Epigenetic Signatures in Antidepressant Treatment Response: a Methylome-wide Association Study in the EMC Trial

Although the currently available antidepressants are well established in the treatment of major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N=40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients’ response before treatment.

PERFORMANCE ASSESSMENT ANALYSIS USING MALCOLM BALDRIGE CRITERIA FOR PERFORMANCE EXELLENCE (MBCfPE) METHOD (Case Study at PT. NYCZ)

PT. NYCZ is a manufacturing company engaged in plastic bottle packaging production that cannot be separated from the problem of competition with similar companies. The problems encountered at PT. NYCZ regarding employee performance, namely lack of communication relations between subordinates and superiors, so that delivery of work instructions from superiors is still not understood by subordinates, it has an impact on employee performance output, Therefore the company must improve more efficient strategies in terms of leadership that is able to run and manage everything in internal and external of the company, more reliable skilled workforces, modern machines and technology, and is able to get a wider market and customers in plastic bottle products marketing. Malcolm Baldrige Criteria for Performance Excellence or Baldrige Criteria is a guide for a company to achieve high quality performance which consists 7 criterias, namely Leadership; Strategic Planning; Customer Focus; Measurement, Analysis and Knowledge Management; Focus on Workforce; Process Management; and Results. This research was conducted by distributing questionnaires to PT. NYCZ employees, respondents were taken according to job desks ranging from cashiers to managers. After questionnaire data was obtained, it was processed using SPSS to test validity and reliability. Then, questionnaire results were processed using Malcolm Baldrige score to determine company performance level. From the research results, it was obtained that the total points from Malcolm Baldrige Criteria for Performance Excellence survey are 411,14. Therefore, according to MBCfPE score, the performance of PT. NYCZ is Early Improvement with Average category

Early full enteral feeding in very low birth weight babies on day one

Background: Nutrition in very low birth weight babies is most important factor in early improvement of neonate. It also decides duration of stay in intensive care unit. Objectives of the current study were to initiate required full enteral feed at the earliest and to know the outcome of such neonates.Methods: It is a hospital based retrospective study conducted from October 2019 to December 2019 in Gulbarga institute of medical sciences, Kalaburagi. 40 clinically stable VLBW neonates on day 1 started on enteral feeding are included in the study. Babies with birth weight more than 1.5 kgs or less than 1 kg, hemodynamically unstable at start of feeds are excluded from the study. Collected data is analysed by SPSS 17.Results: Total 40 VLBW babies were included in the study. Among them, 28 neonates tolerated feeds, were improved & discharged early with an average duration of stay of 16days with early birth weight gain by 14 days. 10 neonates had feed intolerance with signs of Necrotizing enterocolitis during course of treatment, were improved and discharged with an average duration of stay of 22 days. Mortality was seen in 2 neonates due to associated sepsis. Conclusions: Initiation of full enteral feeds in stable VLBW babies is effective mode for improvement, weight gain and early discharge from hospital.

Recovery patterns in patients undergoing revision surgery of the primary knee prosthesis

Purpose Despite good survival rates of revised knee prostheses, little is known about recovery trajectories within the first 12 months after surgery. This retrospective observational study explored recovery trajectories in terms of pain, function and quality of life in patients after revision knee arthroplasty over 12 months. Methods Eighty-eight revision knee arthroplasty patients rated changes in daily physical functioning using the anchor question (0: very much worsened; 7: very much improved). Patient reported outcome measures (PROMs) of pain (range 0–10), function (Oxford Knee Score) and quality of life (EQ-5D-3L) were assessed preoperatively, at 3 and 12 months postoperatively. Four recovery trajectories were identified using the anchor question at 3 and 12 months postoperatively: no improvement, late improvement, early improvement, and prolonged improvement. Repeated measures ANOVA was conducted with recovery trajectories as dependent variable and PROM assessments as independent variables. Results Sixty percent reported improvement in daily physical functioning at 12 months postoperatively. Age and reason for revision differed between groups. Pain, function and EQ-5D-3L differed between groups over time. Late and prolonged improvement groups improved on all PROMs at 12 months. The early improvement group did not report improvement in daily physical functioning at 12 months, while improvements in function and pain during activity were observed. Conclusions Different recovery trajectories seem to exist and mostly match PROMs scores over time. Not all patients may experience beneficial outcome of revision knee arthroplasty. These findings are of importance to provide appropriate information on possible recovery trajectories after revision knee arthroplasty to patients. Level of evidence III

Dynamic Imaging Changes of COVID-19 Pneumonia at Different Stages

Purpose: To investigate the Computed Tomography (CT) imaging characteristics and dynamic changes of COVID-19 pneumonia at different stages. Methods: Forty-six patients infected with COVID-19 who had chest CT scans were enrolled, and CT scans were performed 4-6 times with an interval of 2-5 days. Results: At the early stage (n=25), ground glass opacity was presented in 11 patients (11/25 or 44.0%) and ground glass opacity mixed with consolidation in 13 (13/25 or 52.0%) in the lung CT images. At the progressive stage (n=38), ground glass opacity was presented in only one patient (1/38 or 2.6%) and ground glass opacity mixed with consolidation in 33 (33/38 or 86.8%). In the early improvement stage (n=38), the imaging presentation was ground glass opacity alone in three patients (3/38 or 7.9%) and ground glass opacity mixed with consolidation in 34 (34/38 or 89.5%). In the late improvement (absorption) stage (n=33), the primary imaging presentation was ground glass presentation in eight patients (8/33 or 24.2%) and ground glass opacity mixed with consolidation in 23 (23/33 or 69.7%). The lesion reached the peak at 4-16 days after disease onset, and 26 (26/38 or 68.4%) patients reached the disease peak within ten days. Starting from 6 to 20 days after onset, the disease began to be improved, with 30 (30/38 or 78.9%) patients being improved within 15 days. Conclusion: COVID-19 pneumonia will progress to the peak stage at a mediate time of seven days and enter the improvement stage at twelve days. Computed tomography imaging of the pulmonary lesion has a common pattern from disease onset to improvement and recovery and provides important information for evaluation of the disease course and treatment effect.

