BRAF mutations in thyroid tumors from an ethnically diverse group

BACKGROUND: The molecular etiology of thyroid carcinoma (TC) and other thyroid diseases which may present malignant precursor lesions is not fully explored yet. The purpose of this study was to estimate frequency, type and clinicopathological value of BRAF exon 15 mutations in different types of cancerous and non-cancerous thyroid lesions originating in an ethnically diverse population. METHODS: BRAF exon 15 was sequenced in 381 cases of thyroid lesions including Hashimoto´s thyroiditis, nodular goiters, hyperplastic nodules, follicular adenomas (FA), papillary TC (PTC), follicular variant PTC (FVPTC), microcarcinomas of PTC (micro PTC; tumor size ≤ 1 cm), follicular TC (FTC), and non-well differentiated TC (non-WDTC). RESULTS: We identified BRAF mutations in one of 69 FA, 72 of 115 (63%) PTC, seven of 42 (17%) FVPTC, 10 of 56 (18%) micro PTC, one of 17 (6%) FTC, and one of eight (13%) non-WDTC. Most of the cases showed the common V600E mutation. One case each of PTC, FVPTC, and FTC harbored a K601E mutation. A novel BRAF mutation was identified in a FA leading to deletion of threonine at codon 599 (p.T599del). A rare 3-base pair insertion was detected in a stage III PTC resulting in duplication of threonine at codon 599 (p.T599dup). Patients with PTC harboring no BRAF mutation (BRAF(wt)) were on average younger than those with a BRAF mutation (BRAF(mut)) in the PTC (36.6 years vs. 43.8 years). Older age (≥ 45 years) in patients with PTC was significantly associated with tumor size ≥ 4 cm (P = 0.018), vessel invasion (P = 0.004), and distant metastasis (P = 0.001). Lymph node (LN) involvement in PTC significantly correlated with tumor size (P = 0.044), and vessel invasion (P = 0.013). Of notice, taken the whole TC group, family history of thyroid disease positively correlated with capsular invasion (P = 0.025). CONCLUSIONS: Older age is manifold associated with unfavorable tumor markers in our series. The K601E identified in a PTC, FVPTC, and FTC seems to be more distributed among different histological types of TC than previously thought. The T599del is a yet undescribed mutation and the rare T599dup has not been reported as a mutation in PTC so far

Overview on Blood Transfusion-Transmitted Diseases

As it is important for the Blood transfusion to be extremely safe, some measures have to be taken long safeguarded the blood supply from the major transfusion transmissible diseases (TTIs).  The risk of transfusion-transmitted infection (TTI) rises with the number of donors exposed, and the effects of TTI are frequently more severe in immune compromised people. TTIs (hepatitis B virus [HBV], HIV, and hepatitis C virus [HCV]) are examples of typical transfusion-transmitted infectious agents. As a result of the gradual application of nucleic acid-amplification technology (NAT) screening for HIV, HCV, and HBV, the residual risk of infected window-period donations has been minimized. Nonetheless, infections emerge far more frequently than is commonly acknowledged, needing ongoing surveillance and individual assessment of transfusion-associated risk. Although there is a constant need to monitor present dangers owing to established TTI, the ongoing issues in blood safety are mostly related to surveillance for developing agents, as well as the creation of quick reaction systems when such agents are detected

Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: A multicenter cohort study

Background: Inhaled nitric oxide (iNO) is used as rescue therapy in patients with refractory hypoxemia due to severe COVID-19 acute respiratory distress syndrome (ARDS) despite the recommendation against the use of this treatment. To date, the effect of iNO on the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill COVID-19 patients with moderate-to-severe ARDS. Methods: This multicenter, retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. Eligible patients with moderate-to-severe ARDS were subsequently categorized into two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary endpoint was the improvement in oxygenation parameters 24 h after iNO use. Other outcomes were considered secondary. Propensity score matching (1:2) was used based on the predefined criteria. Results: A total of 1598 patients were screened, and 815 were included based on the eligibility criteria. Among them, 210 patients were matched based on predefined criteria. Oxygenation parameters (PaO2, FiO2 requirement, P/F ratio, oxygenation index) were significantly improved 24 h after iNO administration within a median of six days of ICU admission. However, the risk of 30-day and in-hospital mortality were found to be similar between the two groups (HR: 1.18; 95% CI: 0.77, 1.82; p = 0.45 and HR: 1.40; 95% CI: 0.94, 2.11; p= 0.10, respectively). On the other hand, ventilator-free days (VFDs) were significantly fewer, and ICU and hospital LOS were significantly longer in the iNO group. In addition, patients who received iNO had higher odds of acute kidney injury (AKI) (OR (95% CI): 2.35 (1.30, 4.26), p value = 0.005) and hospital/ventilator-acquired pneumonia (OR (95% CI): 3.2 (1.76, 5.83), p value = 0.001). Conclusion: In critically ill COVID-19 patients with moderate-to-severe ARDS, iNO rescue therapy is associated with improved oxygenation parameters but no mortality benefits. Moreover, iNO use is associated with higher odds of AKI, pneumonia, longer LOS, and fewer VFDs

