate and Velopharyngeal Insufficiency: Management and Outcomes.

Velopharyngeal insufficiency (VPI), a stigmatizing hallmark of palatal dysfunction, occurs in a wide spectrum of pediatric craniofacial conditions. The mainstays for surgical correction include palate repair and/or pharyngeal surgery. However, primary pharyngoplasty has a failure rate of 15% to 20%. Although revision pharyngoplasty may be necessary in those with persistent VPI, little is known regarding the indications for and outcomes after such procedures. The purpose of this study is to describe the authors' experience with indications for and outcomes after revision pharyngoplasty. A single-center retrospective review was performed of all patients undergoing revision pharyngoplasty between 2002 and 2019. Demographic data and Pittsburgh Weighted Speech Scores, diagnoses, comorbidities, and complications were tabulated. Two-tailed Student t test was used, and a P value of 0.05 or less was considered statistically significant. Thirty-two patients (65.6% male) met inclusion criteria for this study. The most common diagnoses included cleft palate (68.8%), submucous cleft palate (SMCP, 18.8%), and congenital VPI (6.3%, likely occult SMCP). Most patients (84.4%) underwent palatoplasty before their initial pharyngoplasty. The primary indication for initial pharyngoplasty was VPI (mean age 7.1 ± 4.6 years). The most common indication for revision pharyngoplasty (mean age 11.2 ± 5.1 years) included persistent VPI (n = 22), followed by obstructive sleep apnea (OSA) (n = 11). Persistent VPI (n = 8) and OSA (n = 6) were the most common complications after secondary pharyngoplasty. Thirteen patients (40.6%) within the revision pharyngoplasty cohort required additional surgical intervention: 4 underwent tertiary pharyngoplasty, 4 underwent takedown for OSA (n = 3) or persistent VPI (n = 1), 3 underwent takedown and conversion Furlow for persistent VPI (n = 2), OSA (n = 2) and/or flap dehiscence (n = 1), and 2 underwent palatal lengthening with buccal myomucosal flaps for persistent VPI. Of the 4 patients who required a tertiary pharyngoplasty, the mean age at repair was 6.6 ± 1.1 years and their speech scores improved from 13.5 to 2.3 after tertiary pharyngoplasty (P = 0.11). The overall speech score after completion of all procedures improved significantly from 19 to 3.3. Patients who fail primary pharyngoplasty represent a challenging population. Of patients who underwent secondary pharyngoplasty, nearly half required a tertiary procedure to achieve acceptable speech scores or resolve complications.

Potential Mechanisms of NUR77‐Mediated Signaling in the Aging Retinal Pigment Epithelium: Implications for Age‐Related Macular Degeneration

