Clinical Laboratory Values Research Articles

A phase I study assessing the safety and tolerability of SPL84, an inhaled antisense oligonucleotide for treatment of cystic fibrosis patients with the 3849 +10kb C->T

BackgroundAntisense Oligonucleotides (ASOs) are small synthetic nucleic acid molecules able to bind specific sequences within target Ribonucleic Acid (RNA) molecules. SPL84 is an ASO drug developed for treatment of cystic fibrosis (CF) patients carrying the 3849 + 10 kb C->T Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) splicing mutation. The 3849 + 10 kb C->T variant leads to inclusion of cryptic exon harboring stop codon leading to the production of truncated non-functional CFTR proteins. in vitro, SPL84 treatment results in splicing modulation, which leads to an increase of correctly spliced CFTR RNA and higher levels of functional CFTR proteins. MethodsSPL84 was tested in a blinded, placebo-controlled phase 1 study in thirty two (32) healthy volunteers (HVs), each received a single dose of either SPL84 or placebo by inhalation. A total of 8 participants were randomized to each of the 4 escalating cohorts in a 3:1 ratio (active: placebo). Safety and tolerability were evaluated by monitoring adverse events (AEs), vital signs, physical exam findings, spirometry, electrocardiograms (ECG), and analyses of safety laboratories. Blood samples were obtained periodically over 24 h for measurement of systemic exposure. ResultsThere were no significant changes from baseline in vital signs, clinical laboratory values, ECG, physical examination, or pulmonary function. There were no Serious Adverse Events (SAEs) in the study, and there were no significant adverse events. The systemic exposure to SPL84 was low and tended to be dose dependent. The exposure, expressed in terms of area under the curve to infinity (AUCinf), at the no observed adverse effect level (NOAEL) in 9-week toxicological mice study was 7.51 µg/ml*hrs, which is ∼20 times higher than the exposure at the 160 mg dose (444 ng/ml*hrs). ConclusionsSPL84 was safe and well-tolerated when administered as a single inhaled dose to HVs at doses up to 160 mg, with minimal systemic exposure. There were no safety issues observed, no SAEs, no significant related AEs, and, importantly, no significant effect on pulmonary function. The successful completion of the study enabled the initiation of multi-dosing of CF patients in a phase 2 clinical study.

Enhancing the accuracy and effectiveness of diagnosis of spontaneous bacterial peritonitis in cirrhotic patients: A machine learning approach utilizing clinical and laboratory data

PurposeSpontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid that develops naturally, without being triggered by any surgical conditions or procedures, and is a common complication of cirrhosis. With a potential mortality rate of 40 ​%, accurate diagnosis and prompt initiation of appropriate antibiotic therapy are crucial for optimizing patient outcomes and preventing life-threatening complications. This study aimed to expand the use of computational models to improve the diagnostic accuracy of SBP in cirrhotic patients by incorporating a broader range of data, including clinical variables and laboratory values. Patients and methodsWe employed 5 machine learning classification methods - Decision Tree, Support Vector Machine, Naive Bayes, K-Nearest Neighbor, and Random Forest, utilizing a variety of demographic, clinical, and laboratory features and biomarkers. ResultsAscitic fluid markers, including white blood cell (WBC) count, lactate dehydrogenase (LDH), total protein, and polymorphonuclear cells (PMN), significantly differentiated between SBP and non-SBP patients. The Random Forest model demonstrated the highest overall accuracy at 86 ​%, while the Naive Bayes model achieved the highest sensitivity at 72 ​%. Utilizing 10 key features instead of the full feature set improved model performance, notably enhancing specificity and accuracy. ConclusionOur analysis highlights the potential of machine learning to enhance the accuracy of SBP diagnosis in cirrhotic patients. Integrating these models into clinical workflows could substantially improve patient outcomes. To achieve this, ongoing multidisciplinary research is crucial. Ensuring model interpretability, continuous monitoring, and rigorous validation will be essential for the successful implementation of real-time clinical decision support systems.

