Radiation drives tertiary lymphoid structures to reshape TME for synergized antitumour immunity.

Radiotherapy (RT) plays a key role in the tumour microenvironment (TME), impacting the immune response via cellular and humoral immunity. RT can induce local immunity to modify the TME. It can stimulate dendritic cell maturation and T-cell infiltration. Moreover, B cells, macrophages and other immune cells may also be affected. Tertiary lymphoid structure (TLS) is a unique structure within the TME and a class of aggregates containing T cells, B cells and other immune cells. The maturation of TLS is determined by the presence of mature dendritic cells, the density of TLS is determined by the number of immune cells. TLS maturation and density both affect the antitumour immune response in the TME. This review summarized the recent research on the impact and the role of RT on TLS, including the changes of TLS components and formation conditions and the mechanism of how RT affects TLS and transforms the TME. RT may promote TLS maturation and density to modify the TME regarding enhanced antitumour immunity.

Endostar acts as a pneumonitis protectant in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiotherapy.

BACKGROUND: CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients. METHODS: This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP. RESULTS: There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC. CONCLUSIONS: When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.

Binary Nano-inhalant Formulation of Icariin Enhances Cognitive Function in Vascular Dementia via BDNF/TrkB Signaling and Anti-inflammatory Effects.

Vascular dementia (VaD) has a serious impact on the patients' quality of life. Icariin (Ica) possesses neuroprotective potential for treating VaD, yet its oral bioavailability and blood-brain barrier (BBB) permeability remain challenges. This research introduced a PEG-PLGA-loaded chitosan hydrogel-based binary formulation tailored for intranasal delivery, enhancing the intracerebral delivery efficacy of neuroprotective agents. The formulation underwent optimization to facilitate BBB crossing, with examinations conducted on its particle size, morphology, drug-loading capacity, in vitro release, and biodistribution. Using the bilateral common carotid artery occlusion (BCCAO) rat model, the therapeutic efficacy of this binary formulation was assessed against chitosan hydrogel and PEG-PLGA nanoparticles loaded with Ica. Post-intranasal administration, enhanced cognitive function was evident in chronic cerebral hypoperfusion (CCH) rats. Further mechanistic evaluations, utilizing immunohistochemistry (IHC), RT-PCR, and ELISA, revealed augmented transcription of synaptic plasticity-associated proteins like SYP and PSD-95, and a marked reduction in hippocampal inflammatory markers such as IL-1ß and TNF-α, highlighting the formulation's promise in alleviating cognitive impairment. The brain-derived neurotrophic factor (BDNF)/tropomyosin related kinase B (TrkB) pathway was activated significantly in the binary formulation compared with the other two. Our study demonstrates that the intranasal application of chitosan hydrogel loaded with Ica-encapsulated PEG-PLGA could effectively deliver Ica into the brain and enhance its neuroprotective effect.

Value of serum CRP and IL-6 Assays combined with Pancreatitis activity scoring system for assessing the severity of patients with acute pancreatitis.

Objective: To evaluate the accuracy of serum CRP and IL-6 assays combined with the pancreatitis activity scoring system (PASS) in assessing the severity of patients with acute pancreatitis (AP). Methods: This was a retrospective study of 223 patients with AP admitted to Baoding Lianchi District People's Hospital between February 2021 and 2023. They were classified into three categories: mild AP (MAP), moderate severe AP (MSAP) and severe AP (SAP). The differences, accuracy and sensitivity of the individual assays, and the three in combination, were compared and analysed in the three groups. Results: PASS scores, IL-6 and CRP levels were significantly higher in the SAP and MSAP groups compared to those in the MAP group, with statistically significant differences between the three groups. Multi-factorial logistic regression analysis suggested that PASS, IL-6 and CRP were correlated indicators of AP severity. The combination of the three assays was higher than that of the PASS score, IL-6 and CRP alone, suggesting optimal diagnostic efficacy when the three assays were combined. Moreover, the levels of PASS score, IL-6 and CRP showed a positive correlation with the degree of disease severity. Conclusions: The serum CRP, IL-6 and PASS scores were significantly elevated in AP patients and showed a positive correlation with disease severity, all of which are beneficial for the diagnosis of AP. PASS is superior to CRP and IL-6 in the assessment of AP. The combination of the three assays can achieve a far superior diagnostic efficacy to that of the individual index assays.

