Enhancing treatment strategies for small bowel cancer: a clinical review of targeted therapy and immunotherapy approaches.

Small bowel cancer (SBC) is a rare and aggressive disease with a poor prognosis, necessitating the exploration of novel treatment approaches. This narrative review examines the current evidence on targeted therapy and immunotherapy for SBC, focusing on the two most common subtypes: adenocarcinoma and neuroendocrine tumor. A comprehensive search of PubMed, Scopus, and Google Scholar databases was conducted to identify relevant clinical trials and case reports published in English up to September 2023. The review includes 17 clinical trials and 10 case reports, indicating that targeted therapy and immunotherapy can have the potential to improve survival rates in patients with SBC. Notably, promising targeted medicines include bevacizumab, cetuximab, and trastuzumab, while pembrolizumab and nivolumab show potential as immunotherapies. However, it should be noted that the magnitude of the increase in survival rates with these interventions was small. Further research is needed to determine the optimal combination of targeted therapy and immunotherapy for individual patients with SBC.

The evaluation of atorvastatin as an adjunct to fluconazole for the anti-fungal prophylaxis in acute myeloid leukemia: a multicenter, triple-blinded, randomized clinical trial.

The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18-70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30 days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03).

Prognosis and complete remission rate of diffuse large B-cell lymphoma patients in standard R-CHOP with reduction of vincristine: A retrospective study.

Background and Aims: The effect of stopping or reducing the dose of vincristine in diffuse large B-cell lymphoma (DLBCL) on the outcome and prognosis of the disease is still in doubt. The present study aimed to investigate and compare the prognosis and complete remission of two R-CHOP treatment regimens with and without vincristine reduction in DLBCL patients. Methods: This retrospective study was conducted on newly diagnosed DLBCL patients during 2018-2021. The patients were over 18 years of age, had been histologically confirmed by a pathologist, and were under treatment with R-CHOP regimen. The clinical information of the subjects as well as the number of treatment courses were extracted from their medical records and then compared. Results: Overall, 269 patients with DLBCL were included in this study, 15.99% of whom (n = 43) had vincristine reduction. There was no significant difference between the studied factors regarding the reduction of vincristine and the complete R-CHOP regimen (p > 0.05). Besides, no difference was observed in the 1-year overall survival (OS) and progression-free survival (PFS) of the patients in the two groups treated with R-CHOP regimen with and without vincristine reduction (p > 0.05). The complete remission rates of the patients treated with R-CHOP regimen with and without vincristine (p > 0.05) were not different either. The results of the Cox multivariate regression showed that reducing the dose of vincristine from the R-CHOP treatment regimen had no relationship with the 1-year OS and PFS of the DLBCL patients (hazard ratio [HR]OS = 1.59, 95% confidence interval [CI]: 3.67-0.690, HRPFS = 1.67, 95% CI: 0.798-3.82). Conclusion: The results of this study showed that the reduction of vincristine from the R-CHOP regimen in the DLBCL patients was not likely to make a difference in the 1-year OS and PFS of the patients. However, further studies are needed on the issue.

Prognostic Role of Red Cell Distribution Width (RDW) in Patients with Diffuse Large B-cell Lymphoma.

INTRODUCTION: Several A number of prognostic blood markers related tofor Diffuse Large B-Cell Lymphoma (DLBCL) have been identified, most of which are costly and not easily availableaccessible. Although the relationship between the prognostic role of RDW and some cancers has been well established, the role it   of RDW plays in DLBCL patients is unclear still questionable and requires more investigations. METHODS: All patients diagnosed with DLBCL who had referred to Imam Reza Hospital, during  were included in this retrospective cohort study. Based onRegarding their RDW, the subjects were divided into two groups of normal (RDW ≤14.6%) and elevated RDW (RDW > 14.6%) RDW, and the outcomes were investigated. RESULTS: One hundred fifty patients with DLBCL were included in this study. The results showed a significant relationship between the RDW values of the DLBCL patients and stage frequency distribution, relapse, mortality, and complete remission (P value<0.05). It was also found out that elevated RDW > 14.6% was associated with the risk of relapse (OR=2.50, P value<0.05), mortality (OR=3.59, P value<0.01), and lack of complete remission (OR=0.115, P value< 0.01). The results of the survival analysis indicated that the subjects with higher RDWs had a lower median survival rate than those with low RDWs. In addition, the mortality risk for the individuals with RDW > 14.6% was 2.44 times that of those with RDW≤14.6% (HR=2.44, P value<0.05). CONCLUSION: The results of this study well indicated that as an independent prognostic factor, RDW was associated with the stage of DLBCL patients, failure to achieve complete remission, disease relapse, and patient mortality. However, further studies are would be needed to realize determine the role of RDW in DLBCL patients.

