Disease Patients Research Articles

Cerebral white matter damage in patients with end stage kidney disease associates with cognitive impairment

Abstract Background and hypothesis Damages in brain white matter often occurs in individuals with chronic kidney disease, which might be related to their cognitive decline. This study aims to investigate tract specific white matter damage in patients with end stage renal disease by using fixel based analysis. Methods Images of 31 end stage renal disease patients and 16 normal controls (aged: 61.1 ± 10.4 years; 11 men) were acquired from a 1.5 T MR scanner. The patients were subsequently divided into with normal cognition (N = 17, aged: 66.9 ± 7.2 years; 10 men) and cognitive impairment (N = 14, aged: 72.4 ± 9.4 years; 7 men). Cognitive assessment, neurologic, hematologic and biochemical samples were collected. Fixel-based analysis was used to examine the tract-specific damage within white matter. Differences between groups were evaluated through connectivity-based fixel enhancement and non-parametric permutation testing. Correlation with biomarkers was conducted through general linear model. Significance was determined with familywise error-corrected p-value < 0.05. Results Reduced fixel-based metrics were observed in specific tract located the cerebral peduncle, internal capsule, corpus callosum, fornix, and superior corona radiata in patients when compared to normal controls, indicating a reduction in fiber content. The fibers crossing the corpus callosum and the fornix/stria terminalis are particularly vulnerable sites, which can be associated with the decrease in both Mini-Mental State Examination (R2 ranged between 0.420 and 0.556) and Montreal Cognitive Assessment (R2 ranged between 0.425 and 0.509), as well as the plasma concentration of calcium (R2 ranged between 0.207 and 0.322). The plasma concentration of indoxyl sulfate was associated with the descending tracts from right posterior limb of internal capsule to cerebral peduncle (R2 ranged between 0.262 and 0.335). Conclusions Tract specific white matter damage can be noticed in the patients with end stage renal disease, and can be associated with their cognitive decline.

Palliative care in terminally ill advanced chronic liver disease patients.

While mortality rates from advanced chronic liver disease (ACLD) are rapidly increasing, patients with an advanced disease stage have acomparable or even higher symptom burden than those with other life-limiting diseases. Although evidence is limited there is increasing recognition of the need to improve care for patients with ACLD; however, there are many limiting factors to providing good palliative care for these patients, including unpredictable disease progression, the misconception of palliative care and end of life care as being equivalent, alack of confidence in prescribing medication and alack of time and resources. Health professionals working with these patients need to develop the skills to ensure effective palliative care, while referral to specialized palliative care centers should be reserved for patients with complex needs. Basic palliative care, along with active disease management, is best delivered by the treating hepatologists. This includes discussions about disease progression and advance care planning, alongside the active management of disease complications. Liver disease is closely associated with significant social, psychological, and financial burdens for patients and their caregivers. Strategies to engage the discussion in multidisciplinary teams early in disease progression help to ensure addressing these issues proactively. This review summarizes the evidence on palliative care for patients with ACLD, provides examples of current best practice and offers suggestions on how disease-modifying and palliative care can coexist, to ensure that patients do not miss opportunities for quality of life improving interventions.

Comparing the outcome of using high-flow nasal cannula oxygen therapy versus noninvasive ventilation for chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure

BackgroundNoninvasive ventilation (NIV) is frequently employed as a treatment option for acute hypercapnic respiratory failure (AHRF) resulting from chronic obstructive pulmonary disease (COPD). Limited research has substantiated the claims made in recent studies regarding the feasibility of employing high flow nasal cannula (HFNC).AimOur study assessed the outcome of using HFNC versus NIV for COPD patients with AHRF.Patients and methodsEighty COPD patients with AHRF were confined to the respiratory intensive care unit (RICU) at Ain-Shams University Hospitals from December 2021 to 2023 and subdivided into two groups (40/group), where the first group was placed on NIV while the second group was placed on HFNC. Data during their hospital stay as demographic data, vital data, arterial blood gases, device duration, treatment failure, and mortality were recorded.ResultsThe majority were males with mean age 63.75 ± 9.05 years along with treatment failure and complications 25%, 12.5.% in NIV versus 45%, and zero% in HFNC, respectively, with longer hospital stay in NIV 10–15 days to 7–10 days in HFNC, and with no difference in mortality rate in both groups.ConclusionBoth modalities NIV and HFNC were effective for treating COPD with AHRF. However, NIV group was significantly superior than HFNC along with apparently faster improvement in ventilatory and respiratory status especially in high CO2 level while less complications and duration of hospital stay in HFNC with no difference in mortality in both groups.