Bacterial diversity of middle ear cholesteatoma by 16S rRNA gene sequencing in China.

In this study, the bacterial diversity of acquired middle ear cholesteatoma (MEC) was evaluated to reveal its pathogenesis and provides a guide for the use of antibiotics. Twenty-nine cases of acquired MEC and eight cases of healthy middle ears undergoing cochlear implantation (CI) were evaluated. Full-length 16S rRNA gene sequencing was performed to profile the bacterial communities in lesions and healthy tissues of the middle ear. ACE (P = 0.043) and Chao1 (P = 0.039) indices showed significant differences in alpha diversity (P < 0.05). Analysis of PERMANOVA/Anosim using the Bray-Curtis distance matrix results suggested that the between-group differences were greater than the within-group differences (R = 0.238, P < 0.05, R2 = 0.066, P < 0.05). Bacterial community analysis revealed that Alphaproteobacteria at the class level and Caulobacterales and Sphingomonadales at the order level were significantly different (P < 0.05). In the LefSe (Linear discriminant analysis effect size) analysis, Porphyromonas bennonis was elevated, and Bryum argenteum and unclassified Cyanobacteriales were reduced at the species level in MEC (P < 0.05). Fifteen metabolic pathways were found to be significantly different between the two groups by analysing the abundance of metabolic pathways in level 2 of the Kyoto Encyclopaedia of Genes and Genomes (KEGG). Seven and eight metabolic pathways were significantly elevated in the MEC and control groups, respectively (P < 0.05). The role of bacteria in the pathogenesis of acquired MEC was further refined through analysis of metabolic pathways. These findings indicate that the acquired MEC and healthy middle ear contain more diverse microbial communities than previously thought.

Establishment of a prognostic model for melanoma based on necroptosis-related genes.

In this study, the clinical implications and potential functions of necroptosis-related genes (NRGs) in melanoma were systematically characterized. A novel NRG signature was then constructed to analyze the immune status and prognosis of patients with melanoma. The NRG signatures for melanoma prognosis were searched using the Cancer Genome Atlas (TCGA) dataset and followed by stepwise Cox regression analysis. Patients with melanoma were divided into two groups, and survival analysis, receiver operating characteristic (ROC), and univariate and multivariate analyses were subsequently performed. The correlation of risk score (RS) with tumor immunity and RT-polymerase chain reaction (PCR) was analyzed to further verify the gene signatures. Data on tumor mutational burden (TMB) and chromosomal copy number variation (CNV) were analyzed. Three NRGs were identified as prognostic risk signatures and were significantly related to overall survival (OS) in melanoma. The signatures had better diagnostic accuracy. Furthermore, analysis of mutations in the NRGs and the incidence of chromosomal CNV helped to reveal the relationship between mutations and melanoma occurrence. A nomogram was established based on RSs. The risk characteristics were significantly associated with immunity and high risk is closely correlated with melanoma development. In vitro experiments revealed that necrostatin-1 (Nec-1) promoted cell viability and repressed the expression levels of interleukin (IL)12A and proprotein convertase subtilisin/kexin type (PCSK)1. Additionally, the expression levels of IL12A, CXCL10, and PCSK1 decreased in tumor tissues of melanoma patients. NRGs exert vital roles in immunity and might be applied as a prognostic factor of melanoma.

Exploring the value of early laboratory indicators combined with pancreatitis activity scoring system in assessing the severity and prognosis of acute pancreatitis.

Objective: To investigate the value of early laboratory indicators combined with the pancreatitis activity scoring system in assessing the severity and prognosis of acute pancreatitis (AP). Methods: This is a retrospective study. A total of 160 patients with AP admitted to the Affiliated Hospital of Hebei University from February 2021 to February 2023 were enrolled and classified into three categories: mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP), with 80 cases with MAP and MSAP as the control group and 80 cases with SAP as the experimental group. The differences of inflammatory markers, blood routine, biochemical markers, coagulation markers and PASS score within 24 hours after admission were compared between the two groups, and independent risk factors for predicting AP severity were analyzed. Moreover, the diagnostic efficacy and prognostic value of independent risk factors were evaluated. Results: The PASS score as well as CRP, PCT, IL-6, WBC, N, AST, DD and PT were higher in the experimental group than in the control group. Logistic regression analysis suggested that PASS, IL-6, PCT and WBC were independent risk factors for predicting severity of AP. In addition, PASS had the highest diagnostic efficacy. Conclusion: Early elevation of PASS, IL-6, PCT and WBC in patients suffering from AP is of great significance in predicting SAP. PASS score combined with IL-6, PCT and WBC has important value in evaluating the severity and prognosis of AP.

