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Background: Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin. Methods: Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC-BAC) provided additional comparators. The primary endpoint was the improvement in C-reactive protein (CRP) over time, analyzed using a repeated-measures mixed model, adjusted for baseline factors. Results: We recruited 39 evaluable participants: 30 randomized to dornase alfa (R-BAC +DA), 9 randomized to BAC (R-BAC), and included 60 CC-BAC participants. Dornase alfa was well tolerated and reduced CRP by 33% compared to the combined BAC groups (T-BAC). Least squares (LS) mean post-dexamethasone CRP fell from 101.9 mg/L to 23.23 mg/L in R-BAC +DA participants versus a 99.5 mg/L to 34.82 mg/L reduction in the T-BAC group at 7 days; p=0.01. The anti-inflammatory effect of dornase alfa was further confirmed with subgroup and sensitivity analyses on randomised participants only, mitigating potential biases associated with the use of CC-BAC participants. Dornase alfa increased live discharge rates by 63% (HR 1.63, 95% CI 1.01–2.61, p=0.03), increased lymphocyte counts (LS mean: 1.08 vs 0.87, p=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 μg/mL, p=0.004). Conclusions: Dornase alfa reduces pathogenic inflammation in COVID-19 pneumonia, demonstrating the benefit of cost-effective therapies that target extracellular chromatin. Funding: LifeArc, Breathing Matters, The Francis Crick Institute (CRUK, Medical Research Council, Wellcome Trust). [ABSTRACT FROM AUTHOR]

Background: The global mortality and morbidity rates of bronchiectasis patients due to nontuberculous mycobacteria (NTM) pulmonary infection are on a concerning upward trend. The aims of this study to identify the phenotype of NTM-positive individuals with bronchiectasis. Methods: A retrospective single-center observational study was conducted in adult patients with bronchiectasis who underwent bronchoscopy in 2007-2020. Clinical, laboratory, pulmonary function, and radiological data were compared between patients with a positive or negative NTM culture. Results: Compared to the NTM-negative group (n=677), the NTM-positive group (n=94) was characterized (P ≤0.05 for all) by older age, greater proportion of females, and higher rates of gastroesophageal reflux disease and muco-active medication use; lower body mass index, serum albumin level, and lymphocyte and eosinophil counts; lower values of forced expiratory volume in one second, forced vital capacity, and their ratio, and lower diffusing lung capacity for carbon monoxide; higher rates of bronchiectasis in both lungs and upper lobes and higher number of involved lobes; and more exacerbations in the year prior bronchoscopy. On multivariate analysis, older age (OR 1.05, 95% CI 1.02-1.07, P=0.001), lower body mass index (OR 1.16, 95% CI 1.16-1.07, P <0.001), and increased number of involved lobes (OR 1.26, 95% CI 1.01-1.44, P=0.04) were associated with NTM infection. Conclusions: Patients with bronchiectasis and NTM pulmonary infection are more likely to be older and female with more severe clinical, laboratory, pulmonary function, and radiological parameters than those without NTM infection. This phenotype can be used for screening patients with suspected NTM disease. [ABSTRACT FROM AUTHOR]

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described. The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group. We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months. Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical significance of combined cerebrospinal fluid (CSF) and routine blood parameter analysis in differentiating between multiple cerebral glioma (MCG) and primary central nervous system lymphoma (PCNSL) . Methods We Rretrospectively analyzed the clinical data, CSF and routine blood indicators levels of 62 MCG patients and 56 PCNSL patients admitted to Beijing Tiantan Hospital, Capital Medical University from November 2017 to March 2023. Additionally, we assessed the diagnostic value of individual meaningful indicators as well as their combinations in distinguishing between MCG and PCNSL. Results The levels of CSF total cell count, CSF white cell count, CSF: pro, lactate, routine bloodperipheral neutrophil count, and neutrophil percentage were significantly higher in the MCG group than in the PCNSL group (P < 0.05) ; while the levels of CSF: Glu, CSF: cl, routine blood lymphocyte count, eosinophil, lymphocyte percentage, and eosinophil percentage were significantly higher in the PCNSL group than in the MCG group (P < 0.05) . The AUCs of CSF cell count, CSF white cell count, CSF: pro, lactate, routine blood neutrophil count, neutrophil percentage for differentiating MCG from PCNSL were 0.900, 0.899, 0.797, 0.867, 0.828 and 0.772 respectively; sensitivities were 72.4%, 77.6%, 63.8%, 67.2%, 72.4%, 82.8%, 77.6% and 81%, with sensitivities of 97.1%, 100%, 88.2%, 91.2%, 88.2%, 64.7%, 100% and 94.1%, respectively. In addition, the combined detection of CSF total cell count, CSF white cell count, CSF: pro, routine blood neutrophil count and neutrophil percentage in CSF had an AUC of 0.919 for differentiating MCG from PCNSL, with a sensitivity and specificity of 77.6% and 100%, respectively. Conclusions Combined detection of CSF indicators including CSF total cell count, CSF white cell count, CSF: pro, along with routine blood markers such as neutrophil count and neutrophil percentage, holds significant clinical utility for differentiating between MCG and PCNSL. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of D-dimer, platelet-lymphocyte rate (PLR) and CT signs for intestinal ischemia in patients with bowel obstruction. Methods: We retrospectively analyzed the clinical and imaging data of 105 patients diagnosed with bowel obstruction, and performed univariate and multivariate analyses to determine the independent risk factors for intestinal ischemia in patients with bowel obstruction. Moreover, the receiver operating characteristic curve (ROC) was plotted to examine the diagnostic value of D-dimer, PLR and CT signs in patients with bowel obstruction. Besides, Kappa tests were used to assess inter-observer agreement. Results: We included 56 men (53%) and 49 women (47%) with mean age of 66.05 ± 16 years. Univariate and multivariate analyses showed that D-dimer, PLR and two significant CT signs (i.e., increased unenhanced bowel-wall attenuation and mesenteric haziness) were independent risk factors for intestinal ischemia in patients with bowel obstruction. ROC analysis showed that the combined use of D-dimer, PLR and the said two CT signs had better performance than single indicators in predicting intestinal ischemia in patients with bowel obstruction. The area under the curve (AUC) of the joint model III was 0.925 [95%CI: 0.876–0.975], with a sensitivity of 79.2% [95CI%: 67.2–91.1] and a specificity of 91.2% [95%CI: 83.7–98.9]. Conclusion: The combined use of D-dimer, PLR and CT signs has high diagnostic value for intestinal ischemia in patients with bowel obstruction and will prompt surgical exploration to evaluate intestinal blood flow. [ABSTRACT FROM AUTHOR]

Background: The low-grade inflammation score (INFLA-score) is a composite index that assesses chronic inflammatory status using multiple inflammatory markers. However, its correlation with cardiometabolic diseases (CMDs) in obese populations remains unclear. Methods: We conducted a prospective cohort study involving 79,160 participants with obesity (BMI ≥ 30 kg/m2) from the UK Biobank. The INFLA-score was calculated based on high-sensitivity C-reactive protein, leukocyte count, platelet count and granulocyte/lymphocyte ratio. We employed Kaplan–Meier survival curves, multivariable Cox regression, restricted cubic splines and accelerated time-to-failure models to analyse the association between the INFLA-score and CMDs risk, including coronary heart disease (CAD), stroke and type 2 diabetes mellitus (T2DM). Results: Over a median follow-up of 161.41 months, we recorded 14,903 CMDs events, comprising 7184 CAD cases, 1914 strokes and 7924 T2DM cases. Cox regression analysis revealed that each unit increase in the INFLA-score corresponded to a 1.5%, 1.1%, 1.2% and 2.4% increase CMDs risk (HR: 1.015, 95% CI 1.013–1.018), CAD risk (HR: 1.011, 95% CI 1.007–1.015), stroke risk (HR: 1.012, 95% CI 1.004–1.020) and T2DM risk (HR: 1.024, 95% CI 1.020–1.028), respectively. Restricted cubic spline analysis indicated a non-linear relationship between cumulative INFLA-score and CMDs risk (P = 0.044). Subgroup analysis revealed interactions between sex, age, history of lipid-lowering drug use, and INFLA-score regarding CMDs risk. Sensitivity analysis corroborated the main findings. Conclusion: Our findings strongly support the close association between INFLA-score and CMDs risk, particularly notable in women, those aged < 55, and individuals with a history of lipid-lowering drug use. These findings offer new insights into the role of inflammation in obesity-related CMDs, suggesting potential applications for prevention and identification of high-risk populations. [ABSTRACT FROM AUTHOR]

