Association of smoking status with non-small cell lung cancer patients harboring uncommon epidermal growth factor receptor mutation.

Introduction: Uncommon epidermal growth factor receptor (EGFR) mutations include single and complex mutations. However, the association of the smoking status of patients with uncommon and complex EGFR mutations remains unclear. Methods: This retrospective study evaluates the spectrum of uncommon EGFR mutations and investigates the influence of smoking status on the frequency of various uncommon EGFR mutations using a multi-institutional medical database. Results: Between 2010 and 2019, 5,608 non-small cell lung cancer (NSCLC) patients were analyzed. EGFR mutations were detected in 3,155 (56.3%) patients. Among the 399 (12.6%) patients with uncommon mutations, 198 had single uncommon and 201 complex mutations, including 87 exon 20 insertions, 79 de novo T790M, 70 complex common, and 52 complex uncommon mutations. For comparison, we also included 402 patients with common EGFR mutations. The percentage of ever-smokers was significantly higher in patients with uncommon EGFR mutations than in patients with common EGFR mutations (25.8% vs. 17.4%, p = 0.005). Furthermore, the percentage of ever-smokers was higher in those with a complex mutation than in those with a single uncommon mutation (30.3% vs. 21.2%, p = 0.040). Among patients carrying uncommon EGFR mutations, ever-smokers had significantly more complex uncommon EGFR mutations than never-smokers (22.3% vs. 9.8%, p = 0.002). Among patients carrying G719X, L861Q, and S768I, ever-smokers tended to have complex EGFR mutations more frequently than never-smokers (64.7% vs. 28.7%, 50.0% vs. 18.7%, 88.9% vs. 81.2%, respectively). Conclusions: Our study demonstrates not only a comprehensive spectrum of uncommon EGFR mutations, but also a positive relationship between smoking status and uncommon EGFR mutation frequency, especially complex uncommon EGFR mutations. The results suggest that smoking contributes to the development of complex EGFR mutations.

Comparing intravenous peramivir with oral oseltamivir for patients with influenza: a meta-analysis of randomized controlled trials.

BACKGROUND: The study was to compare the efficacy between IV peramivir and oral oseltamivir treatments in patients with influenza. METHODS: The PubMed, EMBASE, Scopus, ClinicalTrials.gov, and Cochrane Library databases were searched for studies published before January 2020. RESULTS: The meta-analysis was conducted to calculate the pooled effect size by using a random-effects model. Seven randomized controlled trials (RCTs) including 1,138 patients were reviewed. The incidence of total complications revealed no significant difference between 600 mg IV peramivir (P600) and 75 mg oral oseltamivir (O75) treatments (2.8% vs. 4.1%; risk ratio [RR] = 0.70; 95% confidence interval [CI]: 0.36-1.38). The incidence of pneumonia was not significantly different between the P600 and O75 treatment groups (2.2% vs. 2.7%; RR = 0.74; 95% CI: 0.37-1.51). Regarding the time to the alleviation of symptoms, no difference was found in P600 and O75 treatment (MD = -3.00; 95% CI: -11.07 to 5.06). The rate of fever clearance in 24 h and the time to fever resolution were not statistically different between the IV peramivir and oral oseltamivir treatments (at different dosages) groups. CONCLUSIONS: The treatment of influenza with IV peramivir or oral oseltamivir had similar clinical efficacy.

CRP/IL-6/IL-10 Single-Nucleotide Polymorphisms Correlate with the Susceptibility and Severity of Community-Acquired Pneumonia.