Association of neutrophil-to-lymphocyte ratio and hemodialysis access failure in patients with end stage renal disease: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess the association of neutrophil-to-lymphocyte ratio (NLR) with an elevated risk of vascular access failure in end-stage renal disease (ESRD) patients undergoing hemodialysis. A comprehensive database search of MEDLINE (via PubMed), Scopus, and Cochrane Central was performed. Studies reporting the values of NLR in both functional and non-functional AVF groups in ESRD patients were selected. Quality assessment was performed using the Modified Newcastle-Ottawa scale for observational studies. Meta-analysis was performed using an inverse variance random effects model. Seven observational studies met the inclusion criteria, including 1313 participants with 554 cases and 759 controls. Pooled results showed significantly high NLR levels in patients with non-functional arteriovenous fistula (AVF) compared to functional AVF (SMD = 1.19, 95% CI = 0.74-1.65, p < 0.001). Subgroup analysis confirmed the consistency of the association between NLR and AVF failure across study design (SMD = 1.76, 95% CI = 0.78-2.73, p = 0.0004 in prospective vs SMD = 0.87, 95% CI = 0.42-1.32, p = 0.0001 in retrospective studies), etiology (SMD = 1.63, 95% CI = 0.75-2.52, p = 0.0003 in stenosis or thrombosis; and SMD = 0.80, 95% CI = 0.27-1.34, p = 0.003 in failure to mature of AVF), and NLR measurement timing (SMD = 0.98, 95% CI = 0.42-1.54, p = 0.0006 in preoperative vs SMD = 1.58, 95% CI = 0.47-2.69, p = 0.005 in postoperative NLR). The pooled odds ratio revealed high NLR values as a significant predictor of AVF failure in ESRD patients (OR = 3.91, 95% CI = 1.91-7.98, p = 0.0002). The pooled sensitivity and specificity were 89.72% (95% CI = 77.51%-95.67%) and 72.95% (95% CI = 63.82%-80.47%), respectively. The high NLR is a useful and predictive marker for AVF failure in hemodialysis patients. Future studies should prioritize larger cohort studies to validate and reinforce these observations.

WP5.8 - Robotic versus laparoscopic general surgery in the emergency setting: a systematic review

Abstract Introduction Robot-assisted general surgery, a cutting-edge technology in minimally-invasive procedures, is increasingly utilised in elective general surgery, demonstrating advantages over laparoscopy in select cases. While laparoscopy remains a standard approach for common acute abdominal conditions, the role of robotic surgery in emergency general surgery is unclear. This systematic review aims to compare outcomes in acute general surgery settings for robotic versus laparoscopic surgeries. Method A PRISMA compliant systematic search across MEDLINE, EMBASE, Science Citation Index Expanded, and Cochrane library was performed. The literature review focused on articles comparing perioperative outcomes of emergency general surgery managed laparoscopically versus robot-assisted. A descriptive analysis was performed and outcome measures recorded. Results Six articles, reporting on 1063 patients, compared outcomes of robotic and laparoscopic procedures. Two covered cholecystectomies, while the others addressed ileocaecal resection, subtotal colectomy, hiatal hernia and perforated gastrojejunal ulcer repair. The level of evidence was low. Laparoscopic bowel resection in inflammatory bowel disease (IBD) patients had higher complications; no significant differences were found in complications for other operations. Operative time showed no differences for cholecystectomies, but robotic approaches were longer for other procedures. Robotic cases had shorter hospital length of stay, though the associated costs were significantly higher. Conclusion Perioperative outcomes for emergency robotic surgery in selected general surgery conditions are comparable to laparoscopic surgery. However, recommending robotic surgery in the acute setting requires a well-powered large population study for stronger evidence.

Effect of positional change on cerebral perfusion in Parkinson's disease with orthostatic hypotension.