Clinical and cytokine patterns of uncontrolled asthma with and without comorbid chronic rhinosinusitis: a cross-sectional study.

BACKGROUND: Asthma is significantly related to chronic rhinosinusitis (CRS) both in prevalence and severity. However, the clinical patterns of uncontrolled asthma with and without comorbid CRS are still unclear. This study aimed to explore the clinical characteristics and cytokine patterns of patients with uncontrolled asthma, with and without comorbid CRS. METHODS: 22 parameters associated with demographic characteristics, CRS comorbidity, severity of airflow obstruction and airway inflammation, and inflammation type of asthma were collected and assessed in 143 patients with uncontrolled asthma. Different clusters were explored using two-step cluster analysis. Sputum samples were collected for assessment of Th1/Th2/Th17 and epithelium-derived cytokines. RESULTS: Comorbid CRS was identified as the most important variable for prediction of different clusters, followed by pulmonary function parameters and blood eosinophil level. Three clusters of patients were determined: Cluster 1 (n = 46) characterized by non-atopic patients with non-eosinophilic asthma without CRS, demonstrating moderate airflow limitation; Cluster 2 (n = 54) characterized by asthma patients with mild airflow limitation and CRS, demonstrating higher levels of blood eosinophils and immunoglobulin E (IgE) than cluster 1; Cluster 3 (n = 43) characterized by eosinophilic asthma patients with severe airflow limitation and CRS (46.5% with nasal polyps), demonstrating worst lung function, lowest partial pressure of oxygen (PaO2), and highest levels of eosinophils, fraction of exhaled nitric oxide (FeNO) and IgE. Sputum samples from Cluster 3 showed significantly higher levels of Interleukin (IL)-5, IL-13, IL-33, and tumor necrosis factor (TNF)-α than the other two clusters; and remarkably elevated IL-4, IL-17 and interferon (IFN)-γ compared with cluster 2. The levels of IL-10 and IL-25 were not significantly different among the three clusters. CONCLUSIONS: Uncontrolled asthma may be endotyped into three clusters characterized by CRS comorbidity and inflammatory cytokine patterns. Furthermore, a united-airways approach may be especially necessary for management of asthma patients with Type 2 features.

Patterns of primary prophylactic granulocyte colony-stimulating factor use in older Medicare patients with cancer receiving myelosuppressive chemotherapy.

PURPOSE: Guidelines recommend primary prophylactic (PP) granulocyte colony stimulating factor (G-CSF) for prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy with high risk (HR: > 20%), or intermediate risk (IR:10-20%) of FN and ≥ 1 patient risk factor (e.g., age ≥ 65y). The current retrospective cohort study describes patterns of PP-G-CSF in older Medicare patients undergoing myelosuppressive chemotherapy with HR/IR of FN. METHODS: Patients aged ≥ 66y initiating chemotherapy regimens with HR/IR of FN to treat breast, colorectal, lung, or ovarian cancer, or Non-Hodgkin's Lymphoma were selected using Medicare 20% sample (2013-2015) and 100% cancer patient (2014-2017) data. PP-G-CSF use was identified in the first cycle. Timing of pegfilgrastim pre-filled syringe (PFS) administration, proportion of patients completing all cycles (adherence) with pegfilgrastim PFS or on-body injector (OBI), and duration of short-acting G-CSF (sG-CSF) was described across all cycles. RESULTS: Of 64,893 patients receiving HR/IR for FN, 71% received HR and 29% IR regimens. Overall, PP-G-CSF use in the first cycle was 53% (HR: 74%; IR: 44%) and varied across cancers. Adherence with pegfilgrastim was slightly higher among OBI initiators (78%) than PFS (74%). Number of PP-sG-CSF administrations (mean [SD]) per cycle was 5.1 (SD: 2.7) overall, 5.4 (2.6) for HR, and 4.9 (2.7) for IR. CONCLUSION: Despite cancer treatment guidelines recommending PP-G-CSF use to reduce risk of FN associated with HR and IR (with ≥ 1 patient risk-factor) regimens, PP-G-CSF remains underutilized in older patients, across cancer types and regimens. Opportunities exist for improvement in use of PP-G-CSF.