Plasma microRNA-195, -34c, and - 1246 as novel biomarkers for the diagnosis of trastuzumab-resistant HER2-positive breast cancer patients.

Recently, miRNAs have been regarded as potential candidates for mediating therapeutic functions by targeting genes related to drug response. In this study, we suggested that plasma miRNAs may be correlated with response to trastuzumab in HER2-positive breast cancer patients. To determine whether miR-195, miR-23b-3p, miR-1246, and miR-34c-3p are involved in trastuzumab resistance, we screened their expressions in the BT-474 cell line, which was followed by plasma analysis from 20 trastuzumab-resistant HER2-positive breast cancer patients and 20 nonresistance subjects. Then, TargetScan, Pictar, and miRDB were applied to find the possible targets of the selected miRNAs. In addition, the expression status of admitted targets was evaluated. Our results showed that in resistant BT-474 cells, miR-1246, and miR-23b-3p were significantly upregulated, and miR-195-5p and miR-34c-3p were downregulated. In plasma analysis, we found miR-195-5p, miR-34c-3p, and miR-1246 meaningfully diminished in the resistant group, while the expression of miR-23b-3p was not statistically different. The expression levels of confirmed targets by qRT-PCR showed that the expression of RAF1, AKT3, c-MET, CCND1, PHLPP2, MYB, MAP2K1, and PTEN was significantly upregulated, while the expression of CCNG2 was significantly downregulated. The networks of miRNAs with their confirmed targets improved comprehension of miRNA-mediated therapeutic responses to trastuzumab and might be proposed for more characterization of miRNA functions. Moreover, these data indicated that miR-195-5p, miR-34c-3p, and miR-1246 could be possible biomarkers for prognosis and early detection of the trastuzumab-resistant group from the sensitive group of HER2-positive breast cancer patients.

A critical review of methotrexate clinical interactions: role of transporters.

INTRODUCTION: Methotrexate (MTX) is an antifolate and immunosuppressive drug prescribed for various malignancies and immune diseases. However, delayed elimination of MTX associated with concomitant use of some medications can lead to severe and lifethreatening adverse effects. AREAS COVERED: This paper investigated drugMTX interactions that lead to elevated MTX levels and related adverse effects due to the role of transporters. Methotrexate toxicity occurs at both low and high doses administrations. According to the studies we reviewed in this paper, most interaction records with methotrexate occurred with coadministration of indomethacin, ketoprofen, omeprazole, piperacillin/tazobactam, ciprofloxacin, cotrimoxazole, probenecid, and imatinib, mainly due to the role of transporters. However, most studies were performed as case reports or series, and confirming the exact drugmethotrexate interaction still needs further clinical investigations. EXPERT OPINION: Our findings showed no firm evidence of interactions of proton pump inhibitors (PPIs), levetiracetam, and NSAIDS with MTX. Moreover, patients' risk factors, hypoalbuminemia, renal failure, third space fluid retention, the elderly, polypharmacy, and transport inhibition are the most critical factors for MTX toxicity. If substitution or temporary discontinuation is not possible, healthcare providers should be aware of interactions, especially in patients with risk factors for MTX toxicity.

Prostate cancer, chronic myelogenous leukemia and multiple myeloma in a single patient: a case report and review of the literature.