Orthostatic hypotension (OH) is one of the most common autonomic dysfunctions in Parkinson's disease (PD) patients. However, many patients with OH are asymptomatic. Conversely, orthostatic dizziness (OD) is not always associated with OH. We investigated the effect of positional changes on cerebral perfusion in patients with PD and OH. We enrolled 43 patients, of whom 31 were PD patients and 11 were healthy controls (HC). All subjects underwent the following clinical assessments: OH Questionnaire, head-up tilt test (HUTT) with transcranial Doppler (TCD), near-infrared spectroscopy, measurement of the change in oxygenated hemoglobin (Δ Hboxy) during the squat-to-stand test (SST), measurement of the time derivative of total hemoglobin (DHbtot), and time taken to reach the peak (peak time, PT) of DHbtot after re-standing. The mean flow velocity change (ΔMFV) in the TCD during the HUTT failed to differentiate between the PD-OH(+) and PD-OH(-) groups. The change in oxygenated hemoglobin Δ Hboxy was greater in the PD-OH(+) group, which persisted for 9 min until the end of the HUTT only in the left hemisphere. During SST, PT was significantly delayed in PD-OH (+) in the left hemisphere. Although TCD demonstrated no significant difference in ΔMFV, the parameters measured by NIRS, such as Δ Hboxy during HUTT and PT during SST, showed significantly increased Δ Hboxy or delayed PT in the left hemisphere of PD-OH(+). Positional changes have a detrimental effect on cerebral hemodynamics in patients with PD and OH, especially in the left hemisphere.

C-FLIP and microRNA 708-5p gene expression in newly diagnosed and chemotherapy in acute myeloid leukemia of Iraqi patient

Abstract: BACKGROUND: C-FLICE-like inhibitory protein (c-FLIP) is a protein that does not merely block apoptosis signaling but also adjusts further pathways of cell death. Acute myeloid leukemia (AML), a nonhomogeneous hematologic malignancy, is the highly common form of AML among adults and is described through the clonal enlargement of myeloid blasts in the bone marrow (BM), peripheral blood, and/or else tissues. OBJECTIVES: The aims of this study were to investigate the role of c-FLIP and microRNA (miRNA) 708-5p as a prospective prognostic biomarker as well as the therapeutic goal in AML. PATIENTS MATERIALS AND METHODS: This study includes two groups of patients (40) individuals newly diagnosed AML patients, (20) AML taking chemotherapy, and (50) apparently healthy volunteers. The study was conducted at the National Center of Hematology/Mustansiriyah University. The methods employed in the analysis include total RNA extraction, complementary cDNA synthesis, and quantitative real-time polymerase chain reaction (PCR) were used to evaluate the gene expression of cFLIP and miRNA-708-5p. Complete blood count to estimate some hematological parameters. RESULTS: The expression of c-FLIP was notably higher in both newly diagnosed and patients under chemotherapy compared to controls with fold expression (3.291 and 2.92), respectively, with a highly significant (P = 0.0001). The increase in miRNA 708-5p expression in newly diagnosed patients with fold expression (5.345), whereas downregulation in patients under chemotherapy with fold expression (0.789) indicates that treatment may restore its levels, contributing to the suppression of c-FLIP and promoting apoptosis. CONCLUSION: The c-FLIP and miRNA708-5p gene might be used as a biological marker for the AML initial diagnosis. The researches emphasize the role of miRNA 708-5p as a tumor suppressor, which negatively regulates the antiapoptotic protein c-FLIP, indicating its potential as a therapeutic target in AML treatment. By modulating the levels of miRNA708-5p, it may be possible to regulate the expression of c-FLIP, thus enhancing the effectiveness of apoptosis-inducing therapies. This suggests the promising development of miRNA-based therapies as part of AML treatment strategies. Furthermore, miRNA 708-5p can act as a prognostic indicator in AML, with its expression levels offering valuable insights into disease progression and patient response to treatment. Further research into miRNA 708-5p can lead to a better understanding of its role in AML pathogenesis and its potential applications in clinical practice.

Predictors of Hospitalization in Breakthrough COVID-19 among Fully Vaccinated Individuals with Immune-Mediated Rheumatic Diseases: Data from SAFER-Study

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value &lt; 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9–18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02–8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15–0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients.

Artificial intelligence-based quantification of pulmonary HRCT (AIqpHRCT) for the evaluation of interstitial lung disease in patients with inflammatory rheumatic diseases.

