Molecular Classification of Gastric Cancer With Emphasis on PDL-1 Expression: The First Report From Iran.

Background: Gastric cancer is one of the lethal cancers and there is no effective treatment for these patients and still, 5-year survival rate is about 25% to 30%. Finding reliable biomarkers for early-stage diagnosis, targeted therapy, and survival prediction is a priority in this cancer. Objectives: In this study we were trying to know about the molecular classification of gastric cancers in a group of patients from the South of Iran. Patients and Methods: In a cross sectional study, 50 specimens of gastric cancer were selected that have enough tissue to be stained by immunohistochemistry (IHC). IHC was performed for Her-2, mismatch repair genes (MLH-1, MSH-2, MSH-6, and PMS-2), and PDL-1. Frequency of positive makers was compared with survival and outcome. Results and Conclusion: In our study, deficient MMR (dMMR) was detected in 4 patients (8.0%). PD-L1 expression in tumor cells (TC) was observed in 1 of 4 cases (25%) with PMS2 loss. However, PD-L1 in TCs and TILs (tumor infiltrating lymphocytes) was negative in 1 case with MLH1 loss and in 3 of 4 cases with PMS2 loss, which was not statistically significant. All of our 50 cases were positive for MSH2 and MSH6, 24% of which showed TCs with PDL-1 expression and 32% of them in TIL. HER2 was positive in 2 (2/50, 4.0%) cases, among which all of the cases were positive for PD-L1 expression in TCs and TILs, respectively. However, in HER2-negative group, 26.2% (11/42) and 28.6% (12/42) of tumors were positive for PD-L1 in TCs and TILs, respectively. The expression rate of PD-L1 in HER2 negative TCs was significantly higher than that in HER2 positive TCs (P = .033). Immunohistochemistry for Her-2 was equivocal in 6 cases (12.0%) none of which expressed PD-L1 in tumor cells. In our study minimum and maximum survival times from detection of gastric cancer were 1 and 87 months, respectively. The mean ± SD and median ± SD of overall survival time were 30.69 ± 4.88 and 18 ± 1.45 months, respectively. One and 3-year survival rates of 40% and 24%, respectively. PD-L1 expression was not associated with survival, but its expression was associated with intestinal type Lauren classification and negative HER-2. PD-L1 positivity in tumor cells or tumor infiltrating lymphocytes was not an independent prognostic factor in gastric cancer.

Expression Pattern of Telomerase Reverse Transcriptase (hTERT) Variants and Bcl-2 in Peripheral Lymphocytes of Systemic Lupus Erythematosus Patients.

BACKGROUND & OBJECTIVE: It is not clear whether activated lymphocytes of patients with systemic lupus erythematosus (SLE) are more proliferative or less apoptotic. We aimed to delineate potential differences between B and T cells of SLE patients compared to healthy controls regarding the telomerase activity and apoptosis status. METHODS: In this cross-sectional case control study, Blood samples were taken from 10 SLE patients and 10 healthy controls. B and T cells were separated using magnetic cell sorting system. Telomeric repeat amplification protocol (TRAP) assay and real-time PCR were used to determine the telomerase activity and the expression of alternatively spliced variants. RESULTS: Four patients under treatment showed significant telomerase activity in their T cells. Four of the newly diagnosed patients showed telomerase activity in their B cells (20% of all patients and 40% of new onset patients). There was no specific pattern of human telomerase reverse transcriptase variant expression within the patients' lymphocytes. A significantly reduced expression of Bcl-2 was detected in B cells (P=0.018) and a trend toward lower Bcl-2 expression in T cells was seen in SLE patients compared to healthy controls. CONCLUSION: Although not definitive, our results may suggest that B cells may have more active roles during the earlier phases of the disease attack, while T cells take over when the disease reaches its chronic stages.

Thymoangiolipoma: A rare histologic variant of thymolipoma in a patient with myasthenia gravis.

Thymoangiolipoma is a rare, slow-growing, benign thymic neoplasm that arises from the anterior mediastinum. A 61-year-old man with the chief complaint of right eye ptosis and high serum acetylcholine receptor antibody level is presented here. The spiral computed tomography of the chest revealed a hypodense mass in the anterior mediastinum. Microscopic examination showed admixture of adipose tissue, thymic tissue and blood vessels with the diagnosis of thymoangiolipoma. Thymoangiolipoma is a rare histologic variant of thymolipoma which can be associated with myasthenia gravis and must be considered as a differential diagnosis in anterior mediastinal mass with fat density in radiologic evaluation.

Reduced myocardial reserve in cirrhotic patients: an evaluation by dobutamine stress speckle tracking and tissue Doppler imaging (TDI) echocardiography.

