The feasibility of PETHEMA ALL-96 regimen on treatment of patients with acute lymphoid leukemia.

Background: Asparaginase-based treatment regimen for acute lymphocytic leukemia (ALL) is considered as feasible, but there is still a lack of data. In this study, considering the results of other regimen that were not optimum in previous studies. Here, we aimed to investigate the feasibility of PETHEMA ALL-96 treatment regimen. Materials and Methods: This is a retrospective feasibility study that was performed in 2019-2021 on 13 patients diagnosed with B-cell ALL. Patients were treated by PETHEMA ALL-96 regimen during induction, consolidation, reinduction, and maintenance phases. Patients were followed for 2 years after initiation of PETHEMA ALL-96 regimen for disease-free survival (DFS) and overall survival (OS) of all patients were evaluated after 2 years. Results: Data of 11 patients were analyzed. Within 28 days after treatments, all patients (100%) had no blasts in the bone marrow that was considered as complete remission (CR). The CR rate was 100% within 6 months and 12 months and 81.8% within 2 years after the treatments. Evaluation of OS, CR, and DFS regarding 6, 12, and 24 months showed 100% for all items after 6 and 12 months. After 24 months, the CR was 90.9%, the OS was 81.8% and the DFS was 90.9%. None of the patients died during the induction phase and during the 12 months study. No side effects were observed. Conclusion: The PETHEMA ALL-96 had high feasibility and survival rates with no side effects during the study course. It is believed that PETHEMA ALL-96 regimen has beneficial outcomes in young patients with ALL.

Association of lymphocyte subsets with mortality in severe COVID-19 pneumonia patients.

BACKGROUND: Few studies have investigated the alterations in the T and B cell counts and related subgroups in pulmonary infections especially COVID-19. Here, we aimed to evaluate total T and B lymphocytes and T cell subgroup counts to find the possible correlation between number of these cells and severity and mortality in COVID-19 patients. METHODS: This study was performed on 40 patients with severe COVID-19 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chest HRCT in August 2020. By the time of admission, T lymphocytes profile in peripheral blood was investigated using multicolor flow cytometry. The total number of T lymphocytes, CD4+ T cells, CD8+ T cells, and B lymphocytes were calculated. Expression of CD2, CD3, CD5, and CD7 as pan T cell surface markers and expression of CD38 and HLA-DR as activated markers on T lymphocytes were also evaluated. RESULTS: Nine patients (22.5%) died during the study and 16 patients (40%) were admitted to ICU. Deceased patients demonstrated lower amounts of T cell count and CD4+ T cell count (with a marginal difference (p = 0.07)) compared with survived patients at the time of admission. The chance of mortality was significantly higher for patients with CD7 loss (OR = 14.89). A marginally significant relationship was also indicated between CD4<200/ml and mortality (OR = 8.65), but no other significant relationships were observed between variables and ICU admission. CONCLUSION: Altogether, CD7 loss on T lymphocytes and CD4+ T cell count below 200/ml revealed a significant relationship with mortality. Considering T lymphocytes and T cell subgroup count could have a predictive value for patients suffering from COVID-19.

T-cell immunophenotyping in COVID-19 pneumonia.

The COVID-19 epidemic is currently a global threat that has affected many parts of the world. Some patients require intensive care unit admission due to severe symptoms in the course of the disease. The severity of symptoms in this disease varies from person to person. The effectiveness of the immune response against viral infections depends on the number and activity of T-cells, which play an important role in eliminating virus-infected cells. In this study, we report two patients with COVID-19 pneumonia, one with moderate symptoms and the other with severe symptoms. Although a decrease of absolute lymphocyte count was seen in both patients, a more significant decline reported in the ICU-admitted patient. Expression of activated markers, HLA-DR, CD38, on CD8-positive T-cells was shown in a patient with more severe disease. On the other hand, partial loss of CD7 in the severe case was also observed. Hence, besides of the above parameters that already mentioned in other studies, loss of pan T-markers could be considered as a potentially valuable test for predicting disease severity. We suggest evaluating the predictability of these tests in COVID-19 in larger studies. This study was approved by the Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.MED.REC.1399.238).

