Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

Background:

This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours.

Methods:

In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25).

Results:

The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed.

Conclusions:

MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours.     

Medial calcar of proximal humeral fracture as landmark in restoration of humeral length in case of hemiarthroplasty

Purpose

Several methods to restore the appropriate length of the humerus in the case of proximal humeral fractures treated by hemiarthroplasty have been previously published. Our study evaluates the possibility of using the medial calcar of humerus for humeral length reconstruction not based on preoperative planning.

Methods

Preparations of 320 dry humeral bones were used for the purpose of the study. Points of interest were marked on each bone: the most proximal point of the humeral head, the crest of greater tuberosity, diameters of the head, the anatomical and surgical necks. Proximal parts of bones were then scanned from two angles with a digital camera and all measurements were performed on calibrated photographs. We compared accuracy in humeral length reconstruction using insertion of the pectoralis major and the area of medial calcar where usually a fracture develops.

Results

The distance between the top part of the humeral head and the insertion of pectoralis major was 54.1 ± 6.0 mm. The distance between the lateral margin of the anatomical neck and the medial calcar was 51.4 ± 4.3 mm. We compared these data with diameters of the humeral head.

Conclusions

The site of the fracture can be used for the reconstruction of the humeral length with greater accuracy than area of the pectoralis major insertion. We suggest that to obtain the final distance between the lateral margin of the artificial head and medial calcar of the fracture 2–3 mm should be added to the diameter of the head.     

Evaluation of Non-Invasive Gargle Lavage Sampling for the Detection of SARS-CoV-2 Using rRT-PCR or Antigen Assay

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable disruption worldwide. For efficient SARS-CoV-2 detection, new methods of rapid, non-invasive sampling are needed. This study aimed to investigate the stability of SARS-CoV-2 in a novel medium for gargle-lavage (GL) self-sampling and to compare the performance of SARS-CoV-2 detection in paired self-collected GL and clinician-obtained nasopharyngeal swab (NPS) samples. The stability study for SARS-CoV-2 preservation in a novel medium was performed over 14 days (4 °C, 24–27 °C, and 37 °C). In total, 494 paired GL and NPS samples were obtained at the University Hospital in Olomouc in April 2021. SARS-CoV-2 detection in paired samples was performed with a SARS-CoV-2 Nucleic Acid Detection Kit (Zybio, Chongqing Municipality, Chongqing, China), an Elecsys^® SARS-CoV-2 Antigen assay (Roche Diagnostics, Mannheim, Germany), and a SARS-CoV-2 Antigen ELISA (EUROIMMUN, Lübeck, Germany). The stability study demonstrated excellent SARS-CoV-2 preservation in the novel medium for 14 days. SARS-CoV-2 was detected in 55.7% of NPS samples and 55.7% of GL samples using rRT-PCR, with an overall agreement of 91.9%. The positive percent agreement (PPA) of the rRT-PCR in the GL samples was 92.7%, and the negative percent agreement (NPA) was 90.9%, compared with the NPS samples. The PPA of the rRT-PCR in the NPS and GL samples was 93.2% when all positive tests were used as the reference standard. Both antigen detection assays showed poor sensitivity compared to rRT-PCR (33.2% and 36.0%). rRT-PCR SARS-CoV-2 detection in self-collected GL samples had a similar PPA and NPA to that of NPSs. GL self-sampling offers a suitable and more comfortable alternative for SARS-CoV-2 detection.     

Vector edge operators for cDNA microarray spot localization.

This paper introduces a vector-based framework for edge detection and spot localization in cDNA microarray data. Since cDNA microarray images can be viewed as vector fields, both their spectral and spatial characteristics should be used to determine edges, discontinuities and structural elements. Building upon the powerful nature of nonlinear operators, the proposed vector edge operators can effectively localize microarray spots outperforming the commonly used scalar edge detectors. Moreover, due to the utilization of the principle of robust statistics, vector edge detectors are relatively immune to the noise present in microarray images. Simulation studies reported in this paper indicate that the proposed framework yields excellent performance and it can be readily incorporated in the cDNA microarray processing pipeline.     

Nosocomial rotaviral gastroenteritis in paediatric departments

The authors present a retrospective analysis of community-acquired and hospital-acquired rotaviral gastroenteritis (RVGE) cases in a 5 years period 2001-2005 and prospective analysis in 2006 in the referral area in a population of 7,000 children under 5 years of age. Out of 228 patients with RVGE, nosocomial RVGE accounted for 27.75% of the cases. Children with nosocomial RVGE were in average 9.8 months younger compared to patients with community-acquired RVGE. Nosocomial cases were also characterised by the need for longer stay in intensive care, overall longer hospital stay, longer duration of the illness and by lower age of the patients. The wider implementation of vaccination in the youngest members of the population would be likely to have a significant influence on the occurrence of not only community-acquired but also hospital-acquired RVGE.     

Seminal plasma homocysteine, folate and cobalamin in men with obstructive and non-obstructive azoospermia

Purpose

The aim of this study was to analyze homocysteine, folate and cobalamin in men with normozoospermia, obstructive and non-obstructive azoospermia.

Methods

Analysis of plasma and seminal plasma homocysteine, folate and cobalamin in 72 azoospermic and 62 normozoospermic men. Evaluation of the azoospermic patient included testicular biopsy, endocrine, urological and ultrasound examination.

Results

Homocysteine (1.2 μmol/l) and cobalamin (322.05 pmol/l) concentrations (median values) in seminal plasma were significantly lower (p?<?0.001) in men with azoospermia than in men with normozoospermia (2.5 μmol/l and 579.0 pmol/l). Folate and cobalamin concentrations were significantly higher in obstructive than in non-obstructive azoospermia. Significant correlations were determined between testis volume and seminal plasma homocysteine in azoospermic men.

Conclusion

Lower concentrations of homocysteine and cobalamin (but not folate) were found in azoospermic seminal plasma than normozoospermic. Folate and cobalamin were higher in seminal plasma from obstructive azoospermia than in non-obstructive azoospermia patients.