Early Therapy Research Articles

Correlation Of NAG, NGAL, and Oxidative Parameters For Patients With Diabetic Nephropathy

Background: Diabetic nephropathy is a clinical syndrome that is present in diabetic mellitus patients and characterized by albuminuria {>200 or >300 mg\day}, a gradual glomerular filtration rate decline along with hypertension. Objective: Study the correlation between N_acetyl-ß-D-glucamindase and human neutrophil gelatinase-associated lipocalin and oxidative parameters in diabetic nephropathy patients compared with a control group and several variables by Explaining the results scientifically. Method: The blood sample was collected from forty-five diabetic nephropathy patients and forty-five controls from Merjin Medical Hospital and Al-Imam Al-Sadiq Hospital in Iraq to assess N-acetyl-β-D-glucosaminidase and human neutrophil gelatinase-associated lipocalin levels by used Enzyme-Linked immunosorbent Assay technicality (ELISA) and also to determine the oxidative parameters (total oxidant system, total antioxidant capacity, malondialdehyde and glutathione) by used spectrophotometer. Result: positive correlation for N-acetyl-β-D-glucosaminidase with total oxidant status and malondialdehyde where the correlation coefficient (r=0.893**, 0.809**) at respectively and negative correlation with total antioxidant capacity and glutathione where the (r=-0.851**, -0.465**) at respectively, and exact correlation for human neutrophil gelatinase-associated lipocalin with total oxidant status, malondialdhyde, total antioxidant capacity, glutathione. Conclusion: The assessment of NAG, NAGL, and oxidant parameters can provide crucial information for the early diagnosis, management, and therapy of these patients with diabetic nephropathy.

Pioneering Oral Insulin Formulations and Delivery Techniques: A Review

The development of oral insulin presents significant promise for diabetes treatment, mitigating peripheral hyperinsulinemia, weight gain, and hypoglycemia while enhancing patient convenience and facilitating rapid insulinization of the liver. Effective oral insulin products are crucial for early intensive insulin therapy, which ensures tight glycaemic control and delays diabetes complications. However, despite the need, oral insulin has faced many challenges, and past technologies have had limited success. Repeated insulin injections can result in local hypertrophy over time generating attention to user-friendly oral insulin delivery systems that are not invasive to the body and copy the natural pathway. This review article examines New methods for oral insulin delivery that have shown promise, using techniques like complexation, hydrogels, and nanoparticles to boost effectiveness, though they still trail injectable insulin. Further studies will help determine how well oral insulin works at various doses and inform the development of competing formulations.

Trauma Presentations To The ED, Are We Improving With Frailty Initiatives?

Abstract Background An emergency department serving as a regional Trauma Centre for the Midlands, now has a Rapid Access Frailty Team (RAFT) which provides timely assessments of all Frail patients over 75. The department has an approximate trauma attendance of 111 (2023 figures) annually within this age cohort. In line with our NOCA guidelines we performed a retrospective review of our trauma presentations since the introduction of the RAFT initiative, looking at the patient’s presentations and how interventions can improve our Trauma management. Methods This was a retrospective review of FRAIL positive patients in from January/February 2023 and January/February 2024 based on NOCA 2021 subsets of trauma data. Data was collected using examination of IPIMS and ED notes obtained for review. We compared both years to see we could see if RAFTT interventions improved our trauma triage and care. Results The predominant mechanism of injury remains to be a fall (85% in 2023 and 74% in 2024), and the majority of traumas being in the home setting (70% in 2023 and 78% in 2024). By the early involvement of a nurse specialist, physio/OT and doctor, time to be seen has reduced by 23% since the introduction of the team, time to imaging has improved by 51% and time to bed if admitted has improved by 19%. Pre alerts remain low, similar to national data findings (10% in 2023, but up to 15% in 2024). Conclusion Data points to the team’s provision of timely, patient-focused assessments and interventions for the older person are improving outcomes. The unique assessment skills that the team deliver aids rapid assessment, supports timely decision-making and referral as appropriate; improving the patient’s journey by either facilitating early discharge or providing early goal-setting therapy interventions at the start of the hospital journey.