Abcc6 null mice a model for mineralization disorder PXE show vertebral osteopenia without enhanced intervertebral disc calcification with aging

Chronic low back pain is a highly prevalent health condition intricately linked to intervertebral disc degeneration. One of the prominent features of disc degeneration that is commonly observed with aging is dystrophic calcification. ATP-binding cassette sub-family C member 6 (ABCC6), a presumed ATP efflux transporter, is a key regulator of systemic levels of the mineralization inhibitor pyrophosphate (PPi). Mutations in ABCC6 result in pseudoxanthoma elasticum (PXE), a progressive human metabolic disorder characterized by mineralization of the skin and elastic tissues. The implications of ABCC6 loss-of-function on pathological mineralization of structures in the spine, however, are unknown. Using the ABCC6 -/- mouse model of PXE, we investigated age-dependent changes in the vertebral bone and intervertebral disc. ABCC6 -/- mice exhibited diminished trabecular bone quality parameters at 7-months which remained significantly lower than the wild-type mice at 18 months-of-age. ABCC6 -/- vertebrae showed increased TRAP staining along with decreased TNAP staining, suggesting an enhanced bone resorption as well as decreased bone formation. Surprisingly, however, loss of ABCC6 resulted only in a mild, aging disc phenotype without evidence of dystrophic mineralization. Finally, we tested the utility of oral K3Citrate to treat the vertebral phenotype since it is shown to regulate hydroxyapatite mechanical behavior. The treatment resulted in inhibition of osteoclastic response and an early improvement in mechanical properties of the bone underscoring the promise of potassium citrate as a therapeutic agent. Our data suggest that although ectopic mineralization is tightly regulated in the disc, loss of ABCC6 compromises vertebral bone quality and dysregulates osteoblast-osteoclast coupling.

Usefulness of Hamilton rating scale for depression subset scales and full versions for electroconvulsive therapy

Objectives We investigated the predictive value of subset scales and full versions of the Hamilton Rating Scale for Depression (HAMD) for therapeutic outcomes in ECT. Methods This secondary analysis of patients with major depression (N = 136; 63% female; age = 56.7 [SD = 14.8]) from the EFFECT-Dep trial (NCT01907217) examined the predictive value of Evans-6, Toronto-7, Gibbons-8 and Maier-Philip 6 HAMD subset scales and three ‘full’ versions (HAMD-17, HAMD-21 and HAMD-24) on therapeutic outcomes. We also examined early improvement on subset scales and full versions as predictors of response and remission and explored predictive abilities of individual HAMD-24 items. Results The subset scales and full scales lacked sufficient predictive ability for response and remission. Receiver operating characteristic curves identified a lack of discriminative capacity of HAMD subset scales and full versions at baseline to predict response and remission. Only the Maier-Philip-6 was significantly associated with percentage reduction in HAMD-24 scores from baseline to end of ECT course. Early improvement on most of the subset scales and full versions was a sensitive and specific predictor of response and remission. Four of the HAMD-24 items were significantly associated with response and one with remission. Conclusions Limited utility of the HAMD subset scales and full versions in this context highlight a need for more tailored depression rating scales for ECT.

Abstract 1122‐000176: Incidence and Predictors of Delayed Functional Independence in the TREVO Retriever Registry

Introduction : Chronological heterogeneity in the neurological improvement after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) stroke is commonly observed in clinical practice. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence in patients who do not experience early improvement, is essential for prognostication and rehabilitation. We aim to determine the incidence of early and delayed functional independence and identify associated predictors after EVT. Methods : Demographic, clinical, radiological, treatment, and procedural information were analyzed from TREVO registry (patients undergoing EVT in the setting of anterior circulation LVO using the Trevo stent‐retriever). Incidence and predictors of early functional independence (EFI, modified Rankin Scale (mRS) score 0–2 at discharge) and delayed functional independence (DFI, mRS score 0–2 at 90 days in non‐EFI patients) were analyzed. Results : A total of 1757 patients met study criteria. EFI was observed in 45% (785) of patients. Among non‐EFI patients (972), DFI was observed in 34% (332) of patients. Younger age (p<0.001), lower blood glucose (p<0.001), mTICI > = 2B (p = 0.01), and lower total number of thrombectomy passes (p = 0.004) were independent predictors of DFI. Conclusions : Approximately 45% of patients experience early functional independence. One‐third of non‐early improvers experience delayed functional independence. Younger age, lower blood glucose, better collateral grade, and lower total number of passes were independent predictors of DFI among non‐early improvers. Further studies are required to improve our understanding of DFI. No upload