Lymphopenia and lung complications in patients with coronavirus disease-2019 (COVID-19): A retrospective study based on clinical data.

A rapid outbreak of novel coronavirus, coronavirus disease-2019 (COVID-19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID-19 patient mortality. The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%-50%). Although the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID-19 patients; CRP, ESR, and platelet-to-lymphocyte ratio (PLR) may not indicate the in-hospital mortality of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32-19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.

Apoptosis and immunophenotyping of peripheral blood lymphocytes in Iranian COVID-19 patients: Clinical and laboratory characteristics.

A novel member of human coronavirus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been recently recognized in China and rapidly spread worldwide. Studies showed the decreasing of peripheral blood lymphocytes in a majority of patients. In this study, we have reported the clinical features, laboratory characteristics, the frequency of peripheral blood lymphocyte subpopulations, and their apoptosis pattern in Iranian coronavirus infectious disease (COVID-19) patients. Demographic and clinical data of 61 hospitalized confirmed cases with COVID-19 at Imam Khomeini Hospital were collected and analyzed. Peripheral blood mononuclear cells were isolated from all samples and the apoptosis pattern was evaluated using Annexin V/propidium iodide method. The frequency of lymphocyte subsets, including T-CD4+ , T-CD8+ , NK, B cells, and monocytes, was measured in all patients and 31 controls by flow cytometry. Our findings demonstrated that the percentage of lymphocytes, CD4+ , and CD8+ T cells were decreased in COVID-19 patients compared with the control group. Regarding the clinical severity, the number of lymphocytes, CD4+ , CD8+ T cells, and NK cells were also decreased in severe cases when compared with mild cases. Finally, our data have also indicated the increase in apoptosis of mononuclear cells from COVID-19 patients which was more remarkable in severe clinical cases. The frequency of immune cells is a useful indicator for prediction of severity and prognosis of COVID-19 patients. These results could help to explain the immunopathogenesis of SARS-CoV-2 and introducing novel biomarkers, therapeutic strategies, and vaccine candidates.

Immunologic markers, vasculitis-associated autoantibodies, and complement levels in patients with COVID-19.

BACKGROUND: The cause of coronavirus disease 2019 (COVID-19) is a virus which can lead to severe acute respiratory syndrome-CoV-2 (SARS-COV-2). There are evidences of involvement of immune system in pathogenesis of this disease. We investigated the presence of various vasculitis-associated autoantibodies and complement levels in patients with COVID-19. MATERIALS AND METHODS: Patients with severe or critical type of COVID-19 were evaluated for symptoms, signs, and laboratory tests of vasculitis syndromes including rheumatoid factor (RF), antinuclear antibody (ANA), anti-double-stranded DNA, c and p anti-neutrophilic cytoplasmic antibody (c ANCA and P ANCA), and complement levels. RESULTS: The study was performed in forty patients with severe or critical illness. The mean age of the participants was 48.5 ± 9.8 years. All patients had pulmonary involvement in lung computed tomography scans. Vasculitis laboratory test results included RF in two patients, ANA in three patients, and ANCA in one patient. Seventeen (42.5%) patients had hypocomplementemia in one or more complement tests. Four patients expired, of whom three had a decrease in complement level. CONCLUSION: Decrease in complement levels may predict a critical state of COVID-19 disease. Therefore, measuring its levels may be of great benefit in making earlier decisions to initiate disease-suppressing treatments including corticosteroids.

Evaluation of antibiotic resistance changes in Acinetobacter baumannii in the era of COVID-19 in Northern Iran.

Background and Objectives: During the coronavirus pandemic, the overuse of antibiotics to reduce coinfections and mortality may be contributing to the rise of antimicrobial resistance. In this study, we aim to investigate the antibiotic resistance changes of Acinetobacter baumannii post-COVID-19 pandemic in Northern Iran. Materials and Methods: The current study is a cross-sectional study. Between 2022 and 2023, 2190 clinical samples were collected from patients with healthcare-associated infections (HAIs) at four hospitals in Sari, which served as corona centers after the COVID-19 pandemic. Antimicrobial sensitivity was determined using standard broth macro-dilution, and resistance genes were detected using multiplex PCR. Results: Based on the results co-amoxiclav had a resistance rate of 100%, while piperacillin/tazobactam showed the least resistance rate of 29.82%. In terms of GM MIC values, colistin was the most potent against multi-drug resistant isolates. The frequency of bla OXA-51 , ampC, aphA6, and bla NDM genes were 100%, 99.12%, 90.35%, and 69.30% respectively. Conclusion: Our study revealed high multi-drug resistance rates. Piperacillin/tazobactam recommended for treating multi-drug resistant Acinetobacter baumannii infections in Northern Iran.

