Low neutrophil-to-lymphocyte ratio predicts overall survival benefit in advanced NSCLC patients with low PD-L1 expression and receiving chemoimmunotherapy.

Although combination therapy including chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) of patients with non-small-cell lung cancer (NSCLC), there is a higher incidence of adverse events and treatment discontinuation. Since programmed death-ligand 1 (PD-L1) could not serve as a predictive biomarker, we investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker. In our previous research, we demonstrated that a low NLR could predict survival benefits when patients with high PD-L1 expression (> 50%) received chemoimmunotherapy as opposed to immunotherapy alone. In this current study, our objective is to evaluate this predictive capacity in patients with low PD-L1 expression (< 50%). A total of 142 patients were enrolled, 28 receiving combination therapy and 114 receiving chemotherapy alone. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Patients who received combination therapy had significantly better PFS and OS than those who received monotherapy. In the subgroup of patients with low NLR, those who received combination therapy exhibited extended PFS and OS with clinical significance, which was also confirmed by multivariate Cox regression analysis. Our study demonstrates the potential use of NLR as a biomarker for predicting survival benefits when receiving combination therapy with chemotherapy and ICIs in patients with advanced NSCLC and low PD-L1 expression.

Chemotherapy outcomes in EGFR-TKI resistant patients with common and uncommon EGFR mutation: An exploratory retrospective cohort study.

BACKGROUND: Some prospective studies have shown that second-generation tyrosine kinase inhibitors (TKIs) provide better control in patients with non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. However, studies comparing second-line chemotherapy efficacy between NSCLC patients with common and uncommon EGFR mutations remain rare. This retrospective study compared treatment outcomes in these patients. METHODS: Patients with EGFR-mutated advanced-stage NSCLC who received first-line EGFR-TKIs in a tertiary referral center were retrospectively reviewed between January 2010 and August 2022. Patients with a negative T790M test at disease progression who received second-line chemotherapy were enrolled. We compared progression-free (PFS) and overall (OS) survival between advanced NSCLC patients with common and uncommon EGFR mutations using Kaplan-Meier and log-rank tests. RESULTS: In total, 209 (54.8%) patients had a negative T790M mutation test and received second-line chemotherapy, of which 192 (91.8%) had a common EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and 17 (8.2%) had an uncommon EGFR mutation. Patients with common EGFR mutations had significantly longer PFS than those with uncommon EGFR mutations (4.57 vs. 2.57 months, p = 0.031). A Cox proportional hazard regression analysis controlling for potential confounding factors indicated that an uncommon EGFR mutation was an independent prognostic factor for PFS. CONCLUSION: This study suggests that patients with uncommon EGFR mutations have poorer chemotherapy responses and shorter survival than those with common EGFR mutations. The development of new treatment strategies for these patients remains an unmet need.

Effect of BIM expression on the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs.

The role of Programmed Cell Death Ligand 1 (PD-L1) expression in predicting epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) efficacy remains controversial. Recent studies have highlighted that tumor-intrinsic PD-L1 signaling can be modulated by STAT3, AKT, MET oncogenic pathway, epithelial-mesenchymal transition, or BIM expression. This study aimed to investigate whether these underlying mechanisms affect the prognostic role of PD-L1. We retrospectively enrolled patients with EGFR mutant advanced stage NSCLC who received first-line EGFR-TKI between January 2017 and June 2019, the treatment efficacy of EGFR-TKI was assessed. Kaplan-Meier analysis of progression-free survival (PFS) revealed that patients with high BIM expression had shorter PFS, regardless of PD-L1 expression. This result was also supported by the COX proportional hazard regression analysis. In vitro, we further proved that the knockdown of BIM, instead of PDL1, induced more cell apoptosis following gefitinib treatment. Our data suggest that among the pathways affecting tumor-intrinsic PD-L1 signaling, BIM is potentially the underlying mechanism that affects the role of PD-L1 expression in predicting response to EGFR TKI and mediates cell apoptosis under treatment with gefitinib in EGFR-mutant NSCLC. Further prospective studies are required to validate these results.

Social comparison effects on students' cognitive anxiety, self-confidence, and performance in Chinese composition writing.

