DR Group Research Articles

Correlation Between Blood Glucose Indexes Generated by the Flash Glucose Monitoring System and Diabetic Vascular Complications.

To discuss the relationship between time in range (TIR) which is deprived of the FGMS and the risk of diabetic vascular complications and to provide a theoretical foundation for the clinical application of TIR and other FGMS-deprived indexes. Patients with T2DM who wore the FGMS sensor continuously were enrolled. Relevant indexes such as TIR, time below range (TBR), time above range (TAR), a standard deviation of blood glucose (SDBG), coefficient of variation of blood glucose (CV), and mean amplitude of glycemic excursion (MAGE) generated by the FGMS were recorded, and the risk of diabetic vascular complications were followed up for one year. The TIR was measured by continuous glucose monitoring at baseline, and patients were grouped according to TIR every 20%. Finally, the Cox proportional hazards regression model was used to estimate the association of different levels of TIR with different rates of diabetic vascular complications. TIR was negatively correlated with HbA1C, CV, SDBG, and amplitude of glycemic excursion (MV), wherein, the lower the TIR, the higher the HbA1C, CV, SDBG, and MV. TIR in the diabetic microvascular complication was significantly lower than that in the non-microvascular complication group, and the difference was statistically significant. TIR <40% was identified as a risk factor for DN, DPN, and DR according to the risk assessment. The mean TAR in the DN group was significantly higher than that in the non-DN group. TAR, CV, SD, MAGE, and HbA1C in the DR group were significantly higher than those in the non-DR group. TAR, ABG, CV, SD, MAGE, and HbA1C in the DPN group were significantly higher than those in the non-DPN group. The relationships between the TIR and the prevalence and risk of diabetic vascular complications and the HbA1C may be negative. Other CGM-deprived indexes such as CV and MV should be integrated into glycemic control and diabetes complication prediction.

226-OR: Time in Range Is Associated with Incident Diabetic Retinopathy in Adults with Type 1 Diabetes—A Seven-Year Longitudinal Study

Introduction: Continuous glucose monitoring (CGM) metrics such as time in range (TIR; 70-180 mg/dL) and their goals have been proposed as new metrics to assess diabetes management. However, longitudinal studies validating TIR with diabetes complications are lacking. Methods: We analyzed up to 7 years of retrospective longitudinal CGM data of 90 adults with type 1 diabetes (T1D) without a diagnosis of diabetic retinopathy [DR] (Control group) and 70 adults with new incident diagnosis of DR between June 2018-December 2020 but had normal eye examinations in the past (DR group). Associations between DR and CGM metrics were assessed via linear mixed models adjusting for age and diabetes duration. Results: Baseline characteristics are provided in Figure 1A. A1c was positively associated with development of DR in adults with T1D (Figure 1B). TIR was negatively associated with development of DR (Figure 1C). Time in tight target range (TTIR 70-140 mg/dL) and time above range (TAR&amp;gt;180 mg/dL) were also associated with DR (p&amp;lt;0.001). Conclusion: CGM metrics such as TIR, TTIR and TAR were associated with development of incidental DR in adults with T1D. To our knowledge, this is the first longitudinal study to demonstrate association between CGM metrics and DR. Disclosure V.N.Shah: Advisory Panel; LifeScan Diabetes Institute, Medscape, Consultant; DKSH, Research Support; Novo Nordisk, Tandem Diabetes Care, Inc., Dexcom, Inc., Insulet Corporation, JDRF, National Institutes of Health, Speaker's Bureau; Dexcom, Inc., Insulet Corporation. C.Sakamoto: None. L.Pyle: None. H.K.Akturk: Advisory Panel; Senseonics, MannKind Corporation, Research Support; Medtronic, Tandem Diabetes Care, Inc., Dexcom, Inc., REMD Biotherapeutics, Eli Lilly and Company, IM Therapeutics. S.Polsky: Other Relationship; diaTribe, Research Support; Dexcom, Inc., Medtronic, Hemsley Charitable Trust, JDRF, NIH - National Institutes of Health. G.P.Forlenza: Advisory Panel; Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Lilly Diabetes, Research Support; Medtronic, Abbott, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. J.K.Snell-bergeon: None. Funding JDRF (2-SRA-2021-1069-S-B)

Longitudinal changes of parafoveal vessel density in diabetic patients without clinical retinopathy using optical coherence tomography angiography