Clinical and imaging predictors for the development of diabetes mellitus following a single episode of acute pancreatitis in youth

BackgroundAcute pancreatitis (AP) increases the risk of diabetes mellitus (DM). Our aim was to identify clinical, laboratory and imaging predictors of preDM/DM in youth post index AP. MethodsThis was a prospective cohort study of patients ≤21 years-old with an index admission for AP and follow up at 3 and/or 12 months. Clinical laboratory values, imaging findings, admission course, and plasma chemokine and cytokine measures collected at index admission were tested for association with preDM/DM development. A multivariable regression model was used to predict preDM/DM. ResultsAmong 187 enrolled participants, 137 (73 %) and 144 (77 %) underwent DM screening at 3 and 12 months respectively, and 137 (73 %) had imaging available. PreDM/DM occurred in 22/137 (16 %; preDM n = 21, DM n = 1) at 3 months and 23/144 (16 %; preDM n = 18, DM n = 5) participants at 12 months. Univariate associations with preDM/DM at 12 months included: severe AP (SAP) (52 % preDM/DM vs. 17 % no DM; p = 0.0008), median [IQR] IL-6 (910 pg/ml [618–3438] vs. 196 pg/ml [71–480], p < 0.05) and CRP (4.16 mg/L [1.67–10.7] vs. 1.55 mg/L [0.4–3.68], p = 0.1) at time of AP attack. The optimal multivariable model to predict preDM/DM included with clinical variables was severe acute pancreatitis (SAP), c reactive protein (CRP), interleukin-6 (IL-6), and age [AUC = 0.80; (0.70, 0.88)]. Including imaging markers, the ideal model included SAP, CRP, IL-6, subcutaneous fat area, age and presence of autoimmune disease with an AUC [0.82 (0.71, 0.90)]. ConclusionsDevelopment of preDM/DM following an index AP episode can be predicted by baseline AP severity, baseline CRP, IL-6 levels, and subcutaneous fat area.

Retrospective evaluation of medical information for predicting tazobactam/piperacillin-induced liver injury.

Tazobactam/piperacillin is a first-line treatment option for hospital-acquired pneumonia; however, drug-induced liver injury (DILI) is relatively frequently observed with tazobactam/piperacillin in clinical practice. This study aimed to verify the usefulness of available patient data for predicting DILI prior to tazobactam/piperacillin administration. Tazobactam/piperacillin-treated patients were retrospectively selected and divided into patients with and without DILI. Comparative analysis was performed regarding age, gender, dose, duration of treatment, clinical laboratory values prior to treatment initiation, and the types of organ-specific infections in both groups. Multiple logistic regression analyses indicated that elevated C-reactive protein (odds ratio (OR), 1.284; 95% confidence interval (CI), 1.172 - 1.406; p < 0.001) and high hemoglobin (OR, 1.697; 95% CI, 1.259 - 2.286; p < 0.001) levels prior to the administration of tazobactam/piperacillin were risk factors for DILI in males who received a 4.5-g dose. A predictive model for DILI risk was constructed by combining these test values and analyzed using receiver operating characteristic curves, obtaining 0.910 for the model construction set and 0.845 for the validation set. The development of DILI was predicted with good accuracy in males who received a 4.5-g dose with elevated C-reactive protein and hemoglobin.

Prediction of People With Type 2 Diabetes Not Achieving HbA1c Target After Initiation of Fast-Acting Insulin Therapy: Using Machine Learning Framework on Clinical Trial Data