Homeward Stroke Recovery: Results of a Home Rehabilitation Program

Evaluate the feasibility of a homeward stroke recovery (HSR) program by measuring functional outcomes, intervention fidelity, and Profit & Loss. A retrospective observational analysis of 23 stroke survivors discharged to a home healthcare (HHC) program offering early and intensive rehabilitative therapy within 24 hours of index hospitalization. Functional outcomes include timed up-and-go, transfer functional independent measures, and Barthel Index. Clinical outcomes are mortality, all-cause 30-day hospital readmission, and fall rates. Process measures consist of time-to-first HHC visit, number of physical therapy (PT) and occupational therapy (OT) visits from initial evaluation, and total number of visits by clinician type. Financial outcomes include average daily gross HSR revenue compared with an inpatient rehabilitation facility (IRF) stay and average daily net HSR profit. Functional outcomes significantly improved across all measures ( p < .001) without reported falls, deaths, and only one unrelated readmission. On average, HSR began within 1.6 days from hospital discharge including 4.2 PT and 3.7 OT visits within 5 days of respective initial evaluation. Patients received an average of 9.4 nursing, 9.2 PT, 6.4 OT, and 2.2 speech therapy visits. Exploratory analyses demonstrated similar functional recovery despite longer hospitalization (rs = 0.43; p = .039). Revenue per day was lower for HSR than IRF services but costs exceeded the reimbursement rates for this program. The HSR program is feasible given that patients realized significant functional improvement with negligible consequences. Reimbursement reform is necessary to sustain and scale the program. Further studies with larger sample sizes are warranted.

Poly ADP-ribose signaling is dysregulated in Huntington disease

Huntington disease (HD) is a genetic neurodegenerative disease caused by cytosine, adenine, guanine (CAG) expansion in the Huntingtin (HTT) gene, translating to an expanded polyglutamine tract in the HTT protein. Age at disease onset correlates to CAG repeat length but varies by decades between individuals with identical repeat lengths. Genome-wide association studies link HD modification to DNA repair and mitochondrial health pathways. Clinical studies show elevated DNA damage in HD, even at the premanifest stage. A major DNA repair node influencing neurodegenerative disease is the PARP pathway. Accumulation of poly adenosine diphosphate (ADP)-ribose (PAR) has been implicated in Alzheimer and Parkinson diseases, as well as cerebellar ataxia. We report that HD mutation carriers have lower cerebrospinal fluid PAR levels than healthy controls, starting at the premanifest stage. Human HD induced pluripotent stem cell-derived neurons and patient-derived fibroblasts have diminished PAR response in the context of elevated DNA damage. We have defined a PAR-binding motif in HTT, detected HTT complexed with PARylated proteins in human cells during stress, and localized HTT to mitotic chromosomes upon inhibition of PAR degradation. Direct HTT PAR binding was measured by fluorescence polarization and visualized by atomic force microscopy at the single molecule level. While wild-type and mutant HTT did not differ in their PAR binding ability, purified wild-type HTT protein increased in vitro PARP1 activity while mutant HTT did not. These results provide insight into an early molecular mechanism of HD, suggesting possible targets for the design of early preventive therapies.

Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves

BackgroundThe clinical effectiveness of early therapies for mild-to-moderate COVID-19, comparing antivirals and monoclonal antibodies (mAbs) during the Omicron era, has not been conclusively assessed through a post-approval comparative trial. We present a pooled analysis of two randomized clinical trials conducted during Omicron waves. Methods The MANTICO2/MONET trial is a pooled analysis of two multicentric, independent, phase-4, three-arm, superiority, randomized, open-label trials. Nonhospitalized patients with early mild-to-moderate COVID-19 (≤5 days after symptoms’ onset) and at least one risk factor for disease progression were randomized 1:1:1 to receive 500mg of intravenous sotrovimab (SOT) or 600mg of intramuscular tixagevimab/cilgavimab (TGM/CGM) or oral 5-days course of nirmatrelvir/ritonavir (NMV/r) 300/100mg BID. Primary outcome was COVID-19-related hospitalization or death within 29 days after randomization. Fisher’s exact test for pooled data and incidence of failure was reported as overall and by arm with respective 95% CI.Pairwise comparisons across the arms were conducted using unadjusted exact logistic regression. An analysis by means of a doubly robust marginal model using augmented inverse probability weighting (AIPW) was also conducted to estimate the potential outcomes (Pom) in each treatment group and their difference by the average treatment effect (ATE). Analysis of symptom persistence within 30 days after randomization was performed using a 2-level hierarchical mixed-effects logistic model with a random intercept at the patient’s level. Point estimates and 95% confidence intervals were adjusted for age and sex and calculated using ANOVA-like methods for the mixedeffects logistic model. These trials are registred with the European Clinical Trials Database, EudraCT2021-002612-31 (MANTICO2) and EudraCT2021-004188-28 (MONET) and ClinicalTrials.gov, NCT05321394 (MANTICO2) Findings Between March 2022 and February 2023, 991 patients (SOT=332, TGM/CGM =327, NMV/r=332) were enrolled in 15 Italian centersThe overall mean age was 66 years; 482 participants (48.80%) were male and 856 vaccinated with at least a primary course ( 86%). Among the 8/991 hospitalizations observed, one resulted in death. The overall estimate of failure was 0.81% (95%CI; 0.35-1.58%). The odds ratio (OR) for the primary outcome in the NMV/r arm compared to the TGM/CGM and SOT arms was 8.41 (95% CI 1.21 to infinity; p=0.015) and 2.42 (95% CI 0.19 to infinity; p=0.499), respectively. No significant difference was observed between SOT and TGM/CGM (OR 0.32; 95% CI 0.032-1.83; p=0.174). Results were similar when we applied the marginal weighted model accounting for potential residual confounding bias. There was no evidence for a difference in the prevalence of symptoms between treatment groups, except for cough, which was higher in the SOT group compared to the other two groups at the 21-day follow-up (P=0.039) and a higher prevalence of nausea at the 7-day follow-up in the NMV/r group compared to the mAbs group (p=0.036). Interpretation NMV/r was superior to TGM/CGM in reducing hospital admission or death in clinical vulnerable patients with SARS-CoV-2 infection treated within 5 days of symptoms’ onset. No significant difference in symptom prevalence over time across the arms was found. Funding: The trials were funded by the Italian Agency of Drugs (AIFA) in 2021.

Bilateral tuberculosis psoas abscess in a human immunodeficiency virus-positive patient: a case report

BackgroundWorldwide, there is an increase in the frequency of reports of psoas abscesses due to advances in imaging technology, which has led to early diagnosis and treatment. A bilateral psoas abscess is rare and, when it occurs, is usually secondary and in immunocompromised patients. We present a case of a bilateral tuberculosis psoas abscess in a human immunodeficiency virus-positive patient.Case presentationA 21-year-old Ugandan female undergraduate who contracted human immunodeficiency virus through vertical transmission and has been on highly active antiretroviral drugs presented with bilateral lower abdominal pain with associated fever and headache. Clinical examination revealed abdominal tenderness in both iliac fossae with palpable masses. Ultrasonography revealed fluid collection in both psoas muscles confirming bilateral abscesses. The aspirate was acid-fast bacilli positive. A diagnosis of bilateral tuberculosis psoas abscess was made. Open drainage was performed and antituberculosis drugs were commenced.ConclusionsBilateral tuberculosis psoas abscesses occurring in human immunodeficiency virus-positive patients, although uncommon, is not unexpected. It is a form of secondary psoas abscess in immunocompromised patients. Here, the outcome was successful with a combination of early surgical drainage and appropriate medical therapy.

Macitentan and Tadalafil Combination Therapy in Incident and Prevalent Pulmonary Arterial Hypertension: Real-World Evidence from the OPUS/OrPHeUS Studies.

