Functional Impairment In Patients Research Articles

#2459 Matching-adjusted indirect comparison of eGFR in patients with immunoglobulin A nephropathy treated with Nefecon (TRF budesonide) or sparsentan

Abstract Background and Aims Primary immunoglobulin A nephropathy (IgAN) is an immune-mediated disease that can lead to kidney failure, need for dialysis and kidney transplantation, and early death. IgAN is the most common type of primary glomerulonephritis globally, with an estimated worldwide incidence of 2.5 per 100 000 individuals per year. Estimated glomerular filtration rate (eGFR) is a measure of renal function and is accepted as a surrogate endpoint for clinical trials evaluating kidney function deterioration. In December 2023, the US Food and Drug Administration (FDA) granted full approval to Nefecon (marketed as Tarpeyo® by Calliditas Therapeutics), a targeted-release formulation of budesonide, to reduce the loss of kidney function in adults with IgAN at risk of disease progression, based on the Phase 3 NefIgArd clinical trial. In February 2023, sparsentan (marketed as Filspari™ by Travere Therapeutics) was granted accelerated approval by the FDA to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein–creatinine ratio (UPCR) ≥1.5 g/g, based on the Phase 3 PROTECT study. Matching-adjusted indirect comparison (MAIC) is a widely accepted and relevant methodology for comparing treatments across trials in the absence of head-to-head comparisons. In this analysis, we aimed to compare the effects of Nefecon and sparsentan on kidney function deterioration in patients with IgAN, as assessed by eGFR. Method An anchored MAIC was performed to estimate the relative effect of Nefecon and sparsentan on the absolute eGFR change from baseline at 9, 12 and 24 months, with common comparators of optimized renin–angiotensin system inhibition for NefIgArd and irbesartan for PROTECT. Patient-level data from NefIgArd were used to select a population matched to PROTECT, and the following baseline characteristics were used to determine the weights: mean age (years), sex (% male), race (% white), mean eGFR (mL/min/1.73 m2), mean UPCR (g/g), urine albumin–creatinine ratio (UACR) (% with UACR >1.1 g/g), and urinary protein excretion (% with urinary protein excretion >1.8 g/day). Absolute change in eGFR was analyzed using a mixed model for repeated measures (MMRM) method, including baseline, 3-, 6-, 9-, 12-, 18- and 24-month data, baseline eGFR, baseline eGFR-by-time interaction, treatment, and treatment-by-time interaction. The MAIC weights were incorporated into the MMRM. A Bayesian fixed-effects network meta-analysis was performed on the relative effect from PROTECT and the weighted relative effect from NefIgArd, measured by the estimated absolute change from baseline in eGFR. Results The matching-adjustment of the NefIgArd patient population to the PROTECT population is shown in Table 1. The weighted NefIgArd population exhibits very similar baseline characteristics to the PROTECT population. The effective sample size of the weighted NefIgArd population is 208. Results from the anchored MAIC showed statistically and clinically significant favorable effects of Nefecon versus sparsentan on eGFR for all time points analyzed (Fig. 1). Mean differences in the absolute change in eGFR of 5.68 mL/min/1.73 m2 (95% credible interval [Crl] 3.14, 8.20; p < 0.001), 3.48 mL/min/1.73 m2 (95% Crl 0.97, 5.97; p = 0.006) and 3.28 mL/min/1.73 m2 (95% Crl 0.02, 6.51; p = 0.048) were observed when comparing Nefecon with sparsentan at 9 months vs 36 weeks, 12 months vs 48 weeks, and 24 months vs 106 weeks, respectively. Conclusion After accounting for differences in the patient populations from the NefIgArd and PROTECT trials, the anchored MAIC showed that treatment with Nefecon 16 mg/day for 9 months was associated with greater eGFR benefit compared with continuous treatment with sparsentan 400 mg/day over 2 years, with significant differences observed as early as 9 months after treatment initiation and sustained up to 2-years of follow-up.