Comparison of the effects of pegylated granulocyte-colony stimulating factor and granulocyte-colony stimulating factor on cytopenia induced by dose-dense chemotherapy in breast cancer patients.

BACKGROUND: Myelosuppression is one of the frequent side effects of chemotherapy in breast cancer patients. Granulocyte-colony stimulating factor (G-CSF) and pegylated G-CSF are used for the prevention of neutropenia after chemotherapy. Pegylated G-CSF has longer half-life of action and can be used as a single dose in comparison to G-CSF. The aim of this study is to compare the grade of cytopenia and side effects between G-CSF and biosimilar pegylated G-CSF in breast cancer patients treated with dose-dense chemotherapy. MATERIALS AND METHODS: In the cross-over clinical trial study, 24 women with breast cancer were randomly divided into two groups and treated with dose-dense chemotherapy. The first group was treated with single dose of 6 mg biosimilar pegylated G-CSF 24 h after the first course of chemotherapy and the second course was followed by 300 µg daily injection of G-CSF for 6 days. The chemotherapy regimen was combination of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The second group was treated with G-CSF after the first course and pegylated G-CSF after the second course. Cell blood count (CBC) and side effects were evaluated 1 and 2 weeks after both courses of chemotherapy. RESULTS: In this study, no significant carryover effect and treatment effect about the CBC parameters was found between pegylated G-CSF and G-CSF. Patients who were treated with biosimilar pegylated G-CSF had significantly higher side effects such as bone pain (P = 0.09) and gastrointestinal effects (P = 0.005) in comparison to G-CSF. CONCLUSION: G-CSF and biosimilar pegylated G-CSF are effective in reducing cytopenia in breast cancer patients treated with dose-dense chemotherapy, but side effects induced by pegylated G-CSF (Pegagen) are higher.

Evaluation of Central Nervous System Relapse in Adults with Acute Lymphoblastic Leukemia (ALL) Receiving Hyper-CVAD Treatment in Seyyed Al-Shohada Hospital: Isfahan, 2014-2019.

Background: Recurrence of ALL in the central nervous system, CNS Relapse, is known as a poor prognostic factor. Few studies have been performed on the CNS Relapse in adults with ALL. This study aimed to evaluate the recurrence of acute lymphoblastic leukemia in the central nervous system, CNS relapse, in adults with ALL. Materials and Methods: Seventy newly diagnosed patients with acute lymphoblastic leukemia aged 15 years and older referred to Seyyed Al-Shohada Hospital in Isfahan between 2014 and 2019 were included in this study. All patients treated with the Hyper-CVAD regimen underwent prophylaxis for the central nervous system based on the risk of CNS relapse. All study participants with CNS relapse underwent intrathecal chemotherapy. Results: The median age of patients was 34 years. Four patients (5.7%) had primary central nervous system involvement. Out of 70 patients receiving the Hyper-CVAD regimen, 59 (84.2%) achieved complete remission. Of the 59 patients achieving CR, ten (16.94%) developed CNS relapse. The median duration of CR before CNS relapse was 21 weeks. Out of 10 patients with CNS relapse, seven (70%) achieved complete remission. Of seven patients achieving CR in the central nervous system, one had a second recurrence in the central nervous system, but finally achieved CNS complete remission. The median survival of patients after CNS relapse was four months. The results also showed that out of 10 patients with CNS relapse, four (40%) survived one year. Conclusion: This study shows that the prognosis of CNS relapse in adults with ALL has not improved much. Limited studies have been conducted on the recurrence of the central nervous system in adults with acute lymphoblastic leukemia. Therefore, further studies on CNS relapse after complete remission of ALL are required to clarify more details.

The Effect of Dextrose Hypotonic vs Saline Hydration on Methotrexate-Induced Nephrotoxicity in Male and Female Rats.