PurposeRetinal pigmented epithelium (RPE) dysfunction is associated with age‐related macular degeneration (AMD), the leading cause of vision loss in the elderly in the western world. A better understanding of RPE‐related signaling pathways is the key to developing therapies and potential drug treatments for the early stages of AMD. Nuclear receptors are master regulators of cellular processes including lipid metabolic dysregulation, apoptosis, and inflammation, pathogenic pathways associated with AMD development and progression. Previously we found that orphan nuclear receptor member 1(NR4A1) or NUR77 is expressed by human RPE. The role of NUR77 in the eye or RPE‐mediated signaling pathways, however is not known. Given NUR77’s purported role in regulating inflammation, angiogenesis, and apoptosis in a number of body tissues, herein we investigated the role of NUR77 in RPE as a function of age.MethodsTotal RNA was extracted from RPE/choroid fractions of young and old mouse eyes, RPE/choroid from human donors, and human primary RPE cultures harvested from young and old eye tissue (ages 18‐93). Expression of NUR77/Nurr77 and its target genes were measured by qRT‐PCR. Cellular bioenergetics of young versus old RPE and NUR77 overexpressing RPE were measured using the Seahorse XF Real‐Time ATP Rate Assay. RPE cells overexpressing NUR77 were analyzed for expression of senescence‐related and epithelial‐mesenchymal transition (EMT) markers. To investigate the function of Nur77, in vivo, ocular imaging and retinal function assessments of 4‐8 month old Nur77‐null mice was done. Ex vivo, ocular morphology was examined. Statistical methods for data analysis included two‐tailed Student’s t‐test and two‐way ANOVA. Values were considered statistically significant at p &lt; 0.05.ResultsNur77/NUR77 expression in mouse and human RPE decreases with age. Overexpression of NUR77 (induction of the ‘young phenotype’) in RPE cells isolated from old donors results in a decrease in expression of the senescence associated genes p21 and p16, while low levels of NUR77 were associated with elevated senescence. Expression of the metabolic markers COX III, pyruvate kinase M1 and 2were differentially regulated in the RPE/choroid fractions from old versus young mice. Seahorse assays revealed that overexpression of NUR77 in RPE cells from young but not old donors resulted in a metabolic shift from glycolysis towards mitochondrial respiration. In the absence of Nur77, enhanced expression of markers of inflammation (CCL2, TNFa), oxidative stress (HMOX1, SOD1), metabolism (COXIII, PKM2) and EMT (N‐cadherin, Snail 2, ZEB1, FN1, Vimentin) was observed in the mouse RPE/choroid. Initial assessments of ocular imaging revealed the presence of hypopigmented regions within the posterior pole of Nur77‐null mice at 4 months of age.ConclusionsOur preliminary results indicate an age‐dependent role of NUR77 in balancing a metabolic switch towards mitochondrial respiration in the RPE. Studies are ongoing to further dissect the NUR77‐mediated signaling pathways in aging and ocular disease, and in determining if NUR77 overexpression may serve as potential therapy in diseases wherein RPE is compromised.

Paper 11: Return to Sport Testing vs Time-Based Clearance in Posterior Shoulder Instability

Objectives:Recurrent pain, instability and loss of function is a challenging complication that can occur after arthroscopic treatment of posterior shoulder instability and SLAP tears in athletes. Many surgeons allow return to sport after a designated arbitrary postoperative time point. Recent evidence has demonstrated that a majority of athletes have residual strength and functional limitations at 6 months postoperatively – the time at which most time-based protocols allow full return to sport1. Recent data has also been presented that patients undergoing arthroscopic Bankart repair who are required to meet objective return to sport testing criteria have a 4x lower rate of recurrent anterior instability than those who return based on time elapsed since surgery2. Considering these findings, the purpose of this study is to investigate the use of a similar objective return to sport testing protocol on recurrence rates following arthroscopic surgery for posterior shoulder instability and SLAP tears. We hypothesized that patients who meet objective return to sport criteria would have a lower rate of reoperation and recurrence of symptoms compared to those who did not undergo the testing and were cleared to return based on time from surgery.Methods:Consecutive patients (Group 1) who underwent arthroscopic posterior shoulder stabilization surgery with or without SLAP repair by a single surgeon from 2016 to 2019, had a minimum of 1 year follow up, and completed functional and strength testing to evaluate readiness for return to sport were included in this retrospective case-controlled study. These patients were compared to a control group of historical consecutive cases (Group 2) from 2012-2016 who did not undergo return to sports testing and were cleared for sports after a minimum of 6 months following surgery. Failure was defined as recurrent symptoms of pain or instability requiring reoperation. Exclusion criteria were: patients undergoing isolated anterior stabilization procedures with or without concomitant SLAP tears, multidirectional instability, and open procedures. Chi-square, Fisher exact tests and two-tailed Students T-test were performed. Statistical significance was set at p<0.05.Results:There were 33 patients in Group 1 who underwent return to sport testing, and 90 patients in Group 2, the historical control. There were no differences between groups regarding sex (p=0.46), hand dominance (p=0.16), side affected (p= 0.69. The average age of Group 1 (20.8 +/- 4 yrs) was significantly younger than Group 2 (31.6 +/- 9.1 yrs, p< 0.00001). Patients who underwent return to sport criteria-based testing protocol had a rate of recurrent symptoms of pain or instability of 12.1% compared to 18.9% for those who did not (p= 0.43). Similarly, there were no reoperations for in Group 1, while three patients in group 2 (3.3%) underwent revision surgery for recurrent symptoms. This difference, however, did not reach statistical significance (p= 0.5633).Conclusions:In our cohort of young patients undergoing arthroscopic surgery for posterior shoulder instability, we detected no significant difference in reoperation rate and recurrence of symptoms between athletes who underwent objective return to sport testing and those who were released to sport on a time-based protocol. This may be related to an overall lower rate of reoperation in patients undergoing arthroscopic posterior stabilization or SLAP repairs in general compared to those undergoing arthroscopic anterior stabilization and differences in tolerance and presentation of recurrent posterior instability/SLAP tears versus anterior instability. It is possible that criteria-based return to sport testing prior to clearance to return to sport may be less critical for improving failure rates following arthroscopic posterior stabilization and SLAP repair than for anterior stabilization. Alternatively, given low reoperation rates overall, future studies investigating the role of return to sport testing after arthroscopic surgery for posterior shoulder instability and SLAP repairs may need to include more patients in order to detect differences related to the testing protocol. Objective functional testing may be a viable alternative to arbitrary, time-based criteria for returning to sport in patients who have undergone arthroscopic posterior shoulder stabilization and SLAP repairs.