Historically, patients recently (≤6months) diagnosed with pulmonary arterial hypertension (PAH; incident) have had poorer survival than those with a longer (>6months) time from PAH diagnosis (prevalent). Despite guideline recommendations for initial combination therapy for most patients with PAH, many are initiated and maintained on monotherapy. Real-world evidence to evaluate the benefit of early combination treatment in newly-diagnosed patients is lacking. Patients with PAH initiating combination therapy with the endothelin receptor antagonist macitentan and the phosphodiesterase-5 inhibitor tadalafil (M+T) were identified from the combined dataset of the US, multicenter OPUS (prospective, observational drug registry; NCT02126943) and OrPHeUS (retrospective, medical chart review; NCT03197688) studies (2013-2020). Descriptive analyses were performed for the incident and prevalent cohorts, as well as the subcohort of incident patients who received M+T as first-line combination therapy (incident initial combination). In OPUS/OrPHeUS, 1336 patients with PAH received M+T during the observation period. For the incident [n=453 (33.9%)], incident initial combination [n=272 (20.4%)], and prevalent [n=837 (62.6%)] cohorts: median (Q1, Q3) M+T exposure was 14.2 (4.2, 27.5), 12.2 (3.2, 25.5), and 14.7 (4.5, 28.0) months. 12-month Kaplan-Meier estimates (95% confidence limits) for survival were 91.2% (87.7, 93.7), 88.5% (83.2, 92.2), and 92.9% (90.6, 94.6), for patients free from hospitalization were 59.4% (54.1, 64.4), 56.3% (49.1, 62.9), and 62.3% (58.5, 65.9), and for patients persisting on combination therapy were 68.6% (63.9, 72.8), 65.0% (58.8, 70.6) and 66.9% (63.5, 70.0). Adverse events (OPUS only) were reported in 77.8%, 80.2%, and 80.3% of patients, respectively, with no unexpected adverse events observed. Despite a historically worse prognosis, incident patients receiving M+T, including as initial combination therapy, had similar survival and hospitalization as prevalent patients. Safety profiles were similar across cohorts. Together, these data support the use of early combination therapy with macitentan and tadalafil.

LC–HRMS Lipidomic Fingerprints in Serbian Cohort of Schizophrenia Patients

Schizophrenia (SCH) is a major mental illness that causes impaired cognitive function and long-term disability, so the requirements for reliable biomarkers for early diagnosis and therapy of SCH are essential. The objective of this work was an untargeted lipidomic study of serum samples from a Serbian cohort including 30 schizophrenia (SCH) patients and 31 non-psychiatric control (C) individuals by applying liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) and chemometric analyses. Principal component analysis (PCA) of all samples indicated no clear separation between SCH and C groups but indicated clear gender separation in the C group. Multivariate statistical analyses (PCA and orthogonal partial least squares discriminant analysis (OPLS-DA)) of gender-differentiated SCH and C groups established forty-nine differential lipids in the differentiation of male SCH (SCH-M) patients and male controls (C-M), while sixty putative biomarkers were identified in the differentiation of female SCH patients (SCH-F) and female controls (C-F). Lipidomic study of gender-differentiated groups, between SCH-M and C-M and between SCH-F and C-F groups, confirmed that lipids metabolism was altered and the content of the majority of the most affected lipid classes, glycerophospholipids (GP), sphingolipids (SP), glycerolipids (GL) and fatty acids (FA), was decreased compared to controls. From differential lipid metabolites with higher content in both SCH-M and SCH-F patients groups compared to their non-psychiatric controls, there were four common lipid molecules: ceramides Cer 34:2, and Cer 34:1, lysophosphatidylcholine LPC 16:0 and triacylglycerol TG 48:2. Significant alteration of lipids metabolism confirmed the importance of metabolic pathways in the pathogenesis of schizophrenia.

Assessment of Architectural Heritage and Historic Structures Through Aerial Thermography

Objective: The objective of this study is to verify the applicability of aerial thermography as a complement to common inspections in the heritage field, assessing what it can contribute as a complement to such exclusively visual inspections. Theoretical Framework: The contribution of terrestrial thermography and aerial thermography to the heritage field is briefly presented, justifying the limitations of terrestrial thermography and the advantages of aerial thermography. Method: Within the framework of this research, the inspection was carried out, with a drone with a thermographic camera, on three unique elements of great heritage relevance, previously visually inspected by a drone with a photographic camera: the Roman Bridge of Alcántara, the Aqueduct of Segovia and the Roman Bridge of Alconétar. Results and Discussion: The results obtained in the inspections carried out allow us to draw the first conclusions on the applicability of this technology to architectural heritage: the inspections will demonstrate the usefulness of thermography for the diagnosis of lesions on stone that do not occur at a superficial level. . Implications of the Research: The usefulness of thermography for the diagnosis of lesions on stone that do not occur at a superficial level and that, when they appear on the surface, are already at an advanced stage of development inside the element. Early detection of such lesions can be key when trying to adopt early therapies that are less aggressive and costly, thus avoiding further damage to the constituent elements of the monument to be protected. Originality/Value: This study contributes to verifying the use of microtechnology tools that speed up the control and monitoring processes of damaging phenomena, eliminating the risks to the safety and health of workers and considerably reducing the risks to the architectural monument to be inspected.