Clinical and personal predictors of functioning in affective disorders: Exploratory results from baseline and 6-month follow-up of a randomised controlled trial

Comprehensive knowledge of factors causing and sustaining functional impairment in patients with affective disorders is warranted. The aim is to investigate associations between clinical factors (such as affective symptoms) and personal factors (such as personality traits, coping strategies, and childhood trauma experiences) on functioning and improvement of functioning in patients with affective disorders.This exploratory study includes data from 103 patients with bipolar disorder and unipolar depressive disorder. Clinician-rated functioning was assessed at baseline using the Functioning Assessment Short Test (FAST), and performance-based functioning was assessed at baseline and 6-month follow-up using the Assessment of Motor and Process Skills (AMPS). Data on clinical and personal factors were collected at baseline. Personal factors were measured by the Eysenck Personality Inventory (EPQ), Coping Inventory for Stressful Situations (CISS) and Childhood Trauma Questionnaire (CTQ). Pearson correlations and multiple linear regression models were used to analyse the association of clinical and personal factors with baseline functioning (FAST) and to identify predictors of improvement in functioning (AMPS) from baseline to follow-up.At baseline, greater depressive symptom severity, the personality trait neuroticism, emotional coping, and childhood trauma all correlated with poorer functioning (higher FAST scores). In multiple linear regression models, depression severity, emotional coping and childhood trauma were significant predictors of poorer functioning. More childhood trauma was a predictor of less functional improvement measured by AMPS at 6-month follow-up.In conclusion, maladaptive coping styles and depressive symptoms contribute to functional impairment in patients with affective disorders, while childhood trauma has a negative impact on long-term functional outcomes.

Abstract PO2-12-09: Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer

Abstract Background: SPPADE symptoms (Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression/distress, and Energy deficits/fatigue) may result from cancer and its treatment. The aim of this analysis was to characterize SPPADE symptoms in patients with breast cancer. Methods. SPPADE data were drawn from the Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) study, a stepped-wedge pragmatic cluster-randomized trial designed to evaluate a symptom management intervention in routine practice (NCT03892967). Symptom severity was measured on a 0-10 scale via a survey administered by patient portal, in-clinic tablet, or interactive voice response system (by phone) prior to, during, or soon after an outpatient oncology encounter. Scores of 4-6 were categorized as “moderate” and ≥7 as “severe.” In this analysis, only the data from each patient’s initial survey were included. Results. A total of 9,651 patients with breast cancer completed an initial E2C2 survey between March 2019 and January 2023. The proportion of patients with moderate or severe SPPADE symptoms were as follows: 22% moderate and 10% severe for insomnia; 18% moderate and 7% severe for pain; 17% moderate and 7% severe for anxiety; 15% moderate and 5% severe for emotional distress; 25% moderate and 12% severe for fatigue; and 22% moderate and 8% severe for impaired physical function. Table 1 presents score means and standard deviations by demographic subgroup. Conclusions. SPPADE symptoms are common in patients with breast cancer. These observations warrant routine implementation of symptom surveillance and management in breast oncology. Funding acknowledgement: The Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium is a Cancer Moonshot Research Initiative under the authorization of the 2016 United States 21st Century Cures Act. This research was supported by the National Cancer Institute of the NIH, UM1CA233033 (Mayo Clinic, Rochester, MN). Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer Citation Format: Kathryn Ruddy, Veronica Grzegorczyk, Deirdre Pachman, Sandra Mitchell, Bolun Liu, Deanne Smith, Ciara O'Sullivan, Shawna Ehlers, Jeph Herrin, Parvez Rahman, Andrea Cheville. Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-09.

Intensive care unit follow-up clinic activities: a scoping review.

The importance of ongoing post-discharge follow-up to prevent functional impairment in patients discharged from intensive care units (ICUs) is being increasingly recognized. Therefore, we conducted a scoping review, which included existing ICU follow-up clinic methodologies using the CENTRAL, MEDLINE, and CINAHL databases from their inception to December 2022. Data were examined for country or region, outpatient name, location, opening days, lead profession, eligible patients, timing of the follow-up, and assessment tools. Twelve studies were included in our review. The results obtained revealed that the methods employed by ICU follow-up clinics varied among countries and regions. The names of outpatient follow-up clinics also varied; however, all were located within the facility. These clinics were mainly physician or nurse led; however, pharmacists, physical therapists, neuropsychologists, and social workers were also involved. Some clinics were limited to critically ill patients with sepsis or those requiring ventilation. Ten studies reported the first outpatient visit 1-3months after discharge. All studies assessed physical function, cognitive function, mental health, and the health-related quality of life. This scoping review revealed that an optimal operating format for ICU follow-up clinics needs to be established according to the categories of critically ill patients.