A novel NSC small molecule inhibitor inhibits proliferation of triple‐negative breast cancer cells through metabolic reprograming

BackgroundTreatment of patients with triple‐negative breast cancer (TNBC) has been challenging due to the absence of well‐defined molecular targets and high invasive and proliferative capacities of these cells. Current treatments against TNBC have shown minimal activity due to the high recurrence rate in the patients. There is, therefore, a pressing need for novel and efficacious therapies against TNBC. Here, we found a novel small molecule inhibitor with potent anti‐tumor activity against TNBC cells.MethodsAnti‐proliferative effects of NSC small molecule inhibitor were determined using 2D and 3D culture cell proliferation assays. Using proteomics, NGS and enrichment analysis, we globally investigated top regulatory pathways affected by this compound in TNBC cells. Subsequently, we validated the proteomics and NGS analysis data using seahorse and enzymatic assays. Finally, we showed the inhibitor anti‐tumor effects in vivo. Data were evaluated in triplicate against untreated control cells. Data were graphed and analyzed using GraphPad Prism Software 8.0 using one‐way ANOVA and the unpaired two‐tailed Student’s t‐test.ResultsIn this report, we showed that a novel NSC small molecule inhibitor reduced the proliferation of TNBC cells. Proteomic analysis confirmed a significant metabolic reprograming including suppression of glycolysis and oxidative phosphorylation after treatment. Furthermore, we found that treatment with NSC small molecule inhibitor impaired glycolysis and oxidative phosphorylation via modulating the activity of metabolic regulator enzymes.ConclusionsAltogether, our data indicate that NSC small molecule inhibitor may exhibit anti‐tumor activity in TNBC cells and provide a rationale for further investigation of the potential of NSC small molecule inhibitor as an attractive therapeutic drug for TNBC. Further in‐depth investigations are required to evaluate the exact targets and mechanism of this potent small molecule inhibitor, and its anti‐neoplasm effects on TNBC in vivo.

Faculty and applicant perceptions of virtual interviews on subspecialty fellowship match in obstetrics and gynecology