BACKGROUND: Synchronous or metachronous multiple primary malignancies (MPMs) are a known phenomenon. These occurrences may be spontaneous or related to environmental risk factors or genetic predisposition. Chronic myelogenous leukemia (CML) and Multiple myeloma (MM) are two uncommon hematologic malignancies, arises from two different cell lineage. The coexistence of CML and MM that is a rare phenomenon, with only 29 cases reported in the literature. To the best of our, this combination of triple primary cancers has not been reported in a single patient. CASE PRESENTATION: Herein, we reported a case of an 85-year-old Iranian male with three confirmed primary malignant neoplasms. The patient presented with synchronous prostate cancer and CML, in august 2016. He received imatinib and nilotinib for CML and hormonal therapy for prostate cancer. He remained in good control at further follow-ups for about 5 years. In the follow-up period and after 61 months treatment with tyrosine kinase inhibitors (TKIs), CML was undetectable in molecular tests, but the presence of serum M-protein, abnormal plasma cells in the bone marrow, and CRAB criteria was compatible with MM. CONCLUSION: We must evaluate the possibility of multiple primary cancers during cancer treatment and follow-up and it may be worthwhile to monitor serum electrophoresis and protein levels in TKIs-treated patients.

Evaluation of cytokine levels as possible predicting elements in patients with chronic lymphocytic leukemia.

OBJECTIVE: This study aimed to assess the patterns of serum cytokines in chronic lymphocytic leukemia patients at baseline and post-chemotherapy and investigate their association with response to treatment and chronic lymphocytic leukemia prognosis. METHODS: Blood samples were taken from 32 subjects at their first medical visit after being diagnosed with chronic lymphocytic leukemia and 1 year after chemotherapy. Then, levels of cytokines and blood parameters in peripheral blood were measured. Correlation analysis was used to assess the indexes before and after chemotherapy as well as at different disease stages. RESULTS: Most of the patients (45.80%) had stages I and III before initiation of treatment and after treatment, respectively. There were significant differences between levels of interleukin (IL)-6 (p=0.006) and IL-10 (p=0.009) before and after treatment. Notably, the difference in IL-10 levels before and after treatment was significantly higher in the advanced stages compared to that in the non-advanced stages (p=0.007). IL-6 and IL-10 were also higher in the expired patients compared to the survived cases. CONCLUSIONS: Cytokines such as IL-6 and IL-10 may be considered predicting factors for chronic lymphocytic leukemia prognosis.

The effects of low-dose anthracycline-based chemotherapy on the levels of serum NT-proBNP level and left ventricular systolic and diastolic dysfunctions: A prospective observational study.

Background and Aims: The present study aimed to evaluate the relationship between serum N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and incidence of left ventricular (LV) systolic and diastolic dysfunction in patients who underwent low-dose anthracycline chemotherapy. Methods: This observational, prospective study was conducted on all patients with proven breast cancer, Hodgkin lymphoma, or non-Hodgkin lymphoma and no history of previous cardiac or any chronic diseases who were candidates for low-dose anthracycline chemotherapy from March 2017 to February 2018. We evaluated the serum NT-proBNP level and performed trans-thoracic echocardiography at baseline, 6, and 9 months after the chemotherapy. Results: Among 57 patients who successfully finished the study, 13 (22.8%) patients were men and 44 (77.19%) patients were women, and the total mean age was 52 ± 14.86 years. Our results revealed that the LV systolic and diastolic function and NT-proBNP mean levels were in the normal range at all three measured times. Additionally, no significant differences were observed between the levels of NT-proBNP, LV systolic, and diastolic function at baseline, 6, and 9 months after chemotherapy with low-dose anthracycline (p = 0.6, 0.1, and 0.4, respectively). Conclusion: Following low-dose anthracycline chemotherapy, none of our patients encountered LV systolic and diastolic dysfunctions and changes in serum NT-proBNP level. However, further studies with a larger population, longer follow-up duration, and higher dosage of anthracyclines are required to determine the effects of low-dose anthracycline on NT-proBNP level and LV systolic and diastolic functions.