Evaluation of Innate Lymphoid Cells (ILCs) Population in the Mouse Model of Colorectal Cancer.

BACKGROUND: Innate Lymphoid Cells (ILCs) promote tissue homeostasis, contribute to the immune defense mechanisms, and play important roles in the initiation of immune responses and chronic inflammation. OBJECTIVE: To understand the roles of innate lymphoid cells in the pathophysiology of colorectal cancer (CRC) in the mouse model. METHODS: CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) in Balb/c mice (the chemically induced group=18 mice), or orthotopic injection of CT-26 cell line into the colon of another set of Balb/c mice (the orthotopic group=14mice). Normal saline was injected into 18 mice, as the sham group. After 80 days, the chemically induced group was divided into two subgroups, dysplasia (8 mice) and reparative change (10 mice), based on pathological examinations. The frequencies of ILC1, 2, and 3 were then measured in colon tissues using flow cytometry by four markers including an anti-mouse lineage cocktail (FITC anti-mCD3/FITC anti-mGr-1/FITC anti-mCD11b/ FITC anti-mCD45R (B220)/FITC anti-mTer-119), PE/Cy7 anti-mouse CD45, PE anti-mouse CD117 (c-kit), and APC anti-mouse IL-33 Rα (ST2). RESULTS: The total ILC population was significantly higher in the chemically induced reparative change compared with the sham group. ILC1 percentage in the chemically induced reparative change was significantly higher compared to those in the other three groups (Sham, chemically induced dysplasia and orthotopic dysplasia). The orthotopic dysplasia group showed more ILC3 percentage than the other groups. CONCLUSION: ILC1 and ILC3 subgroups increased significantly in reparative and dysplastic experimental CRC respectively. Thus ILC1 may have an inhibitory effect on tumor growth whereas ILC3 promotes tumor progression.

Reduced Expression of Galectin-8 May Contribute in Carcinogenic Pathway of Head and Neck Squamous Cell Carcinoma.

BACKGROUND & OBJECTIVE: Galectin-8 has relationships with cell growth and metastasis of some cancers. Due to controversy in the clinical significance of this protein in the cancer process, we investigated its roles in the development of head and neck squamous cell carcinoma. METHODS: This study was performed on 93 samples of patients with Squamous Cell Carcinoma or dysplasia of the head and neck, who underwent biopsy or surgery from 2015 till 2017 in Boo-Ali SINA hospital of Sari, Iran. The relevant paraffin embedded tissue blocks were obtained from archive of pathology and evaluated for galectin-8 by immunohistochemistry. The association between expression of galactin-8 and age, sex, location and stage of disease were assessed. To compare expression rate between the groups, Mc-Nemar, Chi-square and Fisher's exact tests were used. The P-value<0.05 was considered significant. RESULTS: Strong cytoplasmic and nuclear galactin-8 staining was observed in 97.6% cases of normal tissues while 77% of dysplastic lesions and 69% of the cancers revealed negative immunoreactivity. The intensity of expression in dysplastic and malignant tissues was significantly reduced compared with normal tissues (P=0.0001). The expression of galectin-8 did not correlate with stage (P=0.303), lymph node involvement (P=0.326), tumor grade (P=0.769), distant metastasis (P=0.748), and age (P=0.574). CONCLUSION: We observed that the expression of galectin-8 in dysplastic and malignant squamous epithelium significantly reduced compared with the normal counterpart of them in the head and neck. It may contribute to malignant transformation of head and neck squamous cells.

Immunohistochemical Investigation of Mutant BRAF V600E in Common Pigmented Skin Neoplasms, Study on a Sample of Iranian Patients.

