Anaplastic thyroid carcinoma: diagnostic challenges,histopathologic features and ancillary testing

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy with high mortality rate. This malignancy arises in thyroid follicular cells either denovo or with an associated differentiated thyroid carcinoma component. Clinically, it usually presents as a rapidly enlarging mass, pain and locally compressive symptoms. Histopathologic variability and heterogeneity often pose diagnostic challenges, especially in scant and paucicellular specimens. This article describes the clinical, histopathologic and molecular features of ATC and also addresses the associated diagnostic limitations and challenges.     

Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

What to expect when you're expecting a hepatopancreatobiliary surgeon: self-reported experiences of HPB surgeons from different training pathways

BackgroundHepatopancreatobiliary (HPB) surgery fellowship training has multiple paths. Prospective trainees and employers must understand the differences between training pathways. This study examines self-reported fellowship experiences and current scope of practice across three pathways.MethodsAn online survey was disseminated to 654 surgeons. These included active Americas Hepato-Pancreato-Biliary Association (AHPBA) members and recent graduates of HPB, transplant–HPB and HPB–heavy surgical oncology fellowships.ResultsA total of 416 (64%) surgeons responded. Most respondents were male (89%) and most were practising in an academic setting (83%). 290 (70%) respondents underwent formal fellowship training. Although fellowship experiences varied, current practice was largely similar. Minimally invasive surgery (MIS) and ultrasound were the most commonly identified areas of training deficiencies and were, respectively, cited as such by 47% and 34% of HPB-, 49% and 50% of transplant-, and 52% and 25% of surgical oncology-trained respondents. Non-HPB cases performed in current practice included gastrointestinal (GI) and general surgery cases (56% and 49%, respectively) for HPB-trained respondents, transplant and general surgery cases (87% and 21%, respectively) for transplant-trained respondents, and GI surgery and non-HPB surgical oncology cases (70% and 28%, respectively) for surgical oncology-trained respondents.ConclusionsFellowship training in HPB surgery varies by training pathway. Training in MIS and ultrasound is deficient in each pathway. The ultimate scope of non-transplant HPB practice appears similar across training pathways. Thus, training pathway choice is best guided by the training experience desired and non-HPB components of anticipated practice.     

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.