Local Transmission of SARS-CoV-2 Lineage B.1.1.7, Brazil,December 2020

In December 2020, research surveillance detected the B.1.1.7 lineage of severe acute respiratory syndrome coronavirus 2 in São Paulo, Brazil. Rapid genomic sequencing and phylogenetic analysis revealed 2 distinct introductions of the lineage. One patient reported no international travel. There may be more infections with this lineage in Brazil than reported.     

10 K: a large‐scale prospective longitudinal study in Israel

European Journal of Epidemiology - The 10 K is a large-scale prospective longitudinal cohort and biobank that was established in Israel. The primary aims of the study include development...     

The impact of P‐glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors

Mitogen/extracellular signal‐regulated kinase (MEK) inhibitors have been tested in clinical trials for treatment of intracranial neoplasms, including glioblastoma (GBM), but efficacy of these drugs has not yet been demonstrated. The blood‐brain barrier (BBB) is a major impediment to adequate delivery of drugs into the brain and may thereby also limit the successful implementation of MEK inhibitors against intracranial malignancies. The BBB is equipped with a range of ATP‐dependent efflux transport proteins, of which P‐gp (ABCB1) and BCRP (ABCG2) are the two most dominant for drug efflux from the brain. We investigated their impact on the pharmacokinetics and target engagement of a panel of clinically applied MEK inhibitors, in order to select the most promising candidate for brain cancers in the context of clinical pharmacokinetics and inhibitor characteristics. To this end, we used in vitro drug transport assays and conducted pharmacokinetic and pharmacodynamic studies in wildtype and ABC‐transporter knockout mice. PD0325901 displayed more promising characteristics than trametinib (GSK1120212), binimetinib (MEK162), selumetinib (AZD6244), and pimasertib (AS703026): PD0325901 was the weakest substrate of P‐gp and BCRP in vitro, its brain penetration was only marginally higher in Abcb1a/b;Abcg2^?/? mice, and efficient target inhibition in the brain could be achieved at clinically relevant plasma levels. Notably, target inhibition could also be demonstrated for selumetinib, but only at plasma levels far above levels in patients receiving the maximum tolerated dose. In summary, our study recommends further development of PD0325901 for the treatment of intracranial neoplasms.     

Gray matter density reduction associated with adjuvant chemotherapy in older women with breast cancer

Purpose

The purpose of this study was to evaluate longitudinal changes in brain gray matter density (GMD) before and after adjuvant chemotherapy in older women with breast cancer.

Methods

We recruited 16 women aged ≥?60 years with stage I–III breast cancers receiving adjuvant chemotherapy (CT) and 15 age- and sex-matched healthy controls (HC). The CT group underwent brain MRI and the NIH Toolbox for Cognition testing prior to adjuvant chemotherapy (time point 1, TP1) and within 1 month after chemotherapy (time point 2, TP2). The HC group underwent the same assessments at matched intervals. GMD was evaluated with the voxel-based morphometry.

Results

The mean age was 67 years in the CT group and 68.5 years in the HC group. There was significant GMD reduction within the chemotherapy group from TP1 to TP2. Compared to the HC group, the CT group displayed statistically significantly greater GMD reductions from TP1 to TP2 in the brain regions involving the left anterior cingulate gyrus, right insula, and left middle temporal gyrus (p_{FWE(family-wise error)-corrected}?<?0.05). The baseline GMD in left insula was positively correlated with the baseline list-sorting working memory score in the HC group (p_{FWE-corrected}?<?0.05). No correlation was observed for the changes in GMD with the changes in cognitive testing scores from TP1 to TP2 (p_{FWE-corrected}?<?0.05).

Conclusions

Our findings indicate that GMD reductions were associated with adjuvant chemotherapy in older women with breast cancer. Future studies are needed to understand the clinical significance of the neuroimaging findings. This study is registered on ClinicalTrials.gov (NCT01992432).