High-resolution computed tomography (HRCT) is important for diagnosing interstitial lung disease (ILD) in inflammatory rheumatic disease (IRD) patients. However, visual ILD assessment via HRCT often has high inter-reader variability. Artificial intelligence (AI)-based techniques for quantitative image analysis promise more accurate diagnostic and prognostic information. This study evaluated the reliability of artificial intelligence-based quantification of pulmonary HRCT (AIqpHRCT) in IRD-ILD patients and verified IRD-ILD quantification using AIqpHRCT in the clinical setting. Reproducibility of AIqpHRCT was verified for each typical HRCT pattern (ground-glass opacity [GGO], non-specific interstitial pneumonia [NSIP], usual interstitial pneumonia [UIP], granuloma). Additional, 50 HRCT datasets from 50 IRD-ILD patients using AIqpHRCT were analysed and correlated with clinical data and pulmonary lung function parameters. AIqpHRCT presented 100% agreement (coefficient of variation = 0.00%, intraclass correlation coefficient = 1.000) regarding the detection of the different HRCT pattern. Furthermore, AIqpHRCT data showed an increase of ILD from 10.7 ± 28.3% (median = 1.3%) in GGO to 18.9 ± 12.4% (median = 18.0%) in UIP pattern. The extent of fibrosis negatively correlated with FVC (ρ=-0.501), TLC (ρ=-0.622), and DLCO (ρ=-0.693) (p < 0.001). GGO measured by AIqpHRCT also significant negatively correlated with DLCO (ρ=-0.699), TLC (ρ=-0.580) and FVC (ρ=-0.423). For the first time, the study demonstrates that AIpqHRCT provides a highly reliable method for quantifying lung parenchymal changes in HRCT images of IRD-ILD patients. Further, the AIqpHRCT method revealed significant correlations between the extent of ILD and lung function parameters. This highlights the potential of AIpqHRCT in enhancing the accuracy of ILD diagnosis and prognosis in clinical settings, ultimately improving patient management and outcomes.

FP2.5 - Predictors for anastomotic leak (AL) in inflammatory bowel disease (IBD) patients and its associated postoperative (PO) complications; A cohort of a single institution experience

Abstract Introduction IBD patients are highly susceptible to PO morbidities. This study aimed to look at the predictors of AL and the associated morbidities during hospital stays to increase the awareness of these patients. Methods A 5-year retrospective study in DGH. All variables were evaluated:patient-dependent (Age, Gender, BMI, ethnic group, comorbidities),disease-dependent (type of IBD, disease location, disease duration), surgery-dependent (duration, CEPOD type, approach, type of resection),Postoperative(CRP level, VTE, ITU admission, LOS, complications).All data were analysed using SPSS22, and Chi-square test. Results 131 patients were admitted for IBD resection. Median age 37 years. 76 (58%) were female, Chron’s disease was 98 (74.8%). 101 (77.1%) were done laparoscopically, 87 (66.4%)were elective, and the median LOS was 7days.63 (48.1%) has bowel anastomosis and 15 (23.8%) have AL. The median CRP on PO day3 for AL patients was 118. There was no significant association between PO day3CRP and IBD type with AL (P=0.4, 0.7); however, DVT and PE were associated with AL (P=0.001 and 0.039). Patients with AL had a high tendency for ITU admission with longer LOS (P=0.000).Long stays were seen in patients with leaks post-emergency than elective resections (P=0.047, 0.112). AL was associated with chest infection (P=0.001), collection (P=0.006),wound infection (p=0.000), and a higher rate of re-operation within 30 days (p=0.019). Conclusion PO day3CRP is not an independent predictor for AL. Our cohort of IBD patients who had bowel anastomosis showed a significant correlation between VTE and AL.AL was associated with chest and wound infections, high chance of a long ITU stay and subsequently, a long hospital stay. IBD patients with AL are vulnerable to VTE so need high care on these regards.