Background: High-dose methotrexate (HDMTX) as a cytotoxic agent might cause various side effects. Hyperhydration has been implemented as the major strategy to decrease the potential risk of toxicities induced by HDMTX. This study aims to assess the renoprotective effect of hydration with dextrose water (DW) 5% versus normal saline (N/S) 0.9% against methotrexate (MTX) induced nephrotoxicity. Materials and Methods: This experimental animal study has been conducted on 36 Wistar rats (200-250 g) categorized into six groups, including male (n = 6) and female (n = 6) rats receiving sodium chloride 0.9% saline plus MTX, DW 5% plus MTX, or MTX alone. By the fifth day after the MTX injection, biochemical indexes were measured. The rats were also sacrificed and renal specimens were evaluated microscopically to determine kidney tissue damage (KTD). Results: The groups were not significantly different with regard to blood urea nitrogen (BUN) (P = 0.5), creatinine (Cr) (P = 0.24), kidney weight (P = 0.34), and urine flow (UF) (P = 0.5), while KTD score was remarkably less in the hydrated groups (P < 0.001). Weight loss in DW-treated rats was significantly more than N/S-treated ones, and creatinine clearance (CrCl) and urine load (UL) of Cr were statistically similar between males and females in the control group, but significantly lower among the DW5% treated males. Conclusion: Based on the findings of this study, hydration with N/S was superior to DW5% for the prevention from HDMTX-induced nephrotoxicity. Besides, we found insignificant differences between male versus female rats in response to the hydration for HDMTX-induced renoprotection; however, females probably benefit more.

A model for prediction of cisplatin induced nephrotoxicity by kidney weight in experimental rats.

BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II; CP) is used widely as an antitumor drug in clinics, but is accompanied with renal toxicity. Cisplatin induced nephrotoxicity consists of change in kidney weight, histological changes in kidney and increase in serum creatinine (Cr) and blood urea nitrogen (BUN). This study was designed to find out a model for prediction of cisplatin induced nephrotoxicity. MATERIALS AND METHODS: Pathological damage score, kidney weight, BUN, and Cr of 227 rats that were involved in different projects were determined. A total of 187 rats were treated with 7 mg/kg cisplatin and sacrificed 1 week later. RESULTS: There was a good significant correlation between normalized kidney weight and logarithmic scale of BUN and Cr. Relationship between BUN, Cr or normalized kidney weight and pathology damage score was significant. CONCLUSION: Normalized kidney weight and pathology damage score is a good predictor of renal function in cisplatin induced nephrotoxicity in experimental rats.

Effects of Fennel Essential Oil on Cisplatin-induced Nephrotoxicity in Ovariectomized Rats.

BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II (CDDP)) is an effective drug in cancer therapy to treat solid tumors. However, the drug is accompanied by nephrotoxicity. Previous reports indicated that estrogen has no protective role against CDDP-induced nephrotoxicity, but the role of phytoestrogen as an estrogenic agent in plants is not determined yet. The major composition of fennel essential oil (FEO) is trans-anethole that has estrogenic activity; so, we used FEO as a phytoestrogen source against CDDP-induced nephrotoxicity. MATERIALS AND METHODS: Fifty-four ovariectomized Wistar rats were divided into seven groups. Groups 1-3 received different doses of FEO (250, 500, and 1000 mg/kg/day, respectively) for 10 days. Group 4 received saline for 10 days plus single dose of CDDP (7 mg/kg, intraperitoneally (ip)) at day 3. Groups 5-7 received FEO similar to groups 1-3, respectively; plus a single dose of CDDP (7 mg/kg, ip) on day 3. On day 10, the animals were sacrificed for histopathological studies. RESULTS: The serum levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW) and body weight changes in CDDP-treated groups increased significantly (P < 0.05). FEO did not reduce the levels of BUN and Cr, KTDS, and KW and body weight changes. Also, the serum and tissue levels of nitrite were not altered significantly by FEO. CONCLUSION: FEO, as a source of phytoestrogen, did not induce kidney damage. In addition, FEO similar to estrogen was not a nephroprotectant agent against CDDP-induced nephrotoxicity.

Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model.

BACKGROUND: Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood. MATERIALS AND METHODS: Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. RESULTS: The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r (2) = 0.63, P < 0.01). CONCLUSION: Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.

Prognostic Factors and Outcome of Patients with Adult Acute Lymphoblastic Leukemia Treated with the Hyper-CVAD Regimen: A Retrospective Study.

Aim: The Hyper-CVAD regimen has shown promising results for adult patients with acute lymphoblastic leukemia (ALL), as designed by the MD Anderson Cancer Center (MDACC). This treatment has resulted in a complete remission rate of 92% and a 5-year overall survival of 38%. However, given the diversity of patient demographics and institutional methods, outcomes may differ between various institutions. This study will compare the outcome of adult ALL patients treated with the Hyper-CVAD regimen in Iran with those obtained in the original series presented at the MDACC. Patients and Method. In this retrospective study, we evaluated the 2-year leukemia-free survival (LFS) and the 2-year overall survival (OS) of 70 ALL patients treated between 2014 and 2019 in the Seyed Al-Shohada Hospital in Isfahan, Iran. Results: In total, 59 ALL patients (84.28%) achieved complete remission (CR). The CR rate had statistical differences by bone marrow transplantation (BMT) and WBC count. The 2-year LFS and OS were 40% and 42%, respectively. There were significant differences in LFS and OS by BMT, myeloid marker, and WBC count. Conclusion: The outcome of the traditional Hyper-CVAD regimen in treating adult ALL was not satisfying. More efficient therapies should be applied for the treatment of adult ALL.

Bacterial spectrum and antimicrobial resistance pattern in cancer patients with febrile neutropenia.

BACKGROUND: Bloodstream infections are serious complications in neutropenic cancer patients. There has been a universal pickup in multidrug resistant (MDR) strains. For individuals who are at high risk for infections caused by MDR bacteria, a novel de-escalation strategy has been developed. Determine the bacterial spectrum and antibiotic resistance pattern in febrile neutropenic cancer patients was the goal of this investigation. MATERIALS AND METHODS: From 2019 to 2020, 60 cancer patients with febrile neutropenia who were sent to Isfahan's Omid Hospital were included in this retrospective analysis. Experiments were done on the antimicrobial susceptibility of isolated bacterial infections. RESULTS: The patients' average age was 43.35±15.59 years. Ninety-one percent (55/61) of the 60 patients had hematologic malignancies, and 8.3 percent (5/61) had solid tumors. The majority of the germs were gram-negative bacteria (66.7 percent). E. coli was the pathogen that was isolated the most frequently (26.7%), followed by Klebsiella (16.7 percent). In addition, the most prevalent identified Gram-positive bacteria was Staphylococcus epidermidis (21.7 percent). Third-generation cephalosporin (ESBL-E) resistance was present in 50% of E. coli, along with 50% resistance to cotrimoxazole, ciprofloxacin, and piperacillin, 31% resistance to amikacin, and 20% resistance to meropenem (CRE). They had an 80% sensitivity to amikacin and a 70% sensitivity to ciprofloxacin. Ten percent of our patients had antibiotic resistance in the antibiogram (XDR). CONCLUSION: In summary, most bacterial infections were resistant to different medications. The emergence and spread of Gram-negative bacteria that are resistant to antibiotics can be stopped by prudent antibiotic use.

Thalidomide for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Clinical Trial.

