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 Final OS was analysed when all patients had either died or withdrawn from the study.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     

Changes in stereocilia micromechanics following overstimulation in metabolically blocked hair cells

Previous studies have demonstrated that stereocilia micromechanics change during exposure to intense stimulation, and then recover after the stimulus has ended. These changes were associated with a loss of stiffness in the sensory hair bundle. The patterns of growth and recovery in these data suggest that active cellular processes control and limit these phenomena. The present investigation further supports this suggestion. The effects of intense stereocilia stimulation were examined before and after the hair cells were metabolically blocked by cooling or by poisoning with NaCN. In normal cells threshold shift increases with exposure duration, reaching a plateau within 5 to 6 min. Moreover, a post-exposure recovery of the threshold was also noted in the control cells within 15 min. In contrast threshold shift after the first minute in the metabolically blocked cells increased monotonically during the exposure without any indication of a plateau. Similarly, no post-exposure recovery of threshold shift was seen in the stereocilia bundles. These data support the hypothesis that metabolic processes in the region of the sensory hairs are important for limiting the loss of stiffness during exposure, as well as for restoring stiffness during recovery.     

The developmental appearance of a major basilar papilla-specific protein in the chick

The sensory epithelium of the chick cochlea, the basilar papilla, contains a major protein of approximately 23,000 daltons. This protein was as abundant as actin in the papilla, yet could not be found in significant quantities in any other cochlear tissue. The protein appeared at a time in development when other studies have shown that the chick embryo develops peripheral auditory competence. These observations suggest a role for this protein in cochlear function.     

Treatment of superior oblique palsy with superior oblique tendon tuck and inferior oblique muscle myectomy

Twelve patients underwent quantitated superior oblique tendon tuck and ipsilateral inferior oblique muscle myectomy in the primary treatment of unilateral superior oblique muscle palsy. Preoperatively, each patient exhibited a vertical deviation of 30-55 prism diopters in at least one position of gaze. Following a single operation, satisfactory ocular alignment was obtained in all but one case, with fusion demonstrable in clinically significant gaze positions. Eight of 12 patients had no measurable vertical deviation in primary position, and two others had residual hyperphorias of only two prism diopters. No tucks were removed for postoperative Brown's syndrome. Superior oblique tendon tuck combined with ipsilateral inferior oblique muscle myectomy appears to be a safe and effective treatment for large angle superior oblique muscle palsy.     

Risk factors for postpartum depression: a retrospective investigation

OBJECTIVE: To search for a possible correlation between incidence of postpartum depression (PPD) and any of the following factors recorded in patient charts at the routine, 4-week postnatal visit: age, breast-feeding status, smoker/nonsmoker, marital status, preexisting depression and type of delivery. STUDY DESIGN: Data were obtained from 588 obstetric charts for women who gave birth between June 1, 2003, and June 1, 2004, at 3 university clinics in Tulsa, Oklahoma. RESULTS: Prior history of depression and smoking cigarettes were significant risk factors for an Edinburgh Postnatal Depression Scale score of 13 or higher, indicating probable PPD. CONCLUSION: Our data and previous findings warrant continued investigation in a larger study to clearly delineate these and other possible risk factors for PPD and to facilitate prophylactic patient education and intervention strategies.     

改良性治疗法联合西地那非治疗勃起功能障碍维吾尔族患者2505例回顾性分析

目的:性治疗法目前尚未普及,本研究旨在评价性治疗法联合西地那非治疗勃起功能障碍(ED)的疗效。方法:根据治疗方法的不同将在本院治疗随访过的3130例维吾尔族ED患者分成2组。对照组625例,单纯口服西地那非3个月;试验组2505例,采用性治疗法联合西地那非治疗3个月。采用国际勃起功能问卷表(IIEF-5)在各组治疗前、后进行疗效评估,并随访12个月。结果:对照组治疗前、后及在6个月、12个月随访的IIEF-5评分分别为12.80±3.76、18.10±2.61、17.35±2.73和16.64±2.63;试验组治疗前、后及在6个月、12个月随访的IIEF-5评分分别为12.73±3.52、19.06±4.07、19.86±2.42和20.47±2.38。两组治疗前后IIEF-5评分自身对比差异均有显著性(P<0.05)。组间比较,试验组较对照组6个月和12个月随访IIEF-5评分均有显著性差异(P<0.05)。结论:性治疗法联合西地那非治疗ED的效果优于单纯西地那非治疗,并在12个月的随访中稳定性良好。     

Treating obesity in patients with cardiovascular disease: the pharmacotherapeutic options

Introduction: Obesity is a growing health problem that has numerous comorbidities, including cardiovascular disease (CVD). The multi-disciplinary treatment of obesity now includes the use of pharmacotherapy. When treating patients with obesity and CVD, certain medications may be more appropriate than others.

Areas covered: Herein, the authors review the most commonly used FDA approved medications for the treatment of obesity, describing their mechanism of action, and the efficacy and safety of the medications as seen in recent studies, particularly in patients with CVD.

Expert opinion: In the population of patients with obesity and CVD, the medications orlistat, lorcaserin and liraglutide are considered the most appropriate options for their treatment, in terms of safety. Sympathomimetic medications, such as phentermine, should be avoided in this group. The recent CAMELLIA-TIMI 61 trial supports the safety of lorcaserin in patients with CVD. Until there are more studies, it is reasonable to extrapolate the findings of the LEADER trial, which found improved CV outcomes in subjects with type 2 diabetes taking liraglutide, to the population of nondiabetic patients being treated for obesity. Further cardiovascular outcomes trials (CVOT) are needed to assess the safety of other pharmacotherapeutic options for weight loss.     

Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis

BACKGROUND AND AIMS: Colonoscopic surveillance for cancer in longstanding extensive ulcerative colitis relies heavily on non-targeted mucosal biopsies. Chromoendoscopy can aid detection of subtle mucosal abnormalities. We hypothesised that routine pancolonic indigo carmine dye spraying would improve the macroscopic detection of dysplasia and reduce the dependence on non-targeted biopsies. PATIENTS AND METHODS: One hundred patients with longstanding extensive ulcerative colitis attending for colonoscopic surveillance underwent "back to back" colonoscopies. During the first examination, visible abnormalities were biopsied, and quadrantic non-targeted biopsies were taken every 10 cm. Pancolonic indigo carmine (0.1%) was used during the second colonoscopic examination, and any additional visible abnormalities were biopsied. RESULTS: Median extubation times for the first and second colonoscopies were 11 and 10 minutes, respectively. The non-targeted biopsy protocol detected no dysplasia in 2904 biopsies. Forty three mucosal abnormalities (20 patients) were detected during the pre-dye spray colonoscopy of which two (two patients) were dysplastic: both were considered to be dysplasia associated lesions/masses. A total of 114 additional abnormalities (55 patients) were detected following dye spraying, of which seven (five patients) were dysplastic: all were considered to be adenomas. There was a strong trend towards statistically increased dysplasia detection following dye spraying (p = 0.06, paired exact test). The targeted biopsy protocol detected dysplasia in significantly more patients than the non-targeted protocol (p = 0.02, paired exact test). CONCLUSIONS: No dysplasia was detected in 2904 non-targeted biopsies. In comparison, a targeted biopsy protocol with pancolonic chromoendoscopy required fewer biopsies (157) yet detected nine dysplastic lesions, seven of which were only visible after indigo carmine application. Careful mucosal examination aided by pancolonic chromoendoscopy and targeted biopsies of suspicious lesions may be a more effective surveillance methodology than taking multiple non-targeted biopsies.