Effect of kinesio taping and exercise on functional impairment in patients with different degrees of knee osteoarthritis

BACKGROUND: Kinesio Taping (KT) is used for musculoskeletal problems. KT optimizes and reduces mechanical stresses on soft tissues. However, the benefits of KT and traditional exercises for different severities of knee osteoarthritis (OA) remains controversial. OBJECTIVES: This study aimed to investigate the effects of tension KT and traditional physical therapy on different severities of knee OA. METHODS: Fifty-six male patients with knee OA, aged 60–75-y years, were allocated to groups A and B based on grades 1 and 2 and grades 3 and 4 on the Kellgren-Lawrence scale, respectively. Tension KT and traditional physical therapy were administrated to both groups for 6-wks. The extensor peak moment of quadriceps and knee flexion range of motion (ROM) were recorded using an isokinetic dynamometer and universal goniometer, respectively. Visual analog scale (VAS) was used to score pain level. Statistical analysis was performed using the ANCOVA test. RESULTS: ANCOVA revealed an increase in peak extensor moment of quadriceps (Pre: 51.6 ± 2.8 Nm; Post: 63.3 ± 4.3 Nm), knee flexion ROM (Pre: 112.8∘7.2; Post: 122.9∘4.8), and pain improvement (Pre: 5.1 ± 1.07; Post: 2.8 ± 1.6) in group A (p< 0.001). Group B showed insignificant improvements in all outcome measures (p> 0.05). CONCLUSION: KT with traditional physical therapy improved knee pain, quadriceps strength, and knee ROM in older males with knee OA grades 1 and 2. KT and traditional physical therapy were insufficient to produce considerable effects on grades 3 and 4 of knee OA.

Functional Impairments in Patients with KCNQ2-DEE: Associations Among Key Clinical Features (P1-1.007)

Functional Impairments in Patients with KCNQ2-DEE: Associations Among Key Clinical Features (P1-1.007)

Efficacy of rTMS in treating functional impairment in post-stroke patients: a systematic review and meta-analysis.

Most stroke patients suffer from an imbalance in blood supply, which causes severe brain damage leading to functional deficits in motor, sensory, swallowing, cognitive, emotional, and speech functions. Repetitive transcranial magnetic stimulation (rTMS) is thought to restore functions impaired during the stroke process and improve the quality of life of stroke patients. However, the efficacy of rTMS in treating post-stroke function impairment varies significantly. Therefore, we conducted a meta-analysis of the number of patients with effective rTMS in treating post-stroke dysfunction. The PubMed, Embase, and Cochrane Library databases were searched. Screening and full-text review were performed by three investigators. Single-group rate meta-analysis was performed on the extracted data using a random variable model. Then subgroup analyses were performed at the levels of stroke acuity (acute, chronic, or subacute); post-stroke symptoms (including upper and lower limb motor function, dysphagia, depression, aphasia); rTMS stimulation site (affected side, unaffected side); and whether or not it was a combination therapy. We obtained 8955 search records, and finally 33 studies (2682 patients) were included in the meta-analysis. The overall analysis found that effective strength (ES) of rTMS was 0.53. In addition, we found that the ES of rTMS from acute/subacute/chronic post-stroke was 0.69, 0.45, and 0.52. We also found that the ES of rTMS using high-frequency stimulation was 0.56, while the ES of rTMS using low-frequency stimulation was 0.53. From post-stroke symptoms, we found that the ES of rTMS in sensory aspects, upper limb functional aspects, swallowing function, and aphasia was 0.50, 0.52, 0.51, and 0.54. And from the site of rTMS stimulation, we found that the ES of rTMS applied to the affected side was 0.51, while the ES applied to the unaffected side was 0.54. What's more, we found that the ES of rTMS applied alone was 0.53, while the ES of rTMS applied in conjunction with other therapeutic modalities was 0.53. By comparing the results of the data, we recommend rTMS as a treatment option for rehabilitation of functional impairment in patients after stroke. We also recommend that rehabilitation physicians or clinicians use combination therapy as one of the options for patients.