Background: Coronavirus disease 2019 has become a public health concern with a high number of fatalities. Thalidomide can target inflammatory mediators and decrease inflammation in SARS-CoV-2. Materials and Methods: An open-label, randomized controlled trial was conducted on patients with compatible lung high-resolution computed tomography scan for COVID-19 pneumonia and moderate involvement. Childbearing-age women were excluded. A total of 20 patients in the control group receiving usual treatment were compared with 26 patients in the case group who in addition to the same regimen also received thalidomide. The primary outcome was time for clinical recovery (TTCR) and intensive-care unit (ICU) admission. Results: From April 25 to August 8, 2020, based on the inclusion criteria, 47 patients were assigned to the study. Patients receiving thalidomide had a mean TTCR of days 5.5 (95% confidence interval [CI], 0.7-10.3), as compared with days 5.3 (95% CI, 1.7-8.9) with control (odds ratio 0.01; 95% CI, -1.58-1.59, P = 0.807). The incidence of ICU admission was 27% in the thalidomide group compared with 20% in the control group (odds ratio 3.89; 95% CI, 0.55-27.4, P = 0.425). The mean length of stay in hospital in both groups was 10 days. Progressive improvement in respiratory rate, fever, and O2 saturation during the study was seen in both groups without a significant difference between the thalidomide and control group (P > 0.05). Conclusion: This study investigated the effects of thalidomide to treat moderate COVID-19 clinical outcomes. The results established that this drug regimen did not add more effect to usual treatment for moderate COVID-19 pneumonia.

Patient and Physician Perspectives in the Management of Immune Thrombocytopenia in Iran: Responses from the ITP World Impact Survey (I-WISh).

Data describing physicians' and patients' perspectives towards immune thrombocytopenia (ITP) management and impact of disease in Iran are limited. This ITP World Impact Survey was conducted between October 2019 and October 2020. Of the 114 patients included in the survey, 17 were aged ≤18 years. Forty-seven physicians, including 22 pediatric hematologists, participated in the survey. Fatigue and anxiety around stable platelet counts were frequent patient-reported symptoms at diagnosis and at survey completion. According to physicians, "watch-and-wait" was the preferred treatment option for mean (standard deviation) proportion of 50.1 (24.1) and 48.6 (21.8) of their adult and pediatric patients, respectively, following first diagnosis. Per adult and pediatric hematologists, the most prescribed treatments for newly diagnosed patients based on available answers were steroids (100%, n = 20/20; 89%, n = 16/18), respectively. Forty percent of adult (n = 10/25) and 38% of pediatric hematologists (n = 8/21) reported that ITP reduced patients' quality of life. Energy levels (46%, n = 52/112) and ability to concentrate on everyday activities (42%, n = 47/113) were the most affected aspects of patients' lives. This I-WISh study in Iran underlined the negative impact of ITP on patients.

The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: gender-related differences.

It is documented that chronic renal diseases are gender related. The protective role of angiotensin II receptor 1 (AT1) blocker losartan against cisplatin (CP)-induced nephrotoxicity was reported in males, but the role of gender is not well known. Six groups of Wistar rats were studied. Rats were divided into two groups of males and females to receive losartan for 9 days plus a single dose of CP (7 mg/kg) at day 3. Two positive control groups of males and females received the same regimen, except that they received saline instead of losartan. The negative control groups received saline instead of CP at day 3 and also saline instead of losartan. The blood samples were obtained, and the kidneys underwent histopathological investigations. All the CP-treated animals lost weight, but losartan promoted weight loss in females (p < 0.05). Coadministration of losartan and CP in females, but not in males, significantly increased the serum levels of blood urea nitrogen and creatinine when compared with the negative and positive control groups (p < 0.05). No significant differences were observed in serum levels of total proteins, magnesium, and nitrite between the groups. Administration of CP increased the kidney tissue damage score (KTDS) and normalized kidney weight (p < 0.05). However, in the presence of AT1 blockade, the KTDS (nonsignificantly) and normalized kidney weight (significantly, p < 0.05) increased in the CP-treated females. Such an observation was not seen in males. Losartan may prevent CP-induced nephrotoxicity in males, but it promotes the CP-induced damage in females, which may be related to the renin-angiotensin system receptors in the kidneys.

The Prevention of Cisplatin-Induced Nephrotoxicity: A General Consensus Statement of a Group of Oncologist-Hematologists, Adult and Pediatric Nephrologists, Radiation Oncologists, Clinical Pathologists, Clinical Pharmacologists, and Renal Physiologists on Cisplatin Therapy in Cancer Patients.