Powerful Identification of Large Quantitative Trait Loci Using Genome-Wide R/glmnet-Based Regression.

R/glmnet has been successfully applied to jointly mapped multiple quantitative trait loci for linkage analysis, along with statistical inference for quantitative trait loci candidates with nonzero genetic effects using R/lm for normally distributed traits, R/glm for discrete traits, and R/coxph for survival times. In this study, we extended R/glmnet to a genome-wide association study by means of parallel computation. A multi-locus genome-wide association study for high-throughput single-nucleotide polymorphisms was implemented in the "Multi-Runking" software written within the R workspace. This software can better detect common and large quantitative trait nucleotides and more accurately estimate than genome-wide mixed model analysis for one single-nucleotide polymorphism at a time and linear mixed models-least absolute shrinkage and selection operator. Its applicability and utility were demonstrated by multi-locus genome-wide association studies for the simulated and real traits distributed normally, binary traits, and survival times.

The ATI-ET Triangle Model: A Novel Approach to Estimate Soil Moisture Applied to MODIS Data.

A simple soil moisture (SM) estimation method is proposed using apparent thermal inertia (ATI) and evapotranspiration (ET) data. Among the methods of estimating SM by using thermal infrared (TIR) remote sensing, the ATI method is widely used in bare soil and low vegetation areas. However, large surface ET will cause ATI error, resulting in lower accuracy of SM estimation. To overcome this problem, the potential of ATI-ET space for estimating the SM of bare and vegetated farmland in the dry season (no irrigation) is studied. ATI and ET data were used to construct triangle feature space, and six distance parameters are extracted from the positions of random pixels in the triangle. Some correlation estimates were made to derive those parameters that were useful for SM estimation, which were three in total. The SM estimation model consisting of these three parameters was built. Compared with the ATI model, the ATI-ET triangle model can not only be applied to areas with high ET, but also has higher accuracy in estimating SM. The ATI-ET triangle model is more suitable for application in bare soil and low vegetation areas. As the Normalized Difference Vegetation Index increases, the accuracy of the model estimates decreases. To show the high portability of the proposed model for SM estimation, we chose another set of in situ SM data acquired in Tibetan Plateau. The results proved the effectiveness of the model in other similar study regions.

Quick approximation of threshold values for genome-wide association studies.

Standard normal statistics, chi-squared statistics, Student's t statistics and F statistics are used to map quantitative trait nucleotides for both small and large sample sizes. In genome-wide association studies (GWASs) of single-nucleotide polymorphisms (SNPs), the statistical distributions depend on both genetic effects and SNPs but are independent of SNPs under the null hypothesis of no genetic effects. Therefore, hypothesis testing when a nuisance parameter is present only under the alternative was introduced to quickly approximate the critical thresholds of these test statistics for GWASs. When only the statistical probabilities are available for high-throughput SNPs, the approximate critical thresholds can be estimated with chi-squared statistics, formulated by statistical probabilities with a degree of freedom of two. High similarities in the critical thresholds between the accurate and approximate estimations were demonstrated by extensive simulations and real data analysis.

Trends in use of primary prophylactic colony stimulating factors and neutropenia-related hospitalization in commercially insured patients receiving myelosuppressive chemotherapy in the United States: 2005-2017.

PURPOSE: Describe temporal changes in use of myelosuppressive chemotherapy, primary prophylactic colony-stimulating factor, and neutropenia-related hospitalization, in commercially insured patients. METHODS: Using a large commercial administrative database, we identified annual cohorts of adult patients diagnosed with breast or lung cancer, or non-Hodgkin lymphoma and initiating myelosuppressive chemotherapy during 2005-2017. We described yearly changes in proportions of myelosuppressive chemotherapy by febrile neutropenia risk category (high, intermediate, unclassified) and proportion of prophylactic colony-stimulating factor use and unadjusted incidence of neutropenia-related hospitalization in the first cycle of myelosuppressive chemotherapy. RESULTS: Annual cohorts included 4383-5888 eligible patients during 2005-2017. The proportion of eligible patients aged ≥ 65 years increased from 26.0% in 2005 to 58.2% in 2017. Myelosuppressive chemotherapy use with regimens with high risk for febrile neutropenia increased from 15.1% in 2005 to 31.0% in 2017; and regimens with intermediate risk for febrile neutropenia decreased from 63.7% to 48.1% in 2017. Prophylactic colony-stimulating factor use increased from 41.6% in 2005 to 54.3% in 2017. Crude incidence of neutropenia-related hospitalization for all cancers increased from 2.0% to 3.1%, with a substantial increase in neutropenia-related hospitalization observed among non-Hodgkin lymphoma patients (2.8% to 8.5%) during 2005-2017. CONCLUSION: Among adult patients with breast and lung cancer, and non-Hodgkin lymphoma receiving myelosuppressive chemotherapy, use of regimens with high risk for febrile neutropenia increased, as did the use of prophylactic colony-stimulating factors after 2005. Incidence of neutropenia-related hospitalization increased slightly, particularly among non-Hodgkin lymphoma patients. Further studies are required to understand this increasing trend of neutropenia-related hospitalization, changing patient-level risk factors, and febrile neutropenia management.