Evaluation of cytokine levels as possible predicting elements in patients with chronic lymphocytic leukemia

SUMMARY OBJECTIVE: This study aimed to assess the patterns of serum cytokines in chronic lymphocytic leukemia patients at baseline and post-chemotherapy and investigate their association with response to treatment and chronic lymphocytic leukemia prognosis. METHODS: Blood samples were taken from 32 subjects at their first medical visit after being diagnosed with chronic lymphocytic leukemia and 1 year after chemotherapy. Then, levels of cytokines and blood parameters in peripheral blood were measured. Correlation analysis was used to assess the indexes before and after chemotherapy as well as at different disease stages. RESULTS: Most of the patients (45.80%) had stages I and III before initiation of treatment and after treatment, respectively. There were significant differences between levels of interleukin (IL)-6 (p=0.006) and IL-10 (p=0.009) before and after treatment. Notably, the difference in IL-10 levels before and after treatment was significantly higher in the advanced stages compared to that in the non-advanced stages (p=0.007). IL-6 and IL-10 were also higher in the expired patients compared to the survived cases. CONCLUSIONS: Cytokines such as IL-6 and IL-10 may be considered predicting factors for chronic lymphocytic leukemia prognosis.

Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

Clinical characteristics of 200 COVID-19 patients in Mashhad, Iran, February and March 2020.

Introduction: Coronavirus disease 2019 (COVID-19) is a pulmonary involvement which was reported for the first time in December 2019 in the city of Wuhan, Hubei province, China. The aim of the study was to describe the demographic, clinical, laboratory, and radiological characteristics of 204 definitive laboratory-confirmed COVID-19 patients hospitalized in Mashhad, Khorasan Razavi province, Iran. Patients and Methods: This study was performed on 204 laboratory-confirmed COVID-19 patients. A set of laboratory tests combined with various patient information and results from lung high-resolution computed tomography (HRCT) were gathered in a checklist and analyzed to give us a better view of patients who are hospitalized due to the complications caused by this disease. Results: The average age of our patients was 58.83 ± 15.93 years. There were 122 (59.8%) male and 82 (40.2%) female patients, and almost all of our patients had at least one underlying disease. Nine (4.4%) of our patients reported having gone for a trip to COVID-19-epidemic areas in the last 2 weeks. The most common signs shared among all our patients were cough, fever, and decreased O2 saturation; the average respiratory rate was 25.50 ± 6.74/min, average axillary body temperature was 37.69°C ± 0.69°C, and average O2 saturation was 88.34% ± 7.34%. Conclusion: Based on our results, the most common signs of this disease are fever, cough, and shortness of breath, similar to seasonal influenza. Our data on disease severity showed that 33 (16.2%) patients had moderate disease, 139 (68.1%) had severe disease, and 28 (13.7%) were critical; 22 (10.8%) of our hospitalized patients died due to the complications of this disease.

A randomized, double-blind, phase III, non-inferiority clinical trial comparing the efficacy and safety of TA4415V (a proposed Trastuzumab biosimilar) and Herceptin (Trastuzumab reference product) in HER2-positive early-stage breast Cancer patients.

BACKGROUND: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. METHODS: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. CONCLUSIONS: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.

Association of SMAD7 genetic markers and haplotypes with colorectal cancer risk.

PURPOSE: Colorectal cancer (CRC) is one of the common cancers with a high mortality rate worldwide. In Iran, there has been a trend of increased incidence of colorectal cancer in the last three decades that necessitates the early diagnosis. Genetic factors have an influential role in its etiology along with the conventional risk factors such as age, diet, and lifestyle. Results from GWAS have shown significant associations between SMAD7 gene variants and risk of CRC. This study aimed to assess the association of certain polymorphisms as well as haplotypes of this gene and risk of colorectal cancer. METHODS AND MATERIALS: This study was designed as a case-control association study. After obtaining ethical approval and informed consent, blood samples from 209 patients with colorectal cancer were collected and DNA was extracted. Four variants: rs4939827, rs34007497, rs8085824 and rs8088297 were genotyped using ARMS-PCR method. RESULTS: SMAD7 rs4939827 in the recessive and co-dominant models was associated with colorectal cancer risk [TT/CT + CC: OR = 2.90, 95%CI (1.38-6.09), p = 0.005; CC + TT/CT: OR = 1.66, 95%CI (1.00-2.75), p = 0.01]. Haplotype analysis indicated that some SNP combinations including two for-SNPs haplotypes of T-T-C-C and T-C-C-A were significantly associated with CRC risk. CONCLUSION: Based on the identified association of SMAD7 gene variations and haplotypes with colorectal cancer risk in our population, genetic variations in this gene region may have a role in CRC development. This data may shed light on the genetic predisposition of CRC which involves different pathways including TGF-ß.