Detection of human papillomavirus in primary site of oraloropharyngeal cancer and in cervical lymph nodes : correlation with clinico-pathological parameters and prognostic significance

Objectives. (1) To Determine the presence of HPV 6, 11, 16, 18, 31, 33, 35, 52b, 58 subtypes in resected oral/oropharyngeal SCCA cancer and associated lymph nodes. (2) To Determine if a relationship exists between koilocytosis, tumor grade, stage, or prognosis.Methods. Retrospective analysis and pathology review of patients with SCCA of the oral cavity at McGill in the last 5 years was performed. Age at diagnosis, risk factors, tumor stage, grade, koilocytosis, treatment, outcome, and presence of HPV by PCR were analysed.Results. 199 patients included were included in the analyses; 5 years mortality was 18.5%. 146 cases reviewed by pathology revealed 67% koilocytosis. One sample was positive for HPV subtype 35 as determined by PCR. Radiotherapy (p<0,5) and complications from radiotherapy (p<0.5) significantly affected survival.Conclusions. Many oral SCCA's do not contain HPV 6, 11, 16, 18, 31, 33, 35, 52b, 58 subtypes. Given the high prevelence of koilocytosis, probe for other subtypes should be utilized. Mortality rates and survival are similar to those published in the literature. The presence of koilocytosis, it is not related grade, stage or prognosis. Only radiotherapy and its complications affect survival

Cerebellum as Initial Site of Distant Metastasis from Papillary Carcinoma of Thyroid: Review of Three Cases

Background. The cerebellum as initial site of distant metastasis from differentiated thyroid carcinoma (DTC) including papillary (PTC) and follicular thyroid carcinoma (FTC) is rare manifestation. Case Presentations. Herein, we present three cases of cerebellar metastasis (CBM) of PTC. Mean age of patients was 67 years (range: 64–72), and mean duration between initial diagnosis and CBM was 49.6 months (range: 37–61). Frequent location was left cerebellar hemisphere and was associated with hydrocephalus. All patients underwent suboccipital craniectomy, and in two patients postoperative intensity modulated radiation therapy (IMRT) was given to deliver 5000 cGy in 25 fractions to residual lesions. Patient without postoperative IMRT had cerebellar recurrence along with lung and bone metastasis after 38 months. However, two patients were found alive and free of disease at the time of last follow-up. Conclusion. CBM from PTC is a rare clinical entity and is often associated with hydrocephalus. Histopathological diagnosis is important to initiate effective treatment, which relies on multidisciplinary approach to prolong the disease-free and overall survival rates

Single nucleotide polymorphisms in CXCR1 gene and its association with hepatitis B infected patients in Saudi Arabia

Background/Aim. This study aims to investigate whether the SNPs of CXCR1 gene, could predict the likelihood of viral persistence and/or disease progression.Material and methods. We investigated the association of two different SNPs (rs2234671, and rs142978743) in 598 normal healthy controls and 662 HBV patients from a Saudi ethnic population. The HBV patients were categorized into inactive carriers (n = 428), active carriers (n = 162), cirrhosis (n = 54) and Cirrhosis-HCC (n = 18) sub-groups. Genetic variants in CXCR1 were determined by polymerase chain reaction (PCR)-based DNA direct sequencing.Results. The frequency of the risk allele ‘C’ for the SNP, rs2234671 was found to be insignificant when the patient group was compared to the uninfected control group, however, a significant distribution of the allele ‘C’ of rs2234671 was observed among active HBV carriers + cirrhosis + cirrhosis - HCC vs. inactive HBV carriers with an OR = 1.631 (95% C.I. 1.016-2.616) and p = 0.032. However, no significant association was observed for rs142978743 when the distribution of risk allele was analyzed among the different patient groups (i.e. inactive carriers, active carriers, cirrhosis and HCC). Furthermore, the most common haplotype, Haplo-1 (AG), was found to have an insignificant frequency distribution between HBV cases and controls, while the same haplotype was found to be significantly distributed when active carriers + cirrhosis + cirrhosis - HCC patients were compared to inactive HBV carriers with a frequency of 0.938 and p = 0.0315. Haplo-2 (AC) was also found to be significantly associated with a frequency of 0.058 and p = 0.0163.Conclusion. The CXCR1 polymorphism, rs2234671 was found to be associated with chronic HBV infection and may play a role in disease activity