Loss Of Function In Patients Research Articles

Virtual Reality Strategies for Promoting Mobility in the Intensive Care Unit: A Case Report.

Prolonged bed rest is a known contributor to muscle atrophy, weakness, and deconditioning. Early active mobilization protocols aim to combat acquired weakness and loss of function in patients in the intensive care unit. Despite these benefits, mobilization of patients in the intensive care unit remains a challenge, most notably for patients with limited ability to get out of bed because of invasive devices and prolonged hospitalization. Virtual reality has gained favor for use in critical care to mitigate patients' stress, pain, and anxiety and to provide distraction and socialization. This case report demonstrates a novel application of virtual reality and the ease with which virtual reality can be used to facilitate early mobility and activity progression in the critically ill.

The impact of duration and severity of obesity exposure on cardiometabolic health

PurposeDuration and severity of exposure to excess adipose tissue are important risk factors for complications, but are generally not examined in conjunction. We developed a metric considering both factors to examine the relationship between obesity-related complications and parameters of cardiometabolic health in patients undergoing a metabolic bariatric procedure (MBS).Materials & MethodsData from patients screened for primary MBS between 2017 and 2021 were analyzed. The Obesity Exposure score (OBES), based on self-reported years of life with a BMI ≥ 25 kg/m2, was calculated with increased weighting applied for higher BMI categories. Multivariate logistic regression analysis was performed, adjusting for multiple potential confounders.ResultsIn total, 2441 patients were included (76% female, age 42.1 ± 11.9 years, BMI 42.0 ± 4.9 kg/m2). OBES was positively related to myocardial infarction, atrial fibrillation and renal function loss (per 10 OBES-units: OR 1.31, 95%CI [1.11–1.52], p = 0.002; OR 1.23, 95% CI [1.06–1.44], p = 0.008; and OR 1.26, 95% CI [1.04–1.51], p = 0.02). OBES was negatively associated with obstructive sleep apnea syndrome (OSAS) (OR 0.90, 95% CI [0.83–0.98], p = 0.02). In patients without obesity-related complications, OBES was related to lower HbA1c and higher HDL-cholesterol levels (ß -0.5 95% CI [-0.08-.0.02] p < 0.001 and ß 0.02 [0.00–0.04] p = 0.01).ConclusionOBES was related to myocardial infarction, atrial fibrillation and renal function loss in patients applying for MBS. OBES was negatively related to OSAS, possibly because undiagnosed years were not taken into account. In the absence of obesity-related complications, OBES was not related to metabolic blood markers. Our data may aid in improving perioperative risk assessments.Graphical

Endoglin mutants retained in the endoplasmic reticulum exacerbate loss of function in hereditary hemorrhagic telangiectasia type 1 (HHT1) by exerting dominant negative effects on the wild type allele.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder affecting 1 in 5000-8000 individuals. Hereditary hemorrhagic telangiectasia type 1 (HHT1) is the most common HHT and manifests as diverse vascular malformations ranging from mild symptoms such as epistaxis and mucosal and cutaneous telangiectases to severe arteriovenous malformations (AVMs) in the lungs, brain or liver. HHT1 is caused by heterozygous mutations in the ENG gene, which encodes endoglin, the TGFβ homodimeric co-receptor. It was previously shown that some endoglin HHT1-causing variants failed to traffic to the plasma membrane due to their retention in the endoplasmic reticulum (ER) and consequent degradation by ER-associated degradation (ERAD). Endoglin is a homodimer formed in the ER, and we therefore hypothesized that mixed heterodimers might form between ER-retained variants and WT protein, thus hampering its maturation and trafficking to the plasma membrane causing dominant negative effects. Indeed, HA-tagged ER-retained mutants formed heterodimers with Myc-tagged WT endoglin. Moreover, variants L32R, V105D, P165L, I271N and C363Y adversely affected the trafficking of WT endoglin by reducing its maturation and plasma membrane localization. These results strongly suggest dominant negative effects exerted by these ER-retained variants aggravating endoglin loss of function in patients expressing them in the heterozygous state with the WT allele. Moreover, this study may help explain some of the variability observed among HHT1 patients due to the additional loss of function exerted by the dominant negative effects in addition to that due to haploinsufficiency. These findings might also have implications for some of the many conditions impacted by ERAD.