     

Risk factors associated with gastroenteropancreatic neuroendocrine tumors in a cohort of 2.3 million Israeli adolescents

We investigated whether obesity and sociodemographic factors at adolescence are associated with incident gastroenteropancreatic neuroendocrine tumors (GEP‐NET).Our cohort included 2.3 million Israeli adolescents examined at ages 16 to 19 years between 1967 and 2010. The baseline database included sex, country of birth, residential socioeconomic status (SES), body‐mass index (BMI) and height. Participants were followed through linkage with the National Cancer Registry up to 2012. We identified 221 cases of GEP‐NET (66 pancreatic, 52 gastric, 39 rectal, 27 appendiceal, 23 small bowel and 14 colonic). Immigration from the Former Soviet Union (FSU) was associated with the risk of small bowel and rectal NET's, [Hazard Ratio (HR) 4.79, 95% Confidence Interval (CI) 1.37–16.76 and 3.43, 95% CI 1.20–9.83, respectively].Height >75th percentile and BMI ≥ 85th percentile were associated with increased risk of gastric NET (HR 2.25 95% CI 1.14–4.42 and HR 2.38, 95% CI 1.19–4.75, respectively). Female sex was associated with appendiceal NET (HR 2.30, 95% CI 1.06–4.96) while male gender was associated with an increased risk for NET of the small bowel [HR 4.72 (95% CI 1.10–20.41)].In conclusion, our findings suggest different risk factor associations with the various GEP‐NETS: immigrants from the FSU were at increased risk for small bowel and rectal NET; increased height and weight were associated with the risk of gastric NET and females were at increased risk for appendiceal NET. Further focus on the FSU population is indicated in addition to studies verifying the association of BMI and height with gastric NET.     

Video-assisted transthoracic sympathectomy in the treatment of primary hyperhidrosis: friend or foe?

The authors hypothesize that palmar hyperhidrosis is a systemic manifestation of abnormal sudomotor function; consequently, thoracoscopic sympathectomy to alleviate symptoms in the hands may result in heat dissipation because sweating is transferred to other sites. To investigate this phenomenon and to determine whether it adversely affects patient satisfaction, a standard questionnaire was administered to 626 patients who underwent sympathectomy at a university-associated public hospital between 1991 and 1998; only patients treated at least 6 months before questionnaire distribution were included in the study. Replies were received from 336 (53.7%) individuals. The surveyed patients underwent bilateral T2, T3 (palmar sweating), or T3, T4 (axillary sweating) sympathectomy by a standard video-assisted transthoracic technique. Main outcome measures included the incidence of dry hands, compensatory sweating, chest pain, upper-limb muscle weakness, shortness of breath, and gustatory phenomena; in addition, patient perception of the success of the surgical procedure was assessed. After sympathectomy, 97.3% (P < 0.0001) and 29.2% (P < 0.001) of patients reported significant improvement in palmar hyperhidrosis and axillary sweating, respectively. Postsurgery, severe compensatory sweating was experienced in 90% of patients (P < 0.0001). The sites of compensatory sweating were the back (75%), abdomen (51%), feet (23%), groin and thigh (13%), chest (13%), and axillae (8%). Transient whole-body sweating for no apparent reason was experienced in 30% of patients. Thirty-seven patients (11%) regretted having undergone the surgical procedure. In contrast, 25% and 64% of patients were either satisfied or very satisfied with the outcome of the procedure. From the survey results, the authors conclude that palmar hyperhidrosis is a systemic manifestation of abnormal sudomotor function and that thoracic sympathectomy may alleviate symptoms in a large proportion of patients. However, for some individuals, compensatory sweating may prove to be an equally troublesome handicap. Because the occurrence of severe compensatory sweating is unpredictable, a reversible sympathectomy may be desirable.     

Refined and whole grain cereals and the risk of oral, oesophageal and laryngeal cancer

OBJECTIVE: To investigate the possible differential role of refined and whole grain cereals on the risk of upper digestive and respiratory tract neoplasms. DESIGN: Hospital-based case-control study. SETTING: University Hospital of Lausanne, Switzerland. SUBJECTS: A total of 156 incident cases of cancers of the oral cavity and pharynx, 101 of the oesophagus, 40 of the larynx, and 349 control subjects admitted for a wide spectrum of acute non-neoplastic conditions. INTERVENTION: Trained interviewers collected information using a structured and validated questionnaire. Odds ratios (OR) of various cancers for a tertile increment of intake of refined and whole grains were estimated using unconditional multiple logistic regression. RESULTS: Refined grains were directly related to the risk of cancer of the oral cavity and pharynx (OR=1.9 for the highest tertile), oesophagus (OR=3.7) and larynx (OR=4.0). In contrast, whole grain cereals were protective, with OR of 0.6 for oral cavity and pharynx, 0.3 for oesophagus, and 0.7 for larynx. For the three sites combined, the OR for the highest tertile was 5.7 for refined grains and 0.5 for wholegrains. The trends in risk for refined grains were significant for all sites and their combination, and for wholegrain for oesophageal cancer and all sites. CONCLUSIONS: Even if inference on causality and the biological interpretation remain open to discussion, the present data indicate and further quantify that refined cereals are an unfavourable, but whole grain ones a favourable indicator of the risk of upper aerodigestive and respiratory tract neoplasms.     

Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer

BACKGROUND:: The antioestrogen tamoxifen and progestins act via differentreceptors and may therefore have complementary effects againsthuman breast cancer. This possibility was tested in a randomizedstudy which compared the effects of tamoxifen, standard-dosemegestrol acetate, and these two agents in combination, in patientswith metastatic breast cancer. PATIENTS AND METHODS:: 184 post-menopausal patients with metastatic breast cancer wererandomized to initial treatment with either tamoxifen (TAM)40 mg daily, megestrol acetate (MA) 160 mgm daily, or the combinationof the two administered simultaneously. Patients crossed overto the alternative single agent on relapse or disease progression.Patients were evaluated for response, time to initial and ultimatetreatment failure, and survival. RESULTS:: There were no significant differences between the three groupswith respect to response rates, nor the other parameters. Patientsurvival was significantly associated with age >60 years,ER positive status, and the absence of visceral metastases. CONCLUSIONS:: TAM and MA are both equally effective in response inductionas initial treatments and the combination has no advantage.Sequential treatment is still optimal, TAM being the preferredinitial agent in view of the reported side effects with MA. breast, cancer, megestrol acetate, randomized, trial, tamoxifen     

The use of robotic surgery in abdominal organ transplantation: A literature review

Minimally invasive surgical approaches in transplantation are gaining increasing interest, and many centers are reporting their, mainly laparoscopic, experiences. Robotic surgery (RS) has some hypothetical advantages over traditional laparoscopy and has been successfully applied, although infrequently to organ transplantation. Our goal was to review and critique the publications reporting RS use in organ transplantation. Most of the RS experience has been with living renal donor organ procurement and, to a lesser extent, with RS procedures in the transplant recipient. The available literature suggests that RS appears to be a safe surgical alternative to standard open procedures. RS in living liver donor surgery remains limited, and more experience is required before commenting on RS‐related outcomes RS in pancreatic transplantation is exceedingly rare. The enhanced precision and ergonomics of RS may expand its applicability to liver living donation and pancreas transplantation at some point in the future.     

Evaluation of Bioelectrical Impedance Analysis in Critically Ill Patients: Results of a Multicenter Prospective Study

Background: In critically ill patients, muscle loss is associated with adverse outcomes. Raw bioelectrical impedance analysis (BIA) parameters (eg, phase angle [PA] and impedance ratio [IR]) have received attention as potential markers of muscularity, nutrition status, and clinical outcomes. Our objective was to test whether PA and IR could be used to assess low muscularity and predict clinical outcomes. Methods: Patients (≥18 years) having an abdominal computed tomography (CT) scan and admitted to intensive care underwent multifrequency BIA within 72 hours of scan. CT scans were landmarked at the third lumbar vertebra and analyzed for skeletal muscle cross‐sectional area (CSA). CSA ≤170 cm² for males and ≤110 cm² for females defined low muscularity. The relationship between PA (and IR) and CT muscle CSA was evaluated using multivariate regression and included adjustments for age, sex, body mass index, Charlson Comorbidity Index, and admission type. PA and IR were also evaluated for predicting discharge status using dual‐energy x‐ray absorptiometry–derived cut‐points for low fat‐free mass index. Results: Of 171 potentially eligible patients, 71 had BIA and CT scans within 72 hours. Area under the receiver operating characteristic (c‐index) curve to predict CT‐defined low muscularity was 0.67 (P ≤ .05) for both PA and IR. With covariates added to logistic regression models, PA and IR c‐indexes were 0.78 and 0.76 (P < .05), respectively. Low PA and high IR predicted time to live ICU discharge. Conclusion: Our study highlights the potential utility of PA and IR as markers to identify patients with low muscularity who may benefit from early and rigorous intervention.