Trends in the use of primary prophylactic colony-stimulating factors and neutropenia-related hospitalization in elderly cancer patients receiving myelosuppressive chemotherapy in the USA: 1995-2015.

PURPOSE: To assess changes in neutropenia-related hospitalization, myelosuppressive chemotherapy, and primary prophylactic colony-stimulating factor (PP-CSF) use in elderly cancer patients receiving myelosuppressive chemotherapy. METHODS: We identified annual cohorts of patients aged ≥ 66 years with breast cancer, lung cancer, or non-Hodgkin lymphoma (NHL) initiating myelosuppressive chemotherapy during 1995-2015 using Medicare 5% (1994-2008) and 20% (2007-2015) data. We described myelosuppressive chemotherapy changes by febrile neutropenia (FN) risk category (high, intermediate, unclassified), PP-CSF use, and, in the first cycle of myelosuppressive chemotherapy, neutropenia-related hospitalization (ICD-9-CM: 288.0X, first 5 positions). We evaluated hospitalization trends using a logistic regression model with spline curve of calendar year adjusting for baseline characteristics. RESULTS: Annual cohorts included 1451-2114 eligible patients for 1995-2007 and 5272-7603 for 2008-2015. Myelosuppressive chemotherapy use with high/intermediate FN risk increased from 31% in 1995 to 56% in 1999, stabilized through 2008 (range 56-61%), then decreased to 52% in 2015. PP-CSF use increased from 5.5% in 1995 to 52.7% in 2015, mainly due to pegfilgrastim introduction in 2002. Crude neutropenia-related hospitalization incidence decreased from 5.2% in 1995 to 2.7% in 2015; adjusted incidence decreased, on average, by 4.7% yearly before 2010 (p < 0.0001) and was flat from 2010 onward (p = 0.53). CONCLUSIONS: Among elderly patients with breast cancer, lung cancer, or NHL receiving myelosuppressive chemotherapy, PP-CSF use increased substantially after 2002. Neutropenia-related hospitalization incidence in the first cycle decreased yearly before 2010 and was flat afterward. Further studies are needed to understand overall decreasing neutropenia-related hospitalization trends and effects of changes in myelosuppressive chemotherapy and FN management.

Febrile neutropenia-related care and associated costs in elderly patients with breast cancer, lung cancer, or non-Hodgkin lymphoma.

PURPOSE: Limited information is available regarding elderly patients experiencing febrile neutropenia (FN). This study evaluated FN-related care among elderly cancer patients who received high/intermediate FN-risk chemotherapy and experienced ≥ 1 FN episodes. METHODS: We used Medicare data to identify patients aged ≥ 66 years who initiated high/intermediate FN-risk chemotherapy between 1 January 2008 and 31 August 2015 to treat breast cancer (BC), lung cancer (LC), or non-Hodgkin lymphoma (NHL) and had ≥ 1 FN episodes. We identified within-cycle FN episodes for each chemotherapy cycle on Part A inpatient claims or outpatient or Part B claims. We described the FN-related care setting (inpatient hospital, outpatient emergency department [ED], or outpatient non-ED) and reported mean total cost of FN-related care per episode overall and by care setting (adjusted to 2015 US$). RESULTS: We identified 2138, 3521, and 2862 patients with BC, LC, and NHL, respectively, with ≥ 1 FN episodes (total episodes: 2407, 3840, 3587, respectively). Most FN episodes required inpatient care (BC, 88.1%; LC, 93.0%; NHL, 93.2%) with mean hospital length of stay (LOS) 6.2, 6.5, and 6.8 days, respectively. Intensive care unit admission was required for 20.4% of BC, 29.0% of LC, and 25.7% of NHL hospitalizations (mean LOS: 4.7, 4.7, 5.5 days, respectively). The mean total cost of FN care per episode was $11,959 BC, $14,388 LC, and $15,006 NHL, with inpatient admission the costliest care component ($11,826; $14,294; and $14,873; respectively). CONCLUSIONS: Among elderly patients with BC, LC, or NHL who experienced FN, most FN episodes required costly hospital care, highlighting the FN burden on healthcare systems.

Patterns of granulocyte colony-stimulating factor prophylaxis in patients with cancer receiving myelosuppressive chemotherapy.

PURPOSE: To evaluate patterns of primary prophylactic (PP) granulocyte colony-stimulating factor (G-CSF) use following chemotherapy by cancer type and febrile neutropenia (FN) risk. METHODS: Using a commercial administrative database, we identified adult patients diagnosed with breast, colorectal, lung, ovarian cancer, or non-Hodgkin lymphoma (NHL) who initiated chemotherapy with high risk (HR) or intermediate risk (IR) for FN between January 1, 2013, and August 31, 2017. We describe use of PP-G-CSF, proportion completing all their cycles with pegfilgrastim, timing of pegfilgrastim, and duration of short-acting G-CSF. RESULTS: Among 22,868 patients (breast 11,513; colorectal 3765; lung 4273; ovarian 1287; and NHL 2030), 36.8% received HR and 63.2% received IR (64.4% of whom had ≥ 1 risk factor [RF] for FN). Proportions of patients receiving PP-G-CSF in the first cycle were 76.1%, 28.2%, and 26.4% among patients receiving HR, IR, and IR plus ≥ 1 RF, respectively. Among breast cancer patients receiving HR regimens and initiating PP-pegfilgrastim, 60.4% (95% confidence interval [CI] 57.2-63.6%) initiating via on-body injector (OBI) and 51.9% (95% CI 48.0-55.8%) initiating via prefilled syringe (PFS) completed all their cycles with OBI and PFS, respectively. Among all cycles with PP-PFS, 8.5% received PFS on the same day as chemotherapy completion. Mean administrations/cycle were 3.2 (standard deviation [SD] 2.3) for filgrastim, 3.0 (SD 1.6) for filgrastim-sndz, and 4.3 (SD 2.5) for tbo-filgrastim. CONCLUSIONS: There is under- and mistimed use of PP-G-CSF among patients at HR for FN. Novel pegfilgrastim delivery devices could help breast cancer patients at HR for FN complete all their cycles with timely prophylaxis.

Positive Correlation between Tinnitus Severity and Poor Sleep Quality Prior to Tinnitus Onset: a Retrospective Study.

The objective of this study was to investigate the correlation of tinnitus severity and sleep quality prior to tinnitus onset in a Chinese population.We recruited patients with primary tinnitus from a tertiary teaching hospital in southwest China, retrospectively. The Pittsburgh Sleep Quality Index (PSQI) and the Mandarin version of the Tinnitus Handicap Inventory (THI-M) were employed to assess tinnitus severity and sleep quality of past, respectively. A battery of hearing tests was also administered to subjects, including TEOAE, pure tone audiometry, and tympanometry, for hearing evaluation.We enrolled 190 patients and nine were excluded. Subjects were divided into two groups: group A (PSQI <7) and group B (PSQI ≥7). The mean duration of tinnitus in both groups was above 6 months. There was a significant difference between THI-M global scores of group A and group B (P < 0.001). The difference in tinnitus severity ranks between the two groups was also significant (P = 0.006). The proportion of severe tinnitus levels in group B was higher than that of group A. Spearman's correlation analysis did not show correlation between the scores of THI-M and that of the PSQI in group A (P = 0.077); in verse, a positive correlation between THI-M and PSQI scores was found in group B (P < 0.001).The tinnitus severity is positively correlated with sleep quality before tinnitus onset, suggesting that the sleep quality of the past may have an impact on tinnitus occurrence.

Comparative Effectiveness of Medical Therapy, Percutaneous Revascularization, and Surgical Coronary Revascularization in Cardiovascular Risk Subgroups of Patients With CKD: A Retrospective Cohort Study of Medicare Beneficiaries.