B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling

Breast cancer mortality results from incurable recurrences thought to be seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling RTC survival is therefore essential for improving patient outcomes. Here, we derive a dormancy-associated RTC signature that mirrors the transcriptional response to neoadjuvant therapy in patients and is enriched for extracellular matrix-related pathways. Invivo CRISPR-Cas9 screening of dormancy-associated candidate genes identifies the galactosyltransferase B3GALT6 as a functional regulator of RTC fitness. B3GALT6 is required for glycosaminoglycan (GAG) linkage to proteins to generate proteoglycans, and its germline loss of function in patients causes skeletal dysplasias. We find that B3GALT6-mediated biosynthesis of heparan sulfate GAGs predicts poor patient outcomes and promotes tumor recurrence by enhancing dormant RTC survival in multiple contexts, and does so via a B3GALT6-heparan sulfate/HS6ST1-heparan 6-O-sulfation/FGF1-FGFR2 signaling axis. These findings implicate B3GALT6 in cancer and nominate FGFR2 inhibition as a promising approach to eradicate dormant RTCs and prevent recurrence.

Association of HbA1c with functional outcome by ischemic stroke subtypes and age.

To determine whether high HbA1c levels are related to short-and long-term functional outcomes in patients with ischemic stroke (IS) and whether this association differs according to the IS subtype and the patient's age. The data of 7,380 IS patients admitted to 16 hospitals or regional stroke centers in South-Korea, between May 2017 and December 2019, were obtained from the Clinical Research Collaboration for Stroke-Korea-National Institute of Health database and retrospectively analyzed. Among these patients, 4,598 were followed-up for one-year. The HbA1c levels were classified into three groups (<5.7, 5.7 to <6.5%, ≥6.5%). Short-and long-term poor functional outcomes were defined using the modified Rankin Scale score of 2 to 6 at three-months and one-year, respectively. IS subtypes were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. There was an association between higher HbA1c (≥6.5%) and poor functional outcomes at three-months in all patients (three-months; OR, 1.299, 95% CI 1.098, 1.535, one-year; OR, 1.181, 95% CI 0.952, 1.465). When grouped by age, the associations after both 3 months and 1 year observed in younger adult group (<65 years), but not in group aged 65 years and older (three-months; <65 years OR, 1.467, 95% CI 1.112, 1.936, ≥65 years OR, 1.220, 95% CI 0.987, 1.507, p for interaction = 0.038, one-year; <65 years OR, 1.622, 95% CI 1.101, 2.388, ≥65 years OR, 1.010, 95% CI 0.778, 1.312, p for interaction = 0.018). Among younger adult group, the higher HbA1c level was related to short-and long-term functional loss in patients with the small vessel occlusion subtype (three-months; OR, 2.337, 95%CI 1.334, 4.095, one-year; OR, 3.004, 95% CI 1.301, 6.938). However, in patients with other TOAST subtypes, a high HbA1c level did not increase the risk of poor outcomes, regardless of the age of onset. High HbA1c levels increase the risk of short-and long-term poor functional outcomes after IS onset. However, this association differs according to stroke subtype and age. Thus, pre-stroke hyperglycemia, reflected by HbA1c, may be a significant predictor for a poor prognosis after ischemic stroke, particular in young- and middle-aged adults.

Gait initiation in multiple sclerosis patients with and without functional loss

BackgroundGait initiation (GI) is an important functional task related to balance and gait performance. In addition, it has predictive importance for falls and postural instability in patient with multiple sclerosis (MS). However, it is uncertain how GI is affected in patients in the early stage of MS (Expanded Disability Status Scale (EDSS) ≤3). In this study, it was aimed to investigate the anticipatory postural adjustments (APAs), posterior center of pressure (COPap) displacement, and spatiotemporal variability during GI in patients with and without functional loss in the early stage of MS. MethodsForty-four participants (31 MS patients and 13 healthy subjects) involved in this prospective cross-sectional study were divided into three groups: Group-I: Patients without functional loss (EDSS 0 to 1.5) (n = 14), Group-II: Patients with functional loss (EDSS 2 to 3) (n = 17) and Group-III: Healthy subjects (n = 13). Electromyographic activity of the bilateral tibialis anterior (TA) and gastrocnemius medialis (GM) and COPap displacement were recorded during the postural phase of GI. Additionally, spatiotemporal parameters were recorded within the first three steps, and the coefficient of variation was calculated with 40 walks for variability. ResultsThere were significant differences in the Kruskal-Wallis tests of variables (p<0.05). Group-I demonstrated smaller APAs magnitudes in TA [stance (p = 0.01), swing (p = 0.01)], GM of swing limb (p<0.0001), and smaller COPap displacement (p<0.0001) compared to group-III. Group-II demonstrated smaller APAs magnitudes in all muscles (p<0.0001) compared to group-III and the smallest COPap displacement (p<0.0001). Group-I showed a significant increase in stride width variability compared to group-III (p = 0.01). Group-II showed a significant increase in several variabilities [first stride length (p<0.0001), second stride time (p<0.0001), first double support time (p<0.0001), stride width (p<0.0001)] compared to group-III. ConclusionPatients in the early stage of MS had impairment in both the postural and locomotor phases of GI with more obvious in the patients with functional loss. The results indicate that MS patients without functional loss have difficulty initiating gait. Although there is no functional loss, the patients have a risk of falls, postural instability, and gait impairment due to their inability to initiate gait effectively. As a result, rehabilitation is necessary even if there is no functional loss in patients with MS.