Purpose The purpose of this study was to identify the rate of parafoveal vessel density (VD) changes associated with the progression from non-diabetic retinopathy (NDR) to early stages of DR over a year. Methods This longitudinal cohort study enrolled diabetic patients from the Guangzhou community in China. The patients with NDR at baseline were included and underwent comprehensive examinations at baseline and after 1 year. A commercial OCTA device (Triton Plus, Topcon, Tokyo, Japan) was employed to quantify the foveal VD in the superficial and deep capillary plexuses. The rates of change in parafoveal VD over time in the incident DR and NDR groups were compared after a year. Results A total of 448 NDR patients were included in the study. Among them, 382 (83.2%) were stable and 66 (14.4%) developed incident DR during the 1-year follow-up. The average parafoveal VD in the superficial capillary plexus (SCP) reduced significantly more quickly in the incident DR group than in the NDR group (-1.95 ± 0.45%/year vs. -0.45 ± 0.19/year, P= 0.002). The VD reduction rate for the deep capillary plexus was not significantly different for the groups (P = 0.156). Conclusions The incident DR group experienced a significantly faster reduction in parafoveal VD in the SCP compared with the stable group. Our findings further provide supporting evidence that parafoveal VD in the SCP may be used as an early indicator of the pre-clinical stages of DR.

#5337 PHENOTYPIC CHANGES OF LYMPHOCYTES FOLLOWING RENAL TRANSPLANTATION

Abstract Background and Aims Phenotypic changes in lymphocytes have been described following renal transplantation (RT), including both CD4 and CD8 subpopulations. The present work aims to prospectively assess of T lymphocyte phenotypic alterations, after RT and compare differences between deceased (DR) and living (LR) donor recipients. Method One hundred six RTRs were included in the study, 78/106 (74%) DR, age 52.5(15)yrs and 28/106 (26%) LD, 35(21)yrs. Lymphocytes, CD4, CD8, CD4CD28null, CD8CD28null, CD16+CD56+ (NK) and CD4+CD25+FoXP3+ (Tregs) were evaluated at peripheral blood, by flow cytometry, at certain time points: RT and 3, 6, 12 months (T0, T3, T6, T12, respectively). Results During follow up, at T3, T6, T12, eGFR was 61(23.6), 62.2(31.1), 63.5(23.9)ml/min/1.73 m2, p=NS and 59.1(24.8), 61(25.3), 62(22.7), p=NS, in DR and LR group, respectively. eGFR showed no significant difference between DR and LR at any time point. At any time point, T0, T3, T6, 12, lymphocytes were significantly increased in DR compared to LR groups, P = .001, p&amp;lt;0.0001, P = .002, p&amp;lt;0.0001, similarly CD4, P = .001, p&amp;lt;0.0001, P = .001, p&amp;lt;0.0001, and CD8 cells, P = .002, p&amp;lt;0.0001, P = .005, P = .006, respectively. Tregs were increased at T0, T3, T6, not at T12, p&amp;lt;0.0001, p&amp;lt;0.0001, P = .001, P = .1, respectively. At this point, Tregs were increased in RTRs with eGFR&amp;gt;50ml/min/1.73 m2, 20.3(9.3) vs. 27.2(18.6), P = .03. CD4CD28null, CD8CD28null cells did not change during follow up, and there was no difference between two groups at any time point. Conclusion Immune profile, was improved in both groups, DR or LR, however a significantly better effect managed in LR, although elimination of CD28 molecule could not be restored. Interestingly, Tregs were associated only by renal function one year following RT.

The Ratio of Fibrinogen to Albumin is Related to the Occurrence of Retinopathy in Type 2 Diabetic Patients.

