Osteochondrodysplasia and the c.1024G>T variant of TRPV4 gene in Scottish Fold cats: genetic and radiographic evaluation.

OBJECTIVES: The objectives of this study were to investigate the c.1024G>T SNP in the TRPV4 gene in Scottish Straight and Fold cats, and to evaluate the pattern of skeletal phenotype and the evolution of radiological signs of Scottish Fold osteochondrodysplasia (SFOCD) over time in heterozygous subjects. METHODS: DNA was obtained from blood samples of 17 cats (Scottish Fold: n = 12; Scottish Straight: n = 5) and subsequently genotyped by sequencing in a 249 bp region of the TRPV4 gene (exon 6), including the known c.1024G>T causative mutation for osteochondrodysplasia. Orthopaedic and radiographic analyses were performed on animals carrying the mutant allele. RESULTS: Genotyping by sequencing confirmed that all and only the Scottish Fold cats carried the mutant allele in a heterozygous asset. Furthermore, two other exon variants, already described in the literature as silent variants, were found in some of the sampled cats. Comparative orthogonal radiographic views of the shoulder, elbow, carpus, hip, stifle and tarsus were obtained. A mediolateral projection of the thoracic and lumbar column was also performed. Three out of four cats were clinically and radiographically examined again 1.5 years later. CONCLUSIONS AND RELEVANCE: Although the presence of the mutant allele in all the tested Scottish Fold cats was confirmed, only 1/12 showed clinical signs of SFOCD. Furthermore, no cats in the 1.5-year follow-up showed skeletal changes. Although significant, the c.1024G>T mutation in the TRPV4 gene, supposedly, is not the only cause or risk of developing SFOCD.

Pleural empyema associated with alveolar-pleural fistulas in severe acute respiratory syndrome coronavirus 2.

Surgery in COVID-19 disease complicated by APF represents the last life-saving treatment option. The choice of the therapeutic period to indicate this approach is fundamental. In fact, the clinical stability of patient is necessary in order to allow single-lung ventilation and to minimize postoperative sequelae.

RET Rearrangement as a Predictor of Unresponsiveness to Immunotherapy in Non-Small Cell Lung Cancer: Report of Two Cases with Review of the Literature.

Patients with epidermal growth factor receptor and anaplastic lymphoma kinase positive non-small cell lung cancer (NSCLC) generally respond poorly to treatment with immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1) given with or without anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) drugs. However, the efficacy of immunotherapy in patients with oncogene-addicted NSCLC harboring minor drivers, such as fusions in the rearranged during transfection (RET) gene, is still unclear. Here we describe two patients with RET-positive advanced NSCLC with PD-L1 expression ≥ 50% who developed progressive disease during first-line treatment with the anti-PD-1 agent pembrolizumab. In particular, while patient 2 was immediately switched to treatment with a selective RET inhibitor within the setting of a clinical trial, patient 1 responded to cytotoxic chemotherapy delivered at the time of progression while on pembrolizumab. These cases of NSCLC are discussed in the context of current literature, which seems to support our observation that patients with RET-positive NSCLC are unlikely to benefit from immunotherapy. Therefore, we suggest that for RET-positive patients with PD-L1 ≥ 50%, consideration should be given to upfront treatment approaches other than single-agent immunotherapy, namely selective RET inhibitors (if available) or regimens including cytotoxic chemotherapy.

Is There a Role for Multiple Lines of Anti-HER2 Therapies Administered Beyond Progression in HER2-Mutated Non-Small Cell Lung Cancer? A Case Report and Literature Review.

Oncogene-addicted non-small cell lung cancer (NSCLC) comprises a number of distinct disease subtypes, each of which is characterised by druggable genetic alterations. Among them, the receptor tyrosine kinase protein human epidermal receptor 2 (HER2) is occasionally found deregulated via gene mutation and/or amplification and/or protein overexpression. HER2 mutation, in particular, is a relatively rare condition which occurs in 1-4% of NSCLC patients, especially in those with adenocarcinoma histology and a never/light smoking history. However, the clinical relevance of a HER2 mutation in NSCLC relies on the fact that this genetic alteration has been associated with sensitivity to anti-HER2 therapies such as the monoclonal antibody trastuzumab or the pan-HER-tyrosine kinase inhibitor poziotinib. Here we describe the case of a NSCLC patient with an activating exon 20 G776VinsC mutation in the HER2 gene who responded well to multiple lines of trastuzumab-based therapies administered beyond progression and poziotinib given sequentially. In this specific case, the discovery of a druggable genetic alteration such as a mutation in the HER2 gene allowed for long-term control of the disease through the use of highly effective anti-HER2 therapies.