Comparing the effectiveness of prolotherapy and percutaneous dry needling in the treatment of lateral epicondylitis: a retrospective cohort study.

Lateral epicondylitis (LE) can result in a functional loss in patients because of pain and has recently become more prevalent. This study compared the effects of minimally invasive prolotherapy (PRO) and percutaneous dry needling (PDN) on LE treatment. Patients were divided into three groups; Group 1 included patients undergoing PDN, Group 2 included those undergoing PRO, and Group 3 included those undergoing PDN+PRO. All these treatments were administered three times and at a 3-week interval in each patient. Data on the visual analog scale (VAS) and patient-rated tennis elbow evaluation (PRTEE) scale scores of the patients were collected at weeks 0, 3, and 6 and month 6 and retrospectively analyzed. The VAS and PRTEE scores decreased in all groups. The decrease in Group 3 was higher than that in the other groups (p<0.001). Upon evaluating within-group differences in VAS and PRTEE scores, the scores at week 3, week 6, and month 6 gradually decreased compared with the baseline in all groups (p<0.001). PDN and PRO are minimally invasive and can successfully treat LE. A combination of PDN+PRO provides better results than PDN or PRO alone. As the materials we used in these treatments are relatively inexpensive and readily available, we believe our study will help reduce the national healthcare costs allocated for the treatment of LE.

Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence

BackgroundIn clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs initiation with long-term kidney outcomes in the Maccabi Healthcare Services database, Israel.MethodsAdults with T2D treated with ≥ 2 glucose-lowering agents who initiated GLP-1 RAs or basal insulin from 2010 to 2019 were propensity-score matched (1:1) and followed until October 2021 (intention-to-treat [ITT]). In an as-treated (AT) analysis, follow-up was also censored at study-drug discontinuation or comparator-initiation. We assessed the risk of a composite kidney outcome, including confirmed ≥ 40% eGFR loss or end-stage kidney disease, and the risk of new macroalbuminuria. Treatment-effect on eGFR slopes was assessed by fitting a linear regression model per patient, followed by a t-test to compare the slopes between the groups.ResultsEach propensity-score matched group constituted 3424 patients, 45% women, 21% had a history of cardiovascular disease, and 13.9% were treated with sodium-glucose cotransporter-2 inhibitors at baseline. Mean eGFR was 90.6 mL/min/1.73 m2 (SD 19.3) and median UACR was 14.6 mg/g [IQR 0.0–54.7]. Medians follow-up were 81.1 months (ITT) and 22.3 months (AT). The hazard-ratios [95% CI] of the composite kidney outcome with GLP-1 RAs versus basal insulin were 0.96 [0.82–1.11] (p = 0.566) and 0.71 [0.54–0.95] (p = 0.020) in the ITT and AT analyses, respectively. The respective HRs for first new macroalbuminuria were 0.87 [0.75–0.997] and 0.80 [0.64–0.995]. The use of GLP-1 RA was associated with a less steep eGFR slope compared with basal insulin in the AT analysis (mean annual between-group difference of 0.42 mL/min/1.73 m2/year [95%CI 0.11–0.73]; p = 0.008).ConclusionInitiation of GLP-1 RAs in a real-world setting is associated with a reduced risk of albuminuria progression and possible mitigation of kidney function loss in patients with T2D and mostly preserved kidney function.

Abstract 3432: Ataxia-telangiectasia mutated loss of function displays variant and tissue specific differences across tumor types