Social comparison is a mind-altering determinant that affects students' learning behavior. To understand the effect, three instructional approaches to teaching Chinese writing skills were designed and implemented in this study: (1) The No Comparison Group (NCG): students were asked to complete compositions on their own; (2) The Upward Comparison Group (UCG): superior composition examples were provided and the students were asked to write compositions on the same topics; and (3) The Downward Comparison Group (DCG): inferior examples were provided for students to critique. Taiwanese junior high school ninth graders participated in three groups, and wrote compositions on six themes. The results revealed that the Chinese composition writing (CCW) skills of the students in the UCG and DCG improved significantly more than those of the students in the NCG. Composition-prompted cognitive anxiety in the DCG declined substantially. The results imply that adopting upward and downward comparisons for students to practice Chinese composition is worth adopting in writing lessons.

IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms.

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

SNP rs4331426 in 18q11.2 is associated with susceptibility to tuberculosis among female Han Taiwanese.

A single nucleotide polymorphism (SNP) rs4331426 located in a gene-poor region on chromosome 18q11.2 has been associated with tuberculosis (TB) by genome-wide association studies in Ghana and Gambia. In this study, we analyzed the SNP rs4331426 for its association with the risk of TB in the Taiwanese population. The SNP rs4331426 was genotyped in a case-control design that included 377 Han Taiwanese (200 TB patients and 177 controls) and was associated with TB (marginally significant p = 0.078). An increasingly significant association was observed after adjusting for sex in the logistic regression analysis (p = 0.029). Furthermore, the G carrier (AG genotype) conferred the risk of TB in females (p = 0.011), but not in males. These findings indicate that the SNP rs4331426 associated with TB in the Han Taiwanese population, especially in females. Further investigations on its role and that of the genomic region surrounding it are warranted.

Effectiveness of sulpiride in adult patients with schizophrenia.

The objective of this study is to compare the effectiveness among sulpiride, risperidone, olanzapine, and haloperidol by evaluating the persistence of drug use. A retrospective cohort study was conducted by analyzing the National Health Insurance Research Database of Taiwan. Patients with schizophrenia aged 18-65 years and newly prescribed with a single oral antipsychotic medication between years 2003 and 2008 were included. The primary outcome was the persistence of antipsychotic agents by calculating the treatment duration till treatment changed. All defined treatment changes were also analyzed separately, including discontinuation, switching, augmentation, and hospitalization. A total of 1324 eligible patients were included, with an average age of 36 years old and approximately 45% of them were female. The most prevalent antipsychotic use was risperidone (42.1%), followed by sulpiride (36.0%), haloperidol (14.2%), and olanzapine (7.7%). After adjusting for patient demographics, mental illness characteristics, and propensity score, the Cox regression models found that the risk of nonpersistence was significantly higher in patients receiving risperidone (hazard ratio [HR], 1.22; 95% CI, 1.06-1.40), haloperidol (HR, 1.98; 95% CI, 1.63-2.40), and olanzapine (HR, 1.34; 95% CI, 1.07-1.68), as compared with sulpiride, suggesting the effectiveness of sulpiride was better than the other 3 antipsychotics. Therefore, this study would provide strong grounds for a properly conducted randomized controlled trial of the clinical- and cost-effectiveness of sulpiride vs atypical antipsychotics.

High prevalence of metabolic disturbances in patients with bipolar disorder in Taiwan.

BACKGROUND: Both ethnicity and lifestyle may contribute to these abnormalities. High prevalences of obesity and metabolic disturbances in patients with bipolar disorder (BD) have been reported in western countries. However, reports about the prevalences in Asian countries remain scant. METHOD: The cross-sectional study included 117 patients diagnosed as BD and treated with lithium (Li), valproate (VPA), or both at a university psychiatric outpatient clinic. Their body mass index and plasma levels of glucose and lipid were measured. The prevalence of metabolic syndrome was determined based on the IDF 2005 criteria. RESULTS: 13.7%, 36.8%, 53.0%, 18.6%, and 61.0% of the patients met the criteria for hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension and large waist circumference, respectively. 33.9% of the patients met the IDF 2005 criterion for metabolic syndrome. The prevalence of metabolic abnormalities was significantly higher in patients who have been cotreated with second-generation antipsychotics (SGAs). CONCLUSION: This study provides evidence of high prevalence of metabolic syndrome in BD patients in Taiwan. Such metabolic disturbances can increase morbidity and mortality. Further studies that focus on the underlying mechanisms and effective intervention strategies are warranted.

