Disease Patients Research Articles

The impact of photobiomodulation on sleep and life quality in hemodialysis patients: A randomized controlled trial.

The quality of life (QoL) and sleep quality are closely linked to the physical and psychological health of end-stage renal disease (ESRD) patients, especially those underwent hemodialysis (HD) therapy. This study aims to investigate the impact of 830nm laser treatment on improving QoL and sleep quality in HD patients. Forty ESRD patients participated in this study. 830nm laser was used to radiate on the palm (at dose of 256.10J/cm2), ST 36 and KI 1 acupoints (at dose of 109.76J/cm2) of HD patients, and QoL and sleep quality questionnaires were utilized to assess changes following the treatment. After 830nm laser radiation, lower global Pittsburgh Sleep Quality Index and Athens Insomnia Scale scores were observed, accompanied by higher physical and mental component summary scores in MOS 36-item short-form health survey version 2 and a global World Health Organization Quality of Life Brief Version score. The laser group also showed significant improvements in QoL and sleep quality indicators. Additionally, pain levels decreased on the third day and after one month according to visual analogue scale. This study revealed the positive effects of 830nm laser on palm, KI 1 and ST 36 acupoints for improving the QoL and sleep quality in ESRD patients underwent HD treatment. The results suggest that 830nm laser applied to specific targets could be used as a complementary and alternative approach to increase the QoL and sleep quality in ESRD patients.

Macrophages as a Source and Target of GDF-15.

Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in cancer172 and metabolic and cardiovascular disorders. Despite these clinical associations, the molecular mechanisms orchestrating its effects remain to be elucidated. The effects of GDF-15 are pleiotropic but cell-specific and dependent on the microenvironment. While GDF-15 expression can be stimulated by inflammatory mediators, its predominant effects were reported as anti-inflammatory and pro-fibrotic. The role of GDF-15 in the macrophage system has been increasingly investigated in recent years. Macrophages produce high levels of GDF-15 during oxidative and lysosomal stress, which can lead to fibrogenesis and angiogenesis at the tissue level. At the same time, macrophages can respond to GDF-15 by switching their phenotype to a tolerogenic one. Several GDF-15-based therapies are under development, including GDF-15 analogs/mimetics and GDF-15-targeting monoclonal antibodies. In this review, we summarize the major physiological and pathological contexts in which GDF-15 interacts with macrophages. We also discuss the major challenges and future perspectives in the therapeutic translation of GDF-15.

O-234 Indication for fertility preservation in patients with endometriosis

Abstract Endometriosis is a complex gynecological condition that not only causes debilitating symptoms but also significantly impacts fertility. As the disease affects approximately 10% of women of reproductive age, addressing fertility preservation strategies becomes paramount. The conventional treatments for endometriosis, such as medical therapy and surgery, often fail to fully address its adverse effects on ovarian reserve and reproductive potential. Consequently, there is a growing interest in exploring fertility preservation options, particularly oocyte cryopreservation (OOC), for endometriosis patients. Despite the prevalence and impact of endometriosis on fertility, comprehensive data and guidelines specifically tailored to fertility preservation in this population remain scarce. The available evidence suggests that endometriosis, particularly when it involves ovarian endometriomas, is associated with a significant reduction in ovarian reserve, as indicated by lower levels of anti-Müllerian hormone (AMH). Surgical interventions, often necessary for managing endometriosis-related complications, can further compromise ovarian function and diminish fertility prospects. However, recent studies have shed light on the potential benefits of OOC in preserving fertility for endometriosis patients. OOC offers a minimally invasive approach with no impact on ovarian reserve compared to other fertility preservation techniques. Despite the lack of randomized controlled trials, our retrospective data have demonstrated promising outcomes, with a notable number needed to treat (NNT) of 16 for one successful pregnancy. This underscores the significance of discussing and considering OOC as part of the treatment plan for endometriosis patients, especially those at risk of ovarian compromise due to the disease or its management. The decision to pursue fertility preservation through OOC should be made on a case-by-case basis, taking into account various factors such as disease severity, patient age, ovarian reserve, and treatment history. French guidelines recommend considering OOC for endometriosis patients with bilateral ovarian endometriomas larger than 3 cm or those with endometriomas on a single ovary. Initiating fertility preservation discussions early, preferably before surgical intervention, allows patients to make informed decisions regarding their reproductive future. It is crucial to acknowledge the challenges and uncertainties associated with fertility preservation in endometriosis patients. Socio-economic factors, patient preferences, and the lack of clear criteria for selecting candidates for OOC pose significant hurdles. Furthermore, the effectiveness and cost-effectiveness of OOC in this population warrant further investigation. In addition to OOC, alternative fertility preservation options, such as ovarian tissue preservation, could be considered, particularly in cases where ovarian stimulation is not feasible or declined by the patient. However, data on the efficacy and safety of ovarian tissue preservation specifically in endometriosis patients are limited, highlighting the need for further research in this area. In conclusion, fertility preservation, particularly through OOC, holds promise for mitigating the adverse effects of endometriosis on ovarian function and fertility. While uncertainties persist, integrating fertility preservation discussions into the comprehensive management of endometriosis is essential. This ensures that patients are empowered to make informed decisions about their reproductive health and maximizes their chances of achieving desired fertility outcomes despite the challenges posed by endometriosis.