Introduction: Despite the normal systolic function at rest, cirrhotic patients often suffer from volume overload and symptoms of heart failure as they face stressful situations. This study investigated the myocardial reserve in cirrhotic patients at resting condition and peak stress by dobutamine speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI). Methods: Twenty cirrhotic patients and 10 normal individuals aged 30-50 were selected randomly. For all of the participants, complete echocardiographic study of 2D, STE and TDI was done at rest and peak stress status with dobutamine. The following parameters were assessed: ejection fraction (EF), global longitudinal LV strain (GLS), strain rate in the septal basal segment and lateral wall and E' in the septal basal segment by color-coded method. Results: At baseline, EF was higher than 55% in both groups. GLS was higher (-22.6±2.4%) in the case group than the control group (-19.2±1.9%) at resting condition. After stress, it showed a greater increase (-22.5±1.7%) in the controls compared to cirrhotic patients (-22.6±3.3%; mean difference = 2.6 ± 2.03, P = 0.02). In cirrhotic patients, the average strain rate in the basal septal segment decreased after stress (-1.2 ± 0.3/s to-1.1 ± 0.3/s), but it increased in the control group (-1.1 ± 0.2/s to -1.8 ± 0.2/s). Conclusion: Despite the presence of normal resting systolic function in cirrhotic patients, there was insufficient increase or even a decrease in myocardial function with stress; this may indicate the absence of sufficient myocardial reserve in cirrhotic patients. These findings would help to explain the reason for occurrence of heart failure or hemodynamic changes in cirrhotic patients.

Low Dose Spironolactone Monotherapy in the Management of Stage I Essential Hypertension: A Pilot Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: High blood pressure (BP) is a common chronic disease needs long life drug consumption to control. Spironolactone could be used as the fourth-line therapy in patients with resistant hypertension. However, there is no study to determine the effects of low dose spironolactone as a first line therapy in treatment of essential hypertension. The aim of this study is to investigate the effect of low dose spironolactone monotherapy in management of essential hypertension. METHODS: In this double blind randomized clinical trial, 40 patients who had stage I essential hypertension were randomly divided into two groups: intervention group received spironolactone 25 milligram once daily for one month and control group received placebo once daily. At the baseline and after one month, 24-hour BP holter-monitoring and serum potassium assay were done. RESULTS: Systolic BP was reduced from 143.5 ± 8.2 mmHg to 137.10 ± 7.57 mmHg in the intervention group, while it did not change significantly in control (between group treatment difference = -4.5 mmHg, p = 0.004). There was no significant reduction of diastolic BP in the intervention group in comparison to placebo group (between group treatment difference = -1.3 mmHg, p = 0.099). CONCLUSIONS: Short course monotherapy with low dose spironolactone is effective in reducing systolic BP in patients with stage I essential hypertension.

Correlation of serum ferritin levels with hepatic MRI T2 and liver iron concentration in nontransfusion beta-thalassemia intermediate patients: A contemporary issue.

BACKGROUND: Beta-thalassemia intermediate is a genetic disease that is milder than beta-thalassemia major. The T2* magnetic resonance imaging (MRI) technique is currently the gold standard for iron load detection. However, it is expensive and needs an expert radiologist to report findings. Therefore, we conducted this study to determine an optimal cut-off value of ferritin in proportion to T2 MRI of liver and measurement of liver iron concentration for early detection of hepatic iron overload in Beta-thalassemia intermediate patients. METHODS: This cross-sectional study was conducted on 108 patients with Beta-thalassemia intermediate who referred to tertiary hospital, Shiraz, Iran. Serum ferritin, hepatic T2 MRI, and liver iron concentration were assessed. Receiver operator characteristic was used to determine the sensitivity and specificity of cut-off value. RESULTS: Serum ferritin levels showed a statistically significant negative correlation with T2 hepatic MRI (r = -0.290, p value =.003) and positive correlation with liver iron concentration (r = 0.426, p value <.001) in the patients with Beta-thalassemia intermediate. According to the receiver operator characteristic, the best cut-off value for ferritin to show early diagnosis of liver iron overload was 412 ng/mL. Calculated sensitivities and specificities were 0.78 and 0.82 for T2 MRI and 0.76 and 0.86 for liver iron concentration, respectively. CONCLUSION: Serum ferritin levels of around 450 ng/mL might be considered as a cut-off point to evaluate hepatic iron overload before using expensive, not readily available T2 MRI. This level of serum ferritin could be considered for starting iron chelation therapy in patients with Beta-thalassemia intermediate in areas where T2 MRI is not available.

The antibiotic susceptibility patterns of uropathogens among children with urinary tract infection in Shiraz.