Decrease in inflammatory cardiovascular risk markers in hyperlipidemic diabetic patients treated with fenofibrate.

The goal was to investigate the effect of micronized fenofibrate, a hypolipidemic drug, on inflammatory markers and proinsulin in patients with type 2 diabetes who had hyperlipidemia. Thirty-nine patients were treated with micronized fenofibrate (200 mg/day for 12 wk). Erythrocyte sedimentation rate (ESR), fibrinogen, high-sensitivity C-reactive protein (hs CRP), and proinsulin levels were measured at baseline and after 12 wk of therapy. Micronized fenofibrate significantly reduced serum triglyceride, cholesterol, and uric acid levels (all p <0.0001) and increased high-density lipoprotein (HDL)-cholesterol (p <0.001) and creatinine levels (p <0.0001). Micronized fenofibrate also significantly decreased fibrinogen (421 +/- 152 vs 344 +/- 81 mg/dl, p <0.001), hs-CRP (3.3 +/- 3.3 vs 2.1 +/- 1.8 mg/L, p <0.01), and ESR (19.1 +/- 24.8 vs 9.7 +/- 8.7 mm/hr, p <0.01), but did not change proinsulin levels. The correlations among changes of hs-CRP, fibrinogen, and ESR were high. Although correlation among the decreases in inflammatory markers (ESR, fibrinogen, and hs-CRP) was significant, there was no significant correlation between the changes of lipid profile and inflammatory markers. In conclusion, after 12 wk, micronized fenofibrate therapy significantly decreased 3 inflammatory markers (hs-CRP, ESR, and fibrinogen) and improved the lipid profile by decreasing serum triglyceride, cholesterol, and non-HDL-cholesterol levels and increasing HDL-cholesterol; however, it did not change serum proinsulin level, a pancreatic stress marker.

Glycopeptide-induced neutropenia: cross-reactivity between vancomycin and teicoplanin.

OBJECTIVE: To report teicoplanin-related neutropenia that developed after an episode of neutropenia induced by vancomycin therapy. CASE SUMMARY: A 57-year-old female suffered from osteomyelitis of the left humerus, with a white blood cell (WBC) count of 2.8 x 10(3)/mm3 and absolute neutrophil count (ANC) of 0.28 x 10(3)/mm3, occurring after 24 days of vancomycin therapy. Vancomycin was changed to teicoplanin and the agranulocytosis resolved 4 days later. However, a new episode of neutropenia, with a WBC count of 2.8 x 10(3)/mm3 and ANC of 0.448 x 10(3)/mm3, occurred 11 days after teicoplanin initiation. Agranulocytosis resolved 4 days following withdrawal of teicoplanin. DISCUSSION: Because of the close time relationship between drug administration and the development of symptoms and signs, as well as between drug withdrawal and changes in WBC count and ANC, the episodes of neutropenia were suspected to be drug related. Teicoplanin-induced agranulocytosis that followed vancomycin-induced agranulocytosis suggests a possible cross-reactivity between the 2 drugs. Both reactions were categorized as probable according to the Naranjo probability scale. CONCLUSIONS: For all patients with vancomycin-induced neutropenia, possible cross-reactivity of teicoplanin should be monitored.

Polyethylene failure of the patellar component in New Jersey low-contact stress total knee arthroplasties.

In a postoperative 5- to 12-year follow-up study of 598 New Jersey low-contact stress total knee arthroplasties, 32 required revision. All retrieved patellar components were examined for polyethylene damage. These 32 cases had 3 types of failure: split rupture (7 cases), peripheral wear (21), and cantilevering breakage (4), respectively 75%, 64.3%, and 100% of which showed subluxation and/or tilting of the patellar component on the prerevision roentgenograms. Misalignment at the joint contact surfaces and rotational blockage of the mobile patellar component were considered the major causes of the failure. A design of a flatter metallic button (giving larger focal thickness of the polyethylene) and a dome-shaped polyethylene (reducing stress concentration at the pinnacle) may alleviate the failure driving mechanism should subluxation or tilting of the patellar component take place.