Percutaneous Pharmacological Thrombolysis as an Effective Primary Mode of Management of Thrombosed Prosthetic Arterio-Venous Grafts

Abstract Background Thrombosis of prosthetic arterio-venous graft (PAVG) is the most common cause of failure of using this access for haemodialysis (HD) in end stage kidney disease (ESKD) patients. Many different open surgical and vascular techniques were described to restore the function of thrombosed PAVG. Objectives We wanted to assess the feasibility and patency rates following the continuous thrombolysis infusion using tissue Plasminogen Activator (tPA) followed by angiogram and angioplasty of stenotic segment(s) in thrombosed PAVG. Methods We performed retrospective analysis of prospectively collected data from patients who had a thrombosed AVG from January 2020 to January 2022. Thrombolysis took place maximum 7 days after thrombosis was diagnosed. We have excluded patients who were referred to us more than a week after thrombosis occurred and patients with relative or absolute contraindication for thrombolysis and/or anticoagulation. Results During the two years of the study, there were 58 patients referred to our centre with thrombosed PAVG. We have excluded 28 patients who didn’t fulfill inclusion criteria. We have performed PAVG continuous thrombolysis infusion using tPA till we have achieved reopening of the thrombosed PAVG followed by angiography and angioplasty. All patients had venous anastomosis stenosis while 17 patients had stenosis in the graft and only 5 had a stenosis at the arterial anastomosis. During the period of follow up primary patency was achieved in 80% of our patients while our primary assisted patency was 86.67% Conclusions Endovascular tPA thrombolysis for early thrombosis of prosthetic AVAs is feasible, safe, and is associated with an excellent technical success and very good 12 months patency rate.

Effect of Central Dialysis Fluid Delivery System (CDDS) using high flux dialyzer versus Regular Water Treatment Stations on Endotoxemia and Inflammatory Markers among Prevalent Patients on Regular Hemodialysis

Abstract Background and Objectives Translocated endotoxins derived either from intestinal bacteria or backfiltration, have a wide range of adverse effects on patients. Most end stage renal disease (ESRD) patients have systemic inflammation which increases the risk of morbidity and mortality. The central dialysis fluid delivery system (CDDS) has been used exclusively in Japan since 1960s, and now is being used in Ain Shams University. Our aim of the study is to evaluate the effect of (CDDS) versus single patient dialysis fluid delivery system (SPDDS) on endotoxemia and inflammatory markers among prevalent patients on regular hemodialysis (HD). Methods Eighty Patients were randomly selected from HD units, then divided into two groups, (group I) doing HD using CDDS water purification system at El Demerdash Hospital, (group II) using regular water purification system at Ain Shams University Specialized Hospital. Pre- dialysis and post-dialysis serum samples were obtained to measure endotoxin levels of both groups, as well as postdialysis serum samples were obtained to measure interleukin 6 (IL6) level and highly sensitive Creactive protein (Hs CRP). Results Circulating endotoxemia was most notable in group II, The mean predialysis endotoxin level in group I was 0.07 ± 0.05 Eu/mL, while in group II was 0.20 ± 0.07 Eu/mL and mean of post-dialysis endotoxin level in group I was 0.04 ± 0.02 Eu/mL, while in group II was 0.15 ± 0.03 Eu/mL. IL6 as well as Hs CRP levels were higher in group II in comparison to group I. Conclusion Our data showed significant reduction in circulating endotoxins in CDDS group.

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.

Time-encoded ASL reveals lower cerebral blood flow in the early AD continuum.

