Post-treatment Counts Research Articles

Anticandidal effect of multiple sessions of erythrosine and potassium iodide-mediated photodynamic therapy

ABSTRACT Background Erythrosine+potassium iodide-mediated photodynamic therapy has shown an anticandidal effect. Single session, however, has inadequate fungal inhibition. Objectives We aimed to examine the effects of multiple aPDT sessions on Candida albicans inhibition and singlet oxygen formation. Methods 220 μM erythrosine +/-100 mM potassium iodide was applied to C. albicans biofilms for 1 min prior to irradiation at 530±10 nm using a 250 mW/cm2 light-emitting diode. Negative and positive controls were phosphate buffer saline and nystatin, respectively. Single, double and triple irradiation sessions with a 5 min resting time between sessions were performed. Post-treatment candidal counts were done at 0, 1 6 and 24 hr while log10 colony forming unit/ml was calculated and compared using a Kruskal-Wallis with Dunn’s post hoc test at a p<0.05 - Singlet oxygen amount was compared using one-way ANOVA with a post hoc test at a p< 0.05. Results Two and three irradiation sessions to erythrosine+potassium iodide could inhibit Candida albicans at 7.92 log10CFU/ml (p < 0.001) . Singlet oxygen from a combination groups was significantly higher than for erythrosine (positive control). Moreover, the correlation coefficient (r) between singlet oxygen production and decreased Candida albicans counts was equal to 1. Conclusion Multiple sessions PDT of 220 μM erythrosine+100 mM potassium iodide effectively inhibited a Candida biofilm.

The Potential Adverse Impact of Post-Treatment Thrombocytopenia on Clinical Outcomes in Cancer Patients Treated With Immune Checkpoint Inhibitors.

The main goal of this study is to explore the prognostic and predictive implications of post-treatment thrombocytopenia on treatment efficacy and clinical outcomes in advanced-stage cancer treated with immune checkpoint inhibitors (ICIs). This retrospective study included 102 patients with advanced-stage cancer who were treated with ICIs. The simultaneous administration of chemotherapy and ICIs was omitted; nevertheless, the selection of chemotherapy agents employed in different treatment lines was left to the discretion of the attending clinician. Patients were stratified into distinct cohorts based on their post-treatment platelet counts (evaluated for up to four to six months after the completion of ICI). The primary endpoint of interest was progression-free survival (PFS), and overall survival (OS) was the secondary endpoint. Patients with superior Eastern Cooperative Oncology Group (ECOG) performance status and those who received ICI as second-line treatment displayed markedly elevated incidences of grade 1 thrombocytopenia (p < 0.05). Kaplan-Meier survival analysis confirmed that patients with high-grade thrombocytopenia had significantly shorter PFS (six vs. 13 vs. 19 months, p < 0.0001) and OS (10 vs. 21 vs. 25 months, p < 0.0001) than those with lower grades or without thrombocytopenia, respectively. Multivariate analysis revealed that decreased platelet levels were a negative independent prognostic factor for both PFS and OS in patients with advanced-stage cancer who received ICIs. The results of this retrospective study suggest that a decline in platelet levels after treatment represents a dependable adverse prognostic biomarker for clinical outcomes. Moreover, a decrease in platelet levels has been linked to reduced treatment efficacy in advanced-stage cancer patients receiving ICIs, thereby providing valuable prognostic insights for the implementation of personalized treatment strategies in cancer immunotherapy.

Strategic control of the cattle tick Rhipicephlaus microplus applied to rotational and silvopastoral grazing systems in subtropical areas.

