Tracheal Stenting has Minimal Impact on Survival in Anaplastic Thyroid Carcinoma

Background

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer and it has an extremely poor prognosis. Rapid airway compromise is the main cause of death in patients with ATC.

Methods

The present study is based on a retrospective review of clinical data of patients with ATC treated over the last decade in a tertiary referral center.

Results

Between January 1998 and December 2010, 31 patients (13 males: 18 females) with a mean age of 74 years (range: 54–90 years) had a diagnosis of ATC made on fine-needle aspiration (n = 29) or biopsy (n = 2). Eight patients underwent total thyroidectomy and lymph node dissection, and five patients had attempted surgery but the procedure was abandoned because of inoperability. Airway compromise was clinically apparent in 11 patients. Five patients had tracheal stents inserted, with a median survival of 2 months (range: 1–36 months). In the whole cohort, 29 patients died of the disease, with a mean survival of 7 months (range: 1–36 months).

Conclusions

Survival of patients with undifferentiated thyroid cancer is severely compromised by airway obstruction. Palliation with tracheal stenting can rescue catastrophic airway obstruction but offers minimal survival benefit.     

Odanacatib Restores Trabecular Bone of Skeletally Mature Female Rabbits With Osteopenia but Induces Brittleness of Cortical Bone: A Comparative Study of the Investigational Drug With PTH,Estrogen, and Alendronate

Cathepsin K (CK), a lysosomal cysteine protease, is highly expressed in mature osteoclasts and degrades type 1 collagen. Odanacatib (ODN) is a selective and reversible CK inhibitor that inhibits bone loss in preclinical and clinical studies. Although an antiresorptive, ODN does not suppress bone formation, which led us to hypothesize that ODN may display restorative effect on the osteopenic bones. In a curative study, skeletally mature New Zealand rabbits were ovarectomized (OVX) and after induction of bone loss were given a steady‐state exposure of ODN (9 mM/d) for 14 weeks. Sham‐operated and OVX rabbits treated with alendronate (ALD), 17b‐estradiol (E2), or parathyroid hormone (PTH) served as various controls. Efficacy was evaluated by assessing bone mineral density (BMD), bone microarchitecture (using micro‐computed tomography), fluorescent labeling of bone, and biomechanical strength. Skeletal Ca/P ratio was measured by scanning electron microscopy (SEM) with X‐ray microanalysis, crystallinity by X‐ray diffraction, and bone mineral density distribution (tissue mineralization) by backscattered SEM. Between the sham and ODN‐treated osteopenic groups, lumbar and femur metaphyseal BMD, Ca/P ratio, trabecular microstructure and geometric indices, vertebral compressive strength, trabecular lining cells, cortical parameters (femoral area and thickness and periosteal deposition), and serum P1NP were largely comparable. Skeletal improvements in ALD‐treated or E2‐treated groups fell significantly short of the sham/ODN/PTH group. However, the ODN group displayed reduced ductility and enhanced brittleness of central femur, which might have been contributed by higher crytallinity and tissue mineralization. Rabbit bone marrow stromal cells expressed CK and when treated with ODN displayed increased formation of mineralized nodules and decreased apoptosis in serum‐deficient medium compared with control. In vivo, ODN did not suppress remodeling but inhibited osteoclast activity more than ALD. Taken together, we show that ODN reverses BMD, skeletal architecture, and compressive strength in osteopenic rabbits; however, it increases crystallinity and tissue mineralization, thus leading to increased cortical bone brittleness. © 2015 American Society for Bone and Mineral Research.     

Isolation and structure elucidation of halymeniaol,a new antimalarial sterol derivative from the red alga Halymenia floresii

A new mono-hydroxy acetylated sterol derivative: 12β-hydroxy-3β, 15α, 16β-triacetoxy-cholest-5-en-7-one (halymeniaol) (1), and cholesterol (2) were isolated from the marine red alga Halymenia floresii. The structure of the compound 1 (halymeniaol) was established from its spectral data, derived from HRMS/MS and 2D NMR. Compound 1 exhibited growth inhibitory activity against chloroquine-resistant Plasmodium falciparum 3D7 strain with an IC₅₀ of 3.0 μM.     

MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker

Purpose:Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis.Methods:Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared.Results:Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis.Conclusion:The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.     

Synthesis of some benzoxazinyl pyrazolone arylidenes as potent antimicrobials and antioxidants

2-[2-(3-Methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl]-2H-1,4-benzoxazin-3(4H)-one (3) was obtained starting from methyl-(3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl) acetate (1) through the corresponding hydrazide (2). Condensation of (3) with different aromatic aldehydes under Knoevengel condensation afforded 2-{2-[3-methyl-4-(2-methylbenzylidine)-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl}-2H-1,4-benzoxazin-3(4H)-ones (4a–k). The structures of the compounds were determined by FT-IR, ¹H NMR, ¹³C NMR, mass spectral data, and elemental analysis. All the synthesized compounds were screened for their in vitro antimicrobial and antioxidant studies.     

Sinus node dysfunction in acute myocardial infarction.

The frequency, clinical course, and prognosis of sinus node dysfunction in 431 patients with acute myocardial infarction admitted to the coronary care unit were studied. Sinus node dysfunction occurred in 20 patients. In 13, the principal manifestation consisted of severe sinus bradycardia. In the remaining 7, periods of bradycardia alternating with episodes of supraventricular tachycardia were noted. Though several of the patients with sinus bradycardia required intravenous atropine or temporary pacing, normal sinus rhythm returned in virtually all during follow-up. The clinical course of patients with both bradycardia and tachycardia was less benign, during the acute phase and during follow-up; 5 of the 6 survivors required continued antiarrhythmic therapy or permanent pacing. The differences in the clinical course between these two groups of patients may reflect distinct underlying pathological changes. The findings in this study suggest that in contrast to sinus bradycardia, the occurrence of bradycardia-tachycardia syndrome during the acute phase of myocardial infarction may have important prognostic implications.     

A randomized phase II trial of tacrolimus,mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation

The study is a randomized phase II trial investigating graft-versus-host disease prophylaxis after non-myeloablative (90 mg/m² fludarabine and 2 Gy total body irradiation) human leukocyte antigen matched unrelated donor transplantation. Patients were randomized as follows: arm 1 – tacrolimus 180 days and mycophenolate mofetil 95 days (n=69); arm 2 – tacrolimus 150 days and mycophenolate mofetil 180 days (n=71); arm 3 – tacrolimus 150 days, mycophenolate mofetil 180 days and sirolimus 80 days (n=68). All patients had sustained engraftment. Grade II-IV acute graft-versus-host disease rates in the 3 arms were 64%, 48% and 47% at Day 150, respectively (arm 3 vs. arm 1 (hazard ratio 0.62; P=0.04). Owing to the decreased incidence of acute graft-versus-host disease, systemic steroid use was lower at Day 150 in arm 3 (32% vs. 55% in arm 1 and 49% in arm 2; overall P=0.009 by hazard ratio analysis). The Day 150 incidence of cytomegalovirus reactivation was lower in arm 3 (arm 1, 54%; arm 2, 47%; arm 3, 22%; overall P=0.002 by hazard ratio analysis). Non-relapse mortality was comparable in the three arms at two years (arm 1, 26%; arm 2, 23%; arm 3, 18%). Toxicity rates and other outcome measures were similar between the three arms. The addition of sirolimus to tacrolimus and mycophenolate mofetil is safe and associated with lower incidence of acute graft-versus-host disease and cytomegalovirus reactivation. (clinicaltrials.gov identifier: 00105001).     

Paediatric T cell Lymphoma with Nephrotic Syndrome: A Rare Association

Renal involvement is frequent in hematologic malignancies especially Hodgkin’s lymphoma. Renal complications in children with malignancies primarily arise from tumour lysis syndrome, malignant infiltration or obstruction of the urinary tract, deposits of immunoglobulin fractions or crystals, renal infiltration by malignant cells, paraneoplastic or storage glomerulopathies. Nephrotic syndrome has been described in B cell type Non Hodgkin’s lymphomas. There are very few reports of association of T cell lymphoma and nephrotic syndrome in pediatric patients. We present a case of peripheral T cell lymphoma with nephrotic syndrome in a 10 year old boy.