Urinary tract infection (UTI) is one of the most common bacterial infections in pediatrics. Delay in diagnosis and treatment can cause significant morbidity. The physicians knowledge regarding the symptoms, microorganisms that caused UTI, and effective antibiotics in a geographical area can help them to select the appropriate antibiotics. This study was performed to determine the prevalence of bacteria that cause UTI and their susceptibility to common antibiotics as well as the common symptoms and associated factors in children of Shiraz, Southern Iran.This cross sectional study was performed among 202 children with UTI, aged 2 months to 18 years old, between August and November 2014 in pediatric medical centers of Shiraz University of Medical Sciences. Urine samples were collected using urinary catheter or suprapubic in children < 2 years and mid-stream in children over 2 years, respectively. The type of micro-organisms causing UTI was determined and evaluation of antibiotic susceptibility for each organism was assayed by the Kirby Bauer method using antibiogram test. Patient's information was collected through checking the medical documents and interview with parents.Our results showed that the frequency of UTI was significantly higher in girls (70.3%) than in boys. The most commonly discovered pathogens were Escherichia coli (E coli) (51.5%), followed by Klebsiella spp. (16.8%), and Enterococcus spp. (9.9%). Overall susceptibility test showed the highest resistance to ampicillin (81.2%) and cotrimoxazole (79.2%), and the highest sensitivity to imipenem (90.1%) and Gentamicin (65.3%). Gram negative and positive bacteria showed the highest antibiotic resistance to amoxicillin (83.8%) and clindamycin (100%), respectively. In addition, production of extended spectrum beta lactamase (ESBL) was 69.2% and 30.8% in E coli and Kelebsiella respectively.The efficacy of third generation of the cephalosporins was reduced because of the high rate of production of ESBL and drug resistance. These results inform the physician as to which antibiotics are appropriate to prescribe for the patient, as well as urine culture reports and following the patient's clinical response so that high antimicrobial resistance is not developed at the community level.

A cross-sectional study of complementary and alternative medicine use in patients with coagulation disorders in Southern Iran.

OBJECTIVE: Complementary and alternative medicine (CAM) use has an increasing trend around the world. Despite the wild application of CAM in patients with coagulation disorders, its efficacy is still questioned by many studies. The aim of this study was to determine the frequency and types of CAM usage, and the factors affecting CAM use among patients with bleeding disorders. METHODS: This cross-sectional study investigated the usage of CAM with a standard validated questionnaire in coagulopathic patients who were referred to Dastgheib Hospital, an educational therapeutic center affiliated to the Shiraz University of Medical Sciences in Shiraz, Southern Iran. RESULTS: Between December 2015 and May 2016, 75 patients were included in this survey. Severe hemophilia A and rare bleeding disorders were the most frequent among our participants. Overall, nearly half of the studied population (49.3%) used at least one CAM product or practices. The most common products were multivitamin (29.3%), followed by folic acid (21.3%) and chamomile (12%). 32% of the patients resorted to faith healing. The main reasons of using CAM were reported to be increased general health, correction of anemia and thrombocytopenia and control of bleeding tendency. CONCLUSION: CAM is being used frequently in patients with coagulation disorders like many other chronic illnesses all around the world. Due to emerging concern regarding the safety and possible interaction with the conventional medicine, it is necessary to develop basic data about the hematologic effects of these methods in order to use them more safely.

Expression Pattern of Alternative Splicing Variants of Human Telomerase Reverse Transcriptase (hTERT) in Cancer Cell Lines Was not Associated with the Origin of the Cells.

Telomerase and systems controlling their activity have been of great attention. There are controversies regarding the role of the alternative splicing forms of the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. Therefore, the correlation between telomerase enzyme activity, the abundance of alternatively spliced variants of hTERT and doubling time of a series of cancer cell lines originated from hematopoietic, breast, colorectal, neural, ovarian, lung, kidney, bladder, prostate and head and neck cancers were investigated. Expression levels of four different variants of hTERT (the full length, α-deletion, ß-deletion and α/ß-deletion) were quantitatively measured by real time PCR. Telomerase activity was determined by the telomerase repeat amplification protocol (TRAP) while doubling time of the cells measured by plotting growth curves. Results showed high diversity in the relative proportions of hTERT transcripts while the majority of the cells expressed the full length variant as the main transcript. Telomerase activity could not be detected in all cells. Relative assessment of hTERT expression showed greater expression of the α-deleted variant in the telomerase negative cells (P= 0.04). Those cells possessed the α/ß-deleted variant to a smaller extent when compared to the cells with telomerase activity. Greater association between full length spliced variant and ß-variant expression was observed in cells presenting telomerase activity (P= 0.0007, r= 0.74). High degrees of variation among the studied cells regarding the pattern of hTERT expression were present. In spite that, the regulatory roles of hTERT on telomerase activity is still a potential to be utilized as targets for cancer therapies.