ABSTRACT Background In response to COVID-19, the AAMC recommended that hospitals conduct interviews in a virtual setting. Objective To evaluate whether fellowship video conference interviews (VCIs) are an acceptable alternative to in-person interviews from both the applicant and program perspectives. Methods Applicants and faculty from a single academic institution with five OBGYN subspecialty fellowship programs were invited to complete surveys regarding their experience using VCIs during the 2020 interview season. Survey responses used a 5-point Likert scale (strongly disagree to strongly agree). Comparative analyses between faculty and applicants responses to survey questions were performed with two-tailed Student’s t-tests. Results 45 faculty members and 131 applicants received the survey. Response rate for faculty members and applicants was 95.6% (n = 43) and 46.6% (n = 61), respectively. Faculty and applicants agreed that the VCIs allowed them to accurately represent themselves (83.7% vs. 88.6%, p = 0.48). Most applicants (62.3%, n = 38) reported a fundamental understanding of the fellowship’s culture. The majority of applicants (77.1%, n = 47) and faculty (72.1%, n = 31) agreed that they were able to develop connections during the virtual interview (p = 0.77). Faculty and applicants stated that VCIs assisted them in determining whether the candidate or program, respectively, was a good fit (83.7% vs. 67.2%, p = 0.98). Conclusions The VCI fellowship recruitment process allowed OBGYN fellowship applicants and programs to accurately represent themselves compared to in-person interviews. Most applicants and faculty were able to develop relationships over the virtual platform. Although not explicitly assessed, it is possible that the virtual interviews can achieve a suitable match between applicant and program across all OBGYN subspecialty fellowships. The VCI process may be a long-term resolution to minimize both the financial burden and time commitment presented by traditional in-person interviews. Follow-up studies should assess the performance of the virtually selected fellows compared to those selected in previous years using traditional in-person interviews.

Development and evaluation of a new test kit for determination of immunosuppressants in blood by UHPLC-MS/MS

In this study, we have developed and validated a new test kit that applied pure solvents instead of blood samples for determination of immunosuppressant drugs in blood by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). We have used commercially available quality control samples to verify this new test kit, and the results showed that the performance of our new kit was comparable with commercially available kits by immunoassays. The new test kit is pure solvent-based, which saves the cost and can be directly loaded without pre-treatment, thus shortening the detection time. The agreement between pure solvent-based kit and blood-based kit was also evaluated by Bland-Altman plot and two-tailed Student’s T-test. For 97.08% of the 137 Tacrolimus clinical samples, the concentration difference between these two kits was laid within 20% of the mean concentration. The concentrations of 12 cyclosporine samples and 15 sirolimus samples obtained by both kits showed no significant difference evaluated by the two-tailed Student’s T-test. These results further demonstrated the good agreement between these two types of test kits. Meanwhile, our pure solvent-based test kit could be stored stably for 14 weeks at -30 °C. Therefore, the newly developed pure solvent-based test kit can be used for detecting the whole blood immunosuppressant concentration and therapeutic drug monitoring of immunosuppressants.

The Role and Mechanism of Tfh and B Cell in Human Chronic Graft-Versus-Host-Disease

Peripheral blood of cGVHD 64 patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Soochow University from 2016 to 2019 were collected. The percentage of cTfh cells, extrafollicular helper T cells, B cells and subsets were detected by flow cytometry. The healthy donors were detected as control. Percentage of each cell subpopulation between the two groups were compared by the two-tailed Students' T test. The percentage of circulating follicular helper T cells (cTfh, CD4+CXCR5+) was markedly decreased in patients with cGVHD as compared with that in the healthy donors (0.53%±0.10% vs 3.91%±0.60%, P<0.001). The percentage of extrafollicular helper T cells (CD44hiCD62LloPSGL-1loCD4+T) of the patients in cGVHD and the healthy donors were 8.86%±0.45% and 5.38%±0.79% (P=0.003). A significant change in B cell subsets was found in the patients with cGVHD. The two types of antigen-stimulate CD27+ B cell: the percentages of pre-GC B cells (CD19+IgD+CD38hiCD27+) and plasmablast/plasma cells (PB/PC, CD19+IgD-CD38hiCD27+) of patients with cGVHD were 20.91%±2.70% and 41.05%±5.00%, respectively, which were significantly higher than those in healthy donors (P=0.005, P=0.014). Meanwhile, the percentage of unstimulated CD27- B cells in patients with cGVHD was significantly reduced, especially the naive B cells (CD19+IgD+CD38loCD27-, 12.59%±2.63%, P=0.025). There was a positive correlation between the percentage of extrafollicular helper T cells and plasmablast/ plasma cells (PB/PC) in cGVHD patients (r=0.43). Compared with healthy donor, cTfh cells, extrafollicular helper T cells and B cell subsets in the peripheral blood of patients with cGVHD after transplantation changed in varying degress.