Cerebral blood flow (CBF) is reduced in cognitively impaired (CI) Alzheimer's disease (AD) patients. We checked the sensitivity of time-encoded arterial spin labeling (te-ASL) in measuring CBF alterations in individuals with positive AD biomarkers and associations with relevant biomarkers in cognitively unimpaired (CU) individuals. We compared te-ASL with single-postlabel delay (PLD) ASL in measuring CBF in 59 adults across the AD continuum, classified as CU amyloid beta (Aβ) negative (-), CU Aβ positive (+), and CI Aβ+. We sought associations of CBF with biomarkers of AD, cerebrovascular disease, synaptic dysfunction, neurodegeneration, and cognition in CU participants. te-ASL was more sensitive at detecting CBF reduction in the CU Aβ+ and CI Aβ+ groups. In CU participants, lower CBF was associated with altered biomarkers of Aβ, tau, synaptic dysfunction, and neurodegeneration. CBF reduction occurs early in the AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF changes in AD. Lower CBF can be detected in CU subjects in the early AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF alterations in AD. CBF is linked to biomarkers of AD, synaptic dysfunction, and neurodegeneration.

A Potential Role for MAGI-1 in the Bi-Directional Relationship Between Major Depressive Disorder and Cardiovascular Disease.

Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption. Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease,ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.

Risk Predictors of Severity in Egyptian Patients with Covid-19 Infection

Abstract Background In modern human history, infectious diseases have posed a threat to public health several times, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a global public health crisis. Objective Identification of demographic, laboratory and radiological predictors of progression of COVID-19 infection in Egyptian patients. A special concern is focused on the poor prognostic factors associated with mortality, this will help to classify and monitor COVID-19 patients to deliver best medical care in order to decrease mortality and morbidity in Egyptian patients. Patients and Methods A single-center, retrospective cohort study. This study was conducted in Almaza Fever Hospital after obtaining approval from the Research Ethical Committee. Results The current study conducted on (325) known positive COVID-19 patients divided into 2 groups: Group I (204) patients and Group II (121) patients. It was found that an increase in age among Group II (mean age was 66.22 ± 12.18) in comparison to Group I (mean age was 47.78 ± 14.73) with a statistically significant difference (p-value <0.001). There was no statistically significant difference (p-value 0.432) between Sex and severe disease patients. Among Group II (121) out of the total study population 103 (85%) of these were found to have co-morbidities (highly significant, p value < 0.001. Moreover, there was a higher prevalence of co-morbidities among non survivors however this didn’t reach the level of statistical significance (p-value 0.174). The current study showed that there was an increase in hematological parameters (TLC, Neutrophils), biochemical parameters (Urea, Creatinine, AST, D-Dimer, Ferritin, CRP, LDH, IL-6) and a decrease in Lymphocytes within Group II in comparison with Group I with statistically Significant difference (p-value < 0.001), also there was a trend toward higher levels of ALT in group II, however this didn’t reach the level of statistical significance (p-value 0.068). Statistically significant difference (p-value < 0.001) was found between disease severity and CT findings as from a total of (121) severe disease patients 105(86.8%) had CORADS (4-5). Conclusion The current study shows old age, elevated biochemical parameters (creatinine, urea, AST, D-dimer, IL-6, CRP, ferritin and LDH), hematological parameters (TLC) and extensive lung affection could be considered predictors of severity and mortality among Covid-19 patients. Also lymphopenia and associated co-morbidities are considered predictors of severity.

Evaluation of Thyroid functions in Patients with End Stage Renal Disease in a Sample of Egyptian Populations

Abstract Background In most cases, hypothyroidism is not linked to kidney disease. However, hypothyroidism has been shown to hasten the development of chronic kidney disease (CKD). Aim of the Work to evaluate thyroid abnormalities in patients with end stage renal disease in a sample of Egyptian populations. Patients and Methods This study was conducted with 70 Egyptian Patients selected from Nephrology department in Theodor Bilharz Research Institute, in a case control study, they were categorized into 2 groups Group 1: Stage V renal disease group (n = 40): patients with eGFR <15 mL/min with no history of thyroid disease or receiving any thyroid medications. Group 2: Age and sex matched health population group (n = 30): with normal renal function with no history of thyroid disease or receiving any thyroid medications. All subjects underwent full thyroid profile, and estimated GFR. Results Symptoms of thyroid dysfunction were more frequent in end stage group, the difference statistically were significant only in muscle weakness. TSH was statistically significantly higher in cases with hypothyroidism. TGABs were statistically significantly higher in cases with hypothyroidism. Antimicrosomal antibodies recorded only in hypothyroid cases, the differences were statistically significant. FT3, TSH, TGABs and thyroid volume statistically had perfect diagnostic performance in diagnosing hypothyroidism among end stage renal disease group. Conclusion Frequency of hypothyroidism was higher in end stage renal disease patients compared to control group. So, it is important to keep monitoring thyroid functions in patients with advanced renal impairment that may enhance quality of life.