The Promise, Mystery, and Perils of Stenting for Symptomatic Internal Jugular Vein Stenosis: A Case Series.

Cerebral venous outflow disorders (CVDs) secondary to internal jugular vein (IJV) stenosis are becoming an increasingly recognized cause of significant cognitive and functional impairment in patients. There are little published data on IJV stenting for this condition. This study aims to report on procedural success. A single-center retrospective analysis was performed on patients with CVD that underwent IJV stenting procedures. From 2019 to 2023, 29 patients with CVD underwent a total of 33 IJV stenting procedures. Most patients (20; 69%) had an underlying connective tissue disorder diagnosis. The mean age of the included patients was 36.3 years (SD 12.4), 24 were female (82.8%), and all were Caucasian except for 2 patients (27; 93.0%). Twenty-eight procedures (85%) involved isolated IJV stenting under conscious sedation, whereas 5 procedures (15%) involved IJV stenting and concomitant transverse sinus stenting under general anesthesia. Thirteen (39%) patients underwent IJV stenting after open IJV decompression and styloidectomy. Three patients had stents placed for stenosis below the C1 tubercle, one of which was for carotid compression. Periprocedural complications occurred in 11 (33%), including intracardiac stent migration in 1 patient, temporary shoulder pain/weakness in 5 (15%), and persistent and severe shoulder pain/weakness in 2 patients (6%). Approximately 75% of patients demonstrated improvement after stenting although only 12 patients (36%) had durable improvement over a mean follow-up of 4.5 months (range 6 weeks-3.5 years). Our experience, along with early published studies, suggests that there is significant promise to IJV revascularization techniques in these patients; however, stenting carries a high complication rate, and symptom recurrence is common. Most neurointerventionalists should not be performing IJV stenting unless they have experience with these patients and understand technical nuances (stent sizing, anatomy, patient selection), which can maximize benefit and minimize risk.

Symptoms and functional impairments in patients with Internet Use Disorders participating in an online short-term therapy

BackgroundInternet use disorders (IUD) have been recognized as a serious mental health concern. In order to promote consensus on core features of IUD, further studies involving clinical samples are required. AimsA clinical evaluation of patients with IUD was conducted as part of the scientific monitoring of a novel online short-term therapy, embedded in the randomized controlled trial Stepped Care Approach for Problematic Internet use Treatment (SCAPIT; ID: DRKS00025994). MethodsAn online diagnostic and a clinical assessment were performed at the baseline measurement of the online intervention. The self-report version of the Assessment of Internet and Computer Game Addiction (AICA-S) was applied to assess symptom severity of IUD. The impact of psychopathological symptoms and impairments of functioning on IUD symptomatology was examined in the sample of patients. Based on a dichotomous classification of the symptom severity of IUD, differences among participants presenting moderate compared to severe addictive Internet behavior were analyzed. ResultsThe sample of this an analysis consisted of 57 patients (57.9% males, mean age of 29.12 years) participating in the online short-term therapy for IUD. Based on the AICA-S sum score (M = 11.60; SD = 3.30) participants exhibited moderate (n = 44; 77.2%) to severe (n = 13; 22.8%) symptoms of addictive Internet use. Psychopathological symptoms and impairments of psychosocial functioning had an effect on symptom severity of IUD. Participants with severe symptoms of IUD showed higher psychopathological strains compared to patients with moderate addictive Internet behavior. ConclusionsThe clinical evaluation of patients participating in a novel online short-term therapy for IUD indicated that psychopathological symptoms and impairments of functioning have an impact on addictive Internet behaviors and consequently, need to be addressed in the treatment of IUD. Based on the results, further implications for clinical practice and research on addictive Internet behavior are derived.

Graph modeling of relational structures among functioning variables with low back pain: an exploratory analysis based on international classification of functioning, disability and health.