Backgrounds: Most of the cancer patients with solid tumor are subjected to chemotherapy with cisplatin (CP) in clinic. However, the most side effect of CP is nephrotoxicity, which limits the treatment. The aim of study was to develop a general consensus statement for CP therapy in clinic to limit the drug-induced nephrotoxicity. Methods: A total of 30 oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologist clinical pharmacologist, and renal physiologist participated in a workshop, and in order to reduce the incidence of CP-induced nephrotoxicity, a general consensus was developed. Results: The developed general consensus was focused on some items such as age, sex, female hormone, nonsteroidal anti-inflammatory drugs (NSAID), renin-angiotensin system inhibitor drugs, glomerular filtration rate, hydration methods, contrasts, antioxidants, dextrose, and magnesium. Conclusion: The agreement between participants for CP therapy in clinic was achieved, and this general consensus was announced to be implemented in the hospitals.

A comparative study of the effects of multimedia training materials on mini CEX scores of internal medicine residents in Isfahan University of Medical Sciences.

BACKGROUND: Role of multimedia training materials on Mini-CEX scores of internal medicine residents. We aimed to assess the effect of multi multimedia training materials on Mini-CEX scores of internal medicine residents of Isfahan University of Medical Sciences. SETTINGS AND DESIGN: A quasi-experimental action research study on 1st, 2nd, and 3rd-year internal medicine residents were implemented. MATERIALS AND METHODS: The Mini-CEX test measures students' performance in six core skills necessary for medical practice. Mini-CEX scores of 135 internal medicine residents in 2017-2018 were compared before and after the training with prepared multimedia materials. We used repeated measured ANOVA and Mann-Whitney U test to compare the distribution of Mini-CEX scores across corresponding groups. Analysis was done using the SPSS software version 23 (IBM SPSS Statistics for Windows. Armonk, NY, USA: IBM Corp). RESULTS: The median Mini-CEX score (IQR) of students in preintervention and postintervention groups were 16.14 (5.19) and 19.62 (3.13), respectively. Findings of this study showed a significant increase in mini-CEX scores of the groups who used the multimedia learning material compared to those who did not use it (P < 0.001). CONCLUSIONS: Multimedia learning resources demonstrated a promising influence on internal residents' mini-CEX scores in this study. They demonstrate significantly greater performance after using multimedia learning materials compared to their same-year residents who did not benefit from it. This demonstrates the favorable effect of multimedia on the acquisition of practical skills such as obtaining a history or performing a physical examination.

Intravenous Administration of Cisplatin with Magnesium Sulfate Supplement May Prevent Kidney Toxicity in Rats: The Role of Gender and Magnesium Sulfate Dose.

BACKGROUND: Cisplatin (CP) is widely used to treat various kinds of malignancies, but to avoid its side effects of nephrotoxicity and hypomagnesemia, magnesium supplementation is a subject of debate. The current study was designed to determine the protective role of intravenous magnesium sulfate (MgSO4) against intravenous administration of CP in male and female rats. METHOD: In this case-control experimental study, 80 Wistar male and female rats in 12 groups of experiments were subjected to receive intravenous administration of CP accompanied with intravenous infusion of different doses (1, 3, and 10 mg/ml solution) of MgSO4 and were compared with the control groups. RESULTS: CP administration increased blood urea nitrogen (BUN), creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW), and they were attenuated by the mid-dose of MgSO4 supplementation in female rats. However, in male rats, the increase of Cr, BUN, KTDS, and KW induced by CP was ameliorated by low, mid-, and high doses of MgSO4 supplements. The levels of these markers were significantly different between male and female rats in the mid-dose of MgSO4-treated group (BUN: P=0.002, Cr: P=0.005, KTDS: P=0.002, and KW: P=0.031). CP reduced clearance of Cr (ClCr) in both male and female rats significantly compared to the control group of saline alone (P male = 0.002 and P female = 0.001), and the mid- and high doses of MgSO4 supplements improved ClCr in female rats. There were also sex differences in ClCr in mid- (P=0.05) and high (P=0.032) doses of MgSO4-treated groups. CP accompanied with the mid-dose of MgSO4 supplement reduced the KTDS (P male = 0.04 and P female = 0.004) and KW (P male = 0.002 and P female = 0.042) in both male and female rats significantly when compared with the CP-alone-treated group, while there were also significant differences between the sexes (KTDS: P=0.002 and KW: P=0.031). CP accompanied with three different doses of MgSO4 supplements did not improve the serum levels of lactate dehydrogenase, urine level of sodium, malondialdehyde, urine flow, and nitrite statistically when compared with the CP-alone-treated group. CONCLUSION: The renal protective effect of MgSO4 could be dose and gender related.