Carotid Intima-Media Thickness as a Cardiovascular Risk Factor in Patients with Chronic Kidney Disease

Abstract Background Atherosclerosis is a systemic arterial disease which frequently involve multiple vascular beds. Etiologically, cases of atherosclerosis occurring in different arterial vascular beds may share the same set of traditional risk factors. Aim of the Work In this present study we aimed to- evaluate the effect of chronic kidney disease on carotid intima media thickness as a cardiovascular risk factor in these patients. Patients and Methods This is a Case-control study conducted at Ain shams university hospitals during the period between January 2022 and June 2022. Results We found that patients with chronic kidney disease had significantly higher values of carotid intima media thickness (mean value of 1.10± 0.16 mm) versus control group (mean value of 0.49± 0.15mm).Also we noticed that with progression of kidney disease carotid intima media thickness (CIMT) becomes higher.CIMT showed a trend of gradual increase with decreased eGFR.Also we found that CIMT correlated positively with age, blood pressure, serum reatinine, urea and total cholesterol, but negatively with eGFR and we found that patients with diabetes and hypertension had CIMT higher than patients without diabetes and hypertension.The ROC curve analysis showed that the AUC for using eGFR cut off value of ≤ 75 mL/min for predicting CIMT thickness (>0.7 mm) was 1.And both the specificity and Sensitivity of eGFR in predicting CIMT thickening to be 100%. Conclusion Carotid IMT is significantly increased in Chronic kidney disease patients and may be usefully applied for risk stratification in this group of patients.Our study shows that, eGFR (≤ 75ml/min) has a positive predictive value for CIMT thickness(>0.7mm) with specificity and sensitivity 100%.

Highly Sensitive Room-Temperature Detection of Ammonia in the Breath of Kidney Disease Patients Using Fe2Mo3O8/MoO2@MoS2 Nanocomposite Gas Sensor.

A novel Fe2Mo3O8/MoO2@MoS2 nanocomposite is synthesized for extremely sensitive detection of NH3 in the breath of kidney disease patients at room temperature. Compared to MoS2, α-Fe2O3/MoS2, and MoO2@MoS2, it shows the optimal gas-sensing performance by optimizing the formation of Fe2Mo3O8 at 900°C. The annealed Fe2Mo3O8/MoO2@MoS2 nanocomposite (Fe2Mo3O8/MoO2@MoS2-900°C) sensor demonstrates a remarkably high selectivity of NH3 with a response of 875% to 30ppm NH3 and an ultralow detection limit of 3.7 ppb. This sensor demonstrates excellent linearity, repeatability, and long-term stability. Furthermore, it effectively differentiates between patients at varying stages of kidney disease through quantitative NH3 measurements. The sensing mechanism is elucidated through the analysis of alterations in X-ray photoelectron spectroscopy (XPS)signals, which is supported by density functional theory (DFT) calculations illustrating the NH3 adsorption and oxidation pathways and their effects on charge transfer, resulting in the conductivity change as the sensing signal. The excellent performance is mainly attributed to the heterojunction among MoS2, MoO2, and Fe2Mo3O8 and the exceptional adsorption and catalytic activity of Fe2Mo3O8/MoO2@MoS2-900°C for NH3. This research presents a promising new material optimized for detecting NH3 in exhaled breath and a new strategy for the early diagnosis and management of kidney disease.