This work evaluated if strategic control based on no more than three or four annual treatments is useful to control Rhipicephalus microplus infestations on cattle when it is applied to intensive rotational grazing and silvopastoral systems with high stocking rates in subtropical areas. In the intensive rotational grazing system, three annual treatments with chemical acaricides were applied on cattle in two different schemes: between spring and early summer and from late winter and late spring. Strategic control based on three treatments with chemical acaricides from late winter to late spring plus an additional fourth treatment in summer was tested in the silvopastoral system. In the intensive rotational grazing systems, the control schemes allow to reach a significant reduction in the tick load on cattle considering a time interval from spring to autumn. However, the efficacy levels were not high enough in some specific moments, namely, the tick counts of summer and autumn (there were not significant differences between treated and control groups). The scheme evaluated in the silvopastoral grazing system yielded better results than those tested for the intensive rotational system, because significant differences in tick load between treated and control groups were observed in all post-treatment counts and when the analysis was performed for the whole study period. However, values of efficacy in the count-by-count comparison were disparate, ranging from 64.1 to 99.7. Although the efficacy values obtained in the silvopastoral system were better than those of the rotational grazing systems, the total tick load on treated cattle in autumn was not low enough (mean abundance values 25.14 and 38.14). Ticks were more evenly distributed among hosts in late summer and autumn than in spring or early summer, where few hosts carry most of the ticks. Some management strategies as intensive rotational systems or silvopastoral structures can lead to a more efficient forage use, but they imply greater tick challenge than in extensive grazing systems. In these situations, the schemes of strategic control bases on three or four annual treatments should be complemented with additional tactical treatments in late summer or autumn.

Circulating tumor cells: a valuable indicator for locally advanced nasopharyngeal carcinoma.

Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.

Treatment intensity affects immune reconstitution even after childhood cancer not treated with hematopoietic stem cell transplantation.

Only a few previous studies examine immune system recovery after completed cancer treatment. The aim of this study was to analyze immune reconstitution after childhood cancer therapy in a non-hematopoietic stem cell transplantation setting. We analyzed children (N = 79) who received chemotherapy with/without irradiation for cancer diagnosed between 2014 and 2019 at Turku University Hospital, Finland. We retrospectively collected data on baseline parameters and post-treatment immunological recovery, namely neutrophil and lymphocyte counts, IgG levels, CD19, CD4 and natural killer cell counts. Immunological parameters were followed until their normalization. Treatment intensity was stratified according to the Intensity of Treatment Rating Scale (ITR-3). We analyzed the effects of treatment intensity on normalization of immunological parameters across the entire treatment range. Treatment intensity had a major effect on immune system recovery after completion of treatment. Most patients had normal immunological parameters 1-4 months post-treatment both in high- and low-intensity treatment groups, but patients classified in the high-intensity group had low parameters more often than patients in the low-intensity group. Our data suggest a fast recovery of studied immunological parameters after the majority of current pediatric oncologic treatments. Treatment for high-risk acute lymphoblastic leukemia, acute myeloid leukemia, medulloblastoma, and mature B-cell lymphoma was associated with prolonged recovery times for a substantial proportion of cases. High treatment intensity was associated with prolonged immunological recovery.

Model-Based Prediction of Irinotecan-Induced Grade 4 Neutropenia in Cancer Patients: Influence of Incorporating Germline Genetic Factors in the Model.

Neutropenia is the major dose-limiting toxicity of irinotecan-based therapy. The objective of this study was to assess whether inclusion of germline genetic variants into a population pharmacokinetic/pharmacodynamic model can improve prediction of irinotecan-induced grade 4 neutropenia and identify novel variants of clinical value. A semimechanistic population pharmacokinetic/pharmacodynamic model was used to predict neutrophil response over time in 197 patients receiving irinotecan. Covariate analysis was performed for demographic/clinical factors and 4,781 genetic variants in 84 drug response- and toxicity-related genes to identify covariates associated with neutrophil response. We evaluated the predictive value of the model for grade 4 neutropenia reflecting different clinical scenarios of available data on identified demographic/clinical covariates, baseline and post-treatment absolute neutrophil counts (ANCs), individual pharmacokinetics, and germline genetic variation. Adding 8 genetic identified covariates (rs10929302 (UGT1A1), rs1042482 (DPYD), rs2859101 (HLA-DQB3), rs61754806 (NR3C1), rs9266271 (HLA-B), rs7294 (VKORC1), rs1051713 (ALOX5), and ABCB1 rare variant burden) to a model using only baseline ANCs improved prediction of irinotecan-induced grade 4 neutropenia from area under the receiver operating characteristic curve (AUC-ROC) of 50-64% (95% confidence interval (CI), 54-74%). Individual pharmacokinetics further improved the prediction to 74% (95% CI, 64-84%). When weekly ANC was available, the identified covariates and individual pharmacokinetics yielded no additional contribution to the prediction. The model including only ANCs at baseline and at week 1 achieved an AUC-ROC of 78% (95% CI, 69-88%). Germline DNA genetic variants may contribute to the prediction of irinotecan-induced grade 4 neutropenia when incorporated into a population pharmacokinetic/pharmacodynamic model. This approach is generalizable to drugs that induce neutropenia and ultimately allows for personalized intervention to enhance patient safety.