Abstract Introduction: ATM loss of function (LOF) in cancer may serve as a predictive biomarker of response for antitumor therapies. However, clinical studies of targeted treatments in ATM-aberrant patients have yielded mixed results; thus, identifying the optimal strategy for selecting patients with ATM LOF tumors remains a critical area of unmet need. Methods: In order to investigate the heterogeneity observed in ATM aberrant tumors, we conducted a pan-cancer genomic and proteomic profiling of ATM LOF, and also performed retrospective review of clinical outcomes for a subset of patients with ATM LOF treated with platinum or ATR inhibition. Results: We identified 10,609 ATM variants in 8,587 patients with cancer. The prevalence of deleterious (Tier 1) versus variants of unknown significance (VUS)/benign (Tier 2) variants differed by cancer tissue type, as did selective pressure for loss of heterozygosity (LOH). Analysis of ATM protein staining in 471 patient tumors showed tumors with null, inactivating variants were significantly (p&amp;lt;0.005) more likely to display ATM loss of protein (LOP) than tumors with missense or wildtype, but 19% (N=27/140) and 9% (N=13/149) of tumors with ATM-VUS and wildtype showed loss of protein. In addition, concordance between inactivating mutations and loss of protein also differed based on tumor tissue context, with ovarian and breast cancer showing stronger concordance (greater than 80%) than melanoma and lung cancer ( less than 20%). Patients treated with platinum chemotherapy with select tumor types with deleterious variants in ATM and ATM LOP display improved progression free survival (PFS) (HR 0.50, P=0.03). Lastly, patients with tumor types that have stronger ATM variant-to-protein loss concordance display increased benefit from ATR inhibition (HR 0.40, P=0.04). Conclusions: Our data highlight that there is heterogeneity in ATM LOF in patients due to multiple variables, including notable tissue-specific differences in the type of variants seen and the relationship between ATM variant status and ATM protein. This genomic heterogeneity and tissue-specificity has implications for predictive biomarker development and clinical trial designs. Citation Format: Patrick G. Pilie, Daniel Mcgrail, Wei-Lien Wang, Natalie Ngoi, Keith Kyewalabye, Khalida Wani, Hung Le, Erick Campbell, Vijaykumar Holla, Kenna R. Shaw, Funda Meric-Bernstam, Alexander J. Lazar, Virginia Giuliani, Timothy Heffernan, Timothy A. Yap. Ataxia-telangiectasia mutated loss of function displays variant and tissue specific differences across tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3432.

Investigation of the Relevant Factors in the Complexity of Chronic Low Back Pain Patients With a Physiotherapy Prescription: A Network Analysis Approach Comparing Chronic Pain-Free Individuals and Chronic Patients.

Chronic low back pain (CLBP) is the leading cause of disability worldwide, and several factors have been proposed as potential causes or cofactors. The aim of this study was to explore their direct and indirect relations to understand CLBP and identify relevant rehabilitation targets. A total of 119 patients with CLBP and 117 chronic pain-free individuals were assessed. A network analysis approach was used to explore the complexity of CLBP by assessing the relations between pain intensity, disability, functionality (physical, social, and psychological), age, body mass index, and education level. The network analysis revealed the independence of pain and disability related to CLBP from age, sex, and body mass index. Crucially, pain intensity and disability are directly and strongly connected in chronic pain-free individuals, but not in patients with CLBP. Psychosocial functioning is related to pain intensity and disability indirectly through the mediation of one's general health perception and perceived physical functionality. Clinicians should pay more attention to perceived physical functionality and psychosocial factors as they are tightly linked to CLBP. Indeed, pain intensity seems a suboptimal rehabilitation target. This study suggests that a biopsychosocial approach is much needed to investigate CLBP, but it also warns against overestimating the direct impact of each potential contributor. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. Upon completion of this article, the reader should be able to: (1) Recognize the relation of pain intensity, disability, and loss of function in patients with CLBP; (2) Determine the impact of the most common biological and psychosocial factors in addressing the assessment of chronic back pain patients; and (3) Enhance confidence in selecting the relevant outcomes for the assessment of patients with CLBP following a multidimensional assessment. Advanced. The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should only claim credit commensurate with the extent of their participation in the activity.

Evaluating the effects of two different kinesiology taping techniques on shoulder pain and function in patients with hypermobile Ehlers-Danlos syndrome.

Ehlers-Danlos Syndrome (EDS) is a group of inherited connective tissue disorders which predominantly affects women and has a prevalence as high as 1 in 5,000 individuals. Hypermobile EDS (hEDS) is the most common subtype of EDS and is characterized by multi-joint pain, particularly in large joints such as the shoulder. Physical therapy is often utilized to address the pain, physical impairments, and functional loss in patients with EDS. Kinesiology Tape (KT) is an intervention commonly used by physical therapists for treating shoulder pain and dysfunction. Studies related to the effectiveness of KT in patients with shoulder pain is equivocal and there are a lack of studies specifically studying the effects of KT in an EDS population. The purpose of this study was to assess the efficacy and short-term effects of two different KT techniques on shoulder pain and function in individuals with hEDS and shoulder pain. Participants were recruited from EDS support groups in the New England area of the United States; were diagnosed with hEDS by their physician; and had shoulder pain. Baseline demographic information was obtained for each participant followed by completion of 4 patient reported outcome (PRO) measures: the Upper Extremity Functional Index, QuickDASH (Disabilities of the Arm, Shoulder, & Hand), Shoulder Pain and Disability Index, and the Western Ontario Shoulder Instability Index. Current pain level, average pain over the past 24 h, and worst pain over the past 24 h were recorded using the numeric pain rating scale (NPRS). Subjects were randomly assigned to receive either an experimental shoulder KT procedure or a control shoulder taping. Immediately after taping, the NPRS was reassessed. Subjects then returned 48 h later to repeat the NPRS and PRO measures. There was no significant difference between the experimental and control tape groups for any outcome measure. There was a significant improvement from pre-taping to 48-hours post taping for each of the 4 PRO measures with large effect sizes (p < 0.001; ƞ p 2 = .517-.719). Likewise, average, and worst pain over the last 24 h significantly improved with large effect sizes over the same period (p = 0.005; ƞ p 2 = .225 and p < 0.001; ƞ p 2 = .382, respectively). Current NPRS levels significantly improved from pre-tape to immediately post-tape (p = .023, ƞ p 2 = .131) and was maintained through the 48-hour follow up, although no further improvement was seen. KT is an inexpensive and relatively safe intervention that is easy to apply and can offer temporary improvements in pain and function for patients with EDS and shoulder pain.