Renoprotective Effect of Febuxostat on Contrast Induced Acute Kidney Injury in Chronic Kidney Disease Patients Stage 3. Randomized Controlled Trial

Abstract Introduction Contrast induced acute kidney injury (CI-AKI) is known to be a complication of using intravascular contrast injection. Unfortunately, It is associated with adverse outcomes as prolonged length of hospitalization and increased burden of health care costs. So, we aimed to determine the efficacy of febuxostat in prevention of contrast induced acute kidney injury among patients with chronic kidney disease Stage 3 performing percutaneous coronary intervention (PCI). Methods In a randomized controlled trial we enrolled 120 CKD stage 3 Patients with acute coronary syndrome referred to the cardiology department Ain-Shams University hospital for performing PCI and stenting. Patients were randomly assigned to two arms: Group I (study group): Included 60 patients who received Febuxostat added to the traditional treatment (IV hydration and N-acetylcysteine). The patients received Feburic 80 mg within 6- 18 hours before and within 6-18 hours after the coronary intervention (a time gap of 24 hours between two doses).Group II (control group): included 60 patients who received only traditional treatment. Results The incidence of AKI was higher in the control group with a statistically significant difference. We found that Independent Significant risk factors that led to AKI were febuxostate avoidance, DM, high urea level, high creatinine level, CKD stage 3B, high Mehran score and high AKI risk. Conclusion We demonstrated that febuxostat has a renoprotective effect and it can help to reduce the incidence CI-AKI in CKD patients stage 3 performing PCI.

Motor improvement in Parkinson’s disease patients receiving caffeine adjuvants: A double-blind randomized controlled trial in Indonesia

Parkinson's disease (PD) manifests as a movement and brain function disorder characterized by symptoms such as resting tremors, rigidity, bradykinesia, and postural instability, leading to disability among patients. The use of psychostimulants such as caffeine has been associated with the improvement of motor symptoms in PD patients; however, studies regarding the effect of caffeine adjuvant therapy on motor function among PD patients in the Indonesian population are lacking. The aim of this study was to evaluate motor improvement as measured by the change in scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) among PD patients receiving caffeine adjuvant. A double-blind randomized controlled trial (RCT) was conducted among PD patients at Dr. Soetomo General Academic Hospital and Universitas Airlangga Hospital, Surabaya, Indonesia, from April to August 2023. A total of 27 patients were enrolled and randomly assigned to an intervention (receiving caffeine adjuvant, n=15) and control group (receiving placebo, n=12). Motor improvement was measured using the UPDRS III score prior to intervention and three weeks after. The Chi-squared test was used to analyze the difference in UPDRS III scores between the two groups. Motor improvement, as demonstrated by a reduction in the UPDRS III score, was observed in patients receiving caffeine adjuvant compared to those receiving placebo (80.0% vs 16.7%; p=0.004). Regarding the safety profile, only four out of 15 (26.6%) patients treated with caffeine reported minor adverse events. These conditions improved over time during the intervention. None of the 12 patients in the placebo reported adverse events. This study provides valuable insights into the initial dosage of caffeine that improves motor function in PD patients with minimum adverse effects.

Comparative Study Evaluating the Effect of the Administration of Vitamin K1 versus Placebo on Vascular Calcification in Haemodialysis Patients

Abstract Background Cardiovascular calcification is a risk factor and contributor to morbidity and mortality in End stage kidney disease patients. Cardiovascular calcification is most likely due to an imbalance of promoters (e.g. Calcium and phosphate) and inhibitors (e.g. fetuin-A and matrix Gla protein). Aim of the Work We aimed to study the effect of oral vitamin k1 on serum carboxylated Matrix gla protein in patients on maintenance hemodialysis and to study its effect as an important marker of vascular calcification. Patients and Methods This Placebo Controlled clinical trial was conducted for 3 months on 80 adult ESRD patients on regular Hemodialysis randomly allocated into 2 groups of either vitamin K1 versus oral placebo tablet administration for 3 months. Patients in both groups were age and sex matched, study group included 18 (45%) males and 22 (55%) females with mean age ± SD 47.350 ± 14.420 years, while the placebo group included 16 (40%) males and 24 (60%) with mean age ± SD 49.500 ± 14.509 years, with no significant difference between both groups as regard demographic data, access of hemodialysis, and duration of Hemodialysis. Results There was no significant change in bone parameters (serum Ca, PO4 & Ca/PO4 product) after 3 months of vit K1 administration compared to baseline in the study group. Serum phosphorus levels showed a minimal, yet statistically significant decrease after 3 months of placebo administration, this might be attributed to the different doses of PO4 binders in patients of both groups. Consequently, Ca/ PO4 product showed a statistically significant decrease after 3 months of placebo administration (P = 0.002), mostly attributed to the significant decrease in serum phosphorus in the same group over the same period. We observed that serum MGP levels significantly increased after administration of vitamin k1 in study group (P < 0.001) with 78.05% increase. However, a much lower increase, yet statistically significant increase in serum MGP level was noticed in the placebo group (P < 0.001) with 40.60 % increase. There was no statistically significant difference between the two groups according to their risk factors regarding smoking, HTN, HCV, DM, and ISHD. Conclusion We concluded that Oral vitamin K1 therapy significantly increased serum active form of Matrix GLA protein levels among hemodialysis patients with potential decrease in cardiovascular calcification and cardiovascular diseases.

