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Bronchiectasis is a common comorbidity in chronic obstructive pulmonary disease (COPD). There are limited data regarding the incidence of bronchiectasis in COPD. The purpose of the study was to use a nationwide database to evaluate the incidence of bronchiectasis in COPD in Taiwan. We used a cohort of 2,000,000 individuals followed from 2005 to 2018. Patients with COPD diagnosed between January 1, 2011, and December 31, 2017, were selected, and those with bronchiectasis before COPD were excluded. In total, 134,366 patients with COPD were enrolled, and propensity score matching was used to ensure homogeneity of baseline characteristics between the COPD and non-COPD groups. The incidence rate of bronchiectasis was higher in the COPD group than in the non-COPD group (87.83 vs 69.80 per 10,000 person-years). The adjusted hazard ratio (1.9; 95% confidence interval 1.75–2.05; P < 0.001) of bronchiectasis indicated that the risk of bronchiectasis was 1.9 times higher for patients with COPD than for patients without COPD. In the COPD group, the age-stratified incidence rates of bronchiectasis increased with age (55.01, 80.92, 101.52, and 105.23 for 40–49, 50–59, 60–69, and over 70 years, respectively). The incidence of bronchiectasis was higher in patients with COPD than in the general population, the risk of bronchiectasis increased with age in COPD, and post-tuberculosis status was an important risk factor for bronchiectasis.

The full theoretical advantages of particle beams in external beam radiotherapy have not been fully exploited, in large part due to uncertainties of the beam range in the patient. For this reason, efforts are underway, either for more precise in-vivo detection of Bragg peak positions or for further reduction of beam range computation errors in treatment planning. Meanwhile, management of the range uncertainty issues with mitigation techniques based on existing technology is critical in providing safe and effective treatments in clinical practice. This paper briefly reviews the definition and causes of particle range uncertainty, the uncertainty estimates currently used in clinical practice, and the corresponding mitigation techniques. It is intended to provide references for clinical practices at new and existing particle therapy centers.

Abstract Background Carcinoma of unknown primary site (CUP) has a poor prognosis and the prognostic factors in these patients are not well established. Furthermore, there are no selection criteria for patients who should benefit from chemotherapy. Methods The medical records of 179 CUP patients who were treated at Taipei Veterans General Hospital from 2000 to 2009 were reviewed. Factors associated with survival were determined by Kaplan-Meier analysis. Differences between the groups with and without palliative chemotherapy were analyzed. Results Univariate analysis revealed multiple prognostic factors, including performance status, lung metastasis, number of metastatic organs, serum albumin, corrected serum calcium, lactate dehydrogenase (LDH), sodium, and cholesterol levels, palliative chemotherapy, and white blood cell and lymphocyte counts. Multivariate analysis showed that performance status < 2, serum albumin level ≥ 3.5 g/dl, corrected serum calcium level < 10.7 mg/dl, single metastatic organ, and palliative chemotherapy were independent factors of better prognosis. Patients with better performance status, higher serum albumin, and lower serum LDH levels had significantly greater benefit from palliative chemotherapy. Conclusions Certain patients with unfavorable CUP will have better survival. Identification of patients with unfavorable CUP who could benefit from palliative chemotherapy warrants future prospective studies.

Abstract Background l-Dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using d-phenylglycine to guard l-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1). Methods d-Phenylglycine was chemically attached on l-dopa to form d-phenylglycine-l-dopa as a dipeptide prodrug of l-dopa. The cross-membrane transport of this dipeptide and l-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV) prepared from rat intestine. The intestinal absorption was compared by in situ jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of d-phenylglycine-l-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+)-methamphetamine (MA). Results The BBMV uptake of d-phenylglycine-l-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or l-dopa. The cross-membrane permeability (Pm*) determined in rat jejunal perfusion of d-phenylglycine-l-dopa was higher than that of l-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10). The oral bioavailability of d-phenylglycine-l-dopa was 31.7 times higher than that of l-dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of d-phenylglycine-l-dopa (50 mg/kg), indicated that d-phenylglycine-l-dopa might be a prodrug of dopamine. d-Phenylglycine-l-dopa was more efficient than l-dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%). Conclusion The BBMV uptake studies indicated that d-phenylglycine facilitated the transport of l-dopa through the intestinal PepT1 transporter. The higher jejunal permeability and the improved systemic bioavailability of d-phenylglycine-l-dopa in comparison to that of l-dopa suggested that d-phenylglycine is an effective delivery tool for improving the oral absorption of drugs like l-dopa with unsatisfactory pharmacokinetics. The gradual release of dopamine in brain striatum rendered this dipeptide as a potential dopamine sustained-releasing prodrug.