A review of regenerative therapy for spinal cord injury using human iPS cells

Spinal cord injury (SCI) has been considered to cause sudden, irreversible loss of function in patients. However, developments in stem cell biology and regenerative medicine are changing this conventional notion. Here we reviewed the overview of regenerative medicine of SCI.As a consequence of the establishment of human induced pluripotent stem cells (hiPSCs), hiPSC-based therapies for SCI, such as neural stem/progenitor cell (NS/PC) transplantation, have emerged as promising therapeutic modalities. Using several animal models, hiPSC-NS/PC transplantation into subacute injured spinal cords has been repeatedly demonstrated to improve locomotor function.Some biological mechanisms underlying this improvement have been proposed. In particular, combined with advanced neuroscience techniques such as designer receptors exclusively activated by designer drugs (DREADDs), neuronal relay theory, in which the transplanted cell-derived neurons reconstruct disrupted neuronal circuits, was proven to be involved histologically, pharmaceutically, electrophysiologically, and via in vivo bioimaging.Based on these findings, hiPSC-NS/PC transplantation for subacute SCI was moved ahead to a clinical study on human patients. At the same time, the search for effective treatments for chronic SCI is proceeding gradually, combining hiPSC-NS/PC transplantation with other treatment modalities such as rehabilitation, pharmaceutical interventions, or optimal scaffolds. In addition to NS/PCs, oligodendrocyte precursor cells (OPCs) are also a promising cell source for transplantation, as demyelinated axons affected by SCI can be repaired by OPCs. Therapies with OPCs derived from hiPSCs are still in preclinical studies but have shown favorable outcomes in animal models.In the future, several therapeutic options may be available according to the pathological conditions and the time period of SCI. Moreover, the application of regenerative therapy for the spinal cord could be broadened to degenerative disorders, such as spinal canal stenosis.Summary sentence: A historical review of human induced pluripotent stem cell (hiPSC) based cell transplantation therapy for spinal cord injury (SCI), in particular about footsteps of hiPSC-derived neural stem/progenitor cell transplantation, recent clinical study, and its future perspective.

IDF21-0024 The non-invasively measured radial pulse and the renal outcomes of SGLT-2 inhibitors in patients with Type 2 diabetes

Background: Many studies had shown SGLT-2 inhibitors prevent diabetic nephropathy. The non-invasive spectrum analysis of radial pulse may be used as an indicator for renal function loss in patients with Type 2 diabetes. Aim: The purpose of this study was to examine if the third harmonic of radial pulse (C3) can be used as a risk marker of diabetic nephropathy for patients and if it is different with those treated with SGLT-2 inhibitors. Method: The study consists of two-year follow-up of 2,095 type 2 diabetes patients under the care of the Division of Endocrinology and Metabolism of Zhongxiao Branch of Taipei City Hospital (IRB: ISRCTN14306167), 57.4% of them were male without prior history of diabetic nephropathy. The two groups were separated by patients taking SGLT-2 inhibitors or not. Per the national insurance prior authorization guidelines, only those patients with eGFR>45 were prescribed with SGLT-2. Radial pulse measurements were taken and analyzed for all patients at the beginning of the trial. The spectrum analysis of the radial pressure wave was calculated and transformed. The patients are under quarterly routine renal function checkups. The results of renal outcome were determined by a specialist. Variables from medical records and from the spectrum analysis of radial pressure wave were calculated at the beginning of the trial in each group using the Student’s t-test. Results: During the 2 years, there were 8 patients (3.13%) developed diabetic nephropathy in the group taking SGLT-2 inhibitor (N=255), and 83 patients (4.51%) in the group not taking SGLT-2 inhibitor (N=1,840). The SGLT-2 inhibitor group had a lower incidence of diabetic nephropathy. In both groups, we found that the lower C3 is associated with diabetic nephropathy. After adjusting for age and gender, C3 is still significantly different (CI 0.200–0.320; P<0.01) between the group with (C3 = 0.239 ± 0.04) or without (C3 = 0.283 ± 0.084) diabetic nephropathy. Discussion: This result of study is consistent with other studies in which SGLT-2 use was associated with a lower incidence of diabetic nephropathy in patients with type 2 diabetes mellitus. Furthermore, C3 may be used as a predictor of diabetic nephropathy. Regardless of treatment with SGLT-2 inhibitors, the patients with lower C3 were more likely to develop diabetic nephropathy.

