Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer

Background

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC.

Methods

This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression.

Results

The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001–1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2.

Conclusion

Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.

     

Sandstorm Appearance of Pulmonary Alveolar Microlithiasis Incidentally Detected in a Young,Asymptomatic Male

Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of symptoms in contrast to the imaging findings. We present a case of a 24-year-old Malay man having an incidental abnormal pre-employment chest radiograph of dense micronodular opacities giving the classical "sandstorm" appearance. High-resolution computed tomography of the lungs showed microcalcifications with subpleural cystic changes. Open lung biopsy showed calcospherites within the alveolar spaces. The radiological and histopathological findings were characteristic of PAM.     

Nitrate-induced Biochemical and Histopathological Changes in the Liver of Rats:Ameliorative Effect of Hyparrhenia hirta

Objective The present study investigated the protective role of Hyparrhenia hirta （H. hirta） against sodium nitrate （NaNO3）-induced hepatoxicity. Methods Male Wistar rats were randomly divided into three groups： a control group and two treated groups during 50 d with NaNO3 administered either alone in drinking water or co-administered with H. hit＇to. Results NaNO3 treatment induced a significant increase in serum levels of glucose, total cholesterol and triglyceride while serum total protein level decreased significantly. Transaminases and lactate deshydrogenase activities in serum were elevated indicating hepatic cells＇ damage after treatment with NaNO3. The hyperbilirubinemia and the increased serum gamma glutamyl transferase activities suggested the presence of cholestasis in NaNO3 exposed rats. In parallel, a significant increase in malondialdehyde level along with a concomitant decrease in total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities were observed in the liver after NaNO3 treatment. Furthermore, nitrate caused a significant induction of DNA fragmentation. These modifications in NaNO3-treated rats corresponded histologically with hepatoceltular necrosis and mononuclear cells infiltration. H. hirta supplementation showed a remarkable amelioration of the abnormalities cited above. Conclusion The results concluded that the treatment with H. hirta had a significant role in protecting the animals from nitrate-induced liver dysfunction.     

Significant heterogeneity in the geographical distribution of diffuse grade II/III gliomas in France

The recognition of stem cells (SC) in the adult CNS and in association with gliomas has spawned an entire field of research and intense investigation. A large body of knowledge is being accumulated to gain insight into the pathobiology of gliomas with the intent of finally improving the grave prognosis that continues to beset patients with high grade gliomas (HGG). In this article, we provide a historical overview of the events leading to the discovery of SC and glioma stem cells (GSC). We then focus on the current understanding of GSC with respect to markers, clinical significance, and their targeting. We discuss current data and developments using SC as vehicles to delivery therapeutic agents to HGG. We conclude with a discussion of opportunities for future development and concepts aimed at reducing tumor recurrence and improving survival for patients with HGG.     

Plötzlicher natürlicher Tod beim Sport

Background

Sudden, unexpected death during sports is often dramatic and may be relevant to criminal and civil law.

Methods

Approximately 33,000 autopsies carried out at the Centre of Legal Medicine at the University of Frankfurt/Main from 1972 to 2007 were analyzed concerning sudden unexpected deaths connected with sports and the results were compared with a control group.

Results

Among 120 fatalities connected with sports (0.36% of all autopsies) there were 114 men (95.0%, average age 53.0 years, range 6 to 83 years) and 6 women (5.0%, average age 38.2 years, range 15 to 59 years). The age groups between 50 and 59 years (31 cases) and between 60 and 69 years (25 cases) were the most affected. In older athletes over 35 years of age cardiovascular diseases were the most frequent cause of death (91 cases; 90.1%). In younger athletes fatal cardiovascular diseases were more seldom, but as frequent as inflammatory cardiac diseases (n=5; 26.3%)

Conclusions

Sudden unexpected death associated with sports is seldom but dramatic. In addition to the autopsy, histological, microbiological and toxicological testing should also be carried out.     

Preparation of cellulosic Ag-nanocomposites using an ionic liquid

Cellulose-based nanocomposites have gained much attention due to their remarkable biological properties such as biodegradability, biocompatibility, and low toxicity. In this research work, 1-h-3-methylimidazolium hydrogen sulfate ionic liquid was employed as an efficient solvent for preparation of cellulosic Ag-nanocomposites (CRC/AgNPs composite) from Neem plant. Ionic liquid plays a dual role in obtaining cellulose-rich compound (CRC; removing lignin and hemicellulose components) and plant’s extract (phenolic compounds such as flavonoids, tannins, etc.) that reduces the AgNO₃ into AgNPs for preparation of CRC/AgNPs composite. The prepared CRC/AgNPs composite was characterized using XRD, FTIR and SEM techniques. The XRD and FTIR spectral analysis showed the characteristic peaks assigned to cellulosic constituent and AgNPs. SEM analysis revealed the particles in the range from 26 to 56 nm. The CRC/AgNPs composite was evaluated for its antibacterial and mechanical properties. The antibacterial activity against S. aureus and E. coli for CRC/AgNPs composite was observed in comparison to CRC. Cell viability and morphology were performed on MC3T3-E1 cells which showed no as such toxicity for the prepared CRC/AgNPs composite. Moreover, the addition of CRC/AgNPs composite as a filler increased the compression strength of polymeric materials.     

Prenatal Nicotine and CNS Development

The teratological effect of nicotine has been studied during different trimesters of pregnancy. Three groups of pregnant albino Swiss mice were used for each trimester. The daily doses of nicotine base used were equivalent to 10 (900 micrograms/kg), 20 (1,800 micrograms/kg), or 30 (2,700 micrograms/kg) cigarettes. The control groups were given normal saline. The drug and the saline solution were administered subcutaneously. The results showed that prenatal nicotine prolonged the latency and delayed the onset and extinction of audiogenic seizures in the offspring. These effects were more pronounced during the third trimester and particularly with the largest dose. These findings indicate that prenatal nicotine might delay the postnatal development of the CNS if it is given during the late stage of pregnancy.     

May-Hegglin anomaly: A rare cause of thrombocytopenia

A family with four and an unrelated family with three individuals affected by the May-Hegglin anomaly are described. Platelet counts were markedly reduced and were correctly determined only in the counting chamber. Bleeding time and platelet aggregation were always normal, but platelet nucleotide concentrations (ATP and ADP) were elevated. The platelet glyco-protein complexes Ib/IX, IIb/IIIa and Ia/IIa were quantitatively normal. Platelet-associated IgG was slightly elevated, although thrombocytopenia was presumably not caused by an immunological mechanism. Morphological investigations showed giant platelets and spindle-shaped inclusion bodies in the granulocytes, while their function (phagocytic capacity, radical production) was normal. To exclude hereditary types of thrombocytopenia, morphological and family investigations are required to avoid misdiagnosis with far-reaching diagnostic and therapeutic consequences.