Type 2 diabetic retinopathy is a long-term chronic inflammatory disease. The aim of this study was to investigate the relationship between fibrinogen to albumin ratio (FAR) and retinopathy in type 2 diabetic patients. This was a retrospective study that included 500 patients with type 2 diabetes mellitus (T2DM), and were divided into non-diabetic retinopathy group (NDR, n=297) and diabetic retinopathy group (DR, n=203) according to fundus examination findings, and the DR group was further divided into non-proliferative retinopathy group (NPDR, n=182) and proliferative retinopathy group (PDR, n=21). Baseline data of patients were collected, and the fibrinogen to albumin ratio (FAR) and neutrophil to lymphocyte ratio (NLR) were calculated to analyze the correlation between FAR and NLR and type 2 diabetic retinopathy. The FAR and NLR were significantly higher in the DR group compared with the NDR group (both P < 0.001). Spearman correlation analysis showed that FAR was positively correlated with NLR and DR (P < 0.05). As the FAR quartile increased, the prevalence of DR increased (14.8%, 16.7%, 25.1%, and 43.30%, respectively; P < 0.05). Multifactorial logistic regression analysis showed that FAR, diabetic course, systolic blood pressure (SBP) and diabetic peripheral neuropathy (DPN) were risk factors for the development of DR in patients with T2DM. The area under the ROC curve for FAR to predict DR progression was 0.708, with an optimal critical value of 7.04, and the area under the ROC curve for diabetes duration and SBP to predict DR was 0.705 and 0.588, respectively. Our findings show for the first time that FAR is an independent risk factor for assessing DR in patients with type 2 diabetes.

Content of mediators of innate immunity in the tears of patients with vascular and neurodegenerative manifestations of diabetic retinopathy

According to the results of recent studies, diabetic retinopathy can be considered not only as a vascular disease, but also as a neurodegenerative process. Study of the composition of the tear fluid is used to assess the state of local immunity in the development of eye diseases. However, studies examining the effect of tear composition in diabetic retinopathy are few. The aim of the study is to determine the levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100b, BDNF and NGF in the tear fluid ofpatients with vascular and neurodegenerative manifestations of diabetic retinopathy. The study included 80 patients diagnosed with type 2 diabetes which were divided into 2 groups: the 1st group included 40 patients who had no clinical signs of diabetic retinopathy on the fundus; the 2nd group included 40 patients with initial signs of non-proliferative diabetic retinopathy. All those included in the study were examined on an optical coherent tomograph RTVue-100 (USA); the volume of focal losses of retinal ganglion cells (FLV) was determined. An increase in FLV above the normative base of the device was regarded as an OCT-sign of retinal neurodegeneration. According to the results of OCT, the participants of the first and second groups were additionally divided into 4 subgroups: 1A — patients without vascular changes in the fundus and without OCT signs of retinal neurodegeneration (n = 12); 1B — patients without vascular changes in the fundus and with the presence of OCT signs of retinal neurodegeneration (n = 28); 2A — patients with initial non-proliferative DR and without OCT signs of retinal neurodegeneration (n = 10); and 2B — patients with initial non-proliferative DR and with OCT signs of retinal neurodegeneration (n = 30). The levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100 b, BDNF, and NGF in tear fluid were determined by enzyme-linked immunosorbent assay. Levels of IL-1β and IL-10 in tear fluid in all subgroups were comparable to controls throughout the study. TGF-β3 content in the tear fluid of patients in the group with initial signs of non-proliferative DR (group 2) was significantly (p = 0.001) lower compared with control and group 2. However, there was no significant difference (p &gt; 0.05) between subgroups A and B within groups. The concentration of MMP-7 in the tear fluid in all subgroups was significantly lower than in the control (p &lt; 0.05). However, in the subgroups with OCT signs of retinal neurodegeneration (1B and 2B), the deficiency of this metalloproteinase was more pronounced (p = 0.0001). The levels of the neuropeptides under study NGF, BDNF and S100 B in tear fluid did not differ from controls in all subgroups.

A randomized controlled trial of postoperative rehabilitation using digital healthcare system after rotator cuff repair

A digital healthcare system based on augmented reality (AR) has promising uses for postoperative rehabilitation. We compare effectiveness of AR-based and conventional rehabilitation in patients after rotator cuff repair (RCR). This study randomly allocates 115 participants who underwent RCR to digital healthcare rehabilitation group (DR group) and conventional rehabilitation group (CR group). The DR group performs AR-based home exercises using UINCARE Home+, whereas the CR group performs brochure-based home exercises. The primary outcome is a change in the Simple Shoulder Test (SST) score between baseline and 12 weeks postoperatively. The secondary outcomes are the Disabilities of the Arm, Shoulder and Hand (DASH) score; Shoulder Pain And Disability Index (SPADI) score; EuroQoL 5-Dimension 5-Level (EQ5D5L) questionnaire score; pain; range of motion (ROM); muscle strength; and handgrip strength. The outcomes are measured at baseline, and at 6, 12, and 24 weeks postoperatively. The change in SST score between baseline and 12 weeks postoperatively is significantly greater in the DR group than in the CR group (p = 0.025). The SPADI, DASH, and EQ5D5L scores demonstrate group×time interactions (p = 0.001, = 0.04, and = 0.016, respectively). However, no significant differences over time are observed between the groups in terms of pain, ROM, muscle strength, and handgrip strength. The outcomes show significant improvement in both groups (all p < 0.001). No adverse events are reported during the interventions. AR-based rehabilitation shows better improvement in terms of shoulder function after RCR compared to conventional rehabilitation. Therefore, as an alternative to the conventional rehabilitation, the digital healthcare system is effective for postoperative rehabilitation.