Success Rate of Non-Operative Treatment of Insertional Achilles Tendinitis

Category:Hindfoot; OtherIntroduction/Purpose:Insertional Achilles tendinitis (IAT) is a common orthopedic condition that can be treated conservatively or surgically. While non-operative treatment is thought to be beneficial in approximately 50-70% of cases, the precise success rate of non-operative treatment is not fully defined in the current literature. The purpose of this study is to define the success rate of modern non-operative treatment of IAT more precisely.Methods:A retrospective chart review was performed to identify patients who received either surgical or non-surgical treatment of IAT with a single fellowship-trained foot and ankle surgeon at an academic medical center between September 2015 and June 2019. A total of 133 patients (137 ankles) were identified. The success rate of non-operative treatment, defined as the lack of need for surgical treatment within two years of initial diagnosis of IAT, was recorded. Patients with IAT were treated with scheduled anti-inflammatory medications, physical therapy with a focus on eccentric strengthening and Achilles stretching and, when needed, controlled ankle motion (CAM) boot, short leg casting, or Platelet-Rich Plasma injections for refractory cases. A demographic and comorbidity comparison was performed between groups. Statistical analysis was performed using two-tailed Student t-test and Chi-squared test.Results:There was no difference in treatment method between those successfully treated conservatively and those who went on to fail conservative management and require surgery. At first encounter, patients who later received surgery were significantly more likely to have higher VAS pain scores (surgery=6.54, conservative=5.10; p=.045) and lower SF-12 physical scores (surgery=25.16, conservative=35.61; p<.001). The overall success rate of non-operative treatment was 78.57% and the average time from initial diagnosis to surgery was 198.83 days (range, 28-486).Conclusion:Based on the results of this study, the success rates of non-operative treatment for IAT may be higher than what is traditionally thought, at just under 80%. Further, patients with worse VAS and SF-12 physical scores were significantly more likely to fail conservative management. Orthopedic surgeons should use this information to provide more accurate counseling on the most appropriate treatment strategies for IAT.

Abstract No.: ABS3221: Comparison of Fentanyl and Dexmedetomidine as adjuvants to 0.2 % Ropivacaine Epidurally in Labour Analgesia

Background & Aims:Childbirth being the most exciting event in the life of a female gets ruined because of cruciating and intolerable labour pain. This study compared quality of labour analgesia by using fentanyl and dexmedetomidine as adjuvants to 0.2% ropivacaine epidurally .Methods:Institutional Ethical Committee approval and patient consent was obtained. 60 enroled patients were divided into 2 groups Group RF: 0.2% ropivacaine + fentanyl 15µg (15ml) Group RD: 0.2% ropivacaine + dexmedetomidine 7.5 µg (15ml) Epidural catheter was inserted at the L2-L3 space and drug was administered. VAS, sensory, motor levels were assessed. Maternal and foetal adverse effects were noted. Maternal satisfaction was evaluated after 24 h. The results were expressed as mean ± standard deviation for continuous variables while frequency and percentage for discrete data. Continuous variables were analysed by using unpaired two-tailed Student t- test. Discrete data was analysed using Chi-square test. P<0.05 considered as statistically significant.Results:The demographical data like age, weight and height were comparable and had no influence on outcome of the study. Quality of analgesia was comparable in both groups (p>0.05) with no patient having poor quality. Early onset and longer duration of analgesia, less epidural top-ups, shorter duration of labour, less incidence of instrumental delivery and adverse effects were observed in Group RD compared with Group RF (p<0.05). Neonatal APGAR score was comparable between the groups.Conclusion:Both fentanyl and dexmedetomidine with 0.2% ropivacaine epidurally provide safe, effective and excellent quality of labour analgesia and equal foetal well-being and neonatal outcomes. Dexmedetomidine as adjuvant prolongs labour analgesia and shortens duration of labour.