IDF21-0022 The non-invasive spectrum analysis of the radial pulse for renal function loss in patients with type 2 diabetes

Background: Renal function loss is the sign of diabetic nephropathy and the risk for adverse renal events. Previous studies have shown some predictive power of Urine ACR (Albumin-Creatinine Ratio, eGFR (estimated glomerular filtration rate), and the radial pulse spectrum for the development or progression of diabetic nephropathy. However, the predicting power of those risk markers had not been surveyed completely. Aim: The purposes of this study was to examine if spectrum analysis of the radial pulse could be used to predict the development of adverse renal events, including 40% eGFR decrease, doubling of serum creatinine or end-stage renal disease (ESRD) in patients with type 2 diabetes. Method: The longitudinal study followed 2,193 patients with type 2 diabetes, 57.5% male, without prior renal failure or ESRD, through the division of Endocrinology and Metabolism of the Zhongxiao Branch of Taipei City Hospital (IRB: ISTCTN14306167) for over four-years. During the initial visit, a 12-second radial pulse was measured using a TD01C. Spectrum analysis of the radial pulse provided the first seven harmonics which were described by the index notation, Cn (n = 1–7). At each three-month follow up appointment kidney function blood tests were taken and correlated with adverse renal events. We identify the harmonics that are associated with the adverse renal event using logistic regression and Cox proportional hazard model. Results: In 2,193 patients, 106 (4.8%) had 40% decline of eGFR, 465 (21.2％) had doubling of serum creatinine, and 12 (<1%) had ESRD. The logistic regression identified C7 and C3 are important and independent predictors of the risk of renal adverse events after adjusting for age, sex, duration of diabetes, and smoking, (C3: HR, 0.288; 95% CI 0.140 to 0.594; P<0.001; C7: HR, 1.567; 95% CI 1.200 to 2.046; P<0.001). A Cox proportional hazard model with the RFLRisk index combining C3 and C7 with equal weight to identify patients who may be at high risk for adverse renal events. The patients with RFLRisk = High (C3<0.491 and C7>0.566) had 1.42 times cumulative incidence of adverse renal events, compared to patients with RFLRisk = Low (C3>0.491 and C7<0.566). Discussion: This study suggested that the specific harmonic profiles of radial pulse waves may be used as indicators to predict the risk of adverse renal events. High RFLRisk index leads to increasing risk of adverse renal events in patients with type 2 diabetes.

Causes, Frequencies And Degrees Of Urological Functional Loss in Patients Applying To The Health Board

Amaç: Çalışmamızda sağlık kuruluna başvuran hastalar arasında ürolojik işlevsel kayıp nedenlerinin, sıklığının ve ayrıca engellilik oranlarının değerlendirilmesini amaçladık.Gereç ve Yöntemler: Ocak 2016 – Aralık 2020 tarihleri arasında XXX Hastanesi üroloji sağlık kuruluna başvuran 3074 hasta çalışmaya dahil edildi. Evde bakım, vergi indirimi, malulen emeklilik, engelli maaşı, durum bildirir raporu, rapor itirazı, yaş tespiti, huzurevi başvurusu ve emniyet güçleri için yapılan değerlendirmeler olmak üzere sağlık kuruluna başvuru sebebine göre hastalar gruplandırıldı. Ürolojik hastalıklar; üst üriner sistem hastalıkları, üro-onkolojik hastalıklar, nöro-ürolojik hastalıklar ve androlojik hastalıklar olmak üzere üst başlıklarda toplandı. Her grup için yaş, cinsiyet, sağlam ve hasta kişilerin oranları ve engellilik oranları kaydedildi.Bulgular: Dahil edilen kişilerin yaş ortalaması 42,1 ± 19,8 yıl olarak tespit edildi ve çoğunluğunu erkekler oluşturmaktaydı (%76,3). Ürolojik açıdan hastalık tanısı olan 1056 kişi (%34,4) tespit edildi. 367 hastada (%11,9) nöro-ürolojik hastalıklar tespit edilmiş olup en sık görülen hastalık grubunu oluşturmaktadır. İkinci en sık görülen hastalık grubu ise androlojik hastalıklardır (%8,1). Üro-onkolojik hastalıklar arasında en yaygın olarak mesane kanseri (%42,6) görülmekteyken, en az testis kanserine (%14,3) rastlandı. Prostat kanseri ortalama 36,6 ± 28,6 engellilik oranı ile üro-onkolojik hastalıklar arasında en çok işlev kaybına sebep olan hastalık olarak göze çarpmaktadır.Sonuç: Üroloji sağlık kurulu başvuruları içinde en sık nöro-ürolojik ve androlojik hastalıklar ile karşılaşılmaktadır. En yüksek engellilik oranları ise sırasıyla üro-onkolojik ve nöro-ürolojik hastalıklarda görülmektedir.