Research on the effect of Dipsaci Radix before and after salt-processed on kidney yang deficiency syndrome rats and the preliminary mechanism study through the BMP-Smad signaling pathway

Ethnopharmacological relevanceDipsaci Radix (DR) is the dry root of Dipsacus asper Wall. ex DC. Aim of the studyThe purpose of this study was to compare the effects of DR on rats before and after salt-processed with kidney yang deficiency syndrome (KYDS), and we selected the BMP-Smad signaling pathway to explore the mechanism of DR. Materials and methodsThe model of KYDS was established by subcutaneous injection of hydrocortisone, the crude DR (CDR) and salt-processed DR (SDR) were given the corresponding dose (2 g/kg, 4 g/kg, and 6 g/kg). The organ index and the contents of adrenocorticotropic hormone (ACTH), cortistatin (CORT), thyroid hormone (T4), tumor necrosis factor-alpha (TNF-α), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na+-K+-ATPase, and growth hormone (GH) in serum were measured to evaluate the intervention effect of DR on KYDS rats. The expression of Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 protein in kidney was determined by immunohistochemistry, quantitative PCR (qPCR) and Western blot analysis. The effects of DR on 5 expression factors in the BMP-Smad signaling pathway were studied. Constituents absorbed into blood were identified by UPLC-Q-TOF/MS. ResultsThe results showed that compared with the model group, the thymus and kidney index, as well as the contents of ACTH, CORT, cAMP, GH, Na+-K+-ATPase, T, T4, and E2 were significantly increased in the CDR and SDR groups, and the contents of cGMP and TNF-α were significantly decreased. Compared with the CDR high dose group, ACTH, Na+-K+-ATPase, T, and T4 were significantly increased in the SDR high dose group. The results of immunohistochemistry, qPCR, and Western blot analysis showed that compared with the model group, the expression levels of Smad 1, Smad 4, Smad 5, Smad 8 and BMP 7 proteins in the kidney of DR groups were significantly increased. And SDR groups tended to be better than CDR groups. 8 constituents migrating to blood were identified. ConclusionThis study showed that both CDR and SDR could have a good therapeutic effect on KYDS, and SDR was better than CDR. This study chose the BMP-Smad signaling pathway to study the mechanism of DR in the treatment of KYDS and provided a scientific basis for the processing mechanism of salt-processed.

Alterations of Thyroid Hormone Levels and the Risks of Diabetic Retinopathy in T2DM

Background: Diabetes mellitus and thyroid disease are linked endocrinopathies. The association between diabetes mellitus complications and thyroid function is characterized by a complicated interdependent interplay that is difficult to understand. Objective: We conducted this study to determine the association between diabetic retina disease (DRD) incidence and normal thyroid hormone levels in T2DM. Methods: Recruit patients in the study, 134 patients with type 2 diabetes and 36 healthy ones with no DM, were screened in the present case-control study. Diabetic retinopathy was tested for all patients, and anthropometric and thyroid functions were assessed. Regression analyses were employed to evaluate the relationship between thyroid hormones and the risk of developing DR. Results: There were significant differences in triiodothyronine (T3) and thyroxine (T4) serum levels among the DR groups and the healthy control. The levels in each TSH and T4 are positively significant between groups of PDR and NDR, while T3 was negatively associated with NPDR. A significant association was found between increasing levels of T3 and the development of severe DR; thus, PDR was less likely to occur in individuals with high T3 levels‎ [OR 0.014(95% CI, 0.001-0.34) P value is 0.009 after adjustment. The risk of PDR had an increased likelihood of developing PDR at the highest levels of serum TSH and T4 [OR 41.07(1.60-1053.1) P= 0.025, OR 65.91(2.10-2067) P= 0.017, respectively). Conclusion: Diabetes retinopathy in euthyroid Iraqi people may be associated with levels of T3 and T4 in the blood. Patients with higher TSH and T4 concentrations had a greater risk of developing sight-threatening PDR in type 2 diabetics.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast,the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

The Correlation between Waist Circumference and the Pro-Inflammatory Adipokines in Diabetic Retinopathy of Type 2 Diabetes Patients.