Objective: Twenty percent of all classical Hodgkin lymphoma (CHL) cases relapse and recur, especially in advanced stages with a high International Prognostic Score (IPS). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a regulatory molecule that can inhibit the immune response and is related to tumor aggressiveness. This study aimed to determine the relationship between CTLA-4 expression in advanced-stage CHL and IPS, identifying it as a potential therapy target. Results: In advanced-stage CHL, the group with a high IPS exhibited significantly higher mean CTLA-4 expression compared to the group with a low IPS (p = 0.003).The group with Hb level < 10.5 g/dl, leukocyte count > 15,000/µL, lymphocyte count < 8%, albumin level < 4 g/dl, and stage 4 exhibited higher CTLA-4 expression than the other group, although only leukocyte count and stage showed statistical significance (p = 0.004 and p = 0.020). Mean CTLA-4 expression was 239.84 ± 76.36 for nodular sclerosis, 293.95 ± 147.94 for mixed cellularity, 271.4 ± 23.56 for lymphocyte depleted, and 225.2 for lymphocyte-rich subtypes. The results suggest that CTLA-4 expression is associated with adverse prognostic factors in the IPS for advanced-stage CHL, supporting the notion that immune checkpoints play a role in cancer progression. [ABSTRACT FROM AUTHOR]

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated with surgical excision, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade to either ductal carcinoma in situ or invasive breast cancer, which occurs in up to 30% of patients. We hypothesised that the stromal immune microenvironment could indicate the presence of carcinoma associated with a ductal B3 lesion and that this could be detected in biopsies by counting lymphocytes as a predictive biomarker for upgrade. A higher number of lymphocytes in the surrounding specialised stroma was observed in upgraded ductal and papillary B3 lesions than non-upgraded (p < 0.01, negative binomial model, n = 307). We developed a model using lymphocytes combined with age and the type of lesion, which was predictive of upgrade with an area under the curve of 0.82 [95% confidence interval 0.77–0.87]. The model can identify some patients at risk of upgrade with high sensitivity, but with limited specificity. Assessing the tumour microenvironment including stromal lymphocytes may contribute to reducing unnecessary surgeries in the clinic, but additional predictive features are needed. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP), an active regulator of the innate immune system, has been related to COVID-19 severity. CRP is a dynamic protein undergoing conformational changes upon activation in inflammatory microenvironments between pentameric and monomeric isoforms. Although pentameric CRP is the circulating isoform routinely tested for clinical purposes, monomeric CRP shows more proinflammatory properties. Therefore, we aimed to determine the potential of monomeric CRP in serum as a biomarker of disease severity in COVID-19 patients (admission to intensive care unit [ICU] and/or in-hospital mortality). We retrospectively determined clinical and biological features as well as pentameric and monomeric CRP levels in a cohort of 97 COVID-19 patients within 72h of hospital admission. Patients with severe disease had higher levels of both pentameric and monomeric CRP. However, multivariate analysis showed increased mCRP but not pCRP to be independently associated to disease severity. Notably, mCRP levels higher than 4000 ng/mL (OR: 4.551, 95% CI: 1.329-15.58), together with number of co-morbidities, low lymphocyte count, and procalcitonin levels were independent predictors of disease severity in the multivariate model. Our results show the potential of mCRP levels as a marker of clinical severity in COVID-19 disease. [ABSTRACT FROM AUTHOR]

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amountswere lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis. [ABSTRACT FROM AUTHOR]

Blood parameters are important indicators for health conditions in animals, but can be influenced by several factors. This study was conducted to explore reference intervals for hematological parameters and investigate their possible relationships with different factors in Lori-Bakhtiari ewes. A total of 96 blood samples were randomly collected from healthy ewes at a research flock. Different hematological parameters, including red blood cell, white blood cell, neutrophil and lymphocyte counts (RBC, WBC, NP and LC, respectively), neutrophil and lymphocyte percentages (NP and LP, respectively), hematocrit (Hct) and hemoglobin (Hb), mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (MCV, MCH and MCHC, respectively) were measured at laboratory. Based on the coefficients of variations, NC (44.4%), LC (43.6%) and WBC (39.0%) were the most variable parameters, while the MCV (1.6%) had the lowest variability. Simple correlation coefficients and cluster analysis showed that erythrocyte-related parameters (Hct, MCH, MCV, Hb and RBC) were independent from the leukocyte traits (WBC, NC, NP, LC and LP). Birth type and age significantly (P<0.05) affected NC and LP, respectively. Heavier animals in 6 and 9 months of age had higher levels of Hb, MCH and MCHC in adulthood. Body weight traits also had some correlations with leukocyte parameters in higher ages, indicating that growth rate of the lambs may influence their immunity in the future or vice versa, the animals with stronger immunity may have higher growth rate. More attention to immunological parameters is needed, when breeding programs are planned for growth rate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between prognostic nutritional index (PNI) and bone mineral density (BMD) values and disability in patients with osteo penia/oste oporo sis. Methods: Between January 2022 and January 2023, 106 postmenopausal women with osteopenia (n = 54) and osteoporosis (n = 52) were included in the study. Patients with a disease or medication causing secondary osteoporosis were excluded. Bone mineral density was evaluated using dualenergy X-ray absorptiometry. Nutritional status was measured using the PNI, which was calculated using total lymphocyte count and serum albumin levels. The Health Assessment Questionnaire Disability Index (HAQ-DI) was used to evaluate disability. Results: The mean age of the participants was 63.78 ± 7.53 years. Prognostic nutritional index was positively correlated with total hip BMD values (r = 0.217, P = .029) and total hip T-scores (r = 0.207, P = .037) and negatively correlated with Fracture Assessment Tool Model (FRAX)-major fracture risk (r = -0.399, P < .001), FRAX-hip fracture risk (r = -0.300, P = .002), and HAQ-DI scores (r = --0.474, P < .001). The mean PNI was lower in patients with a history of falls than in those without falls (P < .001). The mean PNI was lower in patients with a history of osteoporotic fractures than in those without a fracture history (P = .007). Multivariate linear regression analyses showed that PNI was the only independent variable for HAQ-DI (B = -0.040, P < .001) (R2 = 0.17). Conclusion: Using PNI in clinical practice may be beneficial because of its association with BMD values and for predicting the independence of patients with osteo penia/oste oporo sis. If a disability is detected, a multidisciplinary approach should be considered, including rehabilitation and improvement of nutritional condition. [ABSTRACT FROM AUTHOR]

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-ɣ, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties. [ABSTRACT FROM AUTHOR]