Evaluation of the Role of Serum Calprotectin in the Follow Up of Egyptian Inflammatory Bowel Disease Patients

Abstract Background The term inflammatory bowel disease (IBD) describes disorders in which the intestines be inflamed. It has often been thought that they are due to an autoimmune disease. Two major types of IBD are ulcerative colitis (UC) and Crohn's disease (CD). UC is limited to the colon. CD can involve every part of the gastrointestinal tract from the mouth to the anus. Objective To compare between serum and faecal calprotectin regarding their role in follow up of disease activity in inflammatory bowel disease patients. Patients and Methods An observational cross-sectional study was conducted on 25 patients admitted to Tropical medicine department, Ain Shams University Hospitals. Results Calprotectin is highly resistant to proteolysis and can hold in the stool sample for up to 7 days at room temperature. Higher levels of serum calprotectin were linked to a severe inflammatory state in the colon as well as significant clinical symptoms in UC patients. Also, serum calprotectin, CRP, and ESR levels were compared to IBD activity and it was detected that serum calprotectin levels had more sensitivity and specificity than CRP and ESR in identifying IBD activity. Serum calprotectin levels in patients with IBD activity either UC or CD groups, were considerably more than in remission. SC and FC levels were higher levels in clinically active IBD comparing with inactive IBD. Conclusion Serum calprotectin levels are higher in patients with IBD and are related to clinical activity. High serum calprotectin levels can distinguish between patients who are clinically active and those who are in remission in both UC and CD groups. Our findings show that serum calprotectin may be a promising simple diagnostic and prognostic biomarker for IBD however more research is needed to reach a judgment in this regard.

CD34+ Hematopoietic Stem Cell Count as a Novel Predictor of Vascular Event in Sickle Cell Disease Patients

Abstract Background Sickle cell disease (SCD) is one of the most common genetic disorders, it not only has hematological pathophysiological consequences, but also has systemic pathological manifestations such as vascular events (VEs). Prior studies have described that VEs are associated with poor outcomes in the short term and decreased quality of life in patients over the long term. There is no standardized method for predicting vascular injury in Sickle cell disease patients. Aim of the Work Our aim is to evaluate circulating CD34 as a novel predictive marker of occurrence of vascular event in Children with Sickle Cell Disease in their steady state and relate levels to severity of VEs in the following 6 months. Patient and Methods This study was an exploratory study, conducted at Pediatrics Hematology- Oncology Unit at Ain Shams University Children’s Hospital, where 50 children with sickle cell disease were enrolled at their steady state (defined as 2 months free from any Vascular Event prior to the study), aged 6 months - 16 years. Flow cytometry was done for quantification of circulating CD34+ at inclusion and compared to age and sex matched control and patients were followed up for 6 months for vascular events. Results There is statistically significant higher level of CD34+ among SCD patients compared to age and sex matched control with p value < 0.001.Circulating CD34+ showed significantly higher level in patients who developed systemic vascular events after 6 months of follow up with p value 0.022. There was no statistically significant correlation between circulating CD34+ and severity of peripheral vascular events (or any need for hospitalization) on follow up. Conclusion CD34+ cell count at steady state may be a promising biomarker of further vascular event in children with SCD.