Central obesity is one of the major risk factors for type 2 diabetes mellitus (DM), and the most common complication of DM is diabetic retinopathy. However, the exact relationship between obesity and DR remains unknown. In this study, we evaluate the effect of obesity on DR by comparing the aqueous humor-derived adipokines. For the analysis, 37 DR patients and 29 non-DR-patients participated. To evaluate the obesity of the patients, body mass index (BMI) and waist circumference (WC) were used. By comparing the concentrations of adipokines obtained from the aqueous humor of the two groups, the relationship between DR and adipokines was analyzed. In addition, by analyzing the correlation between obesity and adipokines in patients, the relationship between central obesity and DR was finally confirmed. The WC was significantly higher in patients than in the non-patient group. The concentrations of all adipokines compared in this study were significantly higher in the DR group than in the non-DM group (p < 0.05). Among them, adiponectin, leptin, TNF-α, Factor D (adipsin), lipocalin-2 (NGAL), Serpin E1 (PAI-1), and CXCL8 (IL-8) were confirmed to have a positive correlation with central obesity (defined as WC). These findings suggest that central obesity is strongly associated with the risk of DR.

The Timing of Congenital Diaphragmatic Hernia Repair on Extracorporeal Membrane Oxygenation Impacts Surgical Bleeding Risk

BackgroundThe optimal timing of surgical repair for infants with congenital diaphragmatic hernia (CDH) treated with extracorporeal membrane oxygenation (ECMO) support remains controversial. The risk of surgical bleeding is considered by many centers as a primary factor in determining the preferred timing of CDH repair for infants requiring ECMO support. This study compares surgical bleeding following CDH repair on ECMO in early versus delayed fashion. MethodsA retrospective review of 146 infants who underwent CDH repair while on ECMO support from 1995 to 2021. Early repair occurred during the first 48 h after ECMO cannulation (ER) and delayed repair after 48 h (DR). Surgical bleeding was defined by the requirement of reoperative intervention for hemostasis or decompression. Results102 infants had ER and 44 infants DR. Surgical bleeding was more frequent in the DR group (36% vs 5%, p < 0.001) with an odds ratio of 11.7 (95% CI: 3.48–39.3, p < 0.001). Blood urea nitrogen level on the day of repair was significantly elevated among those who bled (median 63 mg/dL, IQR 20–85) vs. those who did not (median 9 mg/dL, IQR 7–13) (p < 0.0001). Duration of ECMO support was shorter in the ER group (median 13 vs 18 days, p = 0.005). Survival was not statistically different between the two groups (ER 60% vs. DR 57%, p = 0.737). ConclusionWe demonstrate a significantly lower incidence of bleeding and shorter duration of ECMO with early CDH repair. Azotemia was a strong risk factor for surgical bleeding associated with delayed CDH repair on ECMO. Level of evidenceLevel III cohort study.

VEGF Genotype and Allele Frequency of Diabetes Mellitus and Diabetic retinopathy in Lahore, Pakistan

Diabetic retinopathy is characterized as basement membrane (BM) thickening, pericyte loss, endothelial cell (EC) dysfunction, microaneurysms, microvascular infarcts and neovascularization in a patient with diabetic retinopathy. Objectives: To determine the VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy in Lahore, Pakistan. Methods: A total of 100 blood samples were taken including diabetes mellitus (50) and diabetic retinopathy patients (50). Diseased and control subjects were selected for blood sampling. Demographic and clinical characteristics was evaluated. The BMI, HbA1c and the blood pressure of both groups were also examined. The VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy was done. The statistical analysis was done by chi-square test and SPSS to study significant differences in control and diabetic retinopathy subjects. Results: The normal estimation of DM group was 46.18 ± 1.23 years while of DR class was 52.86 ± 1.36 years. The mean value of BMI of DM group was 26.0±0.62 while of DR group was 26.57±0.70.&#x0D; DD genetic mutation was substantially higher in diabetic retinopathy bunch (p&lt;0.05) relative to the II gene mutation, the huge contrasts (p&lt;0.05) were seen in diabetic group. Conclusions: This study concluded that Vascular endothelial growth factor gene was detected in both group of diabetes. In retinopathy people with T2DM the substantial elevated VEGF DD genetic variation was seen relative to retinopathy people without diabetes.