Background: Bile duct injury (BDI) repair surgery is usually associated with morbidity/mortality. The neutrophil‐to‐lymphocyte ratio (NLR) easily assesses a patient's inflammatory status. The study aims to determine the possible relationship between preoperative NLR (pNLR) with postoperative outcomes in BDI repair surgery. Methods: Approved Ethics/Research Committee retrospective study, in patients who had a Bismuth‐Strasberg type E BDI repair (2008–2023). Data registered was: morbidity, mortality, and long‐term outcomes (primary patency and loss of primary patency) (Kaplan–Meier). Group comparison (U Mann–Whitney), receiver operator characteristic (ROC): area under curve [AUC]; cut‐off value, and Youden index [J], and logistic regression analysis were used for pNLR evaluation. Results: Seventy‐three patients were studied. Mean age was 44.4 years. E2 was the commonest BDI (38.4%). Perioperative morbidity/mortality was 31.5% and 1.4%. Primary patency was 95.9%. 8.2% have lost primary patency (3‐year actuarial patency: 85.3%). Median pNLR was higher in patients who had any complication (4.84 vs. 2.89 p = 0.015), biliary complications (5.29 vs. 2.86 p = 0.01), and patients with loss of primary patency (5.22 vs. 3.1 p = 0.08). AUC's, cut‐off values and (J) were: any complication (0.678, pNLR = 4.3, J = 0.38, p = 0.007), serious complication (0.667, pNLR = 4.3, J = 0.34, p = 0.04), biliary complications (0.712, pNLR = 3.64, J = 0.46, p = 0.001), and loss of primary patency (0.716, pNLR = 3.24, J = 0.52, p = 0.008). Logistic regression was significant in any complication (Exp [B]: 0.1, p = 0.002), serious complications (Exp [B]: 0.2, p = 0.03), and biliary complications (Exp [B]: 8.1, p = 0.003). Conclusions: pNLR is associated with complications in BDI repair with moderate to acceptable predictive capacity. pNLR could potentially predict patency of a BDI repair. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. Methods: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. Results: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). Conclusions: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] Clinical Trial Registration: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026). Plain Language Summary: Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Dex5AhfAxs29XQspjFnxYi Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB) [ABSTRACT FROM AUTHOR]

Background: Risk factors associated with negative outcomes in dogs with protein‐losing enteropathy (PLE) are well documented. However, mortality before hospital discharge and associated risk factors are not well described. Hypothesis/Objectives: Report the percentage of dogs with PLE that do not survive to hospital discharge and identify associated risk factors. Animals: One‐hundred and seven dogs presented to a referral hospital and diagnosed with PLE caused by inflammatory enteritis, intestinal lymphangiectasia or both. Methods: Retrospective cross‐sectional study assessing hospital records. Data on in‐hospital mortality and cause were assessed, and presenting signs, treatments prescribed, neutrophil count, lymphocyte count, serum albumin, globulin, and C‐reactive protein (CRP) concentrations, and histopathologic findings were compared between survivors and non‐survivors. Results: In‐hospital mortality was 21.5% with the most common causes including financial limitations, failure to improve and aspiration pneumonia. Factors associated with mortality during hospitalization included longer duration of hospitalization (P =.04), longer duration of clinical signs (P =.02) and an increase in serum CRP concentration after 1–3 days of in‐hospital treatment (P =.02). Higher mortality was identified in Pugs (odds ratio [OR], 4.93; 95% confidence interval [CI], 1.41–17.2; P =.01) and was a result of presumptive aspiration pneumonia in 5/6 of these dogs. Conclusions and Clinical Importance: Protein‐losing enteropathy in dogs has substantial mortality during hospitalization. Monitoring for improvement in CRP concentration after treatment during hospitalization may help predict survival to discharge. Pugs have increased in‐hospital mortality because of aspiration pneumonia; measures to prevent, recognize, and promptly treat this complication may improve outcomes in this breed. [ABSTRACT FROM AUTHOR]

This study aimed to develop a normal tissue complication probability (NTCP) model to estimate the risk of severe radiation-induced lymphopenia (SRIL; absolute lymphocyte count [ALC] < 500/μL) by using the blood dose of patients with hepatocellular carcinoma (HCC). We retrospectively collected data from 75 patients with HCC who received radiation therapy (RT) between 2015 and 2018. The hematological dose framework calculated blood dose-volume histograms (DVHs) using a predefined blood flow model, organ DVHs, the number of treatment fractions, and beam delivery time. A Lyman-Kutcher-Burman model with a generalized equivalent dose was used to establish the NTCP model, reflecting the whole-blood DVHs. Optimization of the Lyman-Kutcher-Burman parameters was conducted by minimizing a negative log-likelihood function. There were 6, 4, 18, 33, and 14 patients in the groups with radiation-induced lymphopenia grades 0, 1, 2, 3, and 4, respectively. The median pre- and post-RT ALC values were 1410/μL (range, 520-3710/μL) and 470/μL (range, 60-1760/μL), respectively. There was a correlation between mean blood dose and ALC depletion (Pearson r = −0.664; P <.001). The average mean blood doses in each radiation-induced lymphopenia group were 2.90 Gy (95% CI, 1.96-3.85 Gy) for grade 0 to 1, 5.29 Gy (95% CI, 4.12-6.45 Gy) for grade 2, 8.81 Gy (95% CI, 7.55-10.07 Gy) for grade 3, and 11.69 Gy (95% CI, 9.82-17.57 Gy) for grade 4. When applying the developed NTCP model to predict SRIL, the area under the receiver operating characteristic curve and Brier score values were 0.89 and 0.12, respectively. We developed the first NTCP model based on whole-blood DVHs for estimating SRIL after abdominal RT in patients with HCC. Our results showed a strong correlation between blood dose and ALC depletion, suggesting the potential to predict the risk of SRIL occurrence using blood dose. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the study was to analyze the clinical data of patients with chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome (OS) during hospitalization and to evaluate the risk factors of patients treated with Non-Invasive Ventilation (NIV). METHODS: Demographic and clinical data of patients with confirmed OS during hospitalization were retrospectively collected. The patients were divided into two groups according to whether noninvasive ventilator was used during hospitalization, including OS treated with NIV (244 cases) and OS without NIV (239 cases). The t-test, χ² test, and Kaplan--Meier curve were used to compare the two groups, and multiple logistic regression was used to analyze the risk factors of NIV in patients with OS. RESULTS: Compared with the OS group without NIV, the pulmonary hypertension, lymphocyte count, and left ventricular ejection fraction% of OS patients with NIV were lower, whereas PCO2, uric acid, C-reactive protein, procalcitonin, and N-terminal pro-B-type natriuretic peptide were higher, with statistical differences (P < 0.05). During hospitalization and follow-up, OS patients with NIV had a longer hospital stay (P < 0.001), and there was no significant difference in the rate of readmission within 28 days. The logistic regression analysis showed that the history of diuretic use, previous history of noninvasive ventilator use, and ischemic heart disease were independent risk factors for NIV treatment in OS patients during hospitalization. CONCLUSION: Patients with OS undergoing NIV during hospitalization exhibited more severe overall illness and had prolonged hospital stays compared to OS patients not receiving NIV. History of diuretic use, history of NIV use, and ischemic heart disease are independent risk factors for NIV treatment in OS patients during hospitalization. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between the preoperative Bioenergetic Health Index (BHI) of platelets and the occurrence of postoperative delirium (POD) in elderly patients. Methods: Elderly patients scheduled for major abdominal surgery under general anesthesia were included. The presence of POD was assessed within the 3 days after surgery. Seahorse XF analysis and transmission electron microscopy were utilized to evaluate the mitochondrial metabolism and morphology of platelets. Results: A total of 20 out of 162 participants developed POD. Participants with POD showed lower preoperative Mini‐Mental State Examination scores and total protein levels, fewer educational years, longer surgery duration, higher mean platelet volume, and lower platelet BHI compared with those without POD. Damaged mitochondria with swollen appearance and distorted cristae was detected in platelets from participants with POD. Preoperative platelet BHI was independently associated with the occurrence of POD after adjusting for age, education, preoperative Mini‐Mental State Examination score, preoperative mean platelet volume and total protein levels, surgical type and duration, and lymphocyte counts on the first postoperative day (OR 0.11, 95% CI 0.03–0.37, p < 0.001). The areas under the receiver operating curves for predicting POD were 0.83 (95% CI 0.76–0.88) for platelet BHI. It showed a sensitivity of 85.00% and specificity of 73.24%, with an optimal cutoff value of 1.61. Using a serial combination (mean platelet volume followed by BHI) yielded a sensitivity of 80.00% and specificity of 82.39%. Interpretation: Preoperative platelet BHI was independently associated with the occurrence of POD in elderly patients and has the potential as a screening biomarker for POD risk. ANN NEUROL 2024;96:74–86 [ABSTRACT FROM AUTHOR]