Background and Aims: Glycemic control is crucial for people with type 2 diabetes. However, only about half achieve the advocated HbA1c target of ≤7%. Identifying those who will probably struggle to reach this target may be valuable as they require additional support. Thus, the aim of this study was to develop a model to predict people with type 2 diabetes not achieving HbA1c target after initiating fast-acting insulin. Methods: Data from a randomized controlled trial (NCT01819129) of participants with type 2 diabetes initiating fast-acting insulin were used. Data included demographics, clinical laboratory values, self-monitored blood glucose (SMBG), health-related quality of life (SF-36), and body measurements. A logistic regression was developed to predict HbA1c target nonachievers. A potential of 196 features was input for a forward feature selection. To assess the performance, a 20-repeated stratified 5-fold cross-validation with area under the receiver operating characteristics curve (AUROC) was used. Results: Out of the 467 included participants, 98 (21%) did not achieve HbA1c target of ≤7%. The forward selection identified 7 features: baseline HbA1c (%), mean postprandial SMBG at all meals 3 consecutive days before baseline (mmol/L), sex, no ketones in urine, baseline albumin (g/dL), baseline low-density lipoprotein cholesterol (mmol/L), and traces of protein in urine. The model had an AUROC of 0.745 [95% CI = 0.734, 0.756]. Conclusions: The model was able to predict those who did not achieve HbA1c target with promising performance, potentially enabling early identification of people with type 2 diabetes who require additional support to reach glycemic control.

Identification of biomarkers for COVID-19 associated secondary hemophagocytic lymphohistiocytosis.

We aimed to define and validate novel biomarkers that could identify individuals with COVID-19 associated secondary hemophagocytic lymphohistiocytosis (sHLH) and to test whether fatalities due to COVID-19 in the presence of sHLH were associated with specific defects in the immune system. In two cohorts of adult patients presenting with COVID-19 in 2020 and 2021, clinical lab values and serum proteomics were assessed. Subjects identified as having sHLH were compared to those with COVID-19 without sHLH. Eight deceased patients defined as COVID-sHLH underwent genomic sequencing in order to identify variants in immune-related genes. Two tertiary care hospitals in Seattle, Washington (Virginia Mason Medical Center and Harborview Medical Center). 186 patients with COVID-19. None. Nine percent of enrolled COVID-19 subjects met our defined criteria for sHLH. Using broad serum proteomic approaches (O-link and SomaScan), we identified three biomarkers for COVID-19 associated sHLH (soluble PD-L1, TNF-R1, and IL-18BP), supporting a role for proteins previously associated with other forms of sHLH (IL-18BP and sTNF-R1). We also identified novel biomarkers and pathways of COVID-sHLH, including sPD-L1 and the syntaxin pathway. We detected variants in several genes involved in immune responses in individuals with COVID-sHLH, including in DOCK8 and in TMPRSS15, suggesting that genetic alterations in immune-related genes may contribute to hyperinflammation and fatal outcomes in COVID-19. Biomarkers of COVID-19 associated sHLH, such as soluble PD-L1, and pathways, such as the syntaxin pathway, and variants in immune genes in these individuals, suggest critical roles for the immune response in driving sHLH in the context of COVID-19.

Microbial cell-free DNA-sequencing as an addition to conventional diagnostics in neonatal sepsis.

Bloodstream infections remain a challenge for neonatologists, as traditional culture-based methods are time-consuming and rely on adequate blood volume. Next-generation sequencing (NGS) offers an alternative, as it can identify microbial cell-free DNA (mcfDNA) in a small blood sample, providing rapid pathogen detection. This study aimed to assess the diagnostic performance of DISQVER®-NGS compared to blood cultures in neonatal patients with suspected sepsis. In neonates with suspected sepsis, blood cultures and samples for NGS were prospectively collected. Patients were divided into four categories: 1) sepsis, blood culture positive, 2) clinical sepsis, culture negative, 3) suspected sepsis, 4) validation cohort. NGS detected bacterial, viral or fungal mcfDNA in 24 of 82 samples. Blood cultures were collected in 46 of 84 patients (15/46 positive). DISQVER® correctly identified pathogens in 9/15 patients with a positive blood culture, two with intrinsic resistance to their antibiotic regimen. In seven samples NGS reported the mcfDNA of bacteria that could have theoretically grown in culture but did not. NGS may enhance sensitivity in sepsis diagnostics by detecting mcfDNA in neonates with suspected sepsis. Interpreting NGS results requires correlation with clinical data, laboratory values, and routine microbiological tests for a comprehensive understanding of the patient's condition. Conventional blood culture methods have limitations in accuracy and turnaround time. The study aimed to investigate the diagnostic performance of the Next-Generation Sequencing method DISQVER® compared to traditional blood cultures in neonatal patients with suspected sepsis. Our findings suggest that NGS has the potential to augment the precision of conventional diagnostic techniques, can lead to improved detection of pathogens and targeted treatment approaches in neonatal sepsis. It is emphasized that further validation and integration with clinical and microbiological data are required to ensure optimal clinical utility.

Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). To investigate clinical laboratory markers of SARS-CoV-2 and PASC. Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). 83 enrolling sites. RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. Participants completed questionnaires and standard clinical laboratory tests. Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. National Institutes of Health.

The Effect of Oral Colostrum Application on the Condition of the Mouth and Incidence of Late-Onset Sepsis Among Premature Infants: A Randomized Controlled Trial.

Premature infants have higher risks of infection due to their underdeveloped immune systems and changes to the oral cavity's normal flora colonization. To assess the effect of oral colostrum application on the condition of the mouth and the incidence of late-onset sepsis (LOS) among premature infants. In this randomized controlled trial, 70 newborn premature infants were randomly allocated to colostrum or sterile water groups. The Mouth Care Assessment Tool was used to evaluate the condition of the mouth for 5 days after oral colostrum application. The incidence of LOS was measured using clinical and laboratory indicators from 72hours after birth until discharge. The condition of the mouth was significantly different on days 4 and 5, demonstrating that the colostrum group had less need for oral care ( P <.001) compared to the control group. There was no significant difference between the 2 groups in clinical symptoms and laboratory values related to LOS ( P >.05). Oral colostrum application can benefit oral mucosal health and reduce the need for oral care among premature infants. It is also safe alternative oral care for premature infants who cannot breastfeed during the first few days of life. Future research should include infants of different gestational ages and mechanically ventilated infants to assess the effect of oral colostrum application on serum immune factors.

Non-invasive hemoglobin measurement using optical method

The measurement of Hemoglobin (Hb) by the non-invasive method is gaining popularity. The system, consisting of a photodiode is placed in between a Red (630 nm) and an IR (940 nm) LED, along with the signal conditioning circuits. 10 healthy male (8) and female (2) volunteers in the age group between 21 and 24 were recruited for this study. During measurement, the fingertip of a volunteer was placed on the measurement pad. Visible and IR lights are switched ON one after the other. The optical absorbance of the blood component in the arteries was detected by the photodiode using the reflectance method. The current generated was converted into voltage and was processed to remove the noise associated with the signal. From this, the concentration of Hb of the volunteers was determined. On the same day they were taken to the clinical laboratory and Hb values were obtained by the standard invasive method. Hemoglobin values obtained from the two methods were compared and an accuracy of 96.31 % and correlation coefficient value of 0.932405 was achieved. From the Bland -Altman plot, the results obtained are within the confidence interval of 95 %. The error of 3 % can be reduced further by employing sophisticated signal conditioning techniques. The proposed non-invasive method took only a few seconds to find the hemoglobin concentration than the invasive lab test. This method can accelerate the decision-making process in emergency situations.

Effectiveness of metformin pretreatment for stroke severity: A propensity score matching study.