Enhanced Visual Feedback Using Immersive VR Affects Decision Making Regarding Hand Use With a Simulated Impaired Limb.

The long-term effects of impairment have a negative impact on the quality of life of stroke patients in terms of not using the affected limb even after some recovery (i.e., learned non-use). Immersive virtual reality (IVR) has been introduced as a new approach for the treatment of stroke rehabilitation. We propose an IVR-based therapeutic approach to incorporate positive reinforcement components in motor coordination as opposed to constraint-induced movement therapy (CIMT). This study aimed to investigate the effect of IVR-reinforced physical therapy that incorporates positive reinforcement components in motor coordination. To simulate affected upper limb function loss in patients, a wrist weight was attached to the dominant hand of participant. Participants were asked to choose their right or left hand to reach toward a randomly allocated target. The movement of the virtual image of the upper limb was reinforced by visual feedback to participants, that is, the participants perceived their motor coordination as if their upper limb was moving to a greater degree than what was occurring in everyday life. We found that the use of the simulated affected limb was increased after the visual feedback enhancement intervention, and importantly, the effect was maintained even after gradual withdrawal of the visual amplification. The results suggest that positive reinforcement within the IVR could induce an effect on decision making in hand usage.

Cerliponase Alfa for the Treatment of Atypical Phenotypes of CLN2 Disease: A Retrospective Case Series.

Background:The classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described.Methods:A chart review was conducted of 14 patients (8 male, 6 female) with atypical CLN2 phenotypes who received cerliponase alfa. Pre- and posttreatment CLN2 Clinical Rating Scale Motor and Language (ML) domain scores were compared.Results:Median age at first presenting symptom was 5.9 years. First reported symptoms were language abnormalities (6 [43%] patients), seizures (4 [29%]), ataxia/language abnormalities (3 [21%]), and ataxia alone (1 [7%]). Median age at diagnosis was 10.8 years. ML score declined before treatment in 13 (93%) patients. Median age at treatment initiation was 11.7 years; treatment duration ranged from 11 to 58 months. From treatment start, ML score remained stable in 11 patients (treatment duration 11-43 months), improved 1 point in 1 patient after 13 months, and declined 1 point in 2 patients after 15 and 58 months, respectively. There were 13 device-related infections in 8 patients (57%) and 10 hypersensitivity reactions in 6 (43%).Conclusions:Cerliponase alfa is well tolerated and has the potential to stabilize motor and language function in patients with atypical phenotypes of CLN2 disease.

Effect of Diabetes Control on Rates of Structural and Functional Loss in Patients with Glaucoma

To investigate the association between levels of diabetes mellitus (DM) control and rates of visual field and retinal nerve fiber layer (RNFL) loss over time in glaucoma. Retrospective cohort study. A total of 351 eyes of 222 patients with type 2 DM with concomitant primary open-angle glaucoma (POAG) or suspected glaucoma extracted from the Duke Glaucoma Registry. All patients had at least 2 reliable standard automated perimetry (SAP) tests, 2 spectral domain OCT (SD-OCT) tests, and 2 glycated hemoglobin (HbA1c) measures over time with a minimum follow-up of 6 months. Values of HbA1c were summarized for each patient as mean, peak, and fluctuation across time. Multivariable linear mixed models were used to estimate the effect of HbA1c on rates of change in SAP mean deviation (MD) and OCT RNFL thickness loss over time while adjusting for various confounding factors. Rates of change in MD and RNFL thickness over time. Subjects had a mean baseline age of 62.5 ± 10.2 years and follow-up time of 6.9 ± 5.1 years. Subjects had an average of 4.8 SAP tests (range, 2-28), 3.6 SD-OCT tests (range, 2-10), and 8.3 HbA1c tests (range, 2-21). Average HbA1c mean was 7.1% ± 1.1% (range, 5.4-11.7), peak HbA1c over time was 8.1% ± 2% (range, 5.5-15.6), and HbA1c fluctuation was 0.6% ± 0.6% (range, 0-4.4). Mean rate of SAP MD changewas-0.09 ± 0.20 decibel/year(median -0.06 decibel/year; interquartile range -0.15 to 0.01 decibel/year), and mean rate of RNFL change was-0.83 ± 0.51 μm/year(median -0.76 μm/year; interquartile range -1.06 to 0.56 μm/year). After adjustment for confounding factors, mean, peak, and fluctuation in HbA1c levels were not significantly associated with rates of MD change over time (P= 0.994, P= 0.689, P= 0.920, respectively), nor were rates of change in RNFL loss over time (P= 0.805, P= 0.575, P= 0.770). We did not find a significant association between diabetes control, as measured by levels of HbA1c, and rates of visual field or RNFL loss over time in individuals with glaucoma or suspected glaucoma.