The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy.

Despite significant advances in our knowledge regarding the genetics and molecular biology of gliomas over the past two decades and hundreds of clinical trials, no effective therapeutic approach has been identified for adult patients with newly diagnosed glioblastoma, and overall survival remains dismal. Great hopes are now placed on combination immunotherapy. In clinical trials, immunotherapeutics are generally tested after standard therapy (radiation, temozolomide, and steroid dexamethasone) or concurrently with temozolomide and/or steroids. Only a minor subset of patients with progressive/recurrent glioblastoma have benefited from immunotherapies. In this review, we comprehensively discuss standard therapy-related systemic immunosuppression and lymphopenia, their prognostic significance, and the implications for immunotherapy/oncolytic virotherapy. The effectiveness of immunotherapy and oncolytic virotherapy (viro-immunotherapy) critically depends on the activity of the host immune cells. The absolute counts, ratios, and functional states of different circulating and tumor-infiltrating immune cell subsets determine the net immune fitness of patients with cancer and may have various effects on tumor progression, therapeutic response, and survival outcomes. Although different immunosuppressive mechanisms operate in patients with glioblastoma/gliomas at presentation, the immunological competence of patients may be significantly compromised by standard therapy, exacerbating tumor-related systemic immunosuppression. Standard therapy affects diverse immune cell subsets, including dendritic, CD4+, CD8+, natural killer (NK), NKT, macrophage, neutrophil, and myeloid-derived suppressor cell (MDSC). Systemic immunosuppression and lymphopenia limit the immune system's ability to target glioblastoma. Changes in the standard therapy are required to increase the success of immunotherapies. Steroid use, high neutrophil-to-lymphocyte ratio (NLR), and low post-treatment total lymphocyte count (TLC) are significant prognostic factors for shorter survival in patients with glioblastoma in retrospective studies; however, these clinically relevant variables are rarely reported and correlated with response and survival in immunotherapy studies (e.g., immune checkpoint inhibitors, vaccines, and oncolytic viruses). Our analysis should help in the development of a more rational clinical trial design and decision-making regarding the treatment to potentially improve the efficacy of immunotherapy or oncolytic virotherapy.

Availability of Mean Platelet Volume and Neutrophil/Lymphocyte Ratio in Control of Helicobacter Pylori Eradication

Aim: The most common chronic bacterial infection in humans is Helicobacter pylori (HP) and has been proven to cause gastritis, recurrent peptic ulcers, duodenal ulcers, and gastric cancer. We investigated the neutrophil-lymphocyte ratio (NLR) and the mean platelet volume (MPV) in the control of HP infection eradication success.&#x0D; Material and Method: Patients with HP infection in endoscopic biopsy performed due to dyspeptic complaints were included in this retrospective analysis. Quadruple antibiotic eradication therapy was given to the patients for 14 days. Pre- and post-treatment complete blood count parameters of 217 patients whose eradication treatment was successful were evaluated.&#x0D; Results: There was a statistically significant decrease in the neutrophil count after treatment compared to before treatment (p

The predictive value of systemic immune-inflammatory markers before and after treatment for pathological complete response in patients undergoing neoadjuvant therapy for breast cancer: a retrospective study of 1994 patients.