Metformin pretreatment might have neuroprotective effects. We aimed to determine the therapeutic effects of the antidiabetic medication metformin on ischemic stroke severity and discharge outcomes. We analyzed data on 1303 ischemic stroke patients who were on antidiabetic medications from the Massachusetts General Hospital (MGH) Advanced Comprehensive Stroke Center dataset (n = 8943, 2012-2022). We applied propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses to investigate the effect of current usage of metformin (versus alternate antidiabetic treatment) on acute stroke clinical severity and discharge outcomes. Of the 1303 patients who were on antidiabetic medications at the time of stroke admission, 730 (56%) were taking metformin. Metformin users were younger and more frequently had hypertension, whereas less frequently had prior CAD, AFib, and chronic kidney disease. The clinical features and laboratory values of the two groups were evenly distributed after PSM. Metformin-treated patients had statistically significant lower stroke severity on admission [National Institutes of Health Stroke Scale (NIHSS) (median, interquartile range) 3.0 (1.0-8.0) vs. 4.0 (2.0-11.3), p = 0.011], better functional independence at discharge (modified Rankin scale score 0-2, 36.3% vs. 25.4%, p < 0.001) and less in-hospital mortality (4.5% vs. 11.3%, p = 0.018). IPTW analysis results were consistent with PSM results. Among diabetic patients with acute ischemic stroke, metformin appears to confer neuroprotection. Our results extend previous findings to the general stroke population. Stroke patients with diabetes mellitus who were treated with metformin prior to stroke, even when combined with additional antidiabetic medications, experienced less severe strokes upon admission and had better functional outcomes during hospitalization.

Predictors of massive transfusion protocols activation in patients with trauma in Korea: a systematic review.

Massive transfusion protocols (MTPs) implementation improves clinical outcomes of the patient's resuscitation with hemorrhagic trauma. Various predictive scoring system have been used and studied worldwide to improve clinical decision. However, such research has not yet been studied in Korea. This systematic review aimed to assess the predictors of MTPs activation in patients with trauma in Korea. The PubMed, Embase, Cochrane Library, Research Information Sharing Service databases, KoreaMed, and KMbase were searched from November 2022. All studies conducted in Korea that utilized predictors of MTPs activation in adult patients with trauma were included. Ten articles were eligible for analysis, and the predictors were assessed. Clinical assessments such as systolic and diastolic blood pressure, shock index (SI), prehospital modified SI, modified early warning system (MEWS) and reverse SI multiplied by the Glasgow Coma Scale (rSIG) were used. Laboratory values such as lactate level, fibrinogen degradation product/fibrinogen ratio, and rotational thromboelastometry (ROTEM) were used. Imaging examinations such as pelvic bleeding score were used as predictors of MTPs activation. Our systematic review identified predictors of MTPs activation in patients with trauma in Korea; predictions were performed using tools that requires clinical assessments, laboratory values or imaging examinations only. Among them, ROTEM, rSIG, MEWS, SI, and lactate level showed good effects for predictions of MTPs activation. The application of predictors for MTP's activation should be individualized based on hospital resource and skill set, also should be performed as a clinical decision supporting tools.

Assessing the impact of COVID-19 on acute leukemia patients: a comparative analysis of hematological and biochemical parameters

BackgroundThe impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia.MethodsThis retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained.ResultsThe majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2.ConclusionWhile this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.

Racial Disparity in Microvascular Function in Men with Newly Diagnosed Prostate Cancer