Given the complex etiology, multidimensional impact, and widespread prevalence of low back pain (LBP), it is crucial to prioritize intervention targets based on understanding the relationships between functional impairments in patients. This prioritization maximizes the physical and psychological benefits for patients, and graph modeling holds promise in achieving these objectives. The aim of this study was establishing a graphical model of functioning variables for LBP based on the International Classification of Functioning, Disability, and Health (ICF) to identify the most influential items (i.e., functioning variables) on the physical and mental well-being of patients. Exploring feasible intervention measures by understanding the dysfunction correlations among these variables. Cross-sectional survey. Nine hospitals in Jiangsu Province, China. Three hundred and six persons with LBP aged ≥18 years. All patients were assessed using the Comprehensive ICF Core Sets for LBP. The scoring system was converted to dichotomous data, with 1 indicating dysfunction and 0 indicating no dysfunction. In the graphical model, network parameters and the results of Item Response Theory modeling (as detailed in our other article) were used to determine the importance of items, while partial correlations were utilized to estimate the dysfunction correlations between functioning variables. 1) A total of 56 ICF items were located in the backbone structure of LBP, among which d430 (Lifting and carrying objects) occupied the most central position, followed by b126 (Temperament and personality functions). 2) In the main component of backbone structure, d430 has moderate dysfunction correlation with looking after one's health (0.6027), social norms, practices and ideologies (0.597), stability of joint functions (0.5759), and emotional functions (0.4078). b126 has moderate dysfunction correlation with basic interpersonal interactions (0.6595). d430 and b126 significantly impact the physical and mental well-being of LBP patients. To improve d430, maintaining exercise habits, reducing working hours, enhancing lumbar stability, and overcoming fear-related emotions are recommended. Similarly, improving b126 can be achieved through enhancing interpersonal relationships. Through the identification of crucial functioning variables and the associated dysfunctional correlation relationships, graphical model of Comprehensive ICF Core Set for LBP can offer healthcare decision-makers valuable insights into potential treatment targets and pathways aimed at improving the condition of LBP patients.

Diagnosis of multiple sclerosis using optical coherence tomography supported by explainable artificial intelligence.

Study of retinal structure based on optical coherence tomography (OCT) data can facilitate early diagnosis of relapsing-remitting multiple sclerosis (RRMS). Although artificial intelligence can provide highly reliable diagnoses, the results obtained must be explainable. The study included 79 recently diagnosed RRMS patients and 69 age matched healthy control subjects. Thickness (Avg) and inter-eye difference (Diff) features are obtained in 4 retinal layers using the posterior pole protocol. Each layer is divided into six analysis zones. The Support Vector Machine plus Recursive Feature Elimination with Leave-One-Out Cross Validation (SVM-RFE-LOOCV) approach is used to find the subset of features that reduces dimensionality and optimises the performance of the classifier. SVM-RFE-LOOCV was used to identify OCT features with greatest capacity for early diagnosis, determining the area of the papillomacular bundle to be the most influential. A correlation was observed between loss of layer thickness and increase in functional disability. There was also greater functional deterioration in patients with greater asymmetry between left and right eyes. The classifier based on the top-ranked features obtained sensitivity = 0.86 and specificity = 0.90. There was consistency between the features identified as relevant by the SVM-RFE-LOOCV approach and the retinotopic distribution of the retinal nerve fibres and the optic nerve head. This simple method contributes to implementation of an assisted diagnosis system and its accuracy exceeds that achieved with magnetic resonance imaging of the central nervous system, the current gold standard. This paper provides novel insights into RRMS affectation of the neuroretina.