Vascular Access Related Infections in Hemodialysis Children and the Impact of Implementation of CDC Guidelines and Tools on the Control of these Infections: A Single Centre Experience from Egypt

Background: Vascular access-related infection (VARI) is a serious issue in pediatric end-stage kidney disease (ESKD) patients on regular hemodialysis. Objective: To estimate the frequency of vascular access-related infections in hemodialysis (HD) children and to assess the effect of the implementation of CDC guidelines and tools on the prevention of VARI. Subjects and Methods: This study was conducted on 110 patients with ESKD on regular hemodialysis at the Pediatric Dialysis Unit, Ain Shams University, from August 2019 to September 2021, retrospectively for one year and prospectively for another year after implementing the CDC infection control procedures. Besides full history taking, vascular access history, and thorough clinical examination, lab investigations for VARI diagnosis and echocardiography were performed. CDC infection control procedures were implemented for one year, and VARI was re-evaluated. Results: The total number of patients enrolled in the study was 110, they were 58 males (52.7%) and 52 females (47.3%). The incidence of infection per 1000 vascular access days in both years was highest in patients with NTVCs (10.447 /1000 NTVC days, 6.861 /1000 NTVCs days), followed by patients with TVCs (1.051/1000 TVC days, 0.604 /1000 TVC days) then patients with AVF, (0.141/1000 AVF days, 0.046 /1000 AVF days). The mortality from vascular access-related infections in the first year was higher than in the second year, with 5 patients (10.2%) and 1 patient (3.8%), respectively. The average duration of hospital stays (PPY) due to VARI (total admission days 8.09 and ward admission days 6.41) in the first year were significantly higher than in the second year, 4.04, 3.20 days/PPY, respectively. Conclusion: The incidence of vascular access infection (VAI) is higher with non-tunneled catheters and lowest with Arteriovenous fistulae (AVF). To reduce the risk of VARI and hospitalization, proper infection control procedures must be implemented.

Generic sofosbuvir and daclatasvir for treatment of hepatitis C virus infection in patients with sickle cell disease

Background and purpose of the studySickle cell disease (SCD) patients are at a high risk of chronic liver disease (CLD) due to chronic viral hepatitis infection such as hepatitis C virus (HCV) infection, iron overload, and sickle cell hepatopathy. Nowadays, several oral direct-acting antiviral drugs (DAAs) have been developed and approved by the FDA for hepatitis C treatment. However, the safety and efficacy of DAAs in SCD patients remain insufficiently explored.Purpose of the studyTo evaluate the efficacy and safety of administration of generic sofosbuvir (SOF) and daclatasvir (DCV) for 12 weeks in SCD patients infected with HCV.MethodsA retrospective study included 38 SCD patients infected with HCV treated with generic SOF (400 mg) and DCV (60 mg) for 12 weeks without ribavirin. The effectiveness of the HCV treatment was assessed by the sustained virologic response (SVR) at 24 weeks after the end of the treatment (SVR24).ResultsThe SVR24 rate was 100% (38/38).There were insignificant alterations in hemoglobin and total bilirubin levels during HCV treatment or at end of treatment (EOT). The number of anemic patients who needed blood transfusion two weeks before HCV treatment, at week 4 of treatment, and at EOT was 11 (28.9%), 3 (8%), and 1 (3%) respectively. Moreover, the reductions in serum transaminase levels from baseline were statistically significant compared to the EOT.ConclusionGeneric SOF and DCV regimens appear to be safe and effective in the treatment of chronic HCV in patients with SCD.

The role of peer social support on family psychological resilience in caring for Chronic Kidney Disease patients receiving hemodialysis

Chronic Kidney Disease (CKD) is a disease that necessitates continuous Hemodialysis (HD) therapy, and families, as primary caregivers in Indonesia, play a crucial role in caring for CKD patients. However, HD therapy places a significant burden not only on patients but also on their families, requiring fostering family psychological resilience to mitigate such a burden. Although peer social support is an important external factor in chronic disease, it is still underdeveloped. Therefore, this study aimed to explore the correlation between peer social support and family psychological resilience in caring for CKD patients receiving HD.This cross-sectional study used purposive sampling, engaging 134 families serving as caregivers for patients receiving HD therapy. The Berlin Social Support Scales (BSSS) and The Walsh Family Resilience Questionnaire (WFRQ) were adopted as instruments, and data were analyzed using univariate and Spearman tests.The majority of families reported high levels of peer social support (75,37%), predominantly originating from other members facing similar challenges related to caring for CKD patients. Additionally, a significant relationship was observed between peer social support and family psychological resilience (p-value&lt;0.05), showing that higher levels of peer support corresponded to higher family resilience.In conclusion, there was a strong correlation between peer social support and family resilience in the context of caring for CKD patients. Healthcare professionals should integrate social support intervention by establishing social groups to enhance family resilience.