BACKGROUND & OBJECTIVE: This study was designed for the first time for the detec- tion of mutant BRAF V600E and its correlation with clinicophathologic features in a sample of Iranian patients with pathologically proved pigmented skin neoplasms. METHODS: 82 paraffin-embedded blocks, including melanocytic nevi, malignant melanoma, Basel cell carcinoma, and squamous cell carcinoma were evaluated for BRAF V600E expression by immunohistochemistry in the patients admitted to Ibn Sina Hospital, in the city of Sari, Mazandaran province, North of Iran. The evaluation of immunohistochemical staining was performed by two of the authoring pathologists, and staining intensity was graded from negative (0), weak (1+), moderate (2+) to strong (3+). If twenty percent (or greater) of the tumor cells showed modest to strong cytoplasmic immunoreactivity (score 3+), the neoplasm was considered positive for this tumor marker. RESULTS: Among 82 studied patients, 12 cases (60%) of the malignant melanoma group revealed a high intensity of immunostaining for BRAF V600E, while a signifi- cant expression of this marker did not occur in the other investigated skin neoplasm. A great relation between BRAF (V600E) expression and the histologic type of skin cancer was noted. No significant relationship with other parameters such as gender, age, and the grade differentiation of the non-melanoma skin cancer was found. BRAF V600E was weakly correlated with the Clark level of cutaneous malignant melanoma. CONCLUSION: This data provided further evidence for the strong role of the BRAF V600E mutation in the development of cutaneous malignant melanoma, compared to non-melanoma skin cancers in the North of Iran. We advised future studies to evaluate the beneficial effects of anti-BRAF V600E target therapy on the Iranian melanoma patient who harbors this marker by way of immunostaining tumor tissue.

Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease

Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC. Infection with Helicobacter pylori was determined by the rapid urease test for all participants and H&E staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression was determined by SYBR Green based Real-Time PCR using ß-actin as a reference gene. Tim-3 protein expression was also studied by immunohistochemistry in 7 GC, 7 PUD and 10 NUD tissue samples. Results: Tim-3 was expressed at higher levels in GC (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples obtained from gastric cancer patients, tumor tissues showed elevated Tim-3 expression (p=0.019) in comparison with adjacent non-neoplastic biopsies. Tim-3 mRNA findings were supported by detection of more Tim-3 protein in cancerous (p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was similarly expressed in H. pylori positive and negative cases.Conclusion: Higher Tim-3 expression in patients with gastric cancer and peptic ulcer implies that it might be involved in immune regulation and establishment of these gastrointestinal diseases. Targeted immunotherapy by blocking of inhibitory receptors like Tim-3 could be a promising approach for gastric cancer treatment.

Adenomatous Polyps in Adolescent Girl and Boy: A Report of Two Cases.

A polyp is defined as a mass of the mucosal surface that protrudes into the lumen of the gastrointestinal tract. Neoplastic epithelial polyps are classified histologically as either benign adenoma or malignant carcinoma. The colonic polyps that most commonly present in children occur sporadically and individually and are of the juvenile type; they are most frequently associated with painless rectal hemorrhage (which is the most common symptom). Adenomatous polyps are similar to other nontumoral polyps, and it is very rare for children to have symptoms other than rectal bleeding. This report describes two rare cases of polyps in pediatric patients. An 11-year-old girl presented with tubulovillous adenoma and a 13-year-old boy with tubular adenoma; both patients complained of rectal hemorrhage as well as anemia and abdominal pain. Epithelial adenoma is a tumor that is rarely found in adults or children. Colonoscopic perforation and biopsy are mandatory for establishing a definitive diagnosis and avoiding medical mismanagement.

Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

Immunohistochemical expression of vascular endothelial growth factor and its correlation with tumor grade in breast ductal carcinoma.

Breast cancer is the most common cause of cancer-related death in female, after lung cancer. Angiogenesis is essential for tumor growth and metastasis; therefore, antiangiogenesis strategies for treatment of cancer are currently an issue of interest. The role of vascular endothelial growth factor that assumed to be most potent angiogenesis factor is ambiguous in breast cancer. This study described the correlation between vascular endothelial growth factor expression and tumor grade, to define the breast cancer patients who responder to anti-vascular endothelial growth factor therapy. In this research, 200 cases of histological proved invasive ductal breast carcinomas analyzed for vascular endothelial growth factor expression by immunohistochemical staining via cross-sectional descriptive study. Vascular endothelial growth factor expressed in 72.54% of the breast cancers. The VEGF was more detectable in grade I (78.5%) than grade II (77.4%) and grade III (56.2%). There is a significant correlation between tumor grade and VEGF expression (P<0.05). According to this study, VEGF often expressed in invasive ductal breast carcinomas and inversely correlated with tumor grade. Anti-vascular endothelial growth factor postulated more convenience for tumor progression suppression in low grade tumor than high grade tumor.