How the COVID-19 Pandemic Impacted Oncological Molecular Diagnosis: A Picture from a National Reference Center for Molecular Pathology.

INTRODUCTION: The Portuguese healthcare system had to adapt at short notice to the COVID-19 pandemic. We implemented workflow changes to our molecular pathology laboratory, a national reference center, to maximize safety and productivity. We assess the impact this situation had on our caseload and what conclusions can be drawn about the wider impact of the pandemic in oncological therapy in Portugal. Material and Methods. We reviewed our database for all oncological molecular tests requested between March and April of 2019 and 2020. For each case, we recorded age, sex, region of the country, requesting institution, sample type, testing method, and turnaround time (TAT). A comparison between years was made. RESULTS: The total number of tests decreased from 421 in 2019 to 319 in 2020 (p = 0.0027). The greatest reduction was in clinical trial-related cases. Routine cases were similar between years (267 vs. 256). TAT was higher in 2019 (mean 15 days vs. 12.3 days; p = 0.0003). Medium- to large-sized public hospitals in the north of the country were mostly responsible for the reduction in cases (p = 0.0153). CONCLUSIONS: Case reduction was observed at hospitals that have mostly been involved in the treatment of COVID-19 and in the north of the country, the region worst-hit by the pandemic. Similar to other studies, our TAT decreased, even with a similar number of routine cases. Thus, we conclude that it is possible to successfully adapt the workflow of a molecular pathology laboratory to new safety standards without losing efficiency.

[Impact assessment of the implementation of an integrated care model for thyroid disease at the University Hospital "Federico II" of Naples (Campania Region, Southern Italy): an interrupted time series analysis]. / Valutazione dell'impatto dell'implementazione di un percorso multidisciplinare di presa in carico della patologia nodulare tiroidea presso l'Azienda ospedaliera universitaria "Federico II" di Napoli: studio quasi sperimentale a serie temporale interrotta semplice.

OBJECTIVES: to evaluate the implementation of an integrated care model for thyroid disease on thyroid surgery at the University Hospital "Federico II" of Naples (Campania Region, Southern Italy). DESIGN: quasi-experimental design employing an interrupted time series analysis. SETTING AND PARTICIPANTS: all subjects who were admitted to the University Hospital "Federico II" for thyroid surgery between January 2008 and December 2018. The integrated care model for thyroid disease was implemented starting from January 2016. MAIN OUTCOME MEASURES: rate of partial thyroidectomies over all thyroidectomies; rate of diagnosed thyroid cancers over all diagnosed thyroid tumours; length of stay (LOS). Differences pre- and post-interventions were assessed employing Poisson (for count outcomes) and linear (for continuous outcomes) regression models. Models were adjusted for age, gender, tumour diagnosis (none, benign, malignant), Charlson index, and discharge month. RESULTS: data on 4,233 thyroidectomies were included. There was no difference between pre- and post-intervention trends for the rate of partial thyroidectomies over all thyroidectomies (pre-intervention: IRR 1.00; 95%CI 0.99;1.00 - post-intervention: IRR 1.00; 95%CI 0.98;1.02) and for the rate of diagnosed thyroid cancers over all thyroid tumours (pre-intervention IRR 0.99; 95%CI 0.99;1.00 - post-intervention IRR 1.00; 95%CI 0.99;1.01). On the contrary, the LOS reduced from 4.5 (±4.3) days in 2008 to 3.2 (±3.2) days in 2018. The multivariate analysis confirmed this reduction, estimated to be 1.1 days on average in the pre-intervention eight-year period (pre-intervention coefficient -0.01; 95%CI -0.02;-0.01), followed by an even greater reduction in the post-intervention three-year period which was estimated to be 1.1 day (post-intervention: coefficient -0.03; 95%CI -0.05;-0.01). CONCLUSIONS: the implementation of an integrated care model for thyroid disease contributed to reduce the LOS for thyroidectomies, improving the efficiency in the management of thyroid disease. However, this intervention had no impact in reducing the rate of total thyroidectomies.

Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury.

BACKGROUND: The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial. METHODS AND RESULTS: First, we investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg within 24 hours before contrast media [CM] exposure; n=202) or (2) the control group (n=208). All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution. Second, we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase >10% of serum cystatin C concentration within 24 hours after CM exposure) occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208 patients in the control group (17.8%) (P=0.005; odds ratio=0.22; 95% confidence interval, 0.07-0.69). CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease (estimated glomerular filtration rate, 31-60 mL/min per 1.73 m(2)). In the in vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and (2) restored the survival signals (mediated by Akt and ERK pathways). CONCLUSIONS: A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI. This beneficial effect is observed only in patients at low to medium risk.

Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study.

BACKGROUND: In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate. METHODS: 544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology. FINDINGS: 31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method. INTERPRETATION: Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate.

BRAF is a therapeutic target in aggressive thyroid carcinoma.

PURPOSE: Oncogenic conversion of BRAF occurs in approximately 44% of papillary thyroid carcinomas and 24% of anaplastic thyroid carcinomas. In papillary thyroid carcinomas, this mutation is associated with an unfavorable clinicopathologic outcome. Our aim was to exploit BRAF as a potential therapeutic target for thyroid carcinoma. EXPERIMENTAL DESIGN: We used RNA interference to evaluate the effect of BRAF knockdown in the human anaplastic thyroid carcinoma cell lines FRO and ARO carrying the BRAF V600E (V600EBRAF) mutation. We also exploited the effect of BAY 43-9006 [N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoyl pyridin-4-yl)oxyphenyl)urea], a multikinase inhibitor able to inhibit RAF family kinases in a panel of six (V600E)BRAF-positive thyroid carcinoma cell lines and in nude mice bearing ARO cell xenografts. Statistical tests were two sided. RESULTS: Knockdown of BRAF by small inhibitory duplex RNA, but not control small inhibitory duplex RNA, inhibited the mitogen-activated protein kinase signaling cascade and the growth of ARO and FRO cells (P < 0.0001). These effects were mimicked by thyroid carcinoma cell treatment with BAY 43-9006 (IC50 = 0.5-1 micromol/L; P < 0.0001), whereas the compound had negligible effects in normal thyrocytes. ARO cell tumor xenografts were significantly (P < 0.0001) smaller in nude mice treated with BAY 43-9006 than in control mice. This inhibition was associated with suppression of phospho-mitogen-activated protein kinase levels. CONCLUSIONS: BRAF provides signals crucial for proliferation of thyroid carcinoma cells spontaneously harboring the (V600E)BRAF mutation and, therefore, BRAF suppression might have therapeutic potential in (V600E)BRAF-positive thyroid cancer.