Association between paraspinal muscle fat infiltration and regional kyphosis angle in thoracolumbar fracture patients: a retrospective study

This study aims to evaluate the impact of percutaneous pedicle screw fixation (PPSF) and open pedicle screw fixation (OPSF) on the postoperative paraspinal muscle fat infiltration (FI) rate in patients with thoracolumbar fractures through magnetic resonance imaging (MRI), and explore the association between paraspinal muscle FI rate and regional kyphosis angle. We retrospectively analyzed clinical data from 35 patients who underwent either PPSF or OPSF for thoracolumbar fractures, examining data at preoperative, 1-month postoperative, and 9-months postoperative time points, which included Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and regional kyphosis angle. We obtained preoperative and 9-month postoperative paraspinal muscle FI rates using T2-weighted MRI images and ImageJ software. We analyzed the correlation of FI rates with VAS, ODI, as well as the correction loss percentage of regional kyphosis angle. The analysis revealed a positive correlation between postoperative FI rate increase and correction loss percentage of regional kyphosis angle (r = 0.696, p < 0.001). The increase in paraspinal muscle FI rate was positively correlated with 9-month postoperative ODI (r = 0.763, p < 0.001). These findings indicate that an increase in postoperative paraspinal muscle FI rate may result in more significant correction loss of regional kyphosis angle and can lead to increased functional impairment in patients.

Risk Factors of the Progression of Renal Function Deterioration Among Patients with Diabetic Nephropathy

Objective: To explore the risk factors for the progression of renal function deterioration in patients with diabetic nephropathy (DN). Methods: The clinical data and biochemical indexes of 100 diabetic patients admitted to our hospital from October 2021 to October 2022 were retrospectively analyzed. The patients were divided into a DN group, which consisted of 55 cases, and a nondiabetic nephropathy group (NDN), which consisted of 45 cases. The urinary microalbumin to creatinine ratio, the clinical data (gender, age, duration of the disease, and BMI), and the biochemical indexes (triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], glycated hemoglobin A1c [HbA1c], systolic blood pressure [SBP], diastolic blood pressure [DBP]) of the two groups were compared. Subsequently, the risk factors related to the progression of renal function deterioration in DN were analyzed through multifactorial logistic regression analysis. Results: No statistically significant difference was observed in the comparison of gender, age, BMI, LDL-C, and DBP between the two groups (P &gt; 0.05). The DN group demonstrated a longer disease duration and higher SBP, TC, HDL-C, HbA1c, and TG compared to the NDN group (P &lt; 0.05). Through multifactorial logistic regression analysis, it was found that the duration of the disease, the TC, the HDL-C, the HbA1c, the TG, and the SBP were independent risk factors of the deterioration of renal function in DN patients. Conclusion: Other than conventional indicators, TC, HDL-C, HbA1c, TG, and SBP are also crucial indicators in determining the progression of renal function deterioration in DN patients.

Correlation between electrodiagnostic severity and Boston carpal tunnel questionnaire in surgically treated carpal tunnel syndrome patients.

The objectives of this study were to (1) investigate whether electrodiagnostic (EDX) findings reflect the preoperative symptom severity and functional impairment in patients with carpal tunnel syndrome (CTS) and (2) evaluate the relationship between EDX findings and the clinical outcomes reported according to the self-administered patient questionnaires. Patients diagnosed with idiopathic CTS who underwent carpal tunnel release between May 2016 and July 2018 were included. Carpal tunnel syndrome was clinically diagnosed and confirmed based on the EDX findings. The association between EDX findings, such as motor latency, motor amplitude, sensory latency, sensory amplitude, and severity (mild, moderate, and severe), and the Boston symptom and function scores were analyzed. The change in the Boston symptom and function scores from the preoperative baseline values (visit 1) to those recorded 1 year postoperatively (visit 5) was assessed. The effect of disease severity based on the EDX findings on the change in Boston symptom and function scores by visit was also investigated. The EDX severity, motor latency, motor amplitude, sensory latency, and sensory amplitude were not correlated with the Boston symptom and function scores preoperatively and postoperatively. Electrodiagnostic severity did not affect the improvement in the Boston symptom and function scores recorded at each visit. We found no association between the EDX severity and perioperative Boston questionnaire scores, and the degree of improvement in patient symptoms and function did not differ according to the CTS severity based on the EDX findings. Level IV, Prognostic study.

Mechanisms of Epigenetic Inheritance in Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that causes debilitating functional impairment in patients. Observations from survivors of traumatic historical events solidify that this disease is not only associated with personal experiences but can also be inherited from familial traumas. Over the past decades, researchers have focused on epigenetic inheritance to understand how responses to adverse experiences can be passed down to future generations. This review aims to present recent findings on epigenetic markers related to PTSD and research in the intergenerational inheritance of trauma. By understanding the information, we hope that epigenetic markers can act as biochemical measurements for future clinical practice.