A Dexamethasone Sparing-Regimen with Daratumumab and Lenalidomide in Frail Patients with Newly-Diagnosed Multiple Myeloma: Efficacy and Safety Analysis of the Phase 3 IFM2017-03 Trial

Background. Two-third of patients with newly diagnosed multiple myeloma (NDMM) are over the age of 65. Those patients have heterogeneous fitness and disparate tolerance to treatment. Frailty scoring systems have informed the stratification of elderly patients and treatment guidance. The use of long term dexamethasone is associated with multiple side effects specifically in elderly patients. Here we present the response rates and safety analysis of the randomized phase 3 IFM2017-03 trial, comparing daratumumab lenalidomide (DR) without long term dexamethasone to lenalidomide dexamethasone (Rd) in a frail population of patients with NDMM. Methods. Patients with NDMM over the age of 65 and with an ECOG proxy frailty score ≥ 2 were randomized 1:2 to receive 28-day cycles of lenalidomide (25mg/day, 21/28) and dexamethasone (20mg QW) or daratumumab (1800mg SC QW for 8 weeks, Q2W for 16 weeks and Q4W thereafter), lenalidomide (25mg/day, 21/28) and 2 cycles of dexamethasone (20mg QW for 8 weeks), until progression or unacceptable toxicity. Randomization was stratified on ISS and age. MRD by NGS at 10-5 was performed at 12 months for all patients. Interim analysis endpoints were overall response rate, VGPR or better rate, MRD rate and occurrence of grade 3 or more side effects. The present analysis was done at 12-months-therapy data cut. Results. In total, 295 patients were randomized (95 in Rd arm and 200 in DR arm). Median age was 81 years (68-92) with 84% of patients over the age of 75 years and 61% over the age of 80 years. Baseline demographics and disease characteristics were well balanced between arms. Overall response rates were 77% in Rd arm and 89% in DR arm (p=0.025). 12-months rates of VGPR or better were 42% and 58% in Rd and DR arms, respectively (p=0.013). Depth of response improved during treatment and the median time to reach VGPR was 11 months in Rd group and 5 months in DR group. Treatment benefit for DR was homogeneous across all subgroups defined by age, ECOG, Charlson, ISS, cytogenetics and creatinine clearance. Among patients with VGPR or better at 12 months, 63 were evaluable for MRD at 10-5 by NGS. MRD status at 12 months was negative in 18% of patients in Rd arm and 33% in DR arm (p=0.36). During the first year of treatment, at least one AE (grade ≥ 3) occurred in 64% and 76% of patients in Rd and DR arms, respectively (p=0.052). Patients in DR group had more grade ≥ 3 hematologic AE with neutropenia (Rd 15%, DR 44%, p<0.001) and anemia (Rd 2%, DR 11%, p=0.01) but similar grade ≥ 3 infections, with 17% in Rd and 13% in DR arms (p=0.38). Among patients with infections, 13 had COVID-19 (3 in Rd and 10 in DR). Discontinuations for AEs were similar in both arms (16% in Rd and 13% in DR, p=0.64). Conclusion. In this phase 3 trial dedicated for frail patients with NDMM, a dexamethasone-sparing regimen combining daratumumab and lenalidomide demonstrates deep and rapid responses and a favorable safety profile.

Study of the relation between plasma level of von Willebrand factor and diabetic retinopathy in type 2 diabetes