Multiple positive points during the 75 g oral glucose tolerance test are good predictors for early insulin therapy in gestational diabetes mellitus diagnosed before 24 gestational weeks

ABSTRACTAims/IntroductionThis study evaluated the risk factors for insulin therapy before 24 gestational weeks (early insulin therapy) in pregnant women with gestational diabetes diagnosed before 24 gestational weeks (E‐GDM).Materials and MethodsThis study included 530 singleton mothers with E‐GDM who underwent a 75 g oral glucose tolerance test (OGTT) in the first trimester at Keio University Hospital between January 2013 and December 2021. E‐GDM can be classified according to its management into only diet therapy until delivery (Diet E‐GDM), insulin therapy started before 24 gestational weeks (EarlyIns E‐GDM), and insulin therapy started after 24 gestational weeks (LateIns E‐GDM). We analyzed the risk factors for EarlyIns E‐GDM.ResultsPatients with EarlyIns E‐GDM had a significantly higher maternal age at delivery, pre‐pregnancy BMI, first trimester hemoglobin A1c, 1 h plasma glucose levels (1 h‐PG), and 2 h‐PG, as well as a more pronounced initial increase and subsequent decrease, compared with those in the Diet E‐GDM group. However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E‐GDM than in those with Diet E‐GDM. The number of abnormal values in the OGTT showed the largest area under the receiver operating characteristic curve (AUC) for predicting EarlyIns E‐GDM (0.83, 95% confidence interval [CI]: 0.79–0.86), followed by the 1 h‐PG value (AUC: 0.81, 95% CI: 0.77–0.85). The initial increase showed the third largest AUC (0.78, 95% CI: 0.74–0.82).ConclusionsAlthough further research is needed, our data suggest the importance of early insulin therapy in cases of E‐GDM with multiple abnormal OGTT values, especially with high 1 h‐PG levels and initial increase.

Therapeutic potential of mesenchymal stromal cells on morphological parameters in the hippocampus of rats with brain ischemia-reperfusion modeling

Ischemic stroke is an extremely important pathology with high mortality, in which more than 50 % of patients with occlusion of the main vessels remain disabled, despite early reperfusion therapy by thrombolysis or thrombectomy. As part of the regenerative strategy, stem cell transplantation in ischemic stroke became a new impetus. Cell therapy with the use of mesenchymal stromal cells demonstrated encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic damage to brain structures. The aim of the research is to study the influence of mesenchymal stromal cells of various genesis, lysate of mesenchymal stromal cells obtained from Wharton’s jelly umbilical cord and citicoline on the dynamics of morphological changes in the hippocampal CA1 region of rats with acute cerebral ischemia-reperfusion according to light microscopy and micromorphometry data. The experiment was carried out using 200 male Wistar rats, which were subjected to ischemia-reperfusion by reversible 20-minute bilateral occlusion of the internal carotid arteries. Animals with modeled pathology were intravenously transplanted with mesenchymal stromal cells of various genesis (from Wharton’s jelly of the human umbilical cord, human and rat adipose tissue), and rat embryonic fibroblasts, lysate of mesenchymal stromal cells and citicoline were injected. Histological analysis of rat brain sections was performed on the 7th and 14th day of the experiment. Statistical analysis was performed using “Statistica 6.0” (StatSoft® Snc, USA). The significance of differences was assessed using the Student’s t-test and the nonparametric Mann-Whitney U test. During the study, it was found that modeled ischemia-reperfusion in rats caused almost complete degeneration of the structure of the pyramidal layer of hippocampal CA1 region, gave uniformity to the structure of the radiant layer, infiltration of microglia, contributed to the disruption of the arrangement of apical dendrite bundles and narrowing of blood vessels as a result of perivascular edema. Also, the modeled pathology reduced the total number of neuronal nuclei in the hippocampal CA1 area, the overwhelming majority of which had signs of pathological changes. Transplantation of mesenchymal stromal cells of various origins, lysate of mesenchymal stromal cells and citicoline contributed to a significant increase in the number of neuronal nuclei in the hippocampal CA1 zone and nuclei that did not undergo pathological changes. The most positive effect was found in the transplantation of mesenchymal stromal cells from human Wharton’s jelly-derived cells. Thus, both in the subacute and recovery periods of ischemic stroke in rats, the transplantation of human Wharton’s jelly-derived mesenchymal stromal cells was significantly surpassed the reference drug citicoline in its ability to reduce the number of pathologically changed nuclei by 1.5 times (p<0.05). At the same time, the number of pathologically unchanged nuclei significantly exceeded the number of nuclei with signs of karyorrhexis and karyopyknosis, so it would be advisable to use mesenchymal stromal cells of various genesis, lysate or citicoline in conditions of acute cerebral ischemia-reperfusion, taking into account their ability to reduce the volume of the infarct. In the future, an injectable drug will be created from the most effective culture of mesenchymal stromal cells in terms of cerebroprotective properties for cell therapy of patients with acute ischemic stroke.

HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond.

Even during extended periods of effective immunological control, a substantial dynamic of the viral genome can be observed in different cellular compartments in HIV-1 positive individuals, indicating the persistence of active viral reservoirs. To obtain further insights, we studied changes in the proviral as well as in the viral HIV-1 envelope (Env) sequence along with transcriptional, translational and viral outgrowth activity as indicators for viral dynamics and genomic intactness. Our study identified distinct reservoir patterns that either represented highly sequence-diverse HIV-1 populations or only a single / few persisting virus variants. The single dominating variants were more often found in individuals starting ART during early infection phases, indicating that early treatment might limit reservoir diversification. At the same time, more sequence-diverse HIV reservoirs correlated with a poorer immune status, indicated by lower CD4 count, a higher number of regimen changes and more co-morbidities. Furthermore, we noted that in T-cell populations in the peripheral blood, replication-competent HIV-1 is predominantly present in Lymph node homing TN (naïve) and TCM (central memory) T cells. Provirus genomes archived in TTM (transitional memory) and TEM (effector memory) T cells more frequently tended to carry inactivating mutations and, population-wise, possess changes in the genetic diversity. These discriminating properties of the viral reservoir in T-cell subsets may have important implications for new early therapy strategies, underscoring the critical role of early therapy in preserving robust immune surveillance and constraining the viral reservoir.

Appropriate Use of Antibiotics in Acute Pancreatitis: A Scoping Review.

While selective use of antibiotics for infected pancreatic necrosis (IPN) in acute pancreatitis (AP) is recommended, studies indicate a high rate of inadequate treatment. A search of PubMed, Scopus, and Cochrane databases was conducted, focusing on primary research and meta-analyses. Data were categorized based on core concepts, and a narrative synthesis was performed. The search identified a total of 1016 publications. After evaluating 203 full texts and additional sources from the grey literature, 80 studies were included in the review. The answers obtained were: (1) Preventive treatment does not decrease the incidence of IPN or mortality. Given the risks of bacterial resistance and fungal infections, antibiotics should be reserved for highly suspected or confirmed IPN; (2) The diagnosis of IPN does not always require microbiological samples, as clinical suspicion or computed tomography signs can suffice. Early diagnosis and treatment may be improved by using biomarkers such as procalcitonin and novel microbiological methods; (3) When indicated, early initiation of antibiotics is a key determinant in reducing mortality associated with IPN; (4) Antibiotics with good penetration into pancreatic tissue covering Gram-negative and Gram-positive bacteria should be used. Routine antifungal therapy is not recommended; (5) The step-up approach, including antibiotics, is the standard for IPN management; (6) Antibiotic duration should be kept to a minimum and should be based on the quality of source control and patient condition. Early antibiotic therapy is essential for the treatment of IPN, but prophylactic antibiotics are not recommended in AP. High-quality randomized controlled trials are required to better understand the role of antibiotics and antifungals in AP management.

Early defibrotide therapy and risk factors for post-transplant veno-occlusive disease/sinusoidal obstruction syndrome in childhood.

Veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life-threatening complications of hematopoietic cell transplantation (HCT). We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included. Among 111 patients of less than 20years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post-DF era (2020-2023, n=58) than in the pre-DF era (31% vs. 13%, p=.04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post-DF era than in the pre-DF era (44% vs. 8%, p=.04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS (p<.01) in comparison to non-early therapy started at less than two criteria. A multivariate analysis indicated that a history of cytokine release syndrome (odds ratio [OR]=10.4, p=.01) and juvenile myelomonocytic leukemia (OR=8.98, p=.04), but not an endothelial activation and stress index (EASIX) score of greater than 0.85, were independent risk factors for VOD/SOS. Early DF therapy improves the severity and survival outcomes of post-transplant VOD/SOS in children. However, its incidence is increasing in the era of immunotherapy for progressive diseases.