Demographic and clinical characteristics of severe Covid-19 infections: a cross-sectional study from Mashhad University of Medical Sciences, Iran.

BACKGROUND: Coronavirus Disease 2019 (Covid-19) is expanding worldwide. The characteristics of this infection in patients varies from country to country. To move forward, clinical data on infected patients are needed. Here, we report a comparison between fatalities and recovery of patients with severe Covid-19, based on demographic and clinical characteristics. METHODS: Between 5 March and 12 May 2020 in Mashhad, Iran, 1278 of 4000 suspected Covid-19 patients were confirmed positive by real-time reverse-transcriptase-polymerase-chain-reaction assay of upper respiratory specimens. We compared the demographic, exposure history and clinical symptoms of 925 survivors and 353 fatal cases with confirmed disease. RESULTS: Mean (SD) age for all confirmed patients was 56.9 (18.7) years, 67.1 (15.9) years in fatal cases and 53.0 (18.3) years in survivors. Multivariate logistic regression analysis showed that the outcome of patients was associated with age (odds ratio = 1.049, P = 0.0001, 95% CI = 1.040-1.057). Despite a high burden of Covid-19 infections in the 30-39 and 40-49 year age groups, most of these (89.6 and 87.2%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (6.0-14.0) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Dyspnoea (72.7%), cough (68.1%) and fever (63.8%) were the most frequent clinical symptoms. Healthcare workers, of whom two (3%) died, comprised 5.2% of infected cases. Combination antiviral and antibiotic therapy was used in 43.0% of cases. CONCLUSIONS: The characteristics of severe Covid-19 varied substantially between fatal cases and survivors, with diabetes and cardiovascular disorders the most prevalent co-morbidities. In contrast to other studies, there were a higher number of fatalities in younger patients in our setting.

Clinical features and disease severity in an Iranian population of inpatients with COVID-19.

Coronavirus disease 2019 (COVID-19) can present with a variety of symptoms. Severity of the disease may be associated with several factors. Here, we review clinical features of COVID-19 inpatients with different severities. This cross-sectional study was performed in Imam Reza hospital, Mashhad, Iran, during February-April 2020. COVID-19 patients with typical computed tomography (CT) patterns and/or positive reverse-transcriptase polymerase chain reaction (RT-PCR) were included. The patients were classified into three groups of moderate, severe, and critical based on disease severity. Demographic, clinical, laboratory, and radiologic findings were collected and compared. P < 0.05 was considered statistically significant. Overall, 200 patients with mean age of 69.75 ± 6.39 years, of whom 82 (41%) were female were studied. Disease was severe/critical in the majority of patients (167, 83.5%). Disease severity was significantly associated with age, malignant comorbidities, dyspnea, nausea/vomiting, confusion, respiratory rate, pulse rate, O2 saturation, extent of CT involvement, serum C-reactive protein (CRP), pH, pO2, and aspartate transaminase (P < 0.05). Moreover, complications including shock, coagulopathy, acidosis, sepsis, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, and intubation were significantly higher in patients with higher severities (P < 0.05). O2 saturation, nausea/vomiting, and extent of lung CT involvement were independent predictors of severe/critical COVID-19 (OR 0.342, 45.93, and 25.48, respectively; P < 0.05). Our results indicate O2 saturation, nausea/vomiting, and extent of lung CT involvement as independent predictors of severe COVID-19 conditions. Serum CRP levels and pO2 were also considerably higher patients with higher severity and can be used along with other factors to predict severe disease in COVID-19 patients.

Investigating the association between rs6983267 polymorphism and susceptibility to gastrointestinal cancers in Iranian population.