BACKGROUND:Cardiovascular disease (CVD) is a leading cause of death in men with prostate cancer. In addition, non-Hispanic Black (NHB) men experience worse CVD-related mortality compared to their non-Hispanic White (NHW) counterparts, although the reason for this racial disparity remains unclear. Notably, vascular endothelial dysfunction often precedes the emergence of overt CVD. Indeed, conduit-vessel dysfunction, micro-vascular dysfunction, and arterial stiffness are independent predictors of CVD risk. Thus, the purpose of this study was to comprehensively assess vascular health in recently diagnosed NHB and NHW men with prostate cancer. Methods: Twenty-eight men (10 NHW, 18 NHB) with a new clinical diagnosis of prostate cancer (within 3 months) participated in this study. Flow-mediated dilation (FMD) was performed to represent conduit-vessel vascular endothelial function. Cutaneous post occlusive reactive hyperemia (PORH) with local thermal heating (LTH) and iontophoresis of acetylcholine were performed to represent various mechanisms regulating microvascular function. Lastly, pulse wave velocity (PWV) and pulse wave analysis (PWA) were performed to assess central and aortic stiffness, respectively. Data are reported as mean ± SD. Results: A 4-year age difference ( p=0.131) was observed between NHB (65±7 years) and NHW (69±6 years) men. No differences in BMI or clinical laboratory values were observed between NHB and NHW patients (all p&gt;0.05). NHB men exhibited significantly lower microvascular function compared to NHW men, including PORH (NHB: 117±44 PU vs NHW: 207±47 PU; p&lt;0.001), LTH (NHB: 180±73 PU vs NHW: 281±65 PU; p=0.003), and iontophoresis (NHB: 67±28 PU vs NHW: 136±38 PU; p&lt;0.001). No differences in FMD ( p=0.596), PWV ( p=0.695), or PWA ( p=0.883) were observed between groups. CONCLUSION: The results of the current study provide compelling evidence that microvascular dysfunction is present in NHB men who are recently diagnosed with prostate cancer compared to their NHW counterparts. Given that NHB men were 4 years younger, these data support that the microvascular dysfunction may accelerate vascular aging and contribute to the racial disparity in CVD following prostate cancer diagnosis. Supported by: AHA SFRN 863621 (RAH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Study of Cerebral Venous Sinus Thrombosis with Special Reference to Newer Risk Predictors.

Cerebral venous thrombosis (CVT) is an uncommon and frequently unrecognized type of stroke that affects approximately five people per million annually, accounts for 0.5 to 1% of all strokes, and is more commonly seen in young individuals. The exact incidence of CVT in India remains unknown. The risk factors for venous thrombosis in general are linked classically to the Virchow's triad of stasis of the blood, changes in the vessel wall, and changes in the composition of the blood. There have been numerous studies evaluating long-term as well as short-term outcomes in the presence of these inflammatory mediators. They have been reported to be beneficial in predicting outcome and, hence, potentially in guiding management. Evaluation of prevailing risk factors associated with cerebral venous sinus thrombosis (CVST). Description of the distribution of newer inflammatory markers among the study population and their association with functional and neurologic outcome at 30 days following the occurrence of cerebral VST. Approval from the Institutional Review Board was obtained. Written informed consent was given by willing patients, explained in vernacular. Relevant details were obtained via a clinical history and laboratory values and imaging data obtained from the hospital's electronic health information system, which were then recorded in the proforma. No personal identifying data was collected. The sample size for this study was lower than originally planned, owing to the coronavirus disease 2019 (COVID-19) pandemic. The patients were called for follow-up after 1 month of the detection of VST, and their neurologic status was recorded on the Glasgow Coma Scale (GCS) and functional status on the modified Rankin Scale (mRS). Descriptive analysis of baseline characteristics was done. Mann-Whitney U and Kruskal-Wallis H tests of significant difference between means for nonparametric data were used. Linear regression was carried out on the variables found to differ significantly among subpopulations having good and poor neurologic outcomes. Receiver operating characteristic (ROC) curves were then derived for both outcome categories. The study enrolled 30 patients, with ages from 18 to 70 years, of which 19 (63.3%) were male and 11 (36.67%) were female. No risk factor was identified in 23.3% of cases. The most common risk factor was the presence of substance abuse. Among presenting features, headaches were the most common, followed by seizures and focal neurologic deficits (83.3, 30, and 23.3, respectively). Coexisting intraparenchymal hemorrhage was seen in 46.67% of patients, with the transverse sinuses most commonly involved (28.77%). The median neutrophil-to-lymphocyte ratio (NLR) was 3.415 [interquartile range (IQR) 2.634-5.637], with median platelet-to-lymphocyte ratio (PLR) 160.728 (IQR 107.728-227.776) and median systemic immune-inflammation index (SII) 1067.883 (IQR 509.694-1522.837). The NLR, PLR, and SII values were found to differ significantly among subgroups having good and poor neurologic outcome on the mRS. PLR and SII significantly differed among subgroups with venous involvement and among subgroups with good and poor neurologic status on GCS, on admission as well as 30-day follow-up. NLR, PLR, and SII values on admission showed a positive association with poor neurologic outcomes. Here, a significant correlation is seen between the values of complete blood count (CBC)-derived inflammatory markers on admission. Higher-powered studies are needed to assess the potential benefits of incorporating these markers in existing risk stratification models to improve their predictive accuracy.