Functional recovery with histomorphometric analysis of nerves and muscles after combination treatment with erythropoietin and dexamethasone in acute peripheral nerve injury.

IntroductionPeripheral nerve injury (PNI) often leads to significant functional loss in patients and poses a challenge to physicians since treatment options for improving functional outcomes are limited. Recent studies suggest that erythropoietin and glucocoticoids have beneficial effects as mediators of neuro-regenerative processes. We hypothesized that combination treatment with erythropoietin and glucocoticoids would have a synergistic effect on functional outcome after PNI.Materials and methodsSciatic nerve crush injury was simulated in ten-week-old male C57BL/6 mice. The mice were divided into four groups according to the type of drugs administered (control, erythropoietin, dexamethasone, and erythropoietin with dexamethasone). Motor functional recovery was monitored by walking track analysis at serial time points up to 28 days after injury. Morphological analysis of the nerve was performed by immunofluorescent staining for neurofilament (NF) heavy chain and myelin protein zero (P0) in cross-sectional and whole-mount nerve preparations. Additionally, morphological analysis of the muscle was performed by Hematoxylin and eosin staining.ResultsCombination treatment with erythropoietin and dexamethasone significantly improved the sciatic functional index at 3, 7, 14, and 28 days after injury. Fluorescence microscopy of cross sectional nerve revealed that the combination treatment increased the ratio of P0/NF-expressing axons. Furthermore, confocal microscopy of the whole-mount nerve revealed that the combination treatment increased the fluorescence intensity of P0 expression. The cross-sectional area and minimum Feret’s diameter of the muscle fibers were significantly larger in the mice which received combination treatment than those in the controls.ConclusionOur results demonstrated that combination treatment with erythropoietin and dexamethasone accelerates functional recovery and reduces neurogenic muscle atrophy caused by PNI in mice, which may be attributed to the preservation of myelin and Schwann cell re-myelination. These findings may provide practical therapeutic options for patients with acute PNI.

492-P: Associations between Novel Biomarkers of Inflammation and Estimated Glomerular Filtration Rate in Adults with Recent-Onset Type 1 and Type 2 Diabetes

Background: The development of anti-inflammatory therapies for renal function loss in patients with diabetes requires identification of specific biomarkers which might differ by diabetes type. This study aimed to investigate associations between a novel panel of biomarkers of inflammation and estimated glomerular filtration rate (eGFR) in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). Methods: This study was based on 145 participants with T1D (mean age 33.8 years, 60.7% males) and 250 participants with T2D (mean age 55.3 years, 66.4% males) from the observational prospective German Diabetes Study (GDS), which includes adults with a diabetes duration &amp;lt;1 year. A panel of 74 biomarkers of inflammation was measured in serum of fasted participants using the proximity extension assay technology. eGFR was calculated from serum creatinine and cystatin C using the CKD-EPI equation. Associations between each biomarker and eGFR were assessed using multiple linear regression adjusting for age, sex, BMI, HbA1c, diabetes duration, lipids, hypertension and use of NSAIDs and glucose-lowering drugs. Results: Baseline eGFR was higher in T1D compared to T2D (mean (SD) 101.8 (15.3) vs. 89.3 (15.6) mL/min/1.73 m2; P&amp;lt;0.0001). After correction for multiple testing, 6 and 24 biomarkers were inversely associated with eGFR in T1D and T2D, respectively (all P&amp;lt;0.05). TNFB was T1D-specific, while ADA, CD40, CD244, CCL3, CCL20, CCL25, CX3CL1, CXCL9, CSF1, CST5, FGF23, FGF5, IL-15RA, IL12B, MMP10, NT3, SCF, TGFα and uPA were T2D-specific. CCL23, CD5, IL10RB, PDL1 and TNFRSF9 were associated with eGFR in both diabetes types. Conclusion: We identified novel inflammatory biomarkers, independently associated with eGFR in adults with recently diagnosed T1D and T2D. As a next step, these biomarkers shall be evaluated as potential predictors of incident and progressive diabetic nephropathy. Disclosure H. Maalmi: None. C. Herder: Research Support; Self; Sanofi-Aventis. K. Strassburger: None. S. Urner: None. K. Jandeleit-Dahm: None. O.P. Zaharia: None. Y. Karusheva: None. K. Bodis: None. W. Rathmann: Advisory Panel; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Research Support; Self; Novo Nordisk Inc. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. D.F. Markgraf: None. V. Burkart: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.