Thyroid dysfunction in non-small cell lung cancer patients treated with epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors: Results of a prospective cohort.

OBJECTIVES: Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) are the preferred treatment option for patients with advanced/metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations and ALK rearrangements respectively. TKIs can theoretically induce thyroid dysfunction via actions on many levels of the hypothalamic-pituitary-thyroid axis. However, there are no published studies on occurrence of thyroid dysfunction related to use of EGFR/ALK TKIs in lung cancer. The current study aimed to prospectively and comprehensively evaluate incidence of thyroid dysfunction in NSCLC patients treated with EGFR and ALK inhibitors. METHODS: This prospective observational study at a tertiary care referral hospital included histologically/cytologically proven advanced/metastatic NSCLC patients treated with EGFR and ALK inhibitors over a period of 15 months. Thyroid function tests (including anti-TPO antibody) were done at baseline and repeated every month for first three months and then every three monthly for 12 months. RESULTS: Six different drugs (EGFR and ALK inhibitors) were used for treatment of 50 NSCLC patients enrolled. Of these, four drugs caused thyroid dysfunction (EGFR inhibitors erlotinib, gefitinib and ALK inhibitors ceritinib, crizotinib). Thyroid dysfunction typically occurred at 1 month following start of TKI treatment. Prevalence of thyroid dysfunction was 8%. Distribution of subclinical (not requiring treatment) and overt thyroid dysfunction (requiring specific treatment) was 4% each. All patients were asymptomatic. Both patients with overt thyroid dysfunction had hypothyroidism while subclinical dysfunction was equally distributed between hypo- and hyper- thyroidism. All patients who developed thyroid dysfunction derived expected clinical benefit and none required TKI dose interruption or stoppage. CONCLUSIONS: NSCLC patients may need to be monitored for occurrence of thyroid dysfunction during treatment with EGFR and ALK TKIs.

Co-Occurrence of Familial Hemophagocytic Lymphohistiocytosis Type 2 and Chronic Active Epstein-Barr Virus in Adulthood.

We report, to the best of our best knowledge, the oldest individual to ever be diagnosed with Familial Hemophagocytic Lymphohistiocytosis (FHL) Type 2 from homozygous c.1349C>T (p.T450M) missense variants in the PRF1 gene. This rare case advanced in complexity with a simultaneous diagnosis of Chronic Active Epstein-Barr Virus (CAEBV) - a distinct clinical entity from acute EBV infections and a well-described trigger of Hemophagocytic Lymphohistiocytosis (HLH). This is, to the best of our knowledge, the only individual to ever be diagnosed with CAEBV in the setting of this specific variant and the oldest to be diagnosed with a coexisting perforin variant. This case provides understanding of EBV, human genetics, and lymphoproliferative disorders while adding a unique differential diagnosis to adults who present with fever of unknown origin and diffuse lymphadenopathy without evidence of malignancy. This report explores the diagnosis and treatment of both HLH and CAEBV, encouraging discussion regarding current clinical management and future research needs.

A case report of ruptured amoebic liver abscess causing cardiac tamponade and requiring pericardial window.

BACKGROUND: Amoebiasis is a prevalent infection in the tropics. Amoebic liver abscess is the most common extraintestinal manifestation. Cardiac tamponade is an uncommon complication of amoebic liver abscess that may need urgent pericardiocentesis. CASE SUMMARY: A 25-year-old man presented with abdominal pain and fever for 1 month. Abdominal ultrasound revealed a 4.7 × 4.7 cm abscess in the left lobe of the liver. Percutaneous pigtail drainage was performed to evacuate the abscess. After 2 days, the patient developed signs of cardiac tamponade and bilateral pleural effusion, requiring urgent pericardiocentesis and chest drain insertion. Persistent posterior collection of thick abscess in pericardium needed pericardial window for complete drainage. The patient recovered completely after pericardial window. There was no evidence of chronic constrictive pericarditis after 1 year of follow-up. DISCUSSION: A rare complication of the amoebic liver abscess was observed in this young adult who developed cardiac tamponade, requiring an urgent pericardiocentesis, and later requiring pericardial window. Management includes amoebicidal and luminicidal drugs for complete eradication of Entamoeba histolytica.

Electronic Structure and Room Temperature Ferromagnetism in Gd-doped Cerium Oxide Nanoparticles for Hydrogen Generation via Photocatalytic Water Splitting.

Enhanced visible light photocatalytic activity of Gd-doped CeO2 nanoparticles (NPs) is experimentally demonstrated, whereas there are very few reports on this mechanism with rare earth doping. All-pure and Gd-doped CeO2 NPs are synthesized using a coprecipitation method and characterized using X-ray diffraction (XRD), absorption spectroscopy, surface-enhanced Raman Spectroscopy (SERS), X-ray photoelectron spectroscopy (XPS), and superconducting quantum interference device (SQUID). The effect of Gd-doping on properties of CeO2 is discussed along with defects and oxygen vacancies generation. The XRD confirms the incorporation of Gd3+ at the Ce3+/Ce4+ site by keeping the crystal structure same. The average particle size from transmission electron microscopy (TEM) images is in the range of 5-7 nm. The XPS spectra of Ce 3d, O 1s, and Gd 4d exhibits the formation of oxygen vacancies to maintain the charge neutrality when Ce4+ changes to Ce3+. The gradual increase in hydrogen production is observed with increasing Gd concentration. The observed results are in good correlation with the characterization results and a mechanism of water splitting is proposed on the basis of analyses. The absorption spectra reveal optical band gap (2.5-2.7 eV) of samples, showing band gap narrowing leads to desired optical absorbance and photoactivity of NPs.