Systemic immune-inflammatory markers have a certain predictive role in pathological complete response (pCR) after neoadjuvant treatment (NAT) in breast cancer. However, there is a lack of research exploring the predictive value of markers after treatment. This retrospective study collected data from 1994 breast cancer patients who underwent NAT. Relevant clinical and pathological characteristics were included, and pre- and post-treatment complete blood cell counts were evaluated to calculate four systemic immune-inflammatory markers: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). The optimal cutoff values for these markers were determined using ROC curves, and patients were classified into high-value and low-value groups based on these cutoff values. Univariate and multivariate logistic regression analyses were conducted to analyze factors influencing pCR. The factors with independent predictive value were used to construct a nomogram. After NAT, 383 (19.2%) patients achieved pCR. The area under the ROC curve is generally larger for post-treatment markers compared to pre-treatment markers. Pre-treatment NLR and PLR, as well as post-treatment LMR and SII, were identified as independent predictive factors for pCR, along with Ki-67, clinical tumor stage, clinical lymph node stage, molecular subtype, and clinical response. Higher pre-NLR (OR = 1.320; 95% CI 1.016-1.716; P = 0.038), pre-PLR (OR = 1.474; 95% CI 1.058-2.052; P = 0.022), post-LMR (OR = 1.532; 95% CI 1.175-1.996; P = 0.002), and lower post-SII (OR = 0.596; 95% CI 0.429-0.827; P = 0.002) are associated with a higher likelihood of achieving pCR. The established nomogram had a good predictive performance with an area under the ROC curve of 0.754 (95% CI 0.674-0.835). Both pre- and post-treatment systemic immune-inflammatory markers have a significant predictive role in achieving pCR after NAT in breast cancer patients. Indeed, it is possible that post-treatment markers have stronger predictive ability compared to pre-treatment markers.

Comparison of efficacy and safety of different anticoagulation regimens in plasma exchange: A systematic review and meta-analysis.

Extracorporeal line clotting during plasma exchange (PE) not only delays efficient treatment, but also cause great waste of nursing resources. There is a lack of comprehensive comparison of the efficacy and safety among different anticoagulation regimens in plasma exchange in literature. A systematic search was performed in EMBASE, MEDLINE via PubMed, Cochrane Central Library, and CNKI. Studies that had compared at least two anticoagulation regimens in PE were considered eligible. The anticoagulative efficacy outcome was assessed by the occurrence of extracorporeal circuit clotting. The safety outcome was assessed by the occurrence of bleeding events, post-treatment APTT values, and post-treatment platelets counts. The risk of bias was assessed by the AHRQ tool. Mean differences or standardized mean differences with 95% confidence intervals (CIs) of continuous variables and risk ratios (RRs) with 95% CIs of categorical variables were pooled using a random-effects or a fixed-effects model as appropriate. In all, 7 studies with 1638 patients and 10951 sessions of PE treatment were included. Pooled results indicated the anticoagulative efficacy of UFH was better than that of saline flushing, yet did not differ with those of LMWH or RCA. Although the occurrence of bleeding events had no difference among different pairs of anticoagulation regimens, anticoagulation using UFH might lead to longer post-treatment APTT value and lower post-treatment platelet counts. Only one study was judged to have low risk of bias in each of the five domains in the AHRQ tool. The current anticoagulation regimens are generally effective and well tolerated in PE; however, the number of included studies was too limited to draw definitive conclusions.

Development and Validation of a Three-Parameter Scoring System for Monitoring HIV/AIDS Patients in Low-Resource Settings Using Hematological Parameters.

This study aimed to test the validity of a composite score using complete blood count (CBC) for monitoring HIV patients receiving antiretroviral therapy (ART) in the absence of viral load and CD4 count. This retrospective cohort study analyzed the laboratory data of 82 HIV patients who had pre- and post-treatment viral load, CD4 count, and CBC data. Pre- and post-treatment data were pooled to analyze the correlation of CBC parameters with Polymerase Chain Reaction (PCR) ranks and their performance in indicating a CD4 count<200 cells/mm3 using the Operating Characteristics Curve (ROC), with the determination of cutoffs. A score combining the significant parameters was tested to predict a CD4 count of <200. Total lymphocyte count (TLC), percentage (TLP), and hemoglobin concentration (Hb) were the most significant parameters, showing negative correlations with PCR (Spearman's Rho = -0.357 to -0.242). The risk of acquired immunodeficiency syndrome (AIDS) was independently associated with TLC<1345 cells/mm3 (OR=2.92), TLP<29.07% (OR=3.53), and Hb<10.55 mg/dL (OR=3.60). A combined score of 2-3 indicated a CD4 count<200 with an odds ratio of 8.3-86.7. The proposed 3-parameter score combining the use of TLC, TLP, and Hb, is an affordable and practical approach that may have clinical utility in monitoring HIV patients receiving ART in low-resource settings.