The effect of Clusterin level as a potential marker in women with polycystic ovary syndrome

An organ with high metabolic activity, adipose tissue secretes a variety of adipocytokines that control the metabolism of fats and carbohydrates and advance insulin resistance (IR). It is currently unclear what pathophysiological mechanism underlies PCOS. In most cases, IR and metabolic abnormalities coexist with PCOS, a chronic endocrine and metabolic illness. Prompt identification and intervention aid in enhancing patients' quality of life while delaying the development of associated issues. Adipokine clusterin (encoded by CLU) is new. Diabetes and obesity-related populations have higher serum clusterin levels. In order to establish a foundation for early PCOS screening, diagnosis, and therapy, the current study examined variations in serum CLU levels in PCOS patients along with their relationships to sex hormones and metabolic markers. A case-control study design consisting of ninety newly diagnosed PCOS patients of ages ranging between (18-42) years have been recruited according to the Rotterdam criteria of PCOS diagnosis. To compare the results, 90 apparently healthy women of age were matched with the patients' group as a control group. Serum clusterin, fasting insulin (FIN), and fertile hormones have been measured in sera using the enzyme-linked immune sorbent assay (ELISA) technique. An independent t-test analysis was performed on the data. Pearson correlation was utilized to evaluate the relationship between the variables. It was found that the PCOS patients had considerably greater serum CLU (41.672± 3.85 vs. 28.5845± 3.01 μg/ml, P &lt; 0.001) than healthy women. A multiple stepwise linear regression analysis showed that HOMA-IR was separately linked with BMI, and HOMA-IR were independently associated with CLU (P &lt; 0.05). Serum CLU exhibited a positive connection (P &lt; 0.05) with BMI, FSG, FINS, and HOMA-IR. Serum CLU in the PCOS group correlated well with TG, CLU, HOMA-IR, FSH, FSG, and FINS. The PCOS women group significantly outperformed the fertile, healthy women group regarding BMI, LH, FSH, FSG, FIN, HOMA-IR, TC, TG, and LDL-C levels. They also had lower levels of HDL-C and QUICKI values. Additionally, serum clustrein levels. 31.68 A cut-off value of CLU as a marker for diagnosing PCOS with a sensitivity of 90.0% and a specificity of 87.5% (AUC: P value = ˂0.0001, 0.887-1.000.

Abstract C058: A novel approach to understanding pancreas cancer risk through enhancer- promoter interactions

Abstract Genetic or epigenetic variations in regulatory enhancer elements increase susceptibility to a range of pathologies, including pancreas cancer. Pinpointing genes affecting pancreas cancer risk holds promise for early detection, prevention, and effective therapies. Despite recent advances, linking enhancer elements to target genes and predicting the transcriptional outcome of enhancer dysfunction remain significant challenges. Using 3D chromatin assays, we generated an extensive enhancer interaction dataset for the human pancreas, spanning more than 20 donors and five major cell types, including both the exocrine and endocrine compartments. We employed a network approach to parse chromatin interactions into enhancer-promoter tree models, facilitating quantitative, genome-wide analysis of enhancer connectivity. Using the tree models, we developed a machine learning algorithm capable of estimating the impact of enhancer perturbations on cell-type specific gene expression in the human pancreas. Complementing this computational approach, we streamlined an experimental platform using CRISPR-interference and RNA-FISH coupled with high-throughput imaging to quantitatively measure the effect size of enhancer perturbations in primary human pancreas cells. Our enhancer tree models enabled functional annotation of genetic variants associated with pancreas diseases, revealing novel target genes in specific cell types. For pancreas cancer (PDAC), our data suggests a stronger association of disease susceptibility variants with acinar cells, even though ductal cells historically have been the focus of PDAC. This discovery linked three potentially functional variants associated with PDAC risk to acinar cell enhancers, revealing novel target genes to further investigation. By integrating genomics with mechanistic findings into enhancer function, our work offers a framework for understanding genetic basis of pancreas cancer disease risk. Citation Format: Li Wang, Songjoon Baek, Gauri Prasad, Thucnhi Truongvo, Jason Hoskins, Laufey Amundadottir, Efsun Arda. A novel approach to understanding pancreas cancer risk through enhancer- promoter interactions [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C058.