Integrated Diffusion Tensor Imaging and Renal Parenchymal Volume for Early Detection and Grading of Split Renal Functional Impairment in Lupus Nephritis

To investigate the effectiveness of combining split diffusion tensor imaging (DTI) measurements with split renal parenchymal volume (RPV) for assessing split renal functional impairment in patients with lupus nephritis (LN). Seventy-four participants [48 LN patients and 26 healthy volunteers (HV)] were included in the study. All participant underwent conventional MR and DTI (b = 0, 400, and 600s/mm2) examinations using a 3.0T MRI scanner to determine the split renal DTI measurements and split RPV. In LN patients, renography glomerular filtration rate (rGFR) was measured using 99mTc-DTPA scintigraphy based on Gates' method, serving as the reference standard to categorize all split kidneys of LN patients into LN with mild impairment (LNm, n=65 kidneys) and LN with moderate to severe (LNms, n=31 kidneys) groups according to the threshold of 30ml/min in spilt rGFR. All statistical analyses were performed using SPSS 25.0 and MedCalc 20.0 software packages. Only split medullary fractional anisotropy (FA) and the product of split medullary FA and RPV could distinguish pairwise subgroups among the HV and each LN subgroup (all p<0.05). ROC curve analysis demonstrated that split medullary FA (AUC=0.866) significantly outperformed other parameters in differentiating HV from LNm groups, while the product of split medullary FA and split RPV was superior in distinguishing LNm and LNms groups (AUC=0.793) than other parameters. The combination of split medullary FA and split RPV showed best correlation with split rGFR (r=0.534, p<0.001). Split medullary FA, and its combination with split RPV, are valuable biomarkers for detecting early functional changes in renal alterations and predicting disease progression in patients with LN.

Effect of Tyrosine Kinase Inhibitor Therapy on Estimated Glomerular Filtration Rate in Patients with Chronic Myeloid Leukemia

IntroductionThe advent of tyrosine kinase inhibitors (TKIs) was revolutionary in the management of chronic myeloid leukemia (CML). Although TKIs were generally considered to be safe, they can be associated with renal injury. We evaluated the effect of TKIs on renal functions in a cohort of patients with long-term follow-up. Material and MethodsWe retrospectively examined patients with chronic phase CML treated with TKIs. We analyzed the estimated glomerular filtration rate (eGFR) of patients from the initiation of TKI to the last follow-up. eGFR values of CML patients were compared to those of patients with stage 1 or 2 chronic kidney disease (CKD). ResultsA total of 195 patients with CML and 138 patients with CKD were examined. eGFR decline was 1.556 ml/min/1.73m2/year for patients with CML (P = .221). Patients receiving second-generation TKIs (2GTKI) were estimated to have 0.583 ml/min/1.73m2 higher eGFR value than that of the imatinib group, but it was not significant (P = .871). eGFR of patients who had used bosutinib had a downward trend. Duration of TKI therapy, age, and hypertension were found to be significant factors in eGFR decline for CML patients. Lower baseline GFR was associated with an increased risk of CKD development. ConclusionImatinib could result in a decline in eGFR which was clinically similar to early-stage CKD patients. We did not observe significant kidney function deterioration in patients receiving 2GTKIs including dasatinib and nilotinib. We recommend close renal function monitoring in patients receiving imatinib, especially for elderly patients with lower baseline eGFR and hypertension.