Impact of Head and Neck Cancer Treatment on CD4 T Cell Decline and Recovery in People with HIV

The effect of cancer treatment on immunologic decline and recovery in people with HIV (PWH) is not well-described. This study aims to describe the trajectory of treatment-related immunosuppression in PWH treated for HNC predominantly with radiotherapy with or without chemotherapy and/or surgery. We performed a retrospective chart review of 23 PWH diagnosed with nonmetastatic HNC at our institution between 2002 and 2020. Baseline and longitudinal changes in CD4 count from the time of cancer treatment initiation were investigated. Patients were followed for 3 years after treatment completion. Nonparametric Mann-Whitney tests were used to compare median baseline CD4 count, post-treatment nadir CD4 count within 1 year after start of treatment, and peak recovery CD4 count within 3 years. Nonparametric Kruskal-Wallis and Mann-Whitney tests were used to compare median baseline, nadir, and peak recovery CD4 counts stratified by treatment. The majority of patients were male (20 [87%]), were white (13 [57%]), had a smoking history (21 [91%]), and had stage III-IV disease (17 [74%]). The median age was 58 (IQR 55-62). Primary subsites included oropharynx (11 [48%]), larynx (5 [22%]), oral cavity (4 [17%]), hypopharynx (2 [9%]) and nasal sinus (1 [4%]). Treatment comprised of surgery alone (S, n = 2), radiotherapy +/- surgery (RT, n = 6), and chemoradiotherapy +/- surgery (CRT, n = 15), thereby involving radiotherapy in 21 (91%) patients. All patients were on antiretroviral therapy at the time of diagnosis, and baseline HIV load was <200 copies/ml in 20 (87%) patients. Median baseline CD4 count prior to diagnosis was 592 cells/mm3 (IQR 329 to 834). The median nadir CD4 count was 201 cells/mm3 (IQR 104-282) or 34% of baseline (IQR 23-52%) (p<0.0001 compared to baseline), occurring at a median of 3.8 months (IQR 2.5-6.0). The median CD4 counts at 6 months and 1-year post-treatment were 236 cells/mm3 (IQR 135-337) and 274 cells/mm3 (IQR 150-334), respectively, representing 39% (IQR 31-58%) and 50% (IQR 40-63%) of baseline, respectively. The median peak recovery CD4 count was 431 cells/mm3 (IQR 371-561), or 68% of baseline (IQR 59-102%) (p<0.0001 compared to nadir), occurring at a median of 31 months (IQR 22-34). Stratified by treatment, the median nadir CD4 count as a percentage of baseline was 53% (S), 41% (RT), and 34% (CRT) (p = 0.32) and the peak recovery CD4 count as a percentage of baseline was 82% (S), 88% (RT), and 63% (CRT) (p = 0.45). Among PWH with HNC, CD4 count nadirs to a 1/3 of baseline but gradually rebounds to 2/3 of baseline over the subsequent 2-3 years. While this data supports continuing to treat HNC in PWH with standard-of-care management, CD4 count should be monitored closely for several years following HNC radiotherapy.

Impact of Different Therapies on Haemtological Parameters and Therapeutic Outcome in Subclinical Endometritic Buffaloes