Evaluation of T2 Magnetic Resonance (T2MR®) Technology for the Early Detection of ESKAPEc Pathogens in Septic Patients.

Bloodstream infections (BSIs) and sepsis are a major cause of morbidity and mortality. Appropriate early antibiotic therapy is crucial for improving the survival of patients with sepsis and septic shock. T2 magnetic resonance (T2MR®) technology may enable fast and sensitive detection of ESKAPEc pathogens directly from whole-blood samples. We aimed to evaluate concordance between the T2Bacteria® Panel and standard blood culture and its impact on antibiotic therapy decisions. We conducted a single-centre retrospective study on patients with sepsis-induced hypotension or septic shock admitted to general, post-operative/neurosurgical, and cardiothoracic Intensive Care Units who were tested with the T2Bacteria® Panel from January 2021 to December 2022. Eighty-five consecutively admitted patients were included, for a total of 85 paired tests. A total of 48 ESKAPEc pathogens were identified by the T2Bacteria® Panel. The concordance rate between the T2Bacteria® Panel and blood cultures was 81% (69/85), with 20 concordant-positive and 49 concordant-negative cases. For the 25 microorganisms grown from accompanying blood cultures, blood pathogen coverage by the T2Bacteria® Panel was 88%. In this cohort of severely ill septic patients, the T2Bacteria® Panel was highly concordant and was able to detect more ESKAPEc pathogens, with a significantly shorter turn-around time compared to conventional blood cultures. The T2Bacteria® Panel also significantly impacted decisions on antibiotic therapy.

Trace Elements and Proximate Analysis of &lt;i&gt;Boswellia dalzielii&lt;/i&gt; Stem Bark

Boswellia dalzielii (B. dalzielii) Hutch is a tree plant of the Burseraceae family found in Savannah woodlands. The decoction of stem bark has been reported to be useful in treating gastrointestinal diseases, rheumatism, septic sores, and sexual ailments. Additionally, it has demonstrated antifungal, antibacterial, and anti-inflammatory properties. The research was undertaken to evaluate the trace element contents and nutritional contents of the stem bark of B. dalzielii using standard methods of the Association of Official Analytical Chemists (AOAC). The elemental analysis showed the presence of: Zn (5.82±0.021 mg/kg), Cu (4.22±0.017 mg/kg), Mn (31.24±0.114 mg/kg), and Fe (9.12±0.318 mg/kg), Se (3.13m±0.223 g/kg) Cr (0.0026±0.211 mg/kg), Co (0.00 mg/kg), Mo (0.0016±0.001 mg/kg), Cd (0.0037±0.117 mg/kg), Ni (0.0016±0.324 mg/kg), and I (4.15±0.214 mg/kg). While the proximate analysis revealed the presence of the following: ash content (5.97±0.315%), moisture (6.22±0.115%), protein (18.52±0.018%), fiber 16.2±0.215%), crude fat (6.02±0.002%), and carbohydrate (31.73±0.224%). Trace elements have well-characterized physiological functions within the body. They regulate biological processes, thereby stabilizing the structures of cells when they are supplied at the normal level, but their deficiency leads to different kinds of diseases. The study suggests that the trace elements present in the bark sample of B. dalzielii may be of value and may have prognostic significance in the early diagnosis and therapy evaluation of some diseases, especially various types of cancer, as well as in anti-diabetic agents. The results of the proximate analysis depict the potentiality of the plant as a good source of nutraceuticals.

Classification of suicidal ideation severity from Twitter messages using machine learning

Depression has become a major mental health problem in Thailand and can lead to suicidal ideation. As suicidal ideation may vary in intensity and lead to suicide attempts, early detection of suicidal ideation severity should be implemented. This research presents text classification models for the prediction of suicidal ideation severity. A dataset of Twitter messages in Thai was used to develop several classification models. A web application prototype was also developed to predict suicidal ideation severity and introduce self-therapy based on Cognitive Behavioral Therapy to its users for managing negative automatic thoughts. The application prototype received satisfactory feedback during the user experience assessment. The results of this research highlight the importance and need for socio-technical systems to help with early suicidal ideation detection and early therapy in the social environment where mental health support is inadequate.