Identifying clusters of objective functional impairment in patients with degenerative lumbar spinal disease using unsupervised learning

ObjectivesThe five-repetition sit-to-stand (5R-STS) test was designed to capture objective functional impairment (OFI), and thus provides an adjunctive dimension in patient assessment. It is conceivable that there are different subsets of patients with OFI and degenerative lumbar disease. We aim to identify clusters of objectively functionally impaired individuals based on 5R-STS and unsupervised machine learning (ML).MethodsData from two prospective cohort studies on patients with surgery for degenerative lumbar disease and 5R-STS times of ≥ 10.5 s—indicating presence of OFI. K-means clustering—an unsupervised ML algorithm—was applied to identify clusters of OFI. Cluster hallmarks were then identified using descriptive and inferential statistical analyses.ResultsWe included 173 patients (mean age [standard deviation]: 46.7 [12.7] years, 45% male) and identified three types of OFI. OFI Type 1 (57 pts., 32.9%), Type 2 (81 pts., 46.8%), and Type 3 (35 pts., 20.2%) exhibited mean 5R-STS test times of 14.0 (3.2), 14.5 (3.3), and 27.1 (4.4) seconds, respectively. The grades of OFI according to the validated baseline severity stratification of the 5R-STS increased significantly with each OFI type, as did extreme anxiety and depression symptoms, issues with mobility and daily activities. Types 1 and 2 are characterized by mild to moderate OFI—with female gender, lower body mass index, and less smokers as Type I hallmarks.ConclusionsUnsupervised learning techniques identified three distinct clusters of patients with OFI that may represent a more holistic clinical classification of patients with OFI than test-time stratifications alone, by accounting for individual patient characteristics.

Evidences and therapeutic advantages of donanemab in the treatment of early Alzheimer's disease.

The humanised monoclonal antibody donanemab is being developed to treat early onset Alzheimer's disease (AD). This drug targets N-truncated pyroglutamate amyloid-peptide at position 3 (N3pG), a modified form of deposited amyloid-peptide. The symptoms of Alzheimer's disease include gradual memory loss and other cognitive impairments. This disease is characterized by amyloid plaques, which are formed as a result of an accumulation of amyloid-(A-β) peptides. Despite granting donanemab breakthrough therapy designation in June 2021, the FDA rejected donanemab's accelerated approval application in January 2023, due to inadequate safety data. According to the baseline amyloid level, the time to achieve plaque clearance (amyloid plaque level <24.1 centiloids) varied. Patients with higher baseline levels were more likely to achieve amyloid clearance. The safety of the drug was demonstrated by amyloid-related imaging abnormalities (ARIA), which ranged from 26.1 to 30.5 % in the studies. Clinical trial results have shown that donanemab delays cognitive and functional deterioration in patients with mild to moderate AD. However, it is not yet known whether donenameb offers therapeutic benefits that can change and improve the clinical condition of AD patients. To achieve significant clinical benefits in AD patients with cognitive impairment, further studies may be needed to investigate the interaction between A-β plaque reduction and toxic tau levels.

Upper Extremity Functional Outcomes After Breast Cancer Treatment: An Analysis of DASH Score in Breast Reconstruction Patients.

Patients undergoing postoncologic breast reconstruction can experience upper extremity (UE) functional deficits. In this study, we utilized the disabilities of the arm, shoulder, and hand (DASH) questionnaire to identify patient factors that impacted UE functional recovery. Patients who underwent oncologic followed by reconstructive surgery by a single surgeon from 2014 to 2019 and completed the DASH survey were included. A DASH score was calculated for each patient, with values ranging from 0 (no impairment) to 100 (severe impairment). Regression analysis was conducted to identify significant predictors for DASH score with a significance level for entry and stay set at P = .15. Among 289 patients who underwent breast reconstruction, 157 completed the questionnaire. The average patient age was 52.6yrs ± 8.6 at the time of reconstruction. A total of 111 had implant-based reconstruction, 15 had autologous reconstruction, and 24 had a combination of both. Average DASH score was 7.7 (range 0.0-52.5), with 74.1% of patients having a score greater than 0. Regression analysis showed 5 variables associated with significantly higher DASH scores: age between 50 and 60 years (P = .13), history of radiation (P = .01), placement of a subpectoral implant (P = .06), postoperative complications (P = .10), and lymphedema (P < .01). Autologous breast reconstruction (P = .04) was associated with a significantly lower DASH score. Implant-based reconstruction, radiation history, postoperative complications, and age at reconstruction were associated with increased UE functional impairment in patients who underwent breast reconstructive surgery. Identification of these factors can inform areas for potential practice changes and improve patient counseling regarding postoperative expectations.