Localized Administration of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Refractory Perianal Fistula in Crohn's Disease Patients: A Phase II Clinical Trial.

BACKGROUND: Crohn's disease perianal fistulae are often resistant to standard anti-TNF-α therapies. Mesenchymal stem cell (MSC)-derived exosomes are extracellular vesicles that have highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas. OBJECTIVE: To evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas. DESIGN: Nonrandomized, nonblinded single-center phase II clinical trial. SETTINGS: Tertiary university hospital. PATIENTS: Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least one course of treatment with anti-tumor necrosis facto-α therapy. INTERVENTIONS: After clinical assessment and magnetic resonance imaging, the patients were subjected to general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated three times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and six months after the last injection. MAIN OUTCOME MEASURES: The primary outcome of this study was fistula tract closure on clinical examination and magnetic resonance imaging. The secondary outcome was an improvement in the discharge from the tracts. RESULTS: Fistula tracts were fully closed in 12 (60%) of the patients. Four patients showed clinical improvement, with some tracts remaining open, and four patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 (69.7%) of which showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of cluster of differentiation-68, 20 and 31 reaffirmed these results. CONCLUSIONS: MSC-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract.

Effect of vitamin C on adrenal suppression following etomidate for rapid sequence induction in trauma patients: a randomized clinical trial.

BACKGROUND: Etomidate is an imidazole derivative that is widely used in the emergency department for Rapid Sequence Intubation (RSI). Although it has a safe hemodynamic profile, there are some concerns about its suppressant effects on the adreno-cortical axis. Vitamin C, as an antioxidant, can play a protective role in this issue. METHOD: In a controlled clinical trial, we studied adult traumatic patients who needed RSI with etomidate. In one group underwent RSI with etomidate and cortisol levels were measured three hours later. In the other group, we administered one gram of vitamin C before etomidate administration, and the cortisol level was measured three hours later. RESULTS: Fifty-one patients have been studied. The serum cortisol level was significantly lower after RSI with etomidate in both groups. In the Vitamin C group, there was a significantly higher cortisol level after RSI in comparison to the control group. CONCLUSION: Etomidate can suppress the cortisol level in trauma patients who undergo RSI. Vitamin C can reduce this suppressant effect of etomidate. TRIAL REGISTRATION: IRCT registration number: IRCT20090923002496N11, URL of trial registry record: https://en.irct.ir/trial/34586 , Date of trial registration: 19/04/2019. Full date of the first registration: 30/05/2019.

Subtype distribution of lymphomas in northwestern Iran: a retrospective analysis of 659 cases according to World Health Organization classification.

BACKGROUND: The distribution of lymphoma subtypes differs strikingly by geographic variations. However, there is limited information on this research in northern Iran. This study aims to evaluate the incidence, subtype, age, sex, and extranodal distribution of lymphomas diagnosed according to the latest WHO classification in a large referral center in northwest Iran. METHODS: In a retrospective study, the medical records of all patients with a diagnosis of lymphoma made between 2018 and 2021 were retrieved from the pathology archive of Imam Reza Medical Center, Tabriz. Lymphoma diagnosis was also made based on the appreciation of morphologic and immunophenotypic features and genetic characteristics in the context of clinical presentation. RESULTS: This study includes a total of 659 patients with lymphoma diagnosed from 2018 to 2021. The number of lymphoma patients were increased each year, with 51 (7.7%), 96 (14.6%), 244 (40.7%), and 268 (40.7%) reported from 2018 to 2021, respectively. 59% of the patients were men. The participants' mean age was 50.5 ± 19.8 years, while the mean age at diagnosis was 49.3 ± 19.6 years. 2.1% were precursor lymphoid neoplasm, 61.6% were mature B cell neoplasm, 8.8% were mature T cell neoplasm, and 27.5% were Hodgkin lymphoma. The most prevalent subtype of mature B-cell lymphoma was DLBCL (55.1%), followed by SLL (18.7%). Extranodal involvement was seen in 40.5% of all cases. CONCLUSION: The subtype distribution of lymphomas in northwest Iran is reported and compared with studies all over the world and inside Iran.

Plasma Cell Granuloma of the Jaw and the Infratemporal Fossa: A Clinical Case.

Plasma cell granuloma or inflammatory pseudotumor (IPT) is diagnosed by a process of elimination. The precise etiology is unknown, although it can occur after a bout of periodontal infection. This report describes the various stages of progression for this ailment. A 49-year-old woman with no noteworthy medical history presented with a recurrent periodontal abscess accompanied by progressive and severe destruction of the right maxilla. There was invasion of the infratemporal fossa and very tight trismus. Histologic examination indicated a reactive plasma cell granuloma. IPT is an entity recognized by the World Health Organization. A triggering infectious or inflammatory factor is often present. In the maxilla, progression is very aggressive. Treatment relies on corticotherapy, with or without radiotherapy, and administration of cyclosporine.

Subtype distribution of lymphomas in South of Iran, analysis of 1085 cases based on World Health Organization classification.

Lymphoma is one of the most common malignancies worldwide. Subtype distribution is different throughout the world. Some reports from the Middle East are in record. This article is trying to report the subtype distribution of lymphoma in Iran and compare it to that of Western, Far East Asian and Middle Eastern countries. A retrospective study was done on all lymphomas diagnosed in a large referral center in the South of Iran during a time period between 2009 and 2014. All diagnoses have been made according to 2008 WHO classification. A total number of 1085 cases with diagnoses of lymphoma retrieved. Twenty-nine cases (2.6 % of all) were precursor lymphoid neoplasm, 608 cases (56 % of all) were mature B cell neoplasm, 115 cases (10.5 % of all) were mature T and NK cell neoplasm, and 333 cases (30.6 % of all) were Hodgkin lymphoma. The six most frequent subtypes of mature B cell neoplasm were diffuse large B cell lymphoma, NOS (57 %), Burkitt lymphoma (7 %), small lymphocytic lymphoma (6.9 %), mantle cell lymphoma (5.7 %), extranodal marginal zone B cell lymphoma (5.2 %) and follicular lymphoma (3.6 %). Among mature T and NK cell neoplasm, mycosis fungoides was the most common type (43.4 %) followed by peripheral T cell lymphoma, NOS (20 %) and angioimmunoblastic T cell lymphoma (9.9 %). Of Hodgkin lymphoma cases, 90.6 % were classical type and 9.3 % were nodular lymphocyte predominant Hodgkin lymphoma. Extranodal involvement was seen in 42.2 % and GI tract was the most common site. Lymphoma frequencies were similar to that of Middle Eastern countries except for lower rate of follicular lymphoma and higher incidence of diffuse large B cell lymphoma, NOS and small lymphocