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Objectives: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. Method and materials: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). Results: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. Conclusion: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health. [ABSTRACT FROM AUTHOR]

Background: The cycle threshold (Ct) value is inversely proportional to the number of copies of the target region in a sample, suggesting that a low Ct value indicates a high pathogen load. The relationship between Ct value and clinical presentation in children with pertussis is not well-defined. Methods: We investigated the relationships between the Ct value of nasopharyngeal samples positive for Bordetella pertussis deoxyribonucleic acid via real-time polymerase chain reaction (PCR), collected from children on admission and their adult family members between May 2022 and March 2024 at Hangzhou Children's Hospital, China. The study focused on the correlation between Ct value and clinical presentation in children with pertussis. Results: The Ct value was positively correlated with age (r = 0.362, P = 0.001). The mean Ct value for children with pertussis was 28.0 (range: 22.0–32.0), which was lower than the 32.0 (range: 30.0–34.0) observed in adults. Ct value was inversely correlated with length of stay, an indicator of disease severity (r = -0.356, P = 0.001). Logistic regression analyses revealed that both Ct value (OR: 0.891, 95% CI: 0.799–0.993, P = 0.036) and white blood cell count (OR: 1.127, 95% CI: 1.005–1.263, P = 0.040) were independently associated with severity of pertussis. Conclusions: Real-time PCR Ct values at initial diagnosis for pertussis may potentially predict severe disease outcomes in children. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs.A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020.Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016–1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145–2.913), existing liver disease (OR = 2.464, 95% CI: 1.822–3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681–16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs.Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre‐existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity. [ABSTRACT FROM AUTHOR]

Genome wide association studies (GWAS) have associated thousands of loci with quantitative human blood trait variation. Loci and related genes that impact blood trait variation may regulate blood cell-intrinsic biological processes, or alternatively impact blood cell development and function via systemic factors. Clinical observations have linked tobacco or alcohol use with altered blood traits, but these trait relationships have not been systematically explored at the genetic level. Applying a Mendelian randomization (MR) framework to GWAS summary statistics, we explore relationships between smoking and drinking behaviors with 15 quantitative blood traits. We find that the effects of smoking and drinking are confined to red blood cell traits. An instrumental variable (IV) comprised of 113 single nucleotide polymorphisms (SNPs) associated with smoking initiation is associated with decreased hemoglobin (HGB: Effect = -0.07 standard deviation units [95% confidence interval = -0.03 to -0.10 SD units], P = 1x10-4), hematocrit (HCT: Effect = -0.06 [-0.03 - -0.09] SD units, P = 4x10-4), and red blood cell count (RBC: Effect = -0.05 [-0.02 - -0.09] SD units, P = 5x10-3) without impacting platelet count (P = 0.9) or white blood cell count (P = 0.6). Similarly, an IV associated with an increased number of alcoholic drinks consumed per week is associated with decreased HGB (Effect = -0.22 [-0.42 - -0.02] SD units, P = 3x10-2) and RBC (Effect = -0.27 [-0.51 - -0.03] SD units, P = 3x10-2). Using multivariable MR and causal mediation analyses, we find that an increased genetic predisposition to smoking initiation is associated with increased alcohol intake, and that alcohol use mediates the genetic effect of smoking initiation on red blood cell traits. These findings demonstrate a novel role for genetically influenced behaviors on human blood traits, revealing opportunities to dissect related pathways and mechanisms that influence hematopoiesis and blood cell biology. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to assess the use of machine learning methodologies in the diagnosis of endometriosis (EM). Methods: This study included a total of 106 patients with EM and 203 patients with non-EM conditions (like simple cysts and simple uterine fibroids), all admitted to the Shunyi Women's and Children's Hospital of Beijing Children's Hospital between January 2017 and September 2022. All participants were free of comorbidities and their diagnoses were confirmed via postoperative pathology. Comparative analysis was conducted between the EM and non-EM groups. Baseline data were assessed, including white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, mean platelet volume, hemoglobin, carbohydrate antigen 125 (CA125), carbohydrate antigen 199, coagulation parameters, and other serologic indicators. An optimal predictive model was developed using an artificial intelligence algorithm to determine the presence of EM. The objective is to provide new insights for the clinical diagnosis and treatment of EM. Results: The random forest algorithm demonstrated superior performance when compared to decision trees, LogitBoost, artificial neural networks, naïve Bayes, support vector machines, and linear regression in machine learning methods. Combining CA125 with the NLR yielded a better prediction of EM than using CA125 alone when applying the random forest algorithm. The accuracy of predicting EM with CA125 combined with NLR was 78.16%, with a sensitivity of 86.21% and an area under the curve (AUC) of 0.85 (P < 0.05). In contrast, using CA125 alone resulted in an EM prediction accuracy of 75.8%, with a sensitivity of 79.3% and an AUC of 0.82 (P < 0.05). Conclusion: The diagnostic value of serum CA125 combined with the NLR for EM is higher than that of serum CA125 alone. This finding indicates that NLR could serve as a new supplementary biomarker along with serum CA125 in the diagnosis of EM. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth. Case presentation: A 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/μL to 8490/μL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45. Conclusions: G-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodResultConclusionThe mechanism linking BMI and asthma remains unclear.Mendelian Randomization (MR) analysis was conducted using summary-level GWAS data from the FinnGen Biobank and the Open GWAS project. The analysis considering potential variables as mediators, including blood cell counts, blood pressure, and blood biomarkers. Three commonly used MR methods—the inverse-variance-weighted (IVW) method, weighted median (WM) method, and MR-Egger method—were employed to infer causal links. A two-step approach was used in mediation analysis to evaluate the causal links among BMI, candidate mediators, and asthma.Elevated BMI demonstrated a substantial correlation with increased asthma risk. Thirteen biomarkers mediated the relationship between BMI and asthma, mainly including leukocyte count (5.070%), apolipoprotein A levels (7.395%), cystatin C levels (5.345%), urate levels (9.057%), diastolic blood pressure (7.365%), and albumin levels (10.888%). These factors collectively explained over 50% of the increased asthma risk associated with BMI elevation. Additionally, eosinophil count and C-reactive protein were also identified as important mediators using the WM method.This study highlights the complex relationship between obesity, blood biomarkers, and asthma risk. Additional studies are required to validate these results and investigate causal relationships in various populations. [ABSTRACT FROM AUTHOR]

Background and purpose: Spontaneous aneurysmal subarachnoid hemorrhage (aSAH) is a common acute cerebrovascular disease characterized by severe illness, high mortality, and potential cognitive and motor impairments. We carried out a retrospective study at Fujian Provincial Hospital to establish and validate a model for forecasting functional outcomes at 6 months in aSAH patients who underwent interventional embolization. Methods: 386 aSAH patients who underwent interventional embolization between May 2012 and April 2022 were included in the study. We established a logistic regression model based on independent risk factors associated with 6-month adverse outcomes (modified Rankin Scale Score = 3, mRS). We evaluated the model's performance based on its discrimination, calibration, clinical applicability, and generalization ability. Finally, the study-derived prediction model was also compared with other aSAH prognostic scales and the model's itself constituent variables to assess their respective predictive efficacy. Results: The predictors considered in our study were age, the World Federation of Neurosurgical Societies (WFNS) grade of IV-V, mFisher score of 3-4, secondary cerebral infarction, and first leukocyte counts on admission. Our model demonstrated excellent discrimination in both the modeling and validation cohorts, with an area under the curve of 0.914 (p < 0.001, 95%CI = 0.873-0.956) and 0.947 (p < 0.001, 95%CI = 0.907-0.987), respectively. Additionally, the model also exhibited good calibration (Hosmer-Lemeshow goodness-of-fit test: X2 = 9.176, p = 0.328). The clinical decision curve analysis and clinical impact curve showed favorable clinical applicability. In comparison to other prediction models and variables, our model displayed superior predictive performance. Conclusion: The new prediction nomogram has the capability to forecast the unfavorable outcomes at 6 months after intervention in patients with aSAH. [ABSTRACT FROM AUTHOR]

A 48-year-old female presented to the emergency department with severe fatigue. Admission laboratory test results were hemoglobin 6.6 g/dL, platelet count 287,000/μL, and white blood cell count 25,200/μL. Lactate dehydrogenase was elevated at 898 U/L, haptoglobin was markedly decreased (< 31 mg/dL), indirect bilirubin was elevated (5.3 mg/dL), and the absolute reticulocyte count was low at 0.0050/μL. A sample was sent to the immunohematology reference laboratory. The direct antiglobulin test immunoglobulin G was negative; C3 was 1+. All cells were reactive at immediate spin phase, indirect antiglobulin testing (IAT) with polyethylene glycol, with low ionic strength saline, neat, prewarm, and in the solid phase. All cells were nonreactive at IAT-ficin. Additional testing included a cold antibody titer that was 1:4096 and thermal amplitude studies demonstrating reactivity of 2+ at 37°C. These results were consistent with a clinically significant anti-Pr and cold agglutinin disease (CAD). Although rituximab is effective in autoimmune hemolytic anemia, this may take weeks. The patient was treated with pegcetacoplan, a pegylated peptide that targets C3 inhibiting hemolysis. The patient was discharged on day 29 with a hemoglobin of 8 g/dL. This is a report of one of the first patients successfully treated with pegcetacoplan for CAD. [ABSTRACT FROM AUTHOR]

Background: Tularemia is one of the most prevalent zoonoses across the world. Patients in Turkiye mostly contract the oropharyngeal form, acquired through drinking, or contact with microorganism-contaminated water. Methods: Patients with oropharyngeal tularemia aged under 18 years and diagnosed between January 01, 2017, and December 31, 2020, were evaluated retrospectively. Tularemia was diagnosed in patients with compatible histories, symptoms, clinical presentations, and laboratory test results. Results: The mean age of 38 children was 12.1 ± 3.4 years, and the female/male ratio was 0.58 (14/24). The mean duration of symptoms on admission was 33.8 ± 26.2 days. All children had enlarged lymph nodes. Malaise, fever, and loss of appetite were other frequent symptoms. Patients were treated with antibiotics for a mean of 26.2 ± 18.8 days. Gentamycin was the most frequently used antibiotic (either alone or in combination) (n = 29, 76.3%). Twenty-six (68.4%) patients underwent surgical procedures in addition to antibiotherapy. Five (13.2%) required secondary total excision. Patients with higher leukocyte counts at admission received a combination of antibiotherapy plus surgery, rather than antibiotics alone. No relapses, reretreatment requirement, or mortality were observed after 12 months of follow-up. Conclusions: Oropharyngeal tularemia in children can require longer courses of antibiotic treatment with more than one drug and more frequent surgery than previously suggested in the literature, especially if the patients are admitted late to the hospital, symptom duration is prolonged, and appropriate treatment is initiated late. Higher leukocyte counts on admission may be prognostic for longer antibiotic treatment course and suppurative complications that require surgery. Raising awareness among patients and physicians is essential. [ABSTRACT FROM AUTHOR]

Background: A number of acute ischemic stroke (AIS) cases may be misdiagnosed as transient ischemic attack (TIA), due to no infarct on initial computed tomography scan and/or mild deficits upon presentation. Several studies have found that the neutrophil–lymphocyte ratio (NLR) is an accurate differential diagnostic biomarker for AIS versus TIA; however, no study has evaluated the use of the NLR in differentiating CT negative AIS from TIA. Furthermore, the systemic immune-inflammation index (SII) is a relatively novel immune biomarker that has been shown to be positively correlated with AIS severity, poor functional outcomes and mortality. The purpose of this study is to determine if NLR or SII can be used as a diagnostic biomarker for the differential diagnosis of mild AIS with a negative CT upon admission and TIA. Methods: We performed a retrospective medical record review of patients diagnosed with either AIS or TIA. We collected peripheral white blood cell counts within 24 h of symptom onset and calculated the NLR and SII. Logistic regression was utilized to determine if NLR or SII are significant predictors of CT negative mild AIS. Results: CT negative mild AIS patients were 2 times as likely to have an NLR ≥ 2.71 compared to TIA patients, and CT negative mild AIS patients were 2.1 times as likely to have an SII ≥ 595 compared to TIA patients. Conclusion: NLR and SII are easily obtained biomarkers that can be used in early clinical decision making in cases of mild AIS with negative CT scan upon admission. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in France that examines the role of basophils in asthma. The researchers found that individuals with asthma had higher levels of basophils compared to those without asthma. Basophil count also correlated with eosinophil count and varied depending on the inflammatory phenotype. Participants with high basophil count were more likely to develop eosinophilic/mixed asthma and experience symptoms such as nocturnal cough and chest tightness. The study suggests that basophils may have a role in asthma and could potentially be used as biomarkers, but more research is needed to confirm these findings. [Extracted from the article]

Objective: Development of a nomogram model for predicting the magnitude of risk of transferring hospitalized children with influenza to the ICU. Methods: In a single-center retrospective study, 318 children with influenza who were hospitalized in our hospital from January 2018 to August 2023 were collected as study subjects. Children with influenza were randomly assigned to the training set and validation set in a ratio of 4:1. In the training set, risk factors were identified using univariate and multivariate logistic regression analyses, and a nomogram model was created on this basis. The validation set was used to evaluate the predictive power of the model. Results: Multifactorial logistic regression analysis revealed six independent risk factors for transfer to the ICU in hospitalized children with influenza, including elevated peripheral white blood cell counts, elevated large platelet ratios, reduced mean platelet width, reduced complement C3, elevated serum globulin levels, and reduced total immunoglobulin M levels. Using these six metrics as predictors to construct a nomogram graphical model, the C-index was 0.970 (95% Cl: 0.953–0.988). The areas under the curve for the training and validation sets were 0.966 (95%Cl 0.947–0.985) and 0.919 (95%Cl 0.851–0.986), respectively. Conclusion: A nomogram for predicting the risk of transferring to the ICU for children with influenza was developed and validated, which demonstrates good calibration and clinical benefits. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the dynamic changes and interrelationships between leukocyte components and inflammatory markers in the early stages and sepsis stage in severe burns, and explore their potential clinical significance. This is a 5-year retrospective cohort study involving 107 patients with severe burns (the total body surface area of burn (TBSA) > 50%), in which, neutrophil count, lymphocyte count, monocyte count, the ratio of the product of monocyte and lymphocyte count to neutrophil count (MLPN), procalcitonin (PCT), C-reactive protein (CRP), capillary leakage index (CLI) and creatinine (Scr) were investigated. Within one week after injury, the leukocyte components and MLPN showed a V-shaped change, with a peak immediately after injury and a trough on the 4th or 5th day after injury, while CRP showed a continuous upward trend, and the leukocyte compositions of all patients were negatively correlated with CRP values. The counts of leukocytes components and CRP values in deceased patients were higher than those in surviving patients within 2 days after injury. In the resorption stage, although no significant difference in lymphocyte and monocyte counts between surviving and deceased patients was found, the monocyte and lymphocyte counts in deceased patients were lower than those in surviving patients on the 5th to 7th day after injury, while neutrophils counts and CRP values remained higher than those in surviving patients. And the dynamic changes of MLPN were consistent with those of leukocyte compositions and opposite to those of PCT values. Moreover, MLPN were negatively correlated with CRP, CLI, and Scr values in the early stage of severe burns. In sepsis stage, as the condition worsened, the values of CRP, PCT and neutrophil counts continuously increased with varying degree, while lymphocyte and monocyte counts, and MLPN showed continuously decrease, but rebounded to increase before death. And the occurrence of the trough of monocyte counts was earlier than that of lymphocyte counts, a negative correlation between neutrophil counts and PCT values was found. The results of this study revealed the dynamic interrelationships between leucocyte components and inflammatory indicators in the early stages and sepsis stage in severe burns, reflecting the different weightings of inflammatory responses and immune dysfunction in different disease stages and its correlation with outcomes, which providing useful clinical information for dynamic immunomodulatory therapy. Moreover, dynamic monitoring of MLPN value can provide timely information for clinical evaluation. ● Within one week after injury, the leukocyte components were negatively correlated with CRP values. ● The trend of changes in MLPN values was similar to leukocyte components in the early stage after injury. ● A negative correlation between neutrophil counts and PCT values was found in sepsis stage. ● The occurrence of lowest value of monocyte count was earlier than that of lymphocyte count in sepsis stage. ● Lymphocyte and monocyte counts, and MLPN values rebounded to increase before death in sepsis stage. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the effect of supplementing chitosan, Bacillus subtilis or blends of both on broiler growth performance, immune response, biochemical variables, and intestinal ecology of broiler chickens. Two hundred and eighty day-old chicks were distributed into 4 experimental groups, including T0 (control, basal feed), T1 (basal feed + chitosan 0.1% feed), T2 (basal feed + B. subtilis 0.01% feed), and T3 (basal feed + chitosan 0.1% feed + B. subtilis 0.01% feed). Variables measurements and sample collection were conducted on day 35. The T3 did not differ from T0 and T1, but they consumed less (p=0.05) feed than T2 chickens. Feed conversion ratio (FCR) was lower (p=0.05) in T1 and T3 compared to T0 and T2 groups. Leukocyte counts in T2 and T3 were higher (p=0.05) than those in T0. The T1, T2, and T3 had higher (p=0.05) lymphocyte counts than T0. The T3 had lower (p=0.05) low-density lipoprotein (LDL) levels than the T0 group. The T2 had higher (p=0.05) levels of total protein and globulin than T3 and T0. Compared to T0 and T3, serum albumin levels were greater (p=0.05) in T1 and T2. The T3 had higher (p=0.05) duodenal villi height than that in the other groups. The T2 and T3 chicks had higher (p=0.05) Newcastle disease titer than T0 and T1. Compared to T2 and T3, T0 and T1 showed a worse (p=0.05) microscopic structure of jejunum. The T2 and T3 showed lower (p=0.05) lesion score in bursa of fabricius than that in the other groups. In conclusion, the blends of chitosan and B. subtilis resulted in improved FCR, higher leukocyte and lymphocyte counts, lower LDL, higher duodenal villi height, higher Newcastle disease titer, better microscopic structure of jejunum, and lower lesion score in bursa of fabricius of broiler chickens. [ABSTRACT FROM AUTHOR]

Trastuzumab deruxtecan has shown encouraging activity in patients with treatment-refractory HER2-positive, RAS wild-type and BRAF wild-type metastatic colorectal cancer. Dose optimisation and further antitumour assessments in patients with RAS mutations and those with previous anti-HER2 therapy are warranted. We aimed to evaluate two doses of trastuzumab deruxtecan (5·4 mg/kg and 6·4 mg/kg) to establish the recommended dose in patients with pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer. DESTINY-CRC02 was a multicentre, randomised, two-stage, two-arm, phase 2 study done in 53 research hospitals and medical centres in Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, the UK, and the USA. Eligible patients were aged 18 years and older or 20 years and older (depending on region) with pretreated pathologically documented, unresectable, recurrent, or metastatic HER2-positive, and RAS wild-type or mutant colorectal cancer. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and have received previous chemotherapy, and anti-EGFR, anti-VEGF, or anti-PD-L1 therapy, if clinically indicated. In stage 1, patients were randomly assigned (1:1), via a secure interactive response technology system, to receive 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan administered intravenously every 21 days. Stratification factors were ECOG performance status, HER2 status, and RAS status. In stage 2, patients were assigned into the 5·4 mg/kg treatment group only. The primary endpoint was confirmed objective response rate by blinded independent central review, assessed in all patients for whom treatment was assigned (full analysis set). Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04744831 , and is ongoing (not recruiting). Between March 5, 2021, and March 29, 2022, 135 patients were centrally screened, 122 of whom were enrolled. In stage 1, 40 patients each were randomly assigned to receive trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg. In stage 2, an additional 42 patients were enrolled in the 5·4 mg/kg group. 64 (52%) participants were male and 58 (48%) were female. The median duration of follow-up was 8·9 months (IQR 6·7–10·5) in the 5·4 mg/kg group and 10·3 months (5·9–12·7) in the 6·4 mg/kg group. The confirmed objective response rate by blinded independent central review was 37·8% (31/82 [95% CI 27·3–49·2]) in the 5·4 mg/kg group and 27·5% (11/40 [14·6–43·9]) in the 6·4 mg/kg group. 34 (41%) of 83 patients in the 5·4 mg/kg group and 19 (49%) of 39 in the 6·4 mg/kg group had grade 3 or worse drug-related treatment-emergent adverse events. The most common grade 3 or worse drug-related treatment-emergent adverse events were neutrophil count decreased (13 [16%] of 83 patients), anaemia (six [7%]), nausea (six [7%]), and white blood cell count decreased (five [6%]) in the 5·4 mg/kg group; and were neutrophil count decreased (10 [26%] of 39 patients), anaemia (eight [21%]), platelet count decreased (four [10%]), and white blood cell count decreased (four [10%]) in the 6·4 mg/kg group. Drug-related serious adverse events occurred in 11 (13%) of 83 patients in the 5·4 mg/kg group and six (15%) of 39 patients in the 6·4 mg/kg group; the most common in the 5·4 mg/kg group was nausea (three [4%] patients) and the most common in the 6·4 mg/kg group were fatigue (two [5%] patients), neutropenia (two [5%]), and thrombocytopenia (two [5%]). A drug-related treatment-emergent adverse event related to death occurred in one (1%) patient in the 5·4 mg/kg group (due to hepatic failure). Adjudicated drug-related interstitial lung disease or pneumonitis events were observed in seven (8%) patients in the 5·4 mg/kg group (all grade 1 or 2) and in five (13%) patients in the 6·4 mg/kg group (four grade 1 or 2; one grade 5). The promising antitumour activity and favourable safety profile support trastuzumab deruxtecan 5·4 mg/kg as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer, including those with RAS mutations, previous anti-HER2 therapy, or both. Daiichi Sankyo and AstraZeneca. [ABSTRACT FROM AUTHOR]

We conducted a prospective study of 159 cases of Streptococcus dysgalactiae subspecies equisimilis (SDSE) bacteremia in 157 patients at 2 hospitals in Finland during November 2015–November 2019. Cellulitis was associated with nonsevere disease (p = 0.008); necrotizing fasciitis was associated with severe disease (p = 0.004). Fifty percent of patients had >1 clinical characteristic associated with risk for death. The case-fatality rate was 6%, and 7% of patients were treated in an intensive care unit. Blood leukocyte counts on days 2 (p = 0.032) and 3 (p = 0.020) and C-reactive protein levels on days 3 (p = 0.030) and 4 (p = 0.009) after admission were predictors of severe disease. The Pitt bacteremia score was an accurate predictor of death. Using the Pitt bacteremia score, leukocyte counts, and CRP responses during initial treatment can improve treatment strategies and survival for patients with SDSE. [ABSTRACT FROM AUTHOR]

A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking. Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included. A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, −0.04 to 0.32). The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking. [ABSTRACT FROM AUTHOR]

The JAK2 V617F is a prevalent driver mutation in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph−MPNs), significantly affecting disease progression, immunophenotype, and patient outcomes. The World Health Organization (WHO) guidelines highlight the JAK2 V617F mutation as one of the key diagnostic criterions for Ph−MPNs. In this study, we analyzed 283 MPN samples with the JAK2 V617F mutation to assess the effectiveness of three detection technologies: chip-based digital PCR (cdPCR), real-time quantitative PCR (qPCR), and next-generation sequencing (NGS). Additionally, we investigated the relationship between JAK2 V617F mutant allele burden (% JAK2 V617F) and various laboratory characteristics to elucidate potential implications in MPN diagnosis. Our findings demonstrated high conformance of cdPCR with qPCR/NGS for detecting % JAK2 V617F, but the mutant allele burdens detected by qPCR/NGS were lower than those detected by cdPCR. Moreover, the cdPCR exhibited high sensitivity with a limit of detection (LoD) of 0.08% and a limit of quantification (LoQ) of 0.2% for detecting % JAK2 V617F in MPNs. Clinical implications were explored by correlating % JAK2 V617F with various laboratory characteristics in MPN patients, revealing significant associations with white blood cell counts, lactate dehydrogenase levels, and particularly β2-microglobulin (β2-MG) levels. Finally, a case report illustrated the application of cdPCR in detecting low-allele burdens in a de novo chronic myeloid leukemia (CML) patient with a hidden JAK2 V617F subclone, which expanded during tyrosine kinase inhibitor (TKI) treatment. Our findings underscore the superior sensitivity and accuracy of cdPCR, making it a valuable tool for early diagnosis and monitoring clonal evolution. [ABSTRACT FROM AUTHOR]

This research article explores the potential risk of pelvic hematoma following a prostatic urethral lift (PUL) procedure, which is used to treat benign prostate enlargement. The article identifies factors that can increase the risk of this complication, such as anatomical abnormalities and the use of certain medications. It emphasizes the importance of early diagnosis and monitoring, as well as individualized patient care. The article concludes by offering proactive management strategies to prevent complications and improve patient outcomes. The article was written by Vikas Kumar Panwar from the Department of Urology at the All India Institute of Medical Science and can be found on the website of the Investigative and Clinical Urology journal. [Extracted from the article]

Introduction: Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection, especially in children and older people. However, no effective treatment is currently available. Type I interferons (IFNs) are a group of cytokines that help regulate the activity of the immune system. GB05, human IFNα1b inhalation solution, was developed under US Food and Drug Administration (FDA) standard guidelines to combat RSV infection. This randomized, double-blind, placebo-controlled, dose-escalation phase I trial evaluated the safety, tolerability, and pharmacokinetics of nebulized GB05. Methods: A total of 35 eligible healthy Chinese adult volunteers were enrolled in this study. In the single ascending dose (SAD) study, volunteers were randomized into 0.2, 0.6, 1.2, and 1.8 million IU of GB05 or placebo. In the multiple ascending dose (MAD) study, volunteers received 1.2 or 1.8 million IU of GB05 or placebo for four consecutive days. Safety, tolerability, immunogenicity, and plasma pharmacokinetics were assessed for all groups. Results: All adverse events were mild or moderate and resolved spontaneously. The most common adverse event was decreased white blood cell count (8.6% in SAD and 10% in MAD). No serious adverse events, deaths, or adverse events that reached the termination criteria occurred during the study. In SAD, the maximum concentration and area under the curve increased across the dose range of 1.2–1.8 million IU in a non-linear relationship. The maximum plasma concentration after GB05 nebulization (1.06 IU/ml in the 1.8 million IU group) reflected a low concentration in the blood, suggesting a better lung uptake of GB05 and reduced incidence or risks of adverse events. In MAD, a steady state was reached after continuous administrations of twice daily for 3 days. Conclusions: Overall, nebulized GB05 exhibited satisfactory safety, tolerability, and favorable pharmacokinetic (PK) profiles in healthy adult volunteers, supporting further clinical investigation in patients infected with respiratory syncytial virus. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT06277167. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represented a disruptive pathology that emerged in late 2019 with profound implications ranging from individual health to health systems and world economy. Our study aimed to evaluate clinical, biochemical and computerized tomography (CT) parameters values in determining the severity of pulmonary embolism (PE) associated with COVID-19. We performed an observational cohort study evaluating demographic, clinical, biochemical, coagulation markers, as well as CT imaging parameters. In our study on 186 patients with COVID-19, we found that 31 patients (16,66%) had pulmonary embolism. Significant correlations for the patients with PE were detected in C-reactive protein, lactate dehydrogenase, serum ferritin, IL-6, serum myoglobin, NT-proBNP, D-dimers, serum proteins, transaminases as well as white cell blood counts. Patients with pulmonary embolism had a more severe lung involvement, with thrombi distribution mainly involving the lower lobes. Early identification of PE is an important step for timely and efficient treatment in the intensive care management of COVID-19 patients. Our study showed that high plasmatic values of lactate dehydrogenase, ferritin, IL-6, white blood cells and D-dimers and low proteins serum levels are strongly linked with COVID-19-associated pulmonary embolism. [ABSTRACT FROM AUTHOR]

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Background: Human aging and white blood cell (WBC) count are complex traits influenced by multiple genetic factors. Predictors of chronological age have been developed using epigenetic clocks. However, the bidirectional causal effects between epigenetic clocks and WBC count have not been fully examined. Methods: This study employed Mendelian randomization (MR) to analyze summary statistics from four epigenetic clocks involving 34,710 participants, alongside data from the Blood Cell Consortium encompassing 563,946 individuals. We primarily explored bidirectional causal relationships using the random-effects inverse-variance weighted method, supplemented by additional MR methods for comprehensive analysis. Additionally, multivariate MR was applied to investigate independent effects of WBC count on epigenetic age acceleration. Results: In the two-sample univariate MR (UVMR) analysis, we observed that a decrease in lymphocyte count markedly accelerated aging according to the PhenoAge, GrimAge, and HannumAge metrics (all P < 0.01, β < 0), though it did not affect Intrinsic Epigenetic Age Acceleration (IEAA). Conversely, an increase in neutrophil count significantly elevated PhenoAge levels (β: 0.38; 95% CI 0.14, 0.61; P = 1.65E−03 < 0.01). Reverse MR revealed no significant causal impacts of epigenetic clocks on overall WBC counts. Furthermore, in multivariate MR, the impact of lymphocyte counts on epigenetic aging metrics remained statistically significant. We also identified a marked causal association between neutrophil counts and PhenoAge, GrimAge, and HannumAge, with respective results showing strong associations (PhenoAge β: 0.78; 95% CI 0.47, 1.09; P = 8.26E−07; GrimAge β: 0.55; 95% CI 0.31, 0.79; P = 5.50E−06; HannumAge β: 0.42; 95% CI 0.18, 0.67; P = 6.30E−04). Likewise, eosinophil cell count demonstrated significant association with HannumAge (β: 0.33; 95% CI 0.13, 0.53; P = 1.43E−03 < 0.01). Conclusion: These findings demonstrated that within WBCs, lymphocyte and neutrophil counts exert irreversible and independent causal effects on the acceleration of PhenoAge, GrimAge, and HannumAge. Our findings highlight the critical role of WBCs in influencing epigenetic clocks and underscore the importance of considering immune parameters when interpreting epigenetic age. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop a tool for predicting the early occurrence of acute kidney injury (AKI) in ICU hospitalized cirrhotic patients. Methods: Eligible patients with cirrhosis were identified from the Medical Information Mart for Intensive Care database. Demographic data, laboratory examinations, and interventions were obtained. After splitting the population into training and validation cohorts, the least absolute shrinkage and selection operator regression model was used to select factors and construct the dynamic online nomogram. Calibration and discrimination were used to assess nomogram performance, and clinical utility was evaluated by decision curve analysis (DCA). Results: A total of 1254 patients were included in the analysis, and 745 developed AKI. The mean arterial pressure, white blood cell count, total bilirubin level, Glasgow Coma Score, creatinine, heart rate, platelet count and albumin level were identified as predictors of AKI. The developed model had a good ability to differentiate AKI from non-AKI, with AUCs of 0.797 and 0.750 in the training and validation cohorts, respectively. Moreover, the nomogram model showed good calibration. DCA showed that the nomogram had a superior overall net benefit within wide and practical ranges of threshold probabilities. Conclusions: The dynamic online nomogram can be an easy-to-use tool for predicting the early occurrence of AKI in critically ill patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the clinical characteristics and analysis of related factors associated with early death in newly diagnosed patients with acute promyelocytic leukemia (APL). Methods: This retrospective study included patients who visited our hospital between January 2010 and August 2022 and were diagnosed with APL for the first time. We analyzed their clinical and laboratory characteristics and analysis of related factors associated with early death. Results: A total of 269 patients with a primary diagnosis of APL were collected. The male to female ratio was 6:5, and the median age was 42 years (range 7–80). Among patients with initial APL diagnosis, there were 34 early deaths, resulting in an early mortality rate of 13%. The median time from diagnosis to death was 8.5 days (range 3–24). Comparative analysis of the clinical characteristics between patients who died early and those who did not, using a logistic regression model, revealed that age, white blood cell count (WBC) at initial diagnosis, and prolongation time of prothrombin time (PT) were independent risk factors for early death in patients with primary APL (P < 0.05). Comparing the clinical characteristics during hospitalization between the early death group and the non-early death group, it was observed that the daily mean of WBC during hospitalization was significantly higher in patients who died early than in those who did not (P < 0.001). Conversely, the daily mean of platelet count (PLT) was significantly lower in patients who died early compared to those who did not (P < 0.001). Furthermore, statistically significant differences were found in the mean daily infusion of PLT (P < 0.05), fibrinogen (Fib) (P < 0.05), and fresh frozen plasma (FFP) (P < 0.05) during hospitalization between patients who died early and those who did not. Specifically, the mean daily infusion of PLT and FFP was significantly higher in the early-death group than in the non-early-death group. Cerebral hemorrhage was identified as the immediate cause of death in 25 out of the 34 early-death patients (74%). The remaining causes of death included infection in 5 cases (15%), all of which were severe pulmonary infections, including 2 cases of combined differentiation syndrome, and abandonment of treatment in 4 patients (11%) at initial diagnosis. Conclusion: In patients with primary APL, age, WBC at initial diagnosis, and PT prolongation time were identified as independent risk factors for early death (P < 0.05). Laboratory findings regarding WBC and PLT during hospitalization, as well as the infusion of PLT, Fib, and FFP during hospitalization, were also statistically significant. Cerebral hemorrhage was found to be the main cause of early death in patients with primary APL. [ABSTRACT FROM AUTHOR]

Background: The study aimed to explore clinical indicators that can predict the prognosis of children with acute fulminant myocarditis (AFM) through a retrospective analysis. Methods: A retrospective analysis was conducted on the clinical indices of 79 children diagnosed with AFM and hospitalized from March 2013 to March 2023. Relevant demographic and clinical data, including symptoms at admission, laboratory results, and outcomes were extracted to identify factors associated with in-hospital mortality. Results: A total of 79 children with AFM were analyzed. The survival group (n = 61) had a longer median hospital stay and higher medical expenses compared to the death group (n = 18). Significant differences in the levels of left ventricular ejection fraction (LVEF)(P < 0.001), myoglobin (MYO)(P < 0.001), aspartate aminotransferase (AST)(P < 0.001), lactate dehydrogenase (LDH)(P = 0.004), B-type natriuretic peptide (BNP)(P = 0.005), arterial potential hydrogen (PH)(P < 0.001), bicarbonate (HCO3-)(P = 0.003), serum lactate (Lac)(P = 0.001), peripheral oxygen saturation (SpO2)(P = 0.008), and white blood cell count (WBC)(P = 0.007) were observed between the two groups. Additionally, there were significant differences in the incidences of multi-organ failure (P = 0.003) and respiratory failure (P = 0.001) between the two groups. Conclusions: Severe myocardial injury (AST > 194.00 U/L, LDH > 637.50 U/L, MYO > 265.75 µg/L, BNP > 1738.50 ng/L), acidosis (PH < 7.29, HCO3− <18.45 mmol/L, Lac > 12.30 mmol/L), hypoxia (SpO2 < 97.50%), inflammatory response (WBC > 9.69*109/L), left ventricular systolic dysfunction (LVEF < 28.25%), multi-organ failure, and respiratory failure are significantly associated with higher mortality rates. These factors can accurately identify AFM children at an increased risk of death. [ABSTRACT FROM AUTHOR]

Background: Endoscopic ultrasound (EUS)-guided transluminal drainage has become a first-line treatment modality for symptomatic pancreatic pseudocysts. Despite the increasing popularity of lumen-apposing metal stents (LAMSs), plastic stents may resolve non-necrotic fluid collections effectively with lower costs and no LAMS-specific adverse events. To date, there has been a paucity of data on the appropriate stent type in this setting. This trial aims to assess the non-inferiority of plastic stents to a LAMS for the initial EUS-guided drainage of pseudocysts. Methods: The WONDER-02 trial is a multicentre, open-label, non-inferiority, randomised controlled trial, which will enrol pancreatic pseudocyst patients requiring EUS-guided treatment in 26 centres in Japan. This trial plans to enrol 80 patients who will be randomised at a 1:1 ratio to receive either plastic stents or a LAMS (40 patients per arm). In the plastic stent group, EUS-guided drainage will be performed using two 7-Fr double pigtail stents. In the LAMS group, the treatment will be performed in the same way except for LAMS use. The step-up treatment will be performed via endoscopic and/or percutaneous procedures at the trial investigator's discretion. The primary endpoint is clinical success, which is defined as a decrease in a pseudocyst size to ≤ 2 cm and an improvement in inflammatory indicators (i.e. body temperature, white blood cell count, and serum C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, pseudocyst recurrence, and medical costs. Discussion: The WONDER-02 trial will investigate the efficacy and safety of plastic stents compared to a LAMS in EUS-guided treatment of symptomatic pancreatic pseudocysts with a particular focus on the non-inferior efficacy of plastic stents. The findings will help establish a new treatment algorithm for this population. Trial registration: ClinicalTrials.gov NCT06133023 registered on 9 November 2023. UMIN000052647 registered on 30 October 2023. jRCT1032230444 registered on 7 November 2023. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to establish a predictive model utilizing machine learning techniques to anticipate the likelihood of thrombolysis resistance (TR) in acute ischaemic stroke (AIS) patients undergoing recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis, given that nearly half of such patients exhibit poor clinical outcomes. Methods: Retrospective clinical data were collected from AIS patients who underwent intravenous thrombolysis with rt-PA at the First Affiliated Hospital of Bengbu Medical University. Thrombolysis resistance was defined as ([National Institutes of Health Stroke Scale (NIHSS) at admission − 24-hour NIHSS] × 100％/ NIHSS at admission) ≤ 30%. In this study, we developed five machine learning models: logistic regression (LR), extreme gradient boosting (XGBoost), support vector machine (SVM), the least absolute shrinkage and selection operator (LASSO), and random forest (RF). We assessed the model's performance by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), and presented the results through a nomogram. Results: This study included a total of 218 patients with AIS who were treated with intravenous thrombolysis, 88 patients experienced TR. Among the five machine learning models, the LASSO model performed the best. The area under the curve (AUC) on the testing group was 0.765 (sensitivity: 0.767, specificity: 0.694, accuracy: 0.727). The apparent curve in the calibration curve was similar to the ideal curve, and DCA showed a positive net benefit. Key features associated with TR included NIHSS at admission, blood glucose, white blood cell count, neutrophil count, and blood urea nitrogen. Conclusion: Machine learning methods with multiple clinical variables can help in early screening of patients at high risk of thrombolysis resistance, particularly in contexts where healthcare resources are limited. [ABSTRACT FROM AUTHOR]

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Patients on maintenance hemodialysis (MHD) have been disproportionately affected by COVID-19. Identifying factors associated with disease severity and viral clearance times can inform better clinical management for this high-risk group. Methods: We retrospectively analyzed clinical and hematological data from 85 COVID-19 positive MHD patients. Disease severity was classified as non-severe (mild/moderate) or severe (severe/critical). Logistic regression was used to evaluate factors associated with disease severity. The time to viral clearance was assessed and correlated with clinical variables. Results: Cardiovascular disease (OR=11.19, 95% CI 2.35–53.38), neutrophilia (OR=1.24, 95% CI 1.01–1.53), and elevated inflammatory markers (procalcitonin and white blood cell count) were independent predictors of severe COVID-19. A prognostic model incorporating these factors showed good discrimination for severity risk (AUC=0.835). The median time to viral clearance was 19 days. Delayed clearance was associated with higher levels of C-reactive protein, troponin, and N-terminal pro-B-type natriuretic peptide. Conclusions: We identified key prognostic factors for COVID-19 severity and characterized the time to viral clearance in MHD patients. These findings can aid in risk stratification and optimize management for this vulnerable population. Further research through multicenter collaborative studies is warranted to validate these results. [ABSTRACT FROM AUTHOR]

2,3-dimethylquinoxaline (DMQ) is a broad-spectrum antimicrobial phytochemical. This study aims to assess its toxicological profile. In vitro studies conducted in appropriate cell cultures, included assessment of cardiotoxicity, nephrotoxicity, and hepatotoxicity. An in vivo study was conducted in mice to determine acute oral toxicity (AOT), and subacute oral toxicity (SAOT). Acute dermal toxicity (ADT) was conducted in rats. All in-vitro toxicity studies of DMQ had negative results at concentrations ≤100 μM except for a non-significant reduction in the ATP in human hepatocellular carcinoma cell culture. The median lethal dose of DMQ was higher than 2000 mg/kg. All animals survived the scheduled necropsy and none showed any alteration in clinical signs. Biochemistry analysis revealed a significant difference between the satellite and control groups, showing an increase in platelet counts and white blood cell counts by 99.8% and 188.8%, respectively. Histology revealed enlargement of renal corpuscles; hyperplasia of testosterone-secreting cells; and dilatation of coronaries and capillaries. The present data suggests an acceptable safety profile of DMQ in rodents except for thrombocytosis, leukocytosis, and histological changes in high doses that need further investigation. [ABSTRACT FROM AUTHOR]

Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor. Previous research has demonstrated similar pharmacokinetic (PK) responses to single doses of obicetrapib between Japanese and White males, but the PK responses have not been established in Chinese individuals. The purpose of this randomized, parallel, open‐label trial was to characterize the PK and pharmacodynamic (PD; CETP activity and plasma lipids) responses and safety of single doses (5, 10, or 25 mg; N = 36) and multiple doses (10 mg for 14 days; N = 12) of obicetrapib in healthy Chinese individuals. The maximum concentration and area under the drug concentration‐time curve of obicetrapib from 0 h to infinity increased with dose after all single doses of obicetrapib. After 7 consecutive days of dosing, low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol reached their minimum and maximum changes of 42% reduction and 108% increase, respectively. Primary PK and PD parameters after single‐ and multiple‐dose administration of obicetrapib were similar to those in healthy white participants in previous studies. One participant in the 5 mg dose group experienced a treatment‐emergent adverse event of decreased white blood cell and neutrophil counts, which resolved without intervention. In conclusion, these findings support the inclusion of Chinese individuals in the ongoing phase 3 clinical development program of obicetrapib. [ABSTRACT FROM AUTHOR]

The article discusses the use of ChatGPT, an artificial intelligence language model, in the field of medicine, specifically in providing information about community-acquired pneumonia (CAP). ChatGPT is capable of generating human-like responses to natural language inputs and has been found to produce quality and empathetic responses to patient questions about CAP. However, the accuracy and reliability of ChatGPT-generated responses are not verified or authenticated, as it does not provide references to support the information provided. The article recommends further research to quantify the accuracy of ChatGPT-generated responses and suggests collaboration among physicians to develop a new AI software that can generate cross-referenced and verified responses to patient queries. [Extracted from the article]

Background: Does incorporating Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into endocrine therapy (ET) effectively enhance survival outcomes, notably overall survival (OS), among individuals with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer? This remains a clinical controversy. We compared the antitumor efficacy and adverse effects (AEs) between CDK4/6 inhibitors + ET (CET) and placebo + ET (PET) by conducting a phase III randomized controlled trials (RCTs) based meta-analysis. Methods: Seven databases were searched to identify eligible studies, comprising Phase III RCTs comparing CET to PET. The primary endpoints were OS and progression-free survival (PFS), with secondary endpoints including responses and adverse events (AEs). Results: Seven RCTs (DAWNA-2, MONALEESA-2, MONALEESA-3, MONALEESA-7, MONARCH-3, PALOMA-2, and PALOMA-4) were included. The CET group exhibited significantly improved OS (HR: 0.81 [0.74, 0.88]), PFS (HR: 0.57 [0.52, 0.63]), objective response rate (RR: 1.31 [1.20, 1.43]), and clinical benefit rate (RR: 1.11 [1.07, 1.15]). These benefits were consistent across almost all subgroups. Additionally, the CET group showed better overall survival rates (OSR) from 24 to 60 months (OSR 24–60 m) and progression-free survival rates (PFSR) from 6 to 60 months (PFSR 6–60 m). However, more total AEs, grade 3–5 AEs, and serious AEs were found in CET group. The top 5 grade 3–5 AEs in the CET group were neutropenia (59.39%), leukopenia (24.11%), decreased white blood cell count (12.99%), hypertension (7.03%), and increased alanine aminotransferase (5.91%). Conclusions: The superiority of CET over PET in HR+/HER2- advanced breast cancer is evident, showing improved survival and responses. Nonetheless, the higher incidence of AEs, specifically hematologic AEs, requires cautious attention. [ABSTRACT FROM AUTHOR]