The objective of this study was to compare the effect of administration of intrauterine dextrose, s/c levamisol and intrauterine PGF2α on haematological indices and therapeutic response in endometritic buffaloes. Twenty eight repeat breeder buffaloes with subclinical endometritis were randomly assigned into four groups. Seven animals were kept as Control (untreated C), and the rests were assigned to three treatment group, i.e., T1 (Dextrose I/Ut, 50 mL 4 times on the day of estrus), T2 (Levamisol s/c, @ 2.5 mg/kg b.wt. on day 0, 7 and 14 of the cycle), and T3 (PGF2α I/Ut, @ 0.25 mg in 0.5 mL saline twice, on the day of first and next estrus). Following treatment the values of Hb, TEC and PCV elevated significantly and TLC values dropped to normal or near normal in all three treatment groups as compared to control group. Furthermore, the post-treatment neutrophils and lymphocytes counts were elevated significantly in all four groups. However, there was no any definite pattern of eosinophils and basophils. The therapeutic response (clinical recovery) was 14.29, 71.43, 85.71 and 42.86 % in T0, T1, T2 and T3 group, respectively. The corresponding conception rates were 0.00, 60.00, 66.67 and 66.67 %. The results conclude that, Dextrose intrauterine, Levamisol s/c, and PGF2α intrauterine can be used effectively to manage subclinical endometrtitis in buffaloes.

Prognostic Value of Hematological Markers in Head and Neck Cancer Patients With a History of Hematological Malignancy

Background and Objectives Head and neck cancer can occur as a second primary tumor in patients with a history of hematological malignancy, and the pathological features of those are more aggressive than de novo primary head and neck cancer. However, research related to the prognostic value of hematological markers in the head and neck cancer patients with a history of hematological malignancy is scarce, so we performed this study.Subjects and Method We reviewed a total of 89 head and neck cancer patients with hematological malignancy diagnosed at a single tertiary hospital between 1997 and 2021, and enrolled 29. The analyzed hematological parameters included pre- and post-treatment hemoglobin, hematocrit, lactate dehydrogenase, absolute neturophil count (ANC), absolute platelet count, absolute leukocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio.Results Hematological malignancy was diagnosed almost 62.14±96.10 months before head and neck cancer. The most common hematological malignancy was acute myeloid leukemia. The overall survival (OS) rate was lower in patients with second primary tumor than in those with de novo primary head and neck cancer. The cox-proportional hazard ratio analysis showed that the post-treatment absolute neutrophil count was significantly correlated with disease-free survival but not with OS.Conclusion The post-treatment hematological profile, particularly ANC, can be considered a useful prognostic marker in the head and neck cancer patients with a history of hematological malignancy.

Impact of radiation on host immune system in patients treated with chemoradiotherapy and durvalumab consolidation for unresectable locally advanced non-small cell lung cancer.

The optimal modalities of radiotherapy when combining concurrent chemoradiation (CCRT) and immunotherapy (IO) for locally advanced non-small cell lung cancer (LA-NSCLC) remain to be determined. The aim of this study was to investigate the impact of radiation on different immune structures and immune cells in patients treated with CCRT followed by durvalumab. Clinicopathologic data, pre- and post-treatment blood counts, and dosimetric data were collected in patients treated with CCRT and durvalumab consolidation for LA-NSCLC. Patients were divided into two groups according to the inclusion (NILN-R+) or not (NILN-R-) of at least one non-involved tumor-draining lymph node (NITDLN) in the clinical target volume (CTV). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Fifty patients were included with a median follow-up of 23.2 months (95% CI 18.3-35.2). Two-year PFS and 2-year OS were 52.2% (95% CI 35.8-66.3) and 66.2% (95% CI 46.5-80.1), respectively. In univariable analysis, NILN-R+ (hazard ratio (HR) 2.60, p = 0.028), estimated dose of radiation to immune cells (EDRIC) >6.3 Gy (HR 3.19, p = 0.049), and lymphopenia ≤ 500/mm3 at IO initiation (HR 2.69, p = 0.021) were correlated with poorer PFS; lymphopenia ≤ 500/mm3 was also associated with poorer OS (HR 3.46, p = 0.024). In multivariable analysis, NILN-R+ was the strongest factor associated with PFS (HR 3.15, p = 0.017). The inclusion of at least one NITDLN station within the CTV was an independent factor for poorer PFS in the context of CCRT and durvalumab for LA-NSCLC. The optimal sparing of immune structures might help in achieving better synergy between radiotherapy and immunotherapy in this indication.

Post-treatment neutrophil to lymphocyte ratio as a prognostic tool in patients treated with tocilizumab for severe COVID-19 pneumonia - a single center experience.