The research was undertaken during October, 2022 to June, 2023 to study the changes in haemato-biochemical values of the dogs suffered from respiratory tract infection due to bacteria. Blood samples were collected from healthy control group (Group A) and each dog of different treatment groups (Group B, Group C and Group D) on the 0th day (pre-treatment) and the 10th day (post-treatment) in K3-EDTA vacutainer tubes as well as clot activator-coated vacutainer tubes for haematobiochemical estimation. In the result of haemato-biochemical study the highly significant difference (**p<0.01) was found in total leucocyte count, absolute neutrophil count and C-reactive protein. Statistically no significant difference (p>0.05) was observed in total erythrocyte count, haemoglobin, absolute eosinophil count, absolute lymphocyte count and albumin. In case of total protein a highly significant difference (**p<0.01) was observed between Group A and Group B on day 0 and on day 10. A highly significant difference was also observed between (**p<0.01) Group B and Group C; Group B and Group D on day 0 and day 10. On the other hand no significant difference (p>0.05) was observed within treatment groups. In case of globulin, statistically no significant difference (p>0.05) was obtained between the Group A and all the treatment groups on day 0 and day 10. No significant difference (p>0.05) was observed within treatment groups. However, a significant difference (**p<0.01) was found between Group B and Group C; Group B and Group D on 0th day and on the 10th day. [ABSTRACT FROM AUTHOR]

Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate–high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1β concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that peripheral inflammation is associated with the pathogenesis of Parkinson's disease (PD). We examined peripheral immune profiles and their association with clinical characteristics in patients with DLB and compared these with values in patients with PD. Methods: We analyzed peripheral blood from 93 participants (drug-naïve DLB, 31; drug-naïve PD, 31; controls, 31). Absolute leukocyte counts, absolute counts of leukocyte subpopulations, and peripheral blood inflammatory indices such as neutrophil-to-lymphocyte ratio were examined. Associations with clinical characteristics, cardiac sympathetic denervation, and striatal 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) binding were also examined. Results: Patients with DLB had lower absolute lymphocyte and basophil counts than did age-matched controls (both; p < 0.005). Higher basophil counts were marginally associated with higher global cognition (p = 0.054) and were significantly associated with milder motor severity (p = 0.020) and higher striatal 123I-FP-CIT binding (p = 0.038). By contrast, higher basophil counts were associated with more advanced PD characterized by decreased global cognition and severe cardiac sympathetic denervation. Although lower lymphocyte counts had relevance to more advanced PD, they had little relevance to clinical characteristics in patients with DLB. Higher peripheral blood inflammatory indices were associated with lower body mass index in both DLB and PD. Conclusions: As in patients with PD, the peripheral immune profile is altered in patients with DLB. Some peripheral immune cell counts and inflammatory indices reflect the degree of disease progression. These findings may deepen our knowledge on the role of peripheral inflammation in the pathogenesis of DLB. [ABSTRACT FROM AUTHOR]

VEGF, a key mediator of angiogenesis and resistance to immunotherapy, is overexpressed in head and neck squamous cell carcinoma (HNSCC). We aimed to determine the recommended phase 2 dose of ramucirumab, a selective VEGFR2 inhibitor, given with pembrolizumab and the objective response rate of this combination as first-line treatment for recurrent or metastatic HNSCC. In this single-centre, phase 1/2 trial, which was done at Washington University (St Louis, MO, USA), eligible patients were aged 18 years or older with incurable recurrent or metastatic HNSCC and an Eastern Cooperative Oncology Group performance status of 0–2. Patients in phase 2 were required to have had no previous systemic therapy for recurrent or metastatic disease. In a dose de-escalation phase 1 design, patients received ramucirumab (starting dose 10 mg/kg given intravenously) and pembrolizumab (200 mg intravenously) on day 1 of each 21-day cycle. The recommended phase 2 dose of ramucirumab was defined as the highest dose at which one or fewer of three patients had dose-limiting toxicity during cycle one (primary endpoint of phase 1). In a Simon's two-stage phase 2 design, patients received the recommended phase 2 dose of ramucirumab and pembrolizumab. Tumour response (primary endpoint of phase 2) was assessed by Response Evaluation Criteria in Solid Tumours (version 1.1). We hypothesised that there would be an objective response rate of 32% or higher (null ≤13%). Eight or more responses among 33 evaluable patients (those with at least one response assessment) was evidence for activity (80% power; one-sided α=0·05). Analyses were done per protocol. The trial is registered with ClinicalTrials.gov , NCT03650764 , and is closed to enrolment. Between June 18, 2019, and Feb 11, 2021, three patients enrolled and were treated in phase 1 and 37 patients in phase 2. Median age of all patients was 64 years (IQR 59–72). 36 (90%) of 40 patients were men and four (10%) were women, and 36 (90%) patients were White, three (8%) were Black or African American, and one (3%) was Asian. In phase 1, no dose-limiting toxicity event occurred. The recommended phase 2 dose of ramucirumab was 10 mg/kg. Median follow-up for patients on phase 2 was 14·8 months (IQR 4·9–31·0). In phase 2, 18 (55%; 95% CI 38–70) of 33 evaluable patients had an objective response, including confirmed complete response in 11 patients, confirmed partial response in six patients, and unconfirmed partial response in one patient. The most common grade 3 or worse adverse events were dysphagia (14 [38%] of 37 patients), lung infection (11 [30%]), lymphocyte count decrease (ten [27%]), hypophosphataemia (nine [24%]), and hypertension (eight [22%]). No treatment-related deaths were recorded. Ramucirumab and pembrolizumab were safe to administer to patients with recurrent or metastatic HNSCC, and the objective response rate with this combination as first-line treatment for recurrent or metastatic HNSCC was favourable. Further studies of ramucirumab and pembrolizumab in patients with recurrent or metastatic HNSCC are warranted. Lilly and the Joseph Sanchez Foundation. [ABSTRACT FROM AUTHOR]

Objectives: To explore the predictive significance of baseline absolute peripheral lymphocyte counts (ALC) in the effectiveness of radiation in hypopharyngeal squamous cell carcinoma (HPSCC) patients. Design, Setting, and Participants: A retrospective study of pathologically confirmed HPSCC patients who had definitive radiation between January 2020 and January 2022 at Fudan University Eye and ENT Hospital. The routine blood results of patients were obtained to determine if the baseline ALC was connected with the response to radiation. The receiver operator characteristic (ROC) curve and LASSO‐based Cox regression were employed to assess the predictive value of ALC for the efficacy of radiotherapy (RT). Main Outcome Measures and Results: RT induced a considerable drop in ALC and the level of ALC did not revert to the baseline values 1 year after radiation. The baseline level of ALC was higher in patients who met complete response after RT. The baseline ALC and monocyte counts demonstrated the predictive value of radiation effectiveness and ALC was an independent predictor. Conclusion: In HPSCC, lymphocytes were sensitive to radiation and reduced significantly during RT. The baseline ALC might be regarded as a predictive indicator of the effectiveness of RT. [ABSTRACT FROM AUTHOR]

