First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study

Background Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results.Methods TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m² orally twice daily on days 1–5 and 8–12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m² orally twice daily on days 1–14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS.Results At 1 September 2020, median OS was 22.3 months (95% CI: 18.0–23.7) with TT-B and 17.7 months (95% CI: 12.6–19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55–1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings.Conclusions TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy.Clinical trial information {"type":"clinical-trial","attrs":{"text":"NCT02743221","term_id":"NCT02743221"}}NCT02743221 (clinicaltrials.gov)Subject terms: Colorectal cancer, Colorectal cancer     

Reliability of clinical oral examinations re-examined

Many medical schools still use oral examinations for the evaluation of clinical competence of students in their clerkship, although it has been proven that orals have poor reliability. This study investigates the feasibility and reliability of multiple oral examinations. Students in the last week of their Internal Medicine clerkship in an outpatient clinic were given several patient-based oral examinations. The student's performance was rated on a list of items reflecting clinical competence. A global judgement of the student's performance was also given. The results indicate that it is possible to increase the number of orals and the number of examiners in the day-to-day practice of an outpatient clinic moderately. The reliability when using a number of orals is better than the reliability of the common single oral examination. The reliability using global judgements appeared to be better than the reliability of averaged item scores.     

Chemical constituents and biological activities of Zanthoxylum usambarense.

Bioassay-guided fractionation of the dichloromethane extracts of the roots and the bark of Zanthoxylum usambarense led to the isolation of two physiologically active compounds, i.e. canthin-6-one 1 (fungicide) and pellitorine 4 (insecticide). Together with oxychelerythrine 2, norchelerythrine 3, (+)-sesamin 5 and (+)-piperitol-3,3-dimethylallyl ether 6, they were isolated for the first time from this plant.     

Autosomal dominant cone-rod dystrophy due to a missense mutation (R838C) in the guanylate cyclase 2D gene (GUCY2D) with preserved rod function in one branch of the family

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disorder of photoreceptors. Mutations in several genes encoding different proteins of the visual cascade are described. The inheritance of two intragenic markers within the interstitial retinol binding protein (IRBP) gene was established in 45 Spanish families with a history of ARRP. Homozygosity mapping and cosegregation analyses were positive in 19 families. Only one heterozygous T-C transition at position 3024 (exon 1) was detected in one consanguineous family. This variant was identified as a rare polymorphism and was present in 5% of the chromosomes analyzed.     

Occurrence of <Emphasis Type="Italic">Demodex</Emphasis> species in patients with blepharitis and in healthy individuals: a 10-year observational study

Purpose

Two Demodex species (eyelash mites)—D. folliculorum and D brevis—are believed to be associated with human skin and eye diseases. However, the clinical significance of infection with Demodex species remains controversial.

Study design

The aim of this study was to estimate the prevalence of ocular demodicosis in patients with blepharitis as compared with the prevalence in the healthy population in Poland.

Methods

This case-control prospective study was carried out from 2007 to 2016. The enrolled patients (668) were divided into 2 groups: the study group, comprising 553 patients with blepharitis (349 women and 204 men, aged 17–88 years), and the control group, comprising 115 healthy volunteers without a history of ocular pathologies (78 women and 37 men, aged 17–88 years). A sample of 10 eyelashes was taken aseptically from each eye of the examined person and later studied under a light microscope.

Results

Demodex species were found in 62.4% (345/544) of the patients in the study group and in 24.3% (28/100) of the controls (P = .001, OR = 0.006). The overall prevalence was 55.8% (373/668) in all the examined participants. The presence of Demodex infection increased with age in both groups. No association of Demodex infection with gender was found (119/204 vs 226/349; P > .05, OR 1.086). A high mean number of mites was present more frequently in patients aged older than 50 years and in those who complained especially about itching (P < .05).

Conclusion

The prevalence of ocular demodicosis is significantly correlated with blepharitis and increases with age.

     

Red glasses and visual function in retinitis pigmentosa

As a consequence of animal studies reduction of the light regimes have been tried on patients with retinitis pigmentosa. The trials have been very limited and have not given reason for hope that such reduced light therapy may be beneficial. However, RP patients trying red glasses have reported acute subjective improvement of their visual function. It was the purpose of this study to try to document the reports more objectively. Five visual functions were tested with and without red glasses with the following results: 1. Visual acuity and contrast sensitivity. For one volunteer a small reproducible improvement was found. 2. Color vision. In most cases deterioration was found of already deficient color vision. 3. Visual fields. For volunteers with relatively preserved vision no difference or slight deterioration was found. For the other volunteers slight improvements were found. 4. Intraocular light scatter. No differences were found. 5. Dark adaptation. Improvements were found when the glasses were used as adaptation aid according to the method of Trendelenburg (rod function). For cone function no difference was found upon continuous wearing of red glasses.In conclusion: use of red glasses does not seem to be of great benefit as a rule. On the other hand, apart from the reduction in color discrimination no serious disadvantages seem to be inherent in their wear by RP patients.     

CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

Purpose  The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods  We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results  All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion  These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. Capsule This is the first report that demonstrates the polymorphism at Ile462Val of CYP1A1 to be associated with uterine leiomyoma in Chinese women.