PurposeDiabetic retinopathy (DR) is a major preventable health complication of type 2 diabetes (T2DM). Hyperglycemia represents the main mechanism in the pathogenesis of DR leading eventually to endothelial dysfunction. vWF is a marker of endothelial dysfunction, but its relation to DR is not yet well-established.MethodsThe present study included 60 patients with T2DM divided into three equal groups according to the presence and the stage of retinopathy. Each patient was subjected to full history taking, physical examination including fundus examination, and laboratory investigations including glycemic and lipid profile, urinary albumin to creatinine ratio (UACR), and plasma vWF level.ResultsPlasma vWF was significantly higher in patients with DR than in patients without retinopathy. vWF was positively correlated to age, HbA1c, diabetes duration, and UACR in DR groups and the total sample. Univariate regression analysis revealed that HbA1c, vWF, BMI, diabetes duration, and UACR were independent risk factors for DR, while multivariate regression analysis showed none of them to be an independent risk factor for DR. A vWF cut-off value of > 180 could differentiate patients with DR from patients without DR with a sensitivity of 97.5%, specificity of 75%, and AUC 0.937*.ConclusionsvWF level is higher in patients with DR reflecting the role of endothelial dysfunction in the development of DR. Moreover, it is one of the risk factors affecting DR in univariate but not in multivariate analysis. A cut-off value of vWF level was set to differentiate between patients with and without DR.

Blood Glucose, HbA1c Level, and its Correlation with VEGF-A (+405G/C) Polymorphism as Biomarker Predicts the Risk of Retinopathy and Nephropathy in Type 2 Diabetic Patients.

Diabetes-related vascular complications linked to increase in the expression of VEGF and its receptors. It helps to accelerate tissue damage inflicted by hyperglycemia, which is potential risk for diabetic complications. The study aimed to assess VEGF genetic polymorphism and its correlation with glucose and HbA1C level among Sudanese patients with diabetic retinopathy and nephropathy. A case-control study was conducted among a total of 252 subjects and divided into four groups of 63 subjects each. Glucose and HBA1c were measured then the VEGF gene was amplified using polymerase chain reaction. The data were analyzed using SPSS. The HBA1c, and blood glucose levels had significantly (P value≤0.00001) highest mean in the DR group, DN group followed by DM. There is a non-significant correlation between VEGF Genotypes and HbA1c, and blood glucose levels (P value≤0.102, 0.173) Patients with GC genotypes will be 74.6%, and 54% higher at risk to develop DR, and DN respectively and 40 % lower at risk to develop DM than those without GC genotype. While patients with CC genotypes will be 22.2% higher at risk of developing DM and 9.5%, 12.2% higher at risk of developing DR and DN respectively. The VEGF +405G/C gene polymorphism is linked to diabetic retinopathy, and diabetic nephropathy in type 2 Sudanese diabetics, and the presence of the GC genotypes and G allele is a significant predictor for retinopathy. There is no significant relation between HbA1C serum levels, blood glucose, and the VEGF +405G/C gene polymorphism.

ANALISIS KECACATAN PRODUK PADA PRODUKSI BATU BATA MERAH DENGAN METODE PLAN, DO, CHECK, ACT PADA DR GROUP MAJENANG

DR Group Majenang is an MSME engaged in printing production. One of the products produced is red brick. In January 2022, DR Majenang Group can produce 15,500 red bricks but 840 red bricks fail or are considered defective. There are 2 (two) types of products that occur in red bricks, namely slow drying and brudul. Slow drying defects in January 2022 reached 445 pieces (53%), while the delivery of fruit was 395 pieces (47%). For this purpose, this research was conducted with the aim of knowing the causes of rejection of red brick products and proposed improvements using the PDCA (Plan, Do, Check, Action) method and the tools used are: Pareto diagrams, Fishbone diagrams, p-charts. The result of the research is the cause of the occurrence, namely the soil material that is not in accordance with the standard for the completion of the purchase of soil material with the quality of the soil which is dark red in color and when clenched by hand it clumps. The soil that is said to be not good is soil that is a bit dark black and if it is clenched it will not clump. The absence of supervision is the supervisor of every production process taking place and the use of a 6:2,5 measure. Six (6) for soil and two and a half (2.5) for water with a cast bucket measuring 31x26 cm, but the employee was negligent and gave a dose of 3 buckets or even more.

Composition and diversity of gut microbiota in diabetic retinopathy.

ObjectiveDiabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of gut microbiota in DR patients and explores the correlation between gut microbiota and clinical characteristics of DR.MethodsA total of 50 stool samples were collected from 50 participants, including 25 DR patients and 25 healthy controls (HCs). 16S ribosomal RNA gene sequencing was used to analyze the gut microbial composition in these two groups. DNA was extracted from the fecal samples using the MiSeq platform.ResultsThe microbial structure and composition of DR patients were different from that of HCs. The microbial richness of gut microbiota in DR was higher than that of normal individuals. The alterations of microbiome of DR patients were associated with disrupted Firmicutes, Bacteroidetes, Synergistota, and Desulfobacterota phyla. In addition, increased levels of Bacteroides, Megamonas, Ruminococcus_torques_group, Lachnoclostridium, and Alistipes, and decreased levels of Blautia, Eubacterium_ hallii_group, Collinsella, Dorea, Romboutsia, Anaerostipes, and Fusicatenibacter genera were observed in the DR groups. Additionally, a stochastic forest model was developed to identify a set of biomarkers with seven bacterial genera that can differentiate patients with DR from those HC. The microbial communities exhibited varied functions in these two groups because of the alterations of the above-mentioned bacterial genera.ConclusionThe altered composition and function of gut microbiota in DR patients indicated that gut microbiome could be used as non-invasive biomarkers, improve clinical diagnostic methods, and identify putative therapeutic targets for DR.

Retinal Microvascular and Neuronal Changes Are Also Present, Even If Differently, in Adolescents with Type 1 Diabetes without Clinical Diabetic Retinopathy.

The purpose of this study was to evaluate retinal changes in adolescents with childhood-onset, long-lasting type 1 diabetes mellitus (T1D). Patients and healthy controls (HC) underwent optical coherence tomography (OCT) and OCT-angiography (OCTA). Individual macular layers, peripapillary retinal nerve fiber layer (pRNFL), and vascular parameters (vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI)) of macular superficial vascular (SVP), intermediate (ICP), deep (DCP) and radial peripapillary capillary plexuses (RPCP) were quantified. Thirty-nine patients (5 with (DR group) and 34 without (noDR group) diabetic retinopathy) and 20 HC were enrolled. The pRNFL and ganglion cell layer (GCL) were thicker in noDR compared to HC and DR, reaching statistically significant values versus HC for some sectors. At the macular level, VAD and VLF were reduced in DR versus HC in all plexuses, and versus noDR in SVP (p < 0.005 for all). At the RPCP level, VAD and VDI were increased in noDR versus HC, significantly for VDI (p = 0.0067). Glycemic indices correlated to retinal parameters. In conclusion, in T1D adolescents, retinal capillary and neuronal changes are present after long-lasting disease, even in the absence of clinical DR. These changes modify when clinical retinopathy develops. The precocious identification of specific OCT and OCTA changes may be a hallmark of subsequent overt retinopathy.

Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2.

The etiology of gastric cancer is associated with infectious, environmental and dietary factors, as well as genetic background. Additionally, emerging evidence has supported the vital role of chronic emotional stress on gastric carcinogenesis; however, the underlying mechanism remains unclear. The present study aimed to investigate the effects of chronic stress and a detrimental diet on gastric malignant epithelial transformation in rats. Therefore, 26 Wistar rats were randomly divided into the following four groups: i) Control; ii) detrimental diet (DD); iii) detrimental diet with chronic restraint (DR) and iv) detrimental diet with chronic restraint and propranolol treatment (DRP). ELISA was performed to detect the serum levels of epinephrine and norepinephrine. Epithelial cell apoptosis was analyzed using the TUNEL assay. The mRNA and protein expression levels of Akt and p53 were detected using reverse transcription quantitative PCR and western blotting, respectively. Pathological changes were analyzed using hematoxylin and eosin staining (H&E). The H&E staining results showed that dysplasia in the gastric mucosa occurred in two of eight rats in the DD group and in four of five rats in the DR group, whereas no dysplasia was detected in the DRP group. The apoptotic ratios of gastric epithelial cells were significantly decreased in all treatment groups compared with the control group. Adrenoceptor β2 (ADRB2) protein expression levels were increased significantly only in the DR group and this effect was significantly reduced in the DRP group. The mRNA expression levels of Akt and p53 were significantly upregulated in the DD group, and Akt mRNA expression was further elevated in the DR group. With regard to protein expression, the levels of Akt and p-Akt were significantly increased in the DR group, whereas these effects were reversed in the DRP group. Furthermore, the ratio of p-p53/p53 protein was significantly reduced in the DD or DR groups, but was reversed in the DRP group. Collectively, the findings of the present study suggested that chronic restraint stress potentially aggravates the gastric epithelial malignant transformation induced by a detrimental diet, at least partially via the Akt/p53 signaling pathway mediated via ADRB2.