Neoadjuvant chemoradiotherapy for locally advanced rectal cancer with peritumoral abscesses and fistulas.

PURPOSE: Rectal cancer patients who present with peritumoral abscesses and fistulas at the time of diagnosis may be denied chemoradiotherapy (CRT) as the safety is unknown. The aim of this study was to investigate the safety of preoperative CRT in this patient group. METHODS: We performed a retrospective nested case-control study to compare outcomes between patients with locally advanced rectal cancer with peritumoral abscesses and fistulas (study group) and patients with T4 locally advanced rectal cancer with no evidence of abscesses and fistulas (control group). These groups were matched by treatment center and radiotherapy delivery method. All patients received 50-54 Gy of conventionally fractionated RT with concurrent chemotherapy. Primary endpoint was grade 3-5 toxicity (by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE). Secondary endpoints included postoperative morbidity, pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) at 2 years. RESULTS: A total of 33 patients were included in each group. Grade 3 toxicity was observed in 2 (6.1%) patients in the study group and 4 (12.1%) patients in the control group (p = 0.672). No patients developed grade 4-5 toxicity. Grade 3-4 Clavien-Dindo complications were observed in 5 (15.2%) patients in the study group and in 6 (18.2%) patients in the control group (p = 1.0). Pathologic CR was achieved in 3 (9.1%) and 5 (15.2%) patients, respectively (p = 0.708). Two-year OS was 78.3% vs. 81.8% (p = 0.944), 2­year DFS was 62.8% vs. 69.7% (p = 0.693), respectively. CONCLUSION: The presence of peritumoral abscesses and fistulas in patients with locally advanced rectal cancer is not associated with increased toxicity or inferior clinical outcomes after preoperative CRT.

The use of astronomy VLBA campaign MOJAVE for geodesy.

We investigated the suitability of the astronomical 15 GHz Very Long Baseline Array (VLBA) observing program MOJAVE-5 for estimation of geodetic parameters, such as station coordinates and Earth orientation parameters. We processed a concurrent dedicated VLBA geodesy program observed at 2.3 GHz and 8.6 GHz starting on September 2016 through July 2020 as reference dataset. We showed that the baseline length repeatability from MOJAVE-5 experiments is only a factor of 1.5 greater than from the dedicated geodetic dataset and still below 1 ppb. The wrms of the difference of estimated Earth orientation parameters with respect to the reference IERS C04 time series are a factor of 1.3 to 1.8 worse. We isolated three major differences between the datasets in terms of their possible impact on the geodetic results, i.e. the scheduling approach, treatment of the ionospheric delay, and selection of target radio sources. We showed that the major factor causing discrepancies in the estimated geodetic parameters is the different scheduling approach of the datasets. We conclude that systematic errors in MOJAVE-5 dataset are low enough for these data to be used as an excellent testbed for further investigations on the radio source structure effects in geodesy and astrometry.

Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex.

Mutations in myosin-VIIa (MYO7A) cause Usher syndrome type 1, characterized by combined deafness and blindness. MYO7A is proposed to function as a motor that tensions the hair cell mechanotransduction (MET) complex, but conclusive evidence is lacking. Here we report that multiple MYO7A isoforms are expressed in the mouse cochlea. In mice with a specific deletion of the canonical isoform (Myo7a-ΔC mouse), MYO7A is severely diminished in inner hair cells (IHCs), while expression in outer hair cells is affected tonotopically. IHCs of Myo7a-ΔC mice undergo normal development, but exhibit reduced resting open probability and slowed onset of MET currents, consistent with MYO7A's proposed role in tensioning the tip link. Mature IHCs of Myo7a-ΔC mice degenerate over time, giving rise to progressive hearing loss. Taken together, our study reveals an unexpected isoform diversity of MYO7A expression in the cochlea and highlights MYO7A's essential role in tensioning the hair cell MET complex.