Genome-wide association studies have revealed that some single nucleotide polymorphisms at 8q24, such as rs6983267, might be effective in susceptibility to various cancers in different populations. Therefore, rs6983267 might be useful as a marker for multiple cancers. In this study, we considered a population, including 478 gastrointestinal cancer cases from the Iranian population, to investigate the association between rs6983267 and susceptibility to gastrointestinal cancers. The samples were genotyped using the TaqMan real-time PCR method while 10% of them were also confirmed by sequencing. Higher frequency of G allele was associated with higher grades of tumors in esophageal cancer and the tumors located in the lower portion of the esophagus (OR 3.56; 95% CI 1.13-11.24; P = 0.03) and cardia (OR 5.24; 95% CI 1.26-21.83; P = 0.02), which both locations are involved in esophageal adenocarcinomas with poor prognosis. The results indicated that in the male subgroup, the rs6983267 GG genotype significantly enhanced the gastric cancer susceptibility (OR 4.76; 95% CI 1.57-14.45; P = 0.01). GG genotype also increased the risk of intestinal-type gastric cancer, located in non-cardia (OR 4.62; 95% CI 1.25-17.04; P = 0.02). Moreover, gastric cancer cases and controls with a family history of gastrointestinal tumors were mostly genotyped with the G allele (OR 3.61; 95% CI = 1.09-12.01; P = 0.04). There were no remarkable associations between rs6983267 and susceptibility to esophageal and colon cancers in the Iranian population. However, different genotypes of rs6983267 had significant correlations with tumor grade, cancer type, and family history of gastrointestinal cancers. Further investigations in a larger population and other ethnicities are required to confirm these results.

Efficacy and safety of convalescent plasma therapy in severe COVID-19 patients with acute respiratory distress syndrome.

Since SARS-CoV-2 infection is rapidly spreading all around the world, affecting many people and exhausting health care resources, therapeutic options must be quickly investigated in order to develop a safe and effective treatment. The present study was designed to evaluate the safety and efficacy of convalescent plasma (CP) for treating severe cases of COVID-19 who developed acute respiratory distress syndrome (ARDS). Among 64 confirmed cases of severe COVID-19 with ARDS in this study, 32 patients received CP besides first line treatment. Their clinical response and outcome in regard to disease severity and mortality rate were evaluated and compared with the other 32 patients in the control group who were historically matched while randomly chosen from previous patients with the same conditions except for receiving CP therapy. Analysis of the data was performed using SPSS software. Patients with plasma therapy showed improvements in their clinical outcomes including a reduction in disease severity in terms of SOFA and APACHE II scores, the length of ICU stay, need for noninvasive ventilation and intubation and also showed an increase in oxygenation. They also showed reduction in mortality which was statistically significant in less severe cases with mild or moderate ARDS. Early administration of the convalescent plasma could successfully contribute to the treatment of severe COVID-19 patients with mild or moderate ARDS at risk of progressing to critical state.

Evaluating mRNA expression of tax, B chain of PDGF and PDGF-ß receptors as well as HTLV-I proviral load in ATL patients and healthy carriers.

Adult T-cell leukemia (ATL) is a life-threatening malignant neoplasm of CD4+ T cells resulted from human T-cell leukemia virus type I (HTLV-I). Tax1 protein of HTLV-I can induce malignant proliferation of T-cells by modulating the expression of growth factors such as platelet-derived growth factor (PDGF). Here, we aimed to investigate the proviral load (PVL) of HTLV-I in ATL and also to evaluate the mRNA expression of B chain of PDGF and PDGF-ß receptors in ATL patients and HTLV-I-infected healthy carriers. To this end, peripheral blood mononuclear cells (PBMCs) were isolated by using Ficoll-Histophaque density centrifugation. The mean of HTLV-I PVL in ATL patients (42,759 ± 15,737 copies/104 cells [95% CI, 9557-75962]) was significantly (p = .01) higher than that in healthy carriers (650 ± 107 copies/104 cells [95% CI, 422-879], respectively. The HTLV-I PVL in ATL patients exhibited a significant correlation with PBMC count (R = .495, p = .001). The mRNA expression of Tax, B chain of PDGF, and PDGF-ß receptor genes was significantly higher in healthy carriers than in patients with ATL. In conclusion, the expression of the canonical PDGFß and its receptor, and their correlation with Tax expression cannot be a suitable indicator and/or prognostic factor for progression of ATL in HTLV-I carriers.