Background and Objectives: Patients with inflammatory bowel disease (IBD) are more likely to be confirmed with vitamin D deficiency. However, the association between inflammation and vitamin D remains unclear. The purpose of this study was to evaluate the association between inflammation and vitamin D in hospitalized patients with IBD. Methods and Study Design: All the participants were recruited from one teaching hospital from June 2018 to October 2022. Inflammation was evaluated by serum concentration of C-reactive protein (CRP), using an immunoturbidimetric method at admission. We further divided the participants into five groups based on serum CRP levels: <5, 5–9.9, 10–19.9, 20–39.9, and >40mg/L. Serum 25-hydroxy-vitamin D (25-(OH)-D) was assessed by liquid chromatography tandem mass spectrometry. Additional information, including age, sex, body mass index (BMI), IBD (ulcerative colitis vs. Crohn’s disease) subtype, was abstracted from medical records. Results: This study included 1,989 patients with IBD (average age was 39.4 years, 33.8% of them were women, 1,365 CD and 624 UC patients). The median CRP was 5.49 mg/L (range of quartiles: 1.64~19.5 mg/L) and the prevalence of 25-(OH)-D deficiency was 69.8%. CRP was significantly associated with serum level of 25-(OH)-D. The difference in 25-(OH)-D was -4.28 ng/ml (-5.27 ng/ml, -3.31 ng/ml) between two extremist CRP groups after adjustment of potential covariates (age, sex, BMI, type of IBD, dietary type, season, and lymphocyte count). Subgroup analysis in sex, type of IBD, and age, were similar to the main analysis results. Conclusions: There was a negative association between CRP levels and vitamin D in hospitalized patients with IBD. [ABSTRACT FROM AUTHOR]

Objective: The introduction of cytological screening with the Papanicolau smear significantly reduced cervical cancer mortality. However, Pap smear examination can be challenging, being based on the observer ability to decode different cytological and architectural features. This study aims to evaluate the malignancy rate of AGC (atypical glandular cells) category, investigating the relationships between cytological and histological diagnosis. Methods: Eighty‐nine patients, diagnosed as AGC at cytological evaluation and followed up with biopsy or surgical procedure at Policlinico Gemelli Hospital, Rome, Italy, were included in the study. The cytopathological architectural (feathering, rosette formation, overlapping, loss of polarity, papillary formation, three‐dimensional formation) and nuclear (N/C ratio, nuclear enlargement and hyperchromasia, mitoses, nuclei irregularity, evident nucleoli) features of AGC were evaluated. Statistical analyses were performed to assess cyto‐histological correlation and determine the relevance of architectural and nuclear features in the diagnosis of malignancy. Results: Of the 89 AGC patients, 48 cases (53.93%) were diagnosed as AGC‐NOS and 41 (46.07%) were diagnosed as AGC‐FN, according to the Bethesda classification system. The follow‐up biopsies or surgical resections revealed malignancy in 46 patients (51.69%). The rates of malignancy for AGC‐NOS and AGC‐FN were 35.41% and 70.73% respectively. Furthermore, analysing cytopathological features, we found that both architectural and nuclear criteria were statistically significant (p < 0.05). Only overlapping, nuclear irregularity and increased N/C ratio were not found to be statistically significant for detecting malignancy. Conclusions: Cytological diagnosis of glandular lesions remains a valid tool, when appropriate clinical correlation and expert evaluation are available. [ABSTRACT FROM AUTHOR]

Objective: this study aimed to assess the effects of two isocaloric parenteral nutrition (PN) regimens with different protein content and non-protein calorie to nitrogen ratio (NPCNR) on the evolution of nutritional parameters and outcomes in adult inpatients. Methods: this was a retrospective quasi-experimental study performed in a 400-bed tertiary hospital. Adult inpatients were initially eligible if they had received ≥ 4 days of PN with NPCNR ≥ 100 or ≤ 90 in a period of three years. Patients were propensity-score matched to adjust for differences, resulting in two final cohorts: Cohort "Medium-P" included patients receiving PN with NCPCNR ≥ 100 and cohort "High-P", receiving PN with NCPCNR ≤ 90. The main variables were differences in plasma albumin, prealbumin, cholesterol, and lymphocyte count, days requiring PN, length of stay, and mortality at 90 days. Results: 202 patients were finally recruited and divided into the two equal cohorts. Patients were mainly male (122; 60.4 %), surgical (149; 73.8 %), critically ill (100; 49.5 %), with high nutritional risk (141; 69.8 %) and with a neoplasm (145; 71.8 %). PN provided 25 kcal/kg/day, but protein intake was 0.25 g/kg/day higher in the "High-P" cohort. Baseline characteristics and biochemistry were not different between the two cohorts. The "High-P" cohort presented a smaller difference at the end of PN for lymphocytes, more days with hyperglycaemia, and more days requiring PN. The rest of variables did not differ. Conclusions: high doses of protein (lower NPCNR) did not present advantages compared to medium doses of protein (higher NPCNR) when providing isocaloric PN in adult inpatients. [ABSTRACT FROM AUTHOR]

Objective: To analyze the predictive value of contrast-enhanced ultrasound (CEUS) combined with serum alpha-fetoprotein (AFP), γ-glutamyl transpeptidase (GGT) and lymphocyte count ratio (GLR) for microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Methods: 177 HCC patients who underwent hepatectomy in The 73rd Group Army Hospital of the Chinese People's Liberation Army from October 2018 to October 2023 were selected, all patients underwent CEUS and serum AFP, GGT and GLR examinations 1 week before operation. According to the results of postoperative pathological examination of MVI, patients were divided into MVI positive group (n=52) and MVI negative group (n=125). The risk factors affecting MVI in HCC patients were analyzed by multivariate Logistic regression analysis, the predictive value of CEUS combine with AFP, GGT and GLR for MVI in HCC patients were analyzed by receiver operating characteristic (ROC) curve. Results: The onset time, peak time and clearance time in MVI positive group were shorter than those in MVI negative group (P<0.05). AFP, GGT and GLR in MVI positive group were significantly higher than those in MVI negative group(P<0.05). Multivariate Logistic regression analysis showed that elevated AFP, elevated GGT, elevated GLR, irregular lesion morphology, shortened onset time, shortened peak time, and shortened clearance time were independent risk factors for MVI in HCC patients (P<0.001). The ROC results showed that, the area under the curve of MVI in HCC patients predicted by the combination of serum AFP, GGT and GLR was 0.901, which was significantly larger than that of single detection(P<0.05). Conclusion: The levels of serum AFP, GGT and GLR in patients with MVI after HCC operation increased, and the time of initial increase, peak time and clearance time were shortened, which were independent risk factors for MVI in HCC patients. CEUS combined with AFP, GGT and GLR has a high predictive value for MVI in HCC patients. [ABSTRACT FROM AUTHOR]