OBJECTIVE: To explore the associations of single-nucleotide polymorphisms (SNPs) of the C-reactive protein (CRP), interleukin 6 (IL-6) and IL-10 genes with susceptibility and severity of community-acquired pneumonia (CAP). MATERIALS AND METHODS: Two hundred seventy-nine CAP patients were selected for the case group and 156 healthy individuals for the control group. Polymerase chain reaction-restriction fragment length polymorphism was performed for genotyping of CRP +1059G/C (rs1800947) and +1846C/T (rs1205), IL-6 -597G/A (rs1800797) and -572C/G (rs1800796), and IL-10 -592C/A (rs1800872) and -1082G/A (rs1800896). According to CURB-65 score, the patients were assigned into the severe community-acquired pneumonia (SCAP) and non-SCAP groups. RESULTS: The frequencies of the CRP +1846C/T (rs1205) (CT+TT) genotypes and T allele, the IL-6 -597G/A (rs1800797) (AA+AG) genotypes and A allele, and the IL-10 -592C/A (rs1800872) (CA+AA) genotypes and A allele were higher in the case group than the control group. Furthermore, the frequencies of the CRP +1846C/T (rs1205) (CT+TT) genotypes and T allele, the IL-6 -597G/A (rs1800797) A allele, and the IL-10 -592C/A (rs1800872) (CA+AA) genotypes and A allele were higher in the SCAP group than in the non-SCAP group. CONCLUSION: The CRP +1846C/T (rs1205), IL-6 -597G/A (rs1800797), and IL-10 -592C/A (rs1800872) may be associated with the susceptibility and severity of CAP.

Persistent hypoglycemia as an early, atypical presentation of hepatocellular carcinoma: A case report and systematic review of the literature.

The current study presents a case of persistent hypoglycemia as the initial manifestation of advanced hepatocellular carcinoma (HCC), as well as a systematic review of the management of hypoglycemia associated with HCC. A 42-year-old female presented with loss of consciousness and a blood glucose level of 30 mg/dl (normal range, 80-140 mg/dl). Abdominal ultrasound and computed tomography were performed to investigate tenderness in the right upper quadrant, and the results revealed a hepatic mass of 15 cm in diameter, with metastasis. A diagnosis of insulinoma was ruled out by examining the insulin level. Prednisolone treatment was ineffective for relieving the persistent hypoglycemia, however, a single dose of palliative radiotherapy reduced the hypoglycemic episodes to once monthly. Due to the advanced disease, the patient refused further treatment, with the exception of a palliative therapy with glucose fluid. The patient succumbed to pneumonia with sepsis. A systematic review of the literature indicated that steroids were the most commonly used drug for hypoglycemia associated with HCC, however, in the majority of cases no effect was noted as observed in this study. Cytoreduction by surgery or systemic chemotherapy has been the most effective treatment. Although rare, hypoglycemia may be the initial symptom of HCC. Cytoreduction is the most effective method of treating hypoglycemia associated with HCC.

Zoledronic acid induces apoptosis and autophagy in cervical cancer cells.

Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA-induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL-6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation.

Risk factors and predictors of non-alcoholic fatty liver disease in Taiwan.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: Ultrasound assessment of the severity of non-alcoholic fatty liver disease (NAFLD) shows substantial observer variability. The purpose of this retrospective study is to develop a more objective, quantitative, and applicable assessment method for all physicians. MAIN RESULTS: Male gender, and increases in age, body mass index, alanine aminotransferase (ALT), triglycerides (TG), and total cholesterol (TC) were found to be significantly correlated to higher scores. The following algorithm, derived from a 3,275 member training group, for predicting the extent of fatty liver infiltration was then constructed using these parameters. In (π(1)/π(0)) = -8.360-0.065*Gender+0.010*age+0.256*BMI+0.024*ALT+0.03*TG+0.002*TC. In (π(2)/π(0))= -19.0.92+0.482*Gender+0.043*age+0.529*BMI+0.046*ALT+0.005*TG+0.005*TC. π(0): the probability of non fatty liver. π(1): the probability of degree 1 fatty liver. π(2): the probability of degree 2-3 fatty liver. π(0) + π(1) + π(2) = 1. The resulting algorithm was tested for its predictive power a 1,065 member validation group. The algorithm predicted the actual ultrasound fatty liver score in the validation group with 87.9, 14.2, and 72.6% accuracy for those with no, grade 1, and grade 2-3 fatty liver, respectively. For prediction of grade 2-3 fatty liver, its sensitivity was 70.8%, its specificity 85.2%, its positive predictive power 63.2% and its negative predictive power 88.8%. CONCLUSIONS: The algorithm developed here is fast and has substantial predictive power for grade 2-3 fatty liver. No specialized equipment or expertise is needed, and it can be easily used by the general practitioner to predict the extent of fatty infiltration in cases of NAFLD.