Background: Due to the low incidence of malignant tracheoesophageal fistula and the paucity of relevant clinical studies, the benefits of stent implantation have not been well documented. It remains unclear which factors may affect fistula closure. Methods: Between January 2015 and January 2021, 344 patients who were diagnosed with malignant tracheoesophageal fistula at Zhongda Hospital, Southeast University, were retrospectively enrolled. Demographic and clinical data were collected. Risk factors for fistula closure identified by univariate analysis were further analyzed using multivariable logistic regression. Results: A total of 288 patients were analyzed in this study, of which 94 were treated conservatively, 170 were treated with an esophageal stent, and 24 were treated with a tracheal stent. Among them, the delta Karnofsky's performance status score values (after 2 weeks/before treatment [p = 0.0028], after 1 month/before treatment [p = 0.0103]) were significantly different between conservative and stent treatment. There was a significant reduction of pneumonia incidence in the stenting group (33.53%) compared to the conservative treatment group (77.05%) after one month (p <0.0001). In addition, the closure of fistulas was influenced by four independent risk factors: 1) treatment methods (p < 0.0001), 2) fistula size (p = 0.0003), 3) preoperative white blood cell count (p = 0.0042), and 4) preoperative Karnofsky's performance status score (p = 0.0001). Conclusions: Stent implantation has become an effective method for treating malignant tracheoesophageal fistula compared to conservative treatment. Additionally, stent implantation, smaller fistula size, lower preoperative white blood cell count, and higher preoperative Karnofsky's performance status score suggest a better outcome. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and poor functional outcomes at 90 days in patients with acute ischemic stroke (AIS). Methods: This study retrospectively collected 1988 AIS patients admitted to two hospitals in the Shenzhen area between January 2022 and March 2023. A total of 1255 patients with Fasting Blood-glucose (FBG) and hemoglobin A1c (HbA1C) values at admission were included in this analysis. SHR, measured by FBG/HbA1C, was evaluated as both a tri-categorical variable (Tertile 1: ≤ 0.83; Tertile 2: 0.84 -0.95; Tertile 3: ≥ 0.96). The outcome was poor functional outcomes (modified Rankin Scale [mRS] score 2–6) at 90 days. We performed univariate analysis, multiple equation regression analysis, stratified analysis, and interactive analysis. Results: Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving poor functional outcomes (adjusted odds ratio, OR = 2.84, 95% CI: 2.02–3.99, P < 0.0001) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for white blood cell count, neutrophil count, lymphocyte count, fasting blood glucose, stroke type, intravenous thrombolytic therapy, baseline Glasgow score, and baseline NIHSS score. Conclusion: SHR, as measured by the FBG/HbA1C, was associated with an increased odds of achieving poor functional outcomes in patients with AIS at 90 days. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 outbreak was declared a worldwide emergency as a result of its rapid spread. The number of people infected with COVID-19 is increasing rapidly around the world, and pneumonia can develop in COVID-19 cases. The monoclonal antibody tocilizumab blocks the interleukin-6 receptor, which in turn reduces inflammation. Aim: of the work The study aims to determine how tocilizumab affects inflammatory markers, laboratory indices, and oxygen therapy. Subjects and methods This retrospective observational study aimed to assess the effect of tocilizumab on inflammatory markers, laboratory parameters, and short-term outcomes in COVID-19 cases. Data was collected from 55 patients with COVID-19 who tested positive for SARS-CoV-2 using PCR. These patients were admitted to Ain Shams University Specialized Hospital—Obour between June 1, 2021, and May 31, 2022. Results: After tocilizumab administration, C-reactive protein levels decreased significantly, but there was no statistically significant change in hemoglobin, serum ferritin, or D-dimer levels. Following tocilizumab administration, the leukocyte counts, and platelet count increased significantly. There was a significant correlation between the presence of comorbidities in the studied patients (e.g., heart failure, post-renal transplantation, and hepatitis C virus) and the risk of mortality. The study's final result showed a significant decrease in platelet count in dead patients compared to discharged patients after receiving tocilizumab. Regarding oxygen therapy following tocilizumab administration, the use of face masks and non-rebreather facemasks was high in dead patients, while nasal prong usage was high in discharged patients. After receiving tocilizumab, there was an increase in the mean liters of oxygen required in dead patients compared to discharged patients. Conclusion: After administration of tocilizumab in COVID-19 hospitalized patients who have progressing disease, there was highly and significantly decrease in CRP level with no statistically significant alteration in the levels of hemoglobin, serum ferritin, and D-dimer and an increase in TLC and platelets was observed. Following tocilizumab administration, there was a decrease in oxygen demands, an improvement in oxygen therapy and oxygen saturation. Tocilizumab is a recommended therapy option. [ABSTRACT FROM AUTHOR]

Introduction: Unlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids. Methods: In this study, we utilized a recently described mouse model (BMAd-Cre) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. Nr3c1) whilst maintaining GR expression in other adipose depots. Results: Mice lacking GR in BMAds (BMAd-Nr3c1-/-) and control mice (BMAd-Nr3c1+/+) were fed ad libitum or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female BMAd-Nr3c1-/- mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and BMAd-Nr3c1-/- mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and mCT revealed no difference in BMAT accumulation between control or BMAd-Nr3c1-/- mice. Differences in BMAd size were not observed between BMAd-Nr3c1-/- and control mice. Interestingly, BMAd-Nr3c1-/- mice had decreased circulating white blood cell counts 4 h into the light cycle. Discussion: In conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR. [ABSTRACT FROM AUTHOR]

Objective: Venous thromboembolism (VTE) poses a significant threat to lung cancer patients, particularly those receiving treatment with immune checkpoint inhibitors (ICIs). We aimed to develop and validate a nomogram model for predicting the occurrence of VTE in lung cancer patients undergoing ICI therapy. Methods: The data for this retrospective cohort study was collected from cancer patients admitted to Chongqing University Cancer Hospital for ICI treatment between 2019 and 2022. The research data is divided into training and validation sets using a 7:3 ratio. Univariate and multivariate analyses were employed to identify risk factors for VTE. Based on these analyses, along with clinical expertise, a nomogram model was crafted. The model's predictive accuracy was assessed through receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis, clinical impact curve, and other relevant metrics. Results: The initial univariate analysis pinpointed 13 potential risk factors for VTE. The subsequent stepwise multivariate regression analysis identified age, Karnofsky performance status, chemotherapy, targeted, platelet count, lactate dehydrogenase, monoamine oxidase, D‐dimer, fibrinogen, and white blood cell count as significant predictors of VTE. These 10 variables were the foundation for a predictive model, illustrated by a clear and intuitive nomogram. The model's discriminative ability was demonstrated by the ROC curve, which showed an area under the curve of 0.815 (95% CI 0.772–0.858) for the training set, and 0.753 (95% CI 0.672–0.835) for the validation set. The model's accuracy was further supported by Brier scores of 0.068 and 0.080 for the training and validation sets, respectively, indicating a strong correlation with actual outcomes. Conclusion: We have successfully established and validated a nomogram model for predicting VTE risk in lung cancer patients treated with ICIs. [ABSTRACT FROM AUTHOR]

Background: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. Methods: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. Results: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). Conclusions: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. Trial registration: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892. [ABSTRACT FROM AUTHOR]

Simple Summary: All elephant species are now endangered or critically endangered. It is extremely important for the veterinary care of elephants to be effective at diagnosing diseases and monitoring treatment. Routine blood cell testing is a standard method for monitoring elephant health and detecting possible infections. Elephants naturally have different ratios of white blood cells (WBCs; immune cells) in their blood compared to other animals, with unusually high percentages of one cell type (monocytes). Because elephant WBCs also look different from those of most other animals, a person must identify the cells under the microscope instead of using machine analysis. These elephant-specific WBC features may be important in fighting diseases, but very little is known about elephant monocytes. The aims of this study were to establish methods for isolating elephant monocytes, studying their function, and accurately identifying them using flow cytometry, a more precise technique than microscopy. Blood from Asian elephants was used. Methods were created and tested. An approach to identifying elephant monocytes using flow cytometry was established. These results will lead to better studies of the elephant immune system and can help to more accurately count WBCs in elephant samples. Optimal veterinary care of managed elephant populations is vital due to the continued decline of wild populations. Appropriate health monitoring and accurate disease diagnosis include hematologic evaluation. Elephant hematology is distinctive in that elephants have high percentages of monocytes in health. Elephant monocytes also have unusual morphology, a feature shared with manatees and rock hyraxes. Manual white blood cell counting is used for elephant hematology, as analyzers are generally inaccurate. The aims of this study were to evaluate basic cell isolation and functional testing protocols for use in elephant monocyte research, and to test several available antibodies via flow cytometry for use in elephant monocyte identification. Peripheral blood samples from five Asian elephants (Elephas maximus) were used. Methods for monocyte isolation and evaluation of phagocytic function were established. Putative lymphocyte and monocyte populations were identified using a scatter on flow cytometry. Antibodies against CD11b, CD11c, CD14, and ionized calcium-binding adapter molecule 1 (IBA1) were tested, with IBA1 showing the highest apparent diagnostic utility in labeling monocytes. Combined flow cytometric scatter and IBA1 positivity appear to identify Asian elephant monocytes. These data provide a methodologic basis for further investigation into elephant monocyte function and immune response to infection. [ABSTRACT FROM AUTHOR]