Tocilizumab is used in patients with severe COVID-19 pneumonia and high concentration of IL-6. We studied potential prognostic role of neutrophil and lymphocyte count regarding tocilizumab treatment. We enrolled 31 patients with severe COVID-19 pneumonia and higher serum IL-6 concentration. The samples were taken on the day of tocilizumab administration and five days later. We used ROC analysis to investigate the association between the analysed parameters and 30-day mortality in order to determine the best pre-treatment and post-treatment prognostic factor. Kaplan-Meier curves and log-rank test were used to present and to analyse the difference in survival. Patients had a median age of 63 (55-67) years and were treated with a median tocilizumab dose of 800 mg. During the 30-day follow-up period, 17 patients died (30-day mortality 54%). Among pre-treatment variables, neutrophil count had the best prognostic accuracy (AUC 0.81, 95%CI: 0.65-0.96, P = 0.004), while neutrophil to lymphocyte ratio (NLR) had the highest accuracy among post-treatment variables in predicting 30-day mortality (AUC 0.94, 95%CI: 0.86-1.00, P < 0.001). Among post-treatment parameters, neutrophil count and NLR were equally good prognostic factors. Post-treatment NLR cut-off of 9.8 had the sensitivity of 81% and specificity of 93%. Patients with NLR ≥ 9.8 had the median survival of 7.0 (3-10) days vs. median survival not reached in patients with NLR < 9.8 (P < 0.001). Pre-treatment and post-treatment neutrophil count with post-treatment NLR may represent prognostic tools for patients with higher IL-6 concentration in severe COVID-19 pneumonia treated with tocilizumab.

Network analysis to explore the pharmacological mechanism of Shenmai injection in treating granulocytopenia and evidence-based medicine approach validation.

Shenmai injection is frequently utilized in China to clinically treat granulocytopenia in oncology patients following chemotherapy. Despite this, the drug's therapeutic benefits remain a topic of contention, and its active components and potential treatment targets have yet to be established. The present study utilizes a network pharmacology approach to investigate the drug's active ingredients and possible therapeutic targets, and to evaluate the effectiveness of Shenmai injection in treating granulocytopenia through meta-analysis. In our subject paper, we utilized the TCMID database to investigate the active ingredients present in red ginseng and ophiopogon japonicus. To further identify molecular targets, we employed SuperPred, as well as OMIM, Genecards, and DisGeNET databases. Our focus was on targets associated with granulocytopenia. The DAVID 6.8 database was utilized to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, a protein-protein interaction network was established. The resulting "drug-key component-potential target-core pathway" network was used to predict the mechanism of action of Shenmai injection in the treatment of granulocytopenia. In order to evaluate the quality of the studies included in our analysis, we utilized the Cochrane Reviewers' Handbook. We then conducted a meta-analysis of the clinical curative effect of Shenmai injection for granulocytopenia, utilizing the Cochrane Collaboration's RevMan 5.3 software. After conducting a thorough screening, the study identified 5 primary ingredients of Shenmai injection - ophiopogonoside a, β-patchoulene, ginsenoside rf, ginsenoside re, and ginsenoside rg1-that can potentially target 5 essential proteins: STAT3, TLR4, PIK3CA, PIK3R1, and GRB2. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that Shenmai injection can be beneficial in treating granulocytopenia by interacting with pathways such as HIF-1 signaling, T-cell receptor signaling, PI3K-Akt signaling, chemokine signaling, and FoxO signaling. The results of meta-analysis indicate that the treatment group exhibited superior performance in terms of both efficiency and post-treatment leukocyte count when compared to the control group. In summary, studies in network pharmacology demonstrate that Shenmai injection exerts an impact on granulocytopenia via various components, targets, and mechanisms. Additionally, evidence-based studies provide strong support for the effectiveness of Shenmai injection in preventing and treating granulocytopenia.