Introduction: The goal of the current study was to determine how the leukocyte count varied on a monthly basis during the various stages of the menstrual cycle. Periodic vaginal bleeding is a cyclical phenomenon associated with the menstrual cycle, which impacts all bodily systems. It takes place in the course of a woman's reproductive life and is governed by a planned progression of structural, functional, and hormonal systems. A regular menstrual cycle typically lasts 28 days, with an average blood loss of 20 to 60 millilitres and a flow that lasts 2 to 6 days. The menstrual cycle is regulated by the pituitary-ovarian system. Material and Methods: 38 healthy females in the 16-28 age range with regular cycles lasting 28-28 days were examined.The current study was conducted at the Obstetrics & Gynaecology Department of MKCG MCH, Berhampur, between August 2014 and October 2015. 38 healthy female subjects, ages 16 to 28, with average menstrual cycles lasting 28P2 days participated in the study. Women with irregular periods, gastrointestinal disorders, anaemia, a history of drug usage that interfered with their menstrual cycle, a history of chronic disease, or a fever at the time of sample collection were not included in the research. Each female participant informedly consented to the research after learning about its protocols. The tests were carried out in accordance with ethical standards. Result: During the secretory phase, the total leukocyte count significantly increased. When it came to the differential leukocyte count, the neutrophil count increased significantly during the secretory phase, the lymphocyte count increased during both the menstrual and secretory phases, the monocyte count increased during the proliferative phase but did not significantly change, and the eosinophil count did not significantly change throughout the three phases. Conclusion: In order to better understand a variety of illnesses, this study sought to ascertain the typical fluctuation in the leucocyte count during the various phases of the menstrual cycle.This study shows variations in the total leukocyte count and differential leukocyte count during the various stages of the menstrual cycle and offers information on a variety of disorders that affect women and are linked to monthly swings. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the influence of serum leukocytes on urologic cancers (UC) using observation-based investigations. In the present study, Mendelian randomization (MR) was employed to assess the link between leukocyte count (LC) and the risk of UC development. Methods: Five LC and three major UC patient prognoses were obtained for MR analysis from genome-wide association studies (GWAS). Furthermore, in order to evaluate reverse causality, bidirectional studies were conducted. Finally, a sensitivity analysis using multiple methods was carried out. Results: There was no significant correlation found in the genetic assessment of differential LC between the co-occurrence of bladder cancer (BCA) and renal cell carcinoma (RCC). Conversely, an individual 1-standard deviation (SD) rise in neutrophil count was strongly linked to a 9.3% elevation in prostate cancer (PCA) risk ([odd ratio]OR = 1.093, 95% [confidence interval]CI = 0.864-1.383, p = 0.002). Reverse MR analysis suggested that PCA was unlikely to cause changes in neutrophil count. Additional sensitivity studies revealed that the outcomes of all MR evaluations were similar, and there was no horizontal pleiotropy. Primary MR analysis using inverse-variance weighted (IVW) revealed that differential lymphocyte count significantly influenced RCC risk (OR = 1.162, 95%CI = 0.918-1.470, p = 0.001). Moreover, altered basophil count also affected BCA risk (OR = 1.249, 95% CI = 0.904-1.725, p = 0.018). Nonetheless, these causal associations were not significant in the sensitivity analysis. Conclusion: In summary, the results revealed that increased neutrophil counts represent a significant PCA risk factor. The current research indicates a significant relationship between immune cell activity and the cause of UC. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is common among cirrhotic patients, leading to increased morbidity and mortality. Validated screening tools are essential for the early identification of malnutrition risk, enabling timely nutritional assessment and intervention. Objective: To validate the Nutrition Alert Form (NAF) against the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) in outpatients with cirrhosis, explore the relationship between NAF scores and anthropometric parameters, and evaluate the NAF's diagnostic performance using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Materials and Methods: The authors conducted a cross-sectional study that included 179 randomly selected cirrhotic outpatients. Various nutrition screening and assessment tools were employed, along with anthropometric measurements and biochemical tests. The NAF encompasses patient-directed questions, body weight, and body mass index (BMI). Alternatively, total lymphocyte count (TLC), or serum albumin (ALB) could replace weight and height when they were unavailable. Results: Approximately 43% of patients were identified as being at risk for malnutrition by the RFH-NPT, while the NAF-BMI, NAF-TLC, and NAF-ALB identified 41.9%, 46.9%, and 46.3% of patients, respectively. Using GLIM criteria, the prevalence of malnutrition was 18.4%. The NAFBMI, NAF-ALB, and NAF-TLC showed sensitivities of 93.9%, 96.9%, and 93.9%, with specificities of 69.9%, 65.1%, and 63.7%, respectively. The RFH-NPT exhibited a sensitivity of 90.9% and specificity of 66.4%. A strong correlation (p=0.75, p<0.05) was observed between the RFH-NPT and NAF-BMI scores. NAF-BMI scores moderately correlated with cirrhosis severity (p=0.41, p<0.05). Screening completion times did not differ significantly between methods. Conclusion: Due to its high sensitivity and accuracy, the NAF can serve as a simple and validated tool to screen for risk of malnutrition in cirrhotic patients. It also correlated with the RFH-NPT. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to evaluate the relationship between semen parameters, complete blood count, and hormone levels on the day of spermiogram. METHODS: Semen parameters of 230 patients who were examined for full blood count test and hormone levels on the day of spermiogram were included in the study. Patients were grouped according to the total motile sperm count (TMSC), semen parameters, hemogram, and hormone levels were compared between groups. RESULTS: No statistically significant difference was found between groups in neutrophil ratios, neutrophil, lymphocyte, platelet counts, neutrophile-to-lymphocyte ratio (N/L), and platelet-to-lymphocyte ratio (P/L). However, white blood cell (WBC) and lymphocyte counts were weakly positively correlated with sperm concentration (p=0.021, p=0.026), and a weakly significant positive correlation was found with WBC and neutrophil count for motility (p=0.038, p=0.004). FSH level was found to be lower in cases with TMSC >20 m than those with TMSC <5 m and 5-10 m (p=0.004, p=0.022). LH was found to be lower in cases with TMSC >20 m than those with TMSC <5 m (p=0.048). A negative correlation was found for both FSH and LH levels with sperm concentration, motility, and TMSC (p<0.001, p=0.014). CONCLUSION: In this study, a significant negative correlation was demonstrated between FSH, LH levels and sperm concentration, motility, TMSC. N/L and P/L cannot be used as predictive markers of sperm quality. The results of a significant positive correlation between WBC, neutrophil counts, and sperm parameters encourage researchers to conduct prospective randomized controlled trials with larger sample sizes and different inflammatory and hormonal markers. [ABSTRACT FROM AUTHOR]

Background and Aims: Several studies reported the effect of COVID-19 on inducing gut dysbiosis, which is also correlated with disease severity. This study aims to investigate the effect of a nutraceutical formula on the shift of microbiota profiles and, secondly, on the clinical–pathological parameters of acute and post-acute COVID-19 patients. Methods: In this randomised, double-blind, placebo-controlled trial conducted at National Institute for Infectious diseases (INMI) Lazzaro Spallanzani (Italy), 52 patients were randomly assigned (1:1) to receive a multistrain synbiotic formula (Kebirah®) or placebo orally for 35 days at COVID-19 diagnosis. Health professionals, investigators, and patients were masked to group assignments. The V3–V4 hypervariable region of 16S rRNA gene sequencing was employed to study the gut microbiota composition in the two groups. Results: Supplementation with Kebirah® prevented the decrease in the Shannon diversity index of gut microbiota, which was instead observed in patients receiving the placebo. In addition, decreases in lymphocyte count and haemoglobin levels were observed only in the placebo group and not in the treated group, which was also characterised by an amelioration of the gut microbial profile, with an enrichment in beneficial bacteria and a preservation of species diversity. Conclusions: Our data suggest that modulating the gut microbiota in acute disease through administration of a specific symbiotic formula could be a useful strategy in the frame of SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

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Background: Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR1. In this first-in-human study, icanbelimod was investigated in healthy men in Australia. Methods: Participants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort. Results: Icanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (Tmax 4–7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to nonserious TEAEs. Up-titration attenuated heart rate reductions. Conclusion: Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts. [ABSTRACT FROM AUTHOR]

Purpose: To explore the correlation between hemoglobin, albumin, lymphocyte count, platelet count (HALP) score and type 2 diabetic retinopathy (DR). Methods: The study was conducted on 674 patients with type 2 diabetes (T2DM). According to the results of the fundus examination, they were divided into non-diabetic retinopathy group (NDR, n=388) and diabetic retinopathy group (DR, n=286). Collected patients baseline data, calculated HALP score, analyzed the correlation between HALP score and DR. Results: In all patients, male patients and female patients, the HALP score of the DR group was lower than that of the NDR group (P< 0.001), and the HALP score was negatively correlated with the incidence of DR (P< 0.05). HALP score was independent risk factors for DR, regardless of gender. In male patients, HALP score and DR had a linear relationship, but in female patients, HALP score and DR showed a nonlinear relationship, and HALP score was more sensitive to the onset of DR in male patients. The combined diagnostic model of HALP score, course of disease, SBP and BUN was used to diagnose DR, and it was found that the diagnostic value was the highest among male patients, with AUC of 0.761, sensitivity of 58.3% and specificity of 80.3%. Conclusion: HALP score was an independent risk factor for DR, attention should be paid to monitoring HALP score, especially in male T2DM patients. The accuracy of HALP score, disease course, SBP and BUN combined model diagnosis of DR was high, which can become a biological indicator for early screening of DR. [ABSTRACT FROM AUTHOR]