Periostin as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease

BACKGROUND: Asthma and chronic obstructive pulmonary disease are common chronic respiratory diseases. Given their heterogeneity, the study of periostin is a relevant area for establishing the endotypes of airway inflammation and determining further therapy tactics. AIM: To evaluate periostin levels and determine its significance as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease. MATERIALS AND METHODS: The study included 59 patients with asthma and 33 patients with chronic obstructive pulmonary disease. The control group consisted of 37 apparently healthy people, comparable in age and sex, without allergic and bronchial obstructive diseases in anamnesis. The anamnesis data, the number of peripheral blood eosinophils and induced sputum, indices of external respiratory function were evaluated. Levels of specific immunoglobulin E to allergens, periostin level were determined in blood serum by immunoenzyme method. The obtained data were processed using STATISTICA 13 and SPSS Statistic 27 software systems. RESULTS: The maximum serum periostin concentration 22.5 (17–38) ng/ml was recorded in the patients with asthma, which was significantly higher than in the chronic obstructive pulmonary disease group [16 (12–21) ng/ml; p = 0.006] and control group [20.1 (14.6–24.8) ng/ml; p = 0.044]. The level of periostin in induced sputum in the patients with asthma was significantly higher than in the chronic obstructive pulmonary disease group — 0.05 (0.03–0.6) ng/ml vs 0.03 (0.02–0.04) ng/ml (p = 0.008). The study revealed the correlation between serum periostin level and eosinophil level (r = 0.406; p 0.05) and with forced expiratory volume in the first second after bronchodilator test (r = 0.366; p 0.05) as well as with forced expiratory volume in the first second divided by forced vital capacity after bronchodilator test (r = 0.572; p 0.05). CONCLUSIONS: Periostin is a promising marker of eosinophilic inflammation in patients with asthma, which can be considered as an indicator of fixed bronchial obstruction and a molecule linking T2-inflammation and airway remodelling. In a group of chronic obstructive pulmonary disease patients, the use of periostin for diagnostic and prognostic purposes requires further investigation and larger studies.

Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein.

There is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils. SPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds toward recombinant amyloid-beta (Aβ)42, K18-tau, full-length 2N4R-tau and αSyn fibrils. In silico modeling was performed to examine the binding pockets of ligands on αSyn fibrils. Immunofluorescence staining of postmortem brain tissue slices from Parkinson's disease patients and mouse models was performed with fluorescence ligands and specific antibodies. We optimized the protocol for the immobilization of Aβ42, K18-tau, full-length 2N4R-tau and αSyn fibrils in a controlled aggregation state on SPR-sensor chips and for assessing their binding to ligands. The SPR results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes, benzothiazole derivatives, nonfluorescent methylene blue and lansoprazole. In silico modeling studies for αSyn (6H6B) revealed four binding sites with a preference for one site on the surface. Immunofluorescence staining validated the detection of pS129-αSyn positivity in the brains of Parkinson's disease patients and αSyn preformed-fibril injected mice, 6E10-positive Aβ in arcAβ mice, and AT-8/AT-100-positivity in pR5 mice. SPR measurements of small molecules binding to Aβ42, K18/full-length 2N4R-tau and αSyn fibrils suggested the existence of multiple binding sites. This approach may provide efficient characterization of compounds for neurodegenerative disease-relevant proteinopathies.

Efficacy of Ustekinumab and Vedolizumab Among Postoperative Crohn's Disease Patients as Postoperative Prophylaxis and Rescue Therapy: Real-world Data.

Almost half of patients with Crohn's disease (CD) require bowel surgeries in their lifetime. Due to the high risk of postoperative disease recurrence and high rate of previous antitumor necrosis factor (anti-TNF) failure, often alternative therapy options such as ustekinumab (UST) and vedolizumab (VDZ) are used. We aimed to evaluate the efficacy of UST and VDZ among postoperative CD patients as postoperative prophylaxis and rescue therapy. Consented CD patients who underwent initial ileocecal resection and were treated with UST and VDZ were included in this study. Demographics, clinical characteristics, health care utilization, endoscopy scores, and surgery outcomes were collected. Postoperative early CD recurrence was defined as a Rutgeerts endoscopic score ≥i2 within the first 2 years. The rescue therapy group was defined as patients who received either UST or VDZ after having Rutgeerts endoscopic score ≥i2 postoperatively. During 2009 to 2019, 98 CD patients were treated with UST or VDZ postoperatively. Postoperative early recurrence rates were 5% (n = 1 out of 20) and 6% (1 out of 15) for the UST and VDZ groups, respectively. Two patients from the UST group and 1 patient from the VDZ group required bowel surgery during follow-up with median drug exposure of 51 (95% confidence interval [CI], 29-61) and 30 (95% CI, 14-63) months, respectively; 55% and 69% of patients had at least 1 point of improvement on postoperative endoscopic Rutgeerts score, respectively, for UST and VDZ. Only 3 out of 40 and 1 out of 23 patients required bowel surgery during follow-up while receiving UST and VDZ as rescue therapy. Both UST and VDZ were effective as postoperative therapies either as prophylaxis or rescue therapy.