RATIONALE & OBJECTIVE: Prior studies suggesting that medical therapy is inferior to percutaneous (percutaneous coronary intervention [PCI]) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization in chronic kidney disease (CKD) have not adequately considered medication optimization or baseline cardiovascular risk and have infrequently evaluated progression to kidney failure. We compared, separately, the risks for kidney failure and death after treatment with PCI, CABG, or optimized medical therapy for coronary disease among patients with CKD stratified by cardiovascular disease risk. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 34,385 individuals with CKD identified from a national 20% Medicare sample who underwent angiography or diagnostic stress testing without (low risk) or with (medium risk) prior cardiovascular disease or who presented with acute coronary syndrome (high risk). EXPOSURES: PCI, CABG, or optimized medical therapy (defined by the addition of cardiovascular medications in the absence of coronary revascularization). OUTCOMES: Death, kidney failure, composite outcome of death or kidney failure. ANALYTICAL APPROACH: Adjusted relative rates of death, kidney failure, and the composite of death or kidney failure estimated from Cox proportional hazards models. RESULTS: Among low-risk patients, 960 underwent PCI, 391 underwent CABG, and 6,426 received medical therapy alone; among medium-risk patients, 1,812 underwent PCI, 512 underwent CABG, and 9,984 received medical therapy alone; and among high-risk patients, 4,608 underwent PCI, 1,330 underwent CABG, and 8,362 received medical therapy alone. Among low- and medium-risk patients, neither CABG (HRs of 1.22 [95% CI, 0.96-1.53] and 1.08 [95% CI, 0.91-1.29] for low- and medium-risk patients, respectively) nor PCI (HRs of 1.14 [95% CI, 0.98-1.33] and 1.02 [95% CI, 0.93-1.12], respectively) were associated with reduced mortality compared with medical therapy, but in low-risk patients, CABG was associated with a higher rate of the composite, death or kidney failure (HR, 1.25; 95% CI, 1.02-1.53). In high-risk patients, CABG and PCI were associated with lower mortality (HRs of 0.57 [95% CI, 0.51-0.63] and 0.70 [95% CI, 0.66-0.74], respectively). Also, in high-risk patients, CABG was associated with a higher rate of kidney failure (HR, 1.40; 95% CI, 1.16-1.69). LIMITATIONS: Possible residual confounding; lack of data for coronary angiography or left ventricular ejection fraction; possible differences in decreased kidney function severity between therapy groups. CONCLUSIONS: Outcomes associated with cardiovascular therapies among patients with CKD differed by baseline cardiovascular risk. Coronary revascularization was not associated with improved survival in low-risk patients, but was associated with improved survival in high-risk patients despite a greater observed rate of kidney failure. These findings may inform clinical decision making in the care of patients with both CKD and cardiovascular disease.

Transvaginal natural orifice transluminal endoscopic surgery in the diagnosis of ascites of unknown origin.

BACKGROUND AND AIMS: Natural orifice transluminal endoscopic surgery (NOTES) has been established in animal models and human studies, but few clinical studies have investigated transvaginal NOTES in the diagnosis of unexplained refractory ascites. We aimed to assess the feasibility, efficacy, and safety of transvaginal NOTES for the diagnosis of unexplained ascites in female patients. METHODS: A prospective study was done involving 3 female patients with unexplained ascites. After general anesthesia and disinfection, a 1.0-cm incision was made in the posterior fornix of the vagina. A gastroscope was inserted into the abdominal cavity through the transvaginal incision and an artificial pneumoperitoneum was created; NOTES peritoneoscopy was performed to scrutinize the pathologic changes. Endoscopic biopsy specimens were obtained for pathologic examination. The transvaginal incision was closed by direct suturing. RESULTS: Transvaginal NOTES for diagnostic peritoneoscopy was successfully performed in 3 patients. The mean operative time was 61 minutes. The estimated blood loss was 5 to 10 mL. The pathologic diagnoses were tuberculosis for all patients, and the symptoms and ascites disappeared after antituberculosis therapy. During the 4-year follow-up, no clinically significant adverse events occurred in any patient after NOTES. No patient experienced an annex inflammation, vaginitis, dyspareunia, or sexual dysfunction. All patients were comfortable and satisfied with the nonscarring surgical procedure. CONCLUSIONS: Transvaginal NOTES for the diagnosis of unexplained ascites is feasible, effective, and safe. This method had no long-term effect on female sexual function and is particularly suitable for women who have special aesthetic requirements. (Clinical trial registration number: ChiCTR-TRC-10001053.).