Linear mixed models are traditionally used for jointly modeling (multivariate) longitudinal outcomes and event-time(s). However, when the outcomes are non-Gaussian a quantile regression model is more appropriate. In addition, in the presence of some time-varying covariates, it might be of interest to see how the effects of different covariates vary from one quantile level (of outcomes) to the other, and consequently how the event-time changes across different quantiles. For such analyses linear quantile mixed models can be used, and an efficient computational algorithm can be developed. We analyze a dataset from the Acute Lymphocytic Leukemia (ALL) maintenance study conducted by Tata Medical Center, Kolkata. In this study, the patients suffering from ALL were treated with two standard drugs (6MP and MTx) for the first two years, and three biomarkers (e.g. lymphocyte count, neutrophil count and platelet count) were longitudinally measured. After treatment the patients were followed nearly for the next three years, and the relapse-time (if any) for each patient was recorded. For this dataset we develop a Bayesian quantile joint model for the three longitudinal biomarkers and time-to-relapse. We consider an Asymmetric Laplace Distribution (ALD) for each outcome, and exploit the mixture representation of the ALD for developing a Gibbs sampler algorithm to estimate the regression coefficients. Our proposed model allows different quantile levels for different biomarkers, but still simultaneously estimates the regression coefficients corresponding to a particular quantile combination. We infer that a higher lymphocyte count accelerates the chance of a relapse while a higher neutrophil count and a higher platelet count (jointly) reduce it. Also, we infer that across (almost) all quantiles 6MP reduces the lymphocyte count, while MTx increases the neutrophil count. Simulation studies are performed to assess the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

Background/Aim: The aim of the present study was to evaluate the clinical impact of the Global Immune-NutritionInformation Index (GINI) in patients with gastric cancer (GC) who received curative treatment and to clarify the potential of the GINI as a biomarker. Patients and Methods: Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were selected based on their medical records. The GINI was calculated as follows: GINI=[C-reactive protein × platelet × monocyte × neutrophil]/[albumin × lymphocyte]. Results: A total of 258 patients were included in this study. Of these, 169 patients were categorized into the GINI-low group and 89 into the GINI-high group using a cut-off value of 1,730. The three- and five-year overall survival (OS) rates were 86.4% and 78.4%, respectively, in the GINI-low group, and 66.4% and 58.3% in the GINI-high group (p<0.001). In a multivariate analysis for OS, the GINI was identified as an independent prognostic factor [hazard ratio (HR)=1.772; 95% confidence interval (CI)=1.053-2.979, p=0.031]. Similar results were observed for RFS. In addition, the GINI affected the perioperative clinical course, including postoperative surgical complications and postoperative adjuvant treatment. Conclusion: The GINI is a promising biomarker for the treatment and management of GC. [ABSTRACT FROM AUTHOR]

Background/Aim: Cancer cachexia is associated with poor prognosis in patients with metastatic urothelial carcinoma (mUC). The objective of the study was to assess the cachexia index (CXI), which is a new indicator assessing the status of cancer cachexia, as a prognostic indicator for mUC patients treated with gemcitabine plus cisplatin (GC) chemotherapy. Patients and Methods: The study included 55 patients with mUC who underwent GC chemotherapy between 2008 and 2022 as first-line chemotherapy. The CXI at the start of chemotherapy was determined as follows: CXI=(serum albumin × skeletal muscle mass index)/ (neutrophil count/lymphocyte count). Patients were categorized into two groups based on a median CXI value (CXI-high and CXI low). We used Kaplan–Meier curves and multivariate Cox proportional hazards regression models to assess the association between the CXI and overall survival (OS). Results: At the start of GC chemotherapy, significant differences were not found in patients' characteristics. The median OS was significantly shorter in the CXI-low group [10.0 months (95% confidence interval (CI)=5.1-12.8)] than in the CXI-high group [22.3 months (95% CI=13.6-NA), p<0.05]. Multivariate analysis revealed that low CXI was a predictor of a poor prognosis [hazard ratio (HR)=2.25, 95% CI=1.12-4.52, p<0.05]. Conclusion: CXI might be useful as a prognostic indicator for patients with mUC undergoing first-line GC chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) scheduled for neoadjuvant radiotherapy still have a poor prognosis. This study was to explore the prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with locally advanced ESCC after neoadjuvant radiotherapy (NRT). Materials and Methods: Eighty-two consecutive patients with ESCC scheduled for neoadjuvant radiotherapy between 2011 and 2017 were enrolled in this study. SII values (SII = platelet × neutrophil/lymphocyte), prognostic nutritional index values (PNI = albumin concentration (g/L) + 5 × total lymphocyte count (109/L)), platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR) were retrospectively collected and calculated before treatment. The Cut-off Finder application was applied to find out the cut-off points of the SII, NLR, PNI and PLR. A regression model was used to examine prognostic factors for overall survival (OS) rates. Results: The median follow-up was 44 months (3 to 83). Sixty patients (73.17%) underwent surgery as scheduled. This study found that factors improving OS were a lower SII (≤ 916.6 × 109/L) (P=0.040) and neoadjuvant chemoradiotherapy (NCRT) (P=0.034). The patients with a lower SII and NCRT had a better OS (P< 0.001). Moreover, additionally, a higher SII was associated with a lower resectability rate (P=0.035). Conclusion: The SII can predict resectability in ESCC patients following neoadjuvant radiotherapy. Both the SII and neoadjuvant chemoradiotherapy appear to influence OS. [ABSTRACT FROM AUTHOR]

Introduction: Patients admitted to the icu tend to experience malnutrition, so nutrition is needed in this case energy intake to help reduced the incidence of infection,closely linked to poor prognosis in ICU treatment. This study aims to establish the correlation between energy intake and infection occurrence among critically ill ICU patients undergoing medical nutrition therapy at Central General Hospital (RSUP) Dr. Wahidin Sudirohusodo. Methods: This is a retrospective cohort study on critically ill ICU patients at Dr. Wahidin Sudirohusodo Hospital Makassar. Data were collected through medical records from September 2020 December 2022. Total 551 patients was divided into two groups, first group received enteral, parenteral, and mixed combined enteral and parenteral nutrition, while second group only enteral or parenteral nutrition, Lymphocyte count and leucocyte as a predictor infection for both groups. Results: this study found out, a significant correlation between the use of enteral and parenteral nutrition methods first group and second group (p < 0.000).Specifically, enteral nutrition methods showed a significant relationship with first group or second group (p < 0.000), while parenteral nutrition methods also displayed a significant association (p < 0.007). Adequate energy intake is crucial for the recovery of ICU patients at RSUP dr. Wahidin Sudirohusodo, with medical nutritional therapy, including enteral or parenteral nutrition, playing a supportive role in ensuring patients receive sufficient nutrition. Conclusions: The First Group with Enteral, Parenteral, and mixed Combined of parenthral dan parenteral has lower infection and higher foofd intake compared to second group. [ABSTRACT FROM AUTHOR]