Two cases of diquat poisoning in adolescent children

Diquat (DQ) is among the most widely used herbicides, and its intake can cause severe systemic toxicity that manifests rapidly. The resultant symptoms can cause the dysfunction of a range of tissues and organs,. As there is no specific antidote for diquat poisoning and the efficacy of extant treatments is suboptimal, physicians must acquire a more comprehensive understanding of the most effective approaches to managing affected patients. Relative few studies have been published to date focused on diquat poisoning in pediatric patients. In this report, we compare two similar cases of juvenile diquat poisoning with dynamic changes in clinical manifestations, laboratory values, and imaging results. For the first time, the difference in whether to perform blood flow perfusion and the time difference of initiation of hemoperfusion had a clear clinical difference in the subsequent effects of diquat poisoning in children with diquat poisoning. Limited evidence is available regarding the efficacy of early hemoperfusion for diquat poisoning; however, the differences in clinical outcomes articulated here highlight the benefits of early and timely hemoperfusion therapy in the treatment of DQ toxicity in children, in conjunction with primary supportive care in the management of DQ poisoning in children.

Retrospective Assessment of Metabolic Syndrome and Cardiovascular Disease Risk Following Monthly and Three-Month Long-Acting Paliperidone Palmitate Treatment in Schizophrenia

IntroductionPatients with schizophrenia exhibit a higher prevalence of metabolic syndrome and cardiovascular diseases compared to the general population, resulting in increased mortality rates. The extent of this risk may vary based on the specific treatment employed.ObjectivesThis study aims to compare the risk assessments of metabolic syndrome and cardiovascular diseases in schizophrenia patients who transitioned from monthly long-acting paliperidone palmitate (PP1M) treatment to three-month long-acting paliperidone palmitate (PP3M) treatment during both treatment periods.MethodsThe research was conducted at the Psychiatry Clinic and Psychotic Disorders Outpatient Clinic of Selcuk University Faculty of Medicine. Eligible participants included patients under PP3M treatment for a minimum of 6 months and undergoing continuous monitoring in the psychotic disorders outpatient clinic. Sociodemographic and clinical data, scales, laboratory values, and measurements taken both before and during the use of PP3M and PP1M were retrieved from file records, encompassing assessments, analyses, and examinations conducted in accordance with the “Psychotic Disorders - Treatment Monitoring Protocol.” Ethical approval was obtained from the Selcuk University Ethics Committee.Results Among the 31 patients transitioning from PP1M to PP3M treatment, 15 (48.4%) were female. The mean age of the patients was 44.4±14.4 years. No statistically significant differences were observed in the mean values of clinical evaluation and side effect assessment scales, body mass index (BMI), waist-to-hip ratio, systolic blood pressure, glucose levels, cholesterol levels, prolactin levels, and thyroid-stimulating hormone (TSH) measurements between the pre- and post-treatment phases (p&gt;0.05). However, a significant difference was identified in the mean Qrisk3 values, a cardiovascular risk index, in two distinct measurements (10-year risk score: PP1M 3.7±4.2 and PP3M 4.6±4.8, p=0.003).Conclusions Our study, designed to investigate the impact of the monthly and three-month long-acting formulations of the same antipsychotic drug on patients’ clinical status, side effects, and general health parameters, found that PP3M treatment did not significantly differ from PP1M treatment in terms of Qrisk3 values. Despite the lack of statistical significance between the parameters used in Qrisk3 calculation, the observed significant difference in Qrisk3 values is attributed to variations in age. In order to promote the widespread adoption of long-acting treatments in schizophrenia management, clinicians should engage in comprehensive comparative studies assessing both efficacy and side effects.Disclosure of InterestNone Declared

Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation.

Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC(based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 μg, B: 18 or 36 μg, or C: 36 or 72 μg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35or ≥35 kg) and linaclotide (18, 36, 72, or 145 μg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBMfrequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 μg]and 2.86 in 12- to 17-year-olds [72 μg]). The most reported treatment-emergent AEwas diarrhea, with most cases being mild; none were severe. Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.

Pan-Immune-Inflammation Value Could Be a New Marker to Predict Amyloidosis and Disease Severity in Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is characterized by recurrent episodes of fever and serositis. Blood-based biomarkers determined in FMF patients during attack-free periods could be used to predict the risk of amyloidosis and the severity of the disease. The recently defined pan-immune-inflammation value (PIV) comprises four distinct subsets of blood cells and serves as an easily accessible and cost-effective marker. The objective of this study was to assess the role of PIV in predicting amyloidosis and moderate-to-severe disease. Clinical characteristics and laboratory values during the attack-free period were retrospectively analyzed in 321 patients over 18 years of age diagnosed with familial Mediterranean fever (FMF). In our tertiary adult rheumatology outpatient clinic, disease severity and laboratory markers were evaluated during the first attack-free interval. At baseline, patients with amyloidosis were excluded. Patients were categorized based on the presence of amyloidosis and the severity of the disease. When focusing on amyloidosis in receiver operating characteristic (ROC) analysis, optimal cut-off values for pan-immune-inflammation value (PIV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio were determined as ≥518.1, ≥2.3, and ≥127.2, respectively. In multivariate analysis, PIV, C-reactive protein (CRP), and the presence of the M694V homozygous mutation emerged as independent risk factors for both amyloidosis and moderate-to-severe disease. Additionally, NLR was identified as an independent risk factor for amyloidosis, while red blood cell distribution width was associated with moderate-to-severe disease. In patients with FMF, especially in the presence of the M694V homozygous mutation, CRP and PIV may be useful in predicting both amyloidosis and moderate-to-severe disease.

Safety and Tolerability of the APOL1 Inhibitor, Inaxaplin, following Single- and Multiple-Ascending Doses in Healthy Adults

Introduction: Toxic gain-of-function Apolipoprotein L1 (APOL1) variants contribute to the development of proteinuric nephropathies collectively referred to as APOL1-mediated kidney disease (AMKD). Despite standard-of-care treatments, patients with AMKD experience accelerated progression to end-stage kidney disease. The identification of two APOL1 variants as the genetic cause of AMKD inspired development of inaxaplin, an inhibitor of APOL1 channel activity that reduces proteinuria in patients with AMKD. Methods: We conducted two phase 1 studies evaluating the safety, tolerability, and pharmacokinetics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of inaxaplin in healthy participants. In the SAD cohorts, participants were randomized to receive inaxaplin as a single dose (range, 7.5 mg to 165 mg) or placebo. In the MAD cohorts, participants were randomized to receive multiple doses of inaxaplin (range, 15 to 120 mg daily) or placebo for 14 days. We assessed safety and tolerability based on adverse events (AEs), clinical laboratory values, electrocardiograms (ECGs), and vital signs. Results: A total of 178 participants were randomized in the SAD/MAD cohorts of both studies (mean age: 36.7 years; 94.9% male). The proportion of participants with any AEs was similar in the inaxaplin (24.6%) and placebo (22.7%) groups. All AEs were mild or moderate in severity; there were no serious AEs. Headache was the most common AE: 10.4% and 2.3% in the inaxaplin and placebo groups, respectively. There were no drug-related treatment discontinuations and no clinically relevant trends in laboratory values, ECGs, or vital signs. Discussion/Conclusion: Inaxaplin is safe and well tolerated at single doses up to 165 mg and multiple doses up to 120 mg daily for 14 days. These results are consistent with the favorable safety profile of inaxaplin in a completed phase 2a proof-of-concept study. Together, these findings support continued evaluation of inaxaplin in an ongoing phase 2/3 pivotal trial as a potential precision medicine for patients with AMKD.