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71.
Salivary glands tumours are uncommon tumours showing a large diversity of histological types. This article presents a synthesis of patterns and paths of invasion of parotid glands tumours in order to propose an approach of the delineation of primary tumour clinical target volumes and of the selection of lymph nodes target volumes. This article does not discuss treatment indications but defines clinical target volumes to treat if radiotherapy is indicated. Postoperative situation being the most frequent, the delineation of primary tumour clinical target volume is based on an anatomical approach.  相似文献   
72.

Objective

To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).

Methods

An influenza vaccination or placebo was administered to 47 AChR MG patients. Before and 4?weeks after administration blood samples and clinical outcome scores were obtained. Antibodies to the vaccine strains A/California/7/2009 (H1N1)pdm09, A/Hong Kong/4801/14 (H3N2) and B/Brisbane/060/08 were measured using the hemagglutination-inhibition (HI) assay and disease-specific AChR antibody titers were measured with a radio-immunoprecipitation assay. Forty-seven healthy controls (HC) were vaccinated with the same influenza vaccine to compare antibody titers.

Results

A post-vaccination, seroprotective titer (HI?≥?1:40) was achieved in 89.4% of MG patients vs. 93.6% in healthy controls for the H3N2 strain, 95.7% vs 97.9% for the H1N1 strain and 46.8 vs 51% for the B-strain. A seroprotective titer for all three strains of the seasonal influenza vaccine was reached in 40.4% (19/47) of the MG group and in 51% (24/47) of the HC group. Immunosuppressive medication did not significantly influence post geomean titers (GMT). The titers of disease-specific AChR antibodies were unchanged 4?weeks after vaccination. The clinical outcome scores showed no exacerbation of MG symptoms.

Conclusion

The antibody response to an influenza vaccination in patients with AChR MG was not different from that in healthy subjects, even in AChR MG patients using immunosuppressive medication. Influenza vaccination does not induce an immunological or clinical exacerbation of AChR MG.

Clinical trial registry

The influenza trial is listed on clinicaltrialsregister.eu under 2016-003138-26.  相似文献   
73.
74.
75.
MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.  相似文献   
76.
77.
Definitive radiotherapy is an effective single-modality in T1 glottic cancer. Hypofractionated schemes could offer excellent results in a shorter treatment period. We aimed to evaluate the clinical outcomes and toxicity comparing conventional vs. hypofractionated radiotherapy treatment in T1N0M0-glottic cancer. Between Jan-1st, 2005 and August-1st, 2017, in a prospective cohort study, with 10-year follow-up, 138 patients were treated with conventional schedule 2 Gy/day, total dose 70 Gy/7 weeks (N = 71) or hypofractionated schedule 2, 2–2, 25 Gy/day, total dose 63, 8–63 Gy/5, 5 weeks (N = 67). Endpoints were clinical-response rate, local relapse-free survival (LRFS), laryngectomy-free survival (LFS), toxicity rates, relapse-free survival (RFS), metastasis-free survival (MFS), second tumour-free survival (2TFS), and overall survival (OS). All patients showed a complete clinical response. No differences were found for LRFS (p = 0.869), LFS (p = 0.975), RFS (p = 0.767), MFS (p = 0.601), 2TFS (p = 0.293), or OS (p = 0.685). Acute toxicity for skin and mucosae was similar (p = 0.550 and p = 0.698). Acute laryngeal toxicity was higher in the hypofractionation group (p = 0.004), due to an increase in slight moderate grade. No differences in late laryngeal edema were found (p = 0.989). Radiotherapy offers high rate survival, local control, and larynx preservation after 5–10-year follow-up. A hypofractionation could be preferable, since it offers the same results as conventional with fewer treatment sessions.  相似文献   
78.

Purpose

Understanding the attitudes of physicians toward the use of pre-exposure prophylaxis (PrEP) for HIV prevention among youth is critical to improving access to PrEP. We examined PrEP-related attitudes among physicians who provide primary care to 13- to 21-year-old adolescents.

Methods

Individual, in-depth, semistructured interviews were conducted with 38 physicians from adolescent medicine, family practice, internal medicine/medicine-pediatrics, obstetrics/gynecology, and pediatrics who care for any adolescents younger than 18 years. Interviews assessed familiarity with PrEP, perceived benefits and barriers to providing PrEP to adolescents, facilitating factors for prescribing PrEP, and likelihood of recommending and prescribing PrEP to adolescents.

Results

Mean age was 44.6 years (standard deviation 10.9). Fourteen physicians (37%) reported being somewhat or very familiar with PrEP. Perceived benefits of prescribing PrEP included decreased acquisition/rates of HIV, improved provision of sexual health services, and improved patient awareness of HIV risk. Barriers to PrEP were reported at the patient (e.g., lack of acceptability to patients), provider (e.g., concerns about patient adherence, safety/side effects, parents as a barrier to PrEP use), and system (e.g., high cost) levels. Facilitating factors for prescribing PrEP included low cost/coverage by insurance, physician education about PrEP, patient educational materials, and clinical guidelines for PrEP use in youth. A higher proportion of physicians reported being highly or somewhat likely to recommend (N = 16, 42%) than prescribe PrEP (N = 13, 34%).

Conclusions

In this study of primary care physician attitudes toward PrEP prescribing for adolescents, physicians identified numerous barriers to providing PrEP. Addressing these barriers may increase adolescents' access to PrEP.  相似文献   
79.

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Methods

A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.

Results

The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.

Conclusions

Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.  相似文献   
80.
Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.  相似文献   
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