Copyright of Revista Nutrición Clínica y Dietética Hospitalaria is the property of Sociedad Espanola de Dietetica y Ciencias de la Alimentacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The effect of oxycodone as an opioid receptor agonist on immune function is still controversial. In this study, we investigated the possible effects of oxycodone on immune function in mice and its possible mechanisms of action. Methods: By repeated intraperitoneal injections of 25 mg/kg morphine and 5 mg/kg, 20 mg/kg, and 60 mg/kg oxycodone, we assessed possible changes in the number of splenic lymphocytes and inflammatory cytokines in the serum of mice. CD4+ T cells and CD8+ T cells were sorted from the spleen to observe whether the expression levels of opioid receptors and downstream signals were altered. Results: Repeated administration of oxycodone at a dose above 20 mg/kg resulted in significant weight loss. Repeated administration of oxycodone exhibits significant dose-dependent reduction in CD4+ T cells, with little effect on CD8+ T cells and little effect on inflammatory cytokine levels. Low- and intermediate-dose oxycodone increased the mRNA expression level of MOR, KOR, and DOR to varying degrees. Moreover, oxycodone increases the mRNA expression levels of the TLR4 signaling pathway to varying degrees. Conclusion: Repeated intraperitoneal injection of oxycodone induces immunosuppression in mice. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a common comorbidity in COVID-19 subjects. Hyperglycemia at hospital admission identified as a major risk factor and is responsible for poor prognosis. Hematological and inflammatory parameters have been recognized as predictive markers of severity in COVID-19. In this clinical study, we aimed to assess the impact of hyperglycemia at hospital admission on hematological and several inflammatory parameters in COVID-19 patients. A total of 550 COVID-19 subjects were primarily categorized into two major groups (normoglycemic and hyperglycemic) based on random blood sugar levels. On the first day of hospitalization, subjects' oxygen saturation, random blood sugar, hematological variables, and inflammatory parameters were recorded. The hyperglycemic group exhibited higher levels of serum ferritin, total leukocyte count (TLC), lactate dehydrogenase (LDH), neutrophil count, and neutrophil-to-lymphocyte ratio (NLR). In contrast, oxygen saturation and lymphocyte count were lower compared to the normoglycemic group. Significantly elevated levels of hematological variables (TLC, neutrophil count, NLR) and inflammatory parameters (serum ferritin) were observed in the hyperglycemic group. Among inflammatory parameters, only serum ferritin levels showed statistical significance. This study supports the clinical association between hyperglycemia and an increased severity of COVID-19. Consequently, the identification of these parameters is a crucial and valuable prognostic indicator for assessing disease severity in hyperglycemic subjects. [ABSTRACT FROM AUTHOR]

Lymphopenia is a well-known side effect of radiotherapy and has been shown to have a negative impact on patient outcomes. However, the extent of lymphopenia caused by palliative radiotherapy and its effect on patient prognosis has not been clarified. The aim of this study was to determine the incidence and severity of lymphopenia after palliative radiotherapy for vertebral metastases and to determine their effects on patients' survival outcomes. We conducted a retrospective analysis for patients who underwent palliative radiotherapy for vertebral metastases and could be followed up for 12 weeks. Lymphocyte counts were documented at baseline and throughout the 12-week period following the start of radiotherapy and their medians and interquartile ranges (IQRs) were recorded. Exploratory analyses were performed to identify predictive factors for lymphopenia and its impact on overall survival (OS). A total of 282 cases that met the inclusion criteria were analyzed. The median baseline lymphocyte count was 1.26 × 103/μl (IQR: 0.89–1.72 × 103/μl). Peak lymphopenia occurred at a median of 26 days (IQR: 15–45 days) with a median nadir of 0.52 × 103/μl (IQR: 0.31–0.81 × 103/μl). Long-term analysis of patients surviving for 1 year showed that lymphopenia persisted at 1 year after radiotherapy. The main irradiation site, radiation field length and pretreatment lymphocyte count were significantly related to grade 3 or higher lymphopenia. Lymphopenia was identified as a significant predictor of OS by multivariate Cox regression analysis. This study demonstrated the incidence of lymphopenia after palliative radiotherapy for vertebral metastases and its effect on patients' OS. [ABSTRACT FROM AUTHOR]

Objective: To collect real-world data regarding the attainment of the earlyachieved lupus low disease activity state (LLDAS) in systemic lupus erythematosus (SLE) patients receiving telitacicept or belimumab treatment, and identify factors predictive of target achievement. Methods: Eighty-seven SLE patients who received telitacicept (N=42) or belimumab (N=45) were retrospectively reviewed in this observational study. Clinical and laboratory data, disease activity assessment, and glucocorticoid dosage were collected for analysis. Achieving LLDAS at least once within 24 weeks post-treatment was considered as early-achieved LLDAS. Multivariate regression was used to assess baseline predictive variables for early-achieved LLDAS. Subgroup analysis and interaction tests were also performed to examine the robustness of the results across different sets of baseline characteristics. Prognostic stratification for early-achieved LLDAS was established based on the identified risk factors. Results: During the 24-week follow-up period, LLDAS was achieved by at least one time in 49.43% (43/87) of the patients, with sustained achievement through week 24 observed in 36 out of these 43 patients (83.27%). Multivariate analysis revealed that early achievement of LLDAS was particularly observed in patients with higher baseline lymphocyte counts [HR=1.79, 95% CI (1.19-2.67), P=0.005] and serum albumin levels [HR=1.06, 95% CI (1.003-1.12), P=0.039]. Conversely, hematological involvement [HR=0.48, 95% CI (0.24-0.93), P=0.031] predicted lower attainment of early-achieved LLDAS. The use of telitacicept was associated with a reduced risk of failing to attain early achievement of LLDAS [HR=2.55, 95% CI (1.36-4.79), P=0.004]. Subgroup analyses and interaction tests showed a stable relationship between the telitacicept use and LLDAS achievement. The results remained consistent across all subgroup analyses. Significant differences (P<0.001) were observed in the Kaplan-Meier estimates for LLDAS among risk groups based on the number of identified risk factors. Conclusion: The achievement of LLDAS is attainable in the management of SLE patients undergoing treatment with telitacicept or belimumab in real-life clinical practice. Baseline lymphocyte counts, serum albumin levels, hematological involvement and the use of telitacicept serve as robust predictors for earlyachieved LLDAS, helping to identify patients who are likely to benefit on the treatment. [ABSTRACT FROM AUTHOR]

Background: The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date. Methods: We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY). Results: We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the welldocumented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment. Conclusion: In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles. [ABSTRACT FROM AUTHOR]

Background: 177Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy. Methods: Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6- month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT. Results: Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year (p < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level (p < 0.05) for patients with progressive disease. Conclusion: We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients. [ABSTRACT FROM AUTHOR]

PURPOSE: The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis. MATERIALS AND METHODS: Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed. RESULTS: The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids. CONCLUSION: An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection. The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning model with explainable artificial intelligence to predict one-year survival after palliative radiotherapy (RT) for bone metastasis. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) poses a significant global health challenge, demanding reliable prognostic tools to guide treatment decisions. This study introduces a novel prognostic scoring system, the albumin-total lymphocyte count-RAS index (ALRI), integrating serum albumin, lymphocyte count, and RAS gene mutations. A cohort of 445 stage I–III CRC patients undergoing curative resection was analyzed, revealing ALRI's association with clinicopathological factors, including age, tumor location, and invasion depth. The ALRI demonstrated superior prognostic value, with a cutoff value of 2 distinguishing high and low-risk groups. The high-ALRI group exhibited elevated rates of recurrence. Univariate and multivariate analyses identified ALRI as an independent predictor for both 5 year recurrence-free survival (RFS) and overall survival (OS). Kaplan–Meier curves illustrated significant differences in RFS and OS between high and low-ALRI groups, emphasizing ALRI's potential as a prognostic marker. Importantly, ALRI outperformed existing nutritional indices, such as controlling nutritional status and neutrophil-to-lymphocyte ratio, in predicting overall survival. The study underscores the comprehensive insight provided by ALRI, combining inflammatory, nutritional, and genetic information for robust prognostication in CRC patients. This user-friendly tool demonstrates promise for preoperative prognosis and personalized treatment strategies, emphasizing the crucial role of inflammation and nutrition in CRC outcomes. [ABSTRACT FROM AUTHOR]