The influence of a traditional procedure of washing of smear Taleggio cheese on surface spreading of Listeria innocua was studied. This practice is carried out during ripening to remove molds, to select the surface microflora, and to control the ripening process. One cheese, both of 2 (i) and 4 (ii) weeks of ripening, was surface-inoculated with approximately 3 log CFU of L. innocua per entire cheese surface. The inoculated cheeses and others of the same age were weekly washed with brine solution. Listeria was spread both on the surface of the inoculated cheese and on the other cheeses, and it was also found in the brines and on the wooden boxes where the cheeses were ripened. The time of ripening when contamination occurs influenced the behavior of Listeria. At the moment of contamination, the smear surface microflora of (i) cheese was approximately 2 log CFU/g higher than of (ii) cheese. Listeria inoculated on 2-week-ripened cheese was able to colonize the entire surface of the cheese and to cross-contaminate the other cheeses. On the contrary, Listeria inoculated on a 4-week-ripened cheese was partially spread on the surface of the originally inoculated cheese, and the transfer of contamination by the washing procedure was restrained. Because a random distribution of Listeria on cheese surface was observed, the importance of the mode of sampling was discussed. Because of the lack of critical control points during ripening of Taleggio cheese, the Listeria hazard needs to be controlled by taking appropriate control measures to break off the contamination cycle (cheese --> brine --> wooden boxes --> cheese).
Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) refer to heterogenous rare neoplasms constituted of at least a neuroendocrine population—either well-differentiated, or more frequently poorly differentiated—and a non-neuroendocrine population, both accounting for at least 30% of the whole tumor mass. Several studies recently focused on the key genetic and epigenetic changes underlying MiNENs to better understand how they develop, and explore biological similarities among the two components and their pure counterparts. However, their molecular landscape still remains poorly understood. NGS may represent a useful tool to study this orphan disease by detecting the main genetic alterations and possible therapeutic targets. NGS analysis on tissue and/or blood samples through the Foundation One (F1) platform was performed on consecutive samples collected from four patients diagnosed with MiNENs of the gastroenteric tract. Several genetic alterations were shared among samples from the same patients, thus suggesting a common origin between them, although morphology sometimes changed at histopathological evaluation. Common molecular alterations among samples from different patients that had not been previously described to our knowledge were also detected. Finally, it is of the utmost importance to clarify if the maintenance of the 30% cut-off is still essential in defining MiNENs and really manages to include all of the mixed neoplasms.
Background The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxicity in patients with refractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in a real-world setting is limited. Objective The aim of our work was to provide further evidence on the activity and safety of this combination in a real-world series of Western mCRC patients refractory or intolerant to previous therapies. Patient and Methods We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with trifluridine-tipiracil and bevacizumab. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib, and cetuximab or panitumumab (only RAS wild-type) was allowed, as was previous participation in clinical trials. Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety data were retrospectively collected and analyzed. Results We recorded 31 patients treated between 1 December 2017 and 30 June 2022. Median age was 69 years (range 38–82 years), 39% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, tumor location was left-sided in 77% of cases, 54% had synchronous presentation, 35% were RAS mutant, 3% were BRAF mutant, and 71% underwent primary tumor resection; 64% of patients had liver metastases, 55% had lung metastases, and 23% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range 0–5), and 84% of patients received at least one previous anti-angiogenic agent. The ORR and DCR were 3% and 71%, respectively. With a median follow-up of 8 months (range 2–39), median PFS was 6 months (95% confidence interval [CI] 3.1–8.9 months) and median OS was 14 months (95% CI 10.1–17.8 months). Adverse events of any grade were reported in 58% of patients. The most common grade 3–4 toxicities were neutropenia (19%) and anemia (6%); 35% of patients required either dose delays or dose reductions due to toxicity. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered either on first or subsequent cycles of treatment in 35% of patients. No treatment-related deaths occurred. Sixty percent of the patients who discontinued treatment eventually received one or more lines of subsequent therapy. Conclusions Our series provides further evidence on the activity and safety of the combination of trifluridine-tipiracil and bevacizumab in a real-world series of Western refractory mCRC patients.
Introduction: The mesenchymal-epithelial transition factor (c-MET) receptor is overexpressed in about 14–54% of invasive breast cancers, but its prognostic value in clinical practice is still unclear. Methods: In order to investigate the relationship between c-MET expression levels and prognosis, we retrospectively reviewed the clinical features and outcomes of 105 women with estrogen receptor positive HER2 negative (ER+/HER2-) resected breast cancer. We used the Kaplan Meier method to estimate Disease Free Survival (DFS) and Breast Cancer Specific Survival (BCSS) in the subgroups of patients with high (≥50%) and low (<50%) c-MET expression. Univariate and multivariate Cox proportional regression models were performed to assess the prognostic impact of clinicopathological parameters for DFS an BCSS. Results: High c-MET values significantly correlated with tumor size, high Ki67 and low (<20%) progesterone receptor expression. At a median follow up of 60 months, patients with high c-MET tumor had significantly worse (p = 0.00026) and BCSS (p = 0.0013). Univariate analysis showed a significant association between large tumor size, elevated Ki67, c-MET values and increased risk of recurrence or death. The multivariate COX regression model showed that tumor size and high c-MET expression were independent predictors of DFS (p = 0.019 and p = 0.022). Moreover, large tumor size was associated with significantly higher risk of cancer related death at multivariate analysis (p = 0.017), while a trend towards a poorer survival was registered in the high c-MET levels cohort (p = 0.084). Conclusions: In our series, high c-MET expression correlated with poor survival outcomes. Further studies are warranted to validate the clinical relevance and applicability of c-MET as a prognostic factor in ER+/HER2- early BC.
Despite extensive investigations, the choice of graft material for reconstructive duraplasty after foramen magnum decompression for Chiari type I malformation (CMI) is still a topic of discussion. The authors performed a systematic review and meta-analysis of the literature examining the post-operative complications in adult patients with CMI after foramen magnum decompression and duraplasty (FMDD) using different graft materials. Our systematic review included 23 studies with a total of 1563 patients with CMI who underwent FMDD with different dural substitutes. The most common complications were pseudomeningocele (2.7%, 95% CI 1.5–3.9%, p < 0.01, I2 = 69%) and CSF leak (2%, 95% CI 1–2.9%, p < 0,01, I2 = 43%). The revision surgery rate was 3% (95% CI 1.8–4.2%, p < 0.01, I2 = 54%). A lower rate of pseudomeningocele was observed with autologous duraplasty when compared with synthetic duraplasty (0.7% [95% CI 0–1.3%] vs. 5.3% [95% CI 2.1–8.4%] p < 0.01). The rate of CSF leak and revision surgery was lower after autologous duraplasty than after non-autologous dural graft (1.8% [95% CI 0.5–3.1%] vs. 5.3% [95% CI 1.6–9%], p < 0.01 and 0.8% [95% CI 0.1–1.6%] vs. 4.9% [95% CI 2.6–7.2%] p < 0.01, respectively). Autologous duraplasty is associated with a lower rate of post-operative pseudomeningocele and reoperation. This information should be considered when planning duraplasty after foramen magnum decompression in patients with CMI.
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