The simultaneous inhibition of SLC6A19 and BCRP transporters leads to an increase of indoxyl sulfate (a uremic toxin) in plasma and kidney.

SLC6A19 inhibitors are being studied as therapeutic agents for Phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7{plus minus}7.7 compared to vehicle 0.3{plus minus}0.1 (P=0.01) as determined by tissue mass spectrometry imaging (tMSI) analysis. We hypothesized that increased plasma and kidney levels of IDS could be caused by the simultaneous inhibition of both Slc6a19 and a kidney IDS transporter responsible for excretion of IDS into urine. To test this, we first confirmed the formation of IDS through tryptophan metabolism by feeding rats a Trp-free diet. Inhibiting Slc6a19 with RA836 led to increased IDS in these rats. Next, RA836 and its key metabolites were evaluated in vitro for inhibiting kidney transporters OAT1, OAT3 and BCRP. RA836 inhibits BCRP with an IC50 of 0.045 µM but shows no significant inhibition of OAT1 or OAT3. Finally, RA836 analogs with either potent or no inhibition of SLC6A19 and/or BCRP were synthesized and administered to rats fed a normal diet. Plasma and kidney samples were collected to quantify IDS using LC-MS. Neither a SLC6A19 inactive but potent BCRP inhibitor nor a SLC6A19 active but weak BCRP inhibitor raised IDS levels, while compounds inhibiting both transporters caused IDS accumulation in rat plasma and kidney, supporting the hypothesis that rat Bcrp contributes to the excretion of IDS. In summary, we identified that inhibiting Slc6a19 increases IDS formation, while simultaneously inhibiting Bcrp results in IDS accumulation in the kidney and plasma. Significance Statement This is the first publication to decipher the mechanism for accumulation of IDS (a uremic toxin) in rats via inhibition of both Slc6a19 and Bcrp. Specifically, inhibition of Slc6a19 in the GI track increases IDS formation and inhibition of Bcrp in the kidney blocks IDS excretion. Therefore, we should avoid inhibiting both SLC6A19 and BCRP simultaneously in humans to prevent accumulation of IDS, a known risk factor for cardiovascular disease, psychic anxiety, and mortality in chronic kidney disease patients.

Diagnostic value of microRNA-200 expression in peripheral blood-derived extracellular vesicles in early-stage non-small cell lung cancer

ObjectiveThis study assessed the diagnostic value of microRNA-200 (miR-200) expression in peripheral blood-derived extracellular vesicles (EVs) in early-stage non-small cell lung cancer (NSCLC).MethodsThis study retrospectively analyzed 100 healthy volunteers (the control group) receiving physical examinations, 168 early-stage NSCLC patients (the NSCLC group), and 128 patients with benign lung nodules (the benign group). The basic and clinical data of participants were obtained, including age, sex, smoking history, carbohydrate antigen 242 (CA242), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), forced expiratory volume in 1 s, maximal voluntary ventilation, forced vital capacity, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and miR-200 expression. The correlation of miR-200 expression in peripheral blood-derived EVs with CA242, CEA, and CA199 was analyzed, and the diagnostic value of peripheral blood-derived EV miR-200 for early-stage NSCLC was assessed. The risk factors of early-stage NSCLC development were also determined.ResultsAge, the percentage of patients with smoking history, CA242, CEA, CA199, IL-6, and TNF-α levels, and miR-200 expression in peripheral blood-derived EVs were significantly higher in the NSCLC group than in the benign and control groups. Lung disease patients with high miR-200 expression in peripheral blood-derived EVs comprised a higher percentage of patients with smoking history and mixed lesions and had higher CA242, CEA, CA199, and TNF-α levels than those with low miR-200 expression in peripheral blood-derived EVs. In lung diseases, miR-200 expression in peripheral blood-derived EVs was significantly and positively correlated with CA242, CEA, and CA199. Peripheral blood-derived EV miR-200 combined with CA242, CEA and CA199 had higher diagnostic value (area under the curve = 0.942) than single detection, along with higher specificity, and high expression of peripheral blood-derived EV miR-200 was an independent risk factor for early-stage NSCLC.ConclusionPeripheral blood-derived EV miR-200 expression in patients with lung diseases is closely correlated with CA242, CEA, and CA199, and high expression of peripheral blood-derived EV miR-200 is an independent risk factor for early-stage NSCLC and is of high clinical diagnostic value for early-stage NSCLC.