Background: The serum levels of presepsin correlate with parameters indicating cholestasis in sepsis; however, the probability and significance of this association remain uncertain. We aimed to ascertain whether infection, as signaled by presepsin levels, is the primary determinant of elevated biliary parameters in sepsis. Methods: A unicenter, retrospective study included 396 COVID-free emergency-admitted patients, in which presepsin level was determined. Presepsin, neutrophil count, leukocyte count, C reactive protein, and fibrinogen evaluated the septic/inflammatory state. The statistically significant factors associated with cholestasis, ALT, and AST were analyzed by Fisher's exact test and Spearman regression with Bonferroni's correction. Results: Presepsin emerged as the most likely variable correlated with all cholestasis markers: alkaline phosphatase (p = 7 × 10−8), gamma-glutamyl transferase (p = 5 × 10−10), and conjugated bilirubin (p = 4 × 10−15). Thrombocyte count, C reactive protein, age, creatinine, urea, lactate, and blood pressure, were associated with only one or two of these markers. Conclusions: In a sepsis setting, the increase in cholestasis-related parameters is associated with presepsin with a higher probability than hemodynamic, inflammatory, or coagulation-related variables. Determining this robust link between sepsis and cholestasis could eliminate unnecessary imaging procedures in critically ill patients, enabling clinicians to focus efforts on addressing the primary infectious cause. [ABSTRACT FROM AUTHOR]

Background We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Methods Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020–30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. Results Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P =.005) and hospitalization was longer (P =.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P =.40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. Conclusions In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities. [ABSTRACT FROM AUTHOR]

Objectives Patients and Methods Results Conclusion To evaluate the effects of inserting a Foley catheter after ureteroscopy (URS) and JJ stent placement on pain scores, voiding patterns, biochemical parameters and postoperative complications.A randomised clinical trial (1:1) with adult patients following unilateral URS + JJ stent placement was planned. In Group A, no Foley catheter was placed, in Group B, a Foley catheter was placed following URS + JJ stent placement. The primary objective was to evaluate effect of placing a Foley catheter on International Prostate Symptom Score (IPSS), Ureteric Stent Symptom Questionnaire (USSQ) score and postoperative biochemical parameters. The secondary objective was to evaluate postoperative complications.A total of 112 patients were included (56/group). A ureteric access sheath was used in each patient. Patients had similar demographic and surgical parameters. The pre‐ and postoperative biochemical analyses including white blood cell count, C‐reactive protein, procalcitonin and creatinine levels were similar between the two groups. The IPSS were similar between the two groups. All the subdomains of the USSQ were similar between two groups except Total Body Pain score, which was lower in Group B. The visual analogue scale scores were similar. Complications were all Clavien–Dindo Grade I and II, and the complication rate was 5.4% and 8.9% in Group A and B, respectively.Placing a Foley catheter following URS + JJ stent placement did not show significant effects on postoperative biochemical parameters and voiding symptoms. However, a Foley catheter lowered the Total Body Pain score on the USSQ without having significant effects on VAS scores. The practice of placing a Foley catheter following URS and JJ stent placement should be based on surgeon's preference keeping in mind the potential positive effect on pain scores. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Plain Language Summary PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB‐positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease.This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG‐ALL‐2015 and CCCG‐ALL‐2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions.Pediatric PDGFRB‐positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B‐ALL and 4 T‐ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31‐33 abnormalities, and one suffered from a complex karyotype. The 3‐year event‐free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow‐up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine‐kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p < .05).Pediatric PDGFRB‐positive ALL has a poor outcome associated with high‐risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high‐risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high‐risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse.Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive acute lymphoblastic leukemia (ALL) patients.The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. [ABSTRACT FROM AUTHOR]

Background: The gut-lung axis, pivotal for respiratory health, is inadequately explored in pulmonary and critical care medicine (PCCM) inpatients. Methods: Examining PCCM inpatients from three medical university-affiliated hospitals, we conducted 16S ribosomal RNA sequencing on stool samples (inpatients, n = 374; healthy controls, n = 105). We conducted statistical analyses to examine the gut microbiota composition in PCCM inpatients, comparing it to that of healthy controls. Additionally, we explored the associations between gut microbiota composition and various clinical factors, including age, white blood cell count, neutrophil count, platelet count, albumin level, hemoglobin level, length of hospital stay, and medical costs. Results: PCCM inpatients exhibited lower gut microbiota diversity than healthy controls. Principal Coordinates Analysis revealed marked overall microbiota structure differences. Four enterotypes, including the exclusive Enterococcaceae enterotype in inpatients, were identified. Although no distinctions were found at the phylum level, 15 bacterial families exhibited varying abundances. Specifically, the inpatient population from PCCM showed a significantly higher abundance of Enterococcaceae, Lactobacillaceae, Erysipelatoclostridiaceae, Clostridiaceae, and Tannerellaceae. Using random forest analyses, we calculated the areas under the receiver operating characteristic curves (AUCs) to be 0.75 (95% CIs 0.69–0.80) for distinguishing healthy individuals from inpatients. The four most abundant genera retained in the classifier were Blautia, Subdoligranulum, Enterococcus, and Klebsiella. Conclusions: Evidence of gut microbiota dysbiosis in PCCM inpatients underscores the gut-lung axis's significance, promising further avenues in respiratory health research. [ABSTRACT FROM AUTHOR]

Objective: Accidental oral imidacloprid poisoning occurred in a family in Shandong, China, in May 2023. This study aimed to analyze the clinical characteristics of this imidacloprid poisoning event and investigated the detection of toxicants. Methods: Clinical data of four patients with oral imidacloprid poisoning were collected and retrospectively analyzed. The relevant literature was then reviewed. Results: Four patients from the same family received different oral doses of imidacloprid. The main clinical manifestations were digestive and neurological symptoms, including nausea, vomiting, and varying degrees of consciousness. Laboratory tests showed an increased white blood cell count, neutrophil proportion, and mild elevation of transaminase and urea nitrogen levels in some patients. Following comprehensive treatment, which included hemoperfusion, gastric lavage, total gastrointestinal decontamination, and drug symptomatic treatment, the patient’s symptoms were quickly relieved, and the concentration of imidacloprid in the blood rapidly decreased. Conclusion: Toxicant detection is an important criterion for the differential diagnosis of poisoning and is helpful for disease assessment, treatment plan formulation, and in determining patient prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Leukocyte count is a prognostic marker for cardiovascular diseases, with key role in atherosclerosis development. Specific number of neutrophils, lymphocytes and monocytes can predict cardiovascular risk, also in asymptomatic subjects. Among the lipoprotein fractions, HDL-C is a protective factor in the cardiovascular disorders. For the above reason, we have examined the peripheral count of leukocytes, neutrophils, lymphocytes and monocytes, and the ratios between neutrophils/HDL-cholesterol, lymphocytes/HDL-cholesterol, and monocytes/HDL-cholesterol, to evaluate the possible utility of the obtained values in progression of asymptomatic carotid atherosclerosis. METHODS: We performed our analysis in a cohort of 100 subjects with asymptomatic carotid atherosclerosis, of which 43 men and 57 women. The data were expressed as medians and IQR. To analyse the differences in leukocyte, neutrophil, lymphocyte, monocytes count and their ratio with HDL-cholesterol the Mann-Whitney test was employed. RESULTS: The peripheral count of leukocyte subtypes and the ratios, they change in relation to the number of cardiovascular risk factors and the degree of insulin resistance. CONCLUSIONS: In this cohort of subjects, the percentage of observed cardiovascular risk factors significantly affect some leukocyte parameters. These results, allow us to underline the importance of the leukocyte indices in the evaluation of subjects with asymptomatic vascular atherosclerosis. [ABSTRACT FROM AUTHOR]