Rational, Design and Preliminary Results of a Cohort Study on Breast and Colorectal Cancer to Develop a Risk Assessment Model to Predict Future Cardiovascular Events. "Cardio Vascular Events in Breast and Colorectal Cancers (CIBC) Study".

Breast cancer (BC) and colorectal cancer (CRC) are among the most common cancers in Iran. We aimed to develop a risk assessment model to predict the development of cardiovascular events in these patients by performing a 5 year prospective cohort study on a newly diagnosed patients with BC or CRC before they receive any treatment. A multi-center prospective cohort study of 2700 newly diagnosed BC and CRC patients has been started in Iran since 2019 and will be continued until 2024. Demographics, socioeconomic status, life style behaviors, psychological characteristics and type of cancer treatments will be collected by standard questionnaires and blood pressure, obesity indices will be measured. Blood sampling, ECG, and echocardiography will be done in all patients at base line, 6 and 12 months, then at annual basis for five years. Incidence of heart failure, acute coronary syndrome, stroke and CVD related death are the primary outcome of this study. In this preliminary analysis, 70 patients with BC and 30 patients with CRC were enrolled in this study from April 2019 to November 2019. Mean age of BC and CRC patients was 48 ± 10.5 and 61 ± 13.2 respectively. 98.6% of patients in BC group and 60% of CRC groups were female. This study will be a platform for other cancers to develop CVD risk assessment charts that can cover other cancers. Patients who lie in the high risk category according to the newly developed risk assessment chart, should receive special management and preventive interventions.

Survival of Post-Transplant Lymphoproliferative Disorder after Kidney Transplantation in Patients under Rapamycin Treatment.

Background: One of the important causes of mortality and morbidity in kidney transplanted patients is Post Transplant Lymphoproliferative Disease (PTLD), which is due to immunosuppression therapy and viral activity. It seems that Rapamycin, with dual antineoplastic and immunosuppressive effects, may have a pivotal role in the treatment of PTLD patients and preserving transplanted kidneys. Methods and Materials: Twenty patients with PTLD were enrolled. Immunosuppressive therapy was reduced or ceased, and Rapamycin was initiated at the time of PTLD diagnosis. We evaluated the effects of switching immunosuppressive drugs to Rapamycin on graft status, the response of tumor, and 6, 12 months, and 5-year survival in patients. Results: PTLD remission was achieved in 14 patients, while six patients died; no relapse was detected in recovered patients. The median of PTLD free time was 25 months, and the mean overall survival in patients with PTLD treated by Rapamycin was 84.8 (95% CI=61.3-108.23).The five-year survival rate was 67%, 12 months survival was 73.8%, and six months' survival was 80%. The response rate to Rapamycin and immunosuppression reduction alone was 46.6%. Four out of 13 Diffuse Large B-Cell Lymphoma patients achieved a complete response just only after the reduction of immunosuppressive drugs and the consumption of Rapamycin. Conclusion: The present study demonstrated the effectiveness of conversion from immunosuppressive medication, particularly of Calcineurin inhibitors to Rapamycin in PTLD patients. However, more research is needed to confirm the Rapamycin effect on patients with PTLD.