Effectiveness and safety of finerenone in diabetic kidney disease patients: a real-world observational study from China

Aims Finerenone has been approved for treating diabetic kidney disease (DKD) with reducing cardiorenal risk. Real-world data on finerenone treatment for the management of DKD are presently lacking. This study aimed to investigate the effect of finerenone on the renal parameters of the Chinese DKD population in the real-world medical setting for the first time, especially in combination with renin–angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Methods Forty-two DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters and adverse effects were collected at every visit. Results The median urine albumin-to-creatinine ratio (UACR) was 1426.11 (755.42, 3638.23) mg/g. Among them, the proportion of patients with a UACR of 300–5000 mg/g was 76.2%, and the proportion of patients with a UACR of >5000 mg/g was 14.3%. The median estimated glomerular filtration rate (eGFR) was 54.50 (34.16, 81.73) mL/min/1.73 m2. Finerenone decreased the UACR significantly throughout the study period (p < .05). The maximal decline of UACR at month 6 was 73%. Moreover, the proportion of patients with a 30% or greater reduction in UACR was 68.42% in month 6. There was a smaller decline (9–11%) in the eGFR after initiating finerenone (p > .05). One patient each discontinued finerenone due to hyperkalemia (2.4%) and acute kidney injury (2.4%). No patient reported hypotension, breast pain, and gynecomastia. Conclusions This study from China first demonstrated finerenone decreased UACR with manageable safety in real-world DKD treatment. A triple regimen of RASi, SGLT2i, and finerenone may be a promising treatment strategy for lowering albuminuria and reducing hyperkalemia risk in advanced DKD patients.

Characteristics of intestinal flora in nonobese nonalcoholic fatty liver disease patients and the impact of ursodeoxycholic acid treatment on these features.

The study aimed to investigate the alterations in gut microbiota among nonobese individuals with nonalcoholic fatty liver disease (NAFLD) and their response to treatment with ursodeoxycholic acid (UDCA). A total of 90 patients diagnosed with NAFLD and 36 healthy subjects were recruited to participate in this study. Among them, a subgroup of 14 nonobese nonalcoholic steatohepatitis (NASH) were treated with UDCA. Demographic and serologic data were collected for all participants, while stool samples were obtained for fecal microbiome analysis using 16S sequencing. In nonobese NAFLD patients, the alpha diversity of intestinal flora decreased (Shannon index, p < 0.05), and the composition of intestinal flora changed (beta diversity, p < 0.05). The abundance of 20 genera, including Fusobacterium, Lachnoclostridium, Klebsiella, etc., exhibited significant changes (p < 0.05). Among them, nine species including Fusobacterium, Lachnoclostridium, Klebsiella, etc. were found to be associated with abnormal liver enzymes and glucolipid metabolic disorders. Among the 14 NASH patients treated with UDCA, improvements were observed in terms of liver enzymes, CAP values, and E values (p < 0.05), however, no improve the glucolipid metabolism. While the alpha diversity of intestinal flora did not show significant changes after UDCA treatment, there was a notable alteration in the composition of intestinal flora (beta diversity, p < 0.05). Furthermore, UCDA treatment led to an improvement in the relative abundance of Alistipes, Holdemanella, Gilisia, etc. among nonobese NASH patients (p < 0.05). Nonobese NAFLD patients exhibit dysbiosis of the intestinal microbiota. UDCA can ameliorate hepatic enzyme abnormalities and reduce liver fat content in nonobese NASH patients, potentially through its ability to restore intestinal microbiota balance.

Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease

Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.

Frequency of Asymptomatic Spontaneous Bacterial Peritonitis in Patients of Chronic Liver Disease with Ascites

Frequency of Asymptomatic Spontaneous Bacterial Peritonitis in Patients of Chronic Liver Disease with Ascites

Knowledge and Attitude Towards Decompensated Liver Disease Patients Assessment Amongst Health Care Providers of a Tertiary Care Hospital- A Cross Sectional Study

Knowledge and Attitude Towards Decompensated Liver Disease Patients Assessment Amongst Health Care Providers of a Tertiary Care Hospital- A Cross Sectional Study