FIELD EVALUATION OF AUTOCIDAL GRAVID OVITRAP AND SIRENIX TRAP AGAINST CONTAINER INHABITING MOSQUITOES IN SAINT AUGUSTINE, NORTHEASTERN FLORIDA

Mosquito control programs are utilizing cost-effective long-term autocidal traps targeting the gravid population of container-inhabiting and other mosquito species, with the aim of reducing vector populations and disease transmission risk. In this field study we directly compared the efficacy of two autocidal trap types-the Autocidal Gravid Ovitrap (AGO) and SIRENIX mosquito trap in reducing mosquito abundances in St. Augustine, Florida to a control only site that had no autocidal traps deployed. Pre-treatment (wk1-4) and post-treatment (wk 5-14) adult mosquitoes were captured in all three sites using BG traps baited with BG lure and dry ice. Pre- and post-treatment trap counts of Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and total mosquitoes (three species together) were compared to determine significant changes in abundance. Percent reduction in abundance of each species/group at the two trap sites were calculated to evaluate the trap efficacy at controlling Aedes and Culex container mosquitoes. Aedes albopictus populations were significantly reduced (86.6%) at the SIRENIX site compared to the populations at the AGO site (67.7% reduction). Ae. aegypti populations were reduced by 72.4% at the SIRENIX site compared to 25% at the AGO site. Culex quinquefasciatus population reduction at the SIRENIX site was 59.6% compared to 11.8% at the AGO site. The total mosquito group had only 45.1% and 10.3% reduction at the SIRENIX and AGO sites, respectively. Furthers studies conducted across the entire mosquito season would be required for full understanding of the effectiveness of these traps.

Effects of Gender and Baseline CD4 Count on Post-Treatment CD4 Count Recovery and Outcomes in Patients with Advanced HIV Disease: A Retrospective Cohort Study.

Presentation to care with advanced HIV disease (AHD) is a significant problem in sub-Saharan Africa. We evaluated factors associated with immune recovery among individuals presenting to care with AHD in Zimbabwe. We conducted a retrospective evaluation of outcomes among adult (>18 years old) individuals with AHD (CD4 count ≤200 cells/mm3) receiving care at 18 outpatient primary care clinics in Harare, Zimbabwe. Baseline and 12-month CD4 count data were extracted from medical records. CD4 count recovery (defined as CD4 count >200 cells/mm3) after 12 months on non-nucleotide reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) regimen was determined and factors associated with CD4 count recovery were established using logistic regression. All statistical analysis was performed on SPSS v23. A total of 1,338 participant records were included in the analysis. The median interquartile range (IQR) age was 37 (30-43) years and 52% were females. The baseline median (IQR) CD4 count was 50 (28-75) cells/mm3 and was significantly lower among patients with history of cryptococcal meningitis compared to those without [25 (10-52) vs. 52 (32-77), respectively; p = .0009]. The median (IQR) CD4 count at 12 months after ART initiation increased from 50 (28-75) at baseline to 180 (92-290) cells/mm3. Immune recovery with a CD4 count >200 cells/mm3 was observed in 181/417 (43%). Male gender and low baseline CD4 count were strong predictors of poor immunological recovery on ART. Immunological recovery following ART initiation was 43% among individuals with AHD. Male patients are most vulnerable to persistent immunological failure. Clinical Trial Registration number: NCT02434172.

Anti-fasciolic effect of raw seeds of Nigella sativa, Fumaria parviflora (aerial), in naturally infected Buffaloes

In the present study Nigella sativa (seeds) and Fumaria parviflora (aerial), were used to treat buffaloes naturally infected with fasciolosis and their efficacy (%) was compared. In vivo, pre-and post-treatment (50 mg, 100 mg, and 150 mg/ kg body weight of the two medicinal plants) fecal egg counts were determined following standard fecal egg count reduction in buffaloes (Babulus sp.) of Nili Ravi breed naturally parasitized with Fasciola sp. The infected buffaloes were randomly divided into 3 main groups’ i.e. A, B, and C. Animals in groups A and B were further subdivided into three subgroups i.e. A1, A2, A3; B1, B2, B3. Sub-groups A1 and B1 were given dose levels of 50mg/kg body weight, A2, and B2, 100mg while A3 and B3, 150mg/kg body weight of Nigella sativa (seeds) and Fumaria parviflora (aerial), respectively. Group C with infected animals served as a control. 2 medicinal plants has been found significantly (P&lt;0.05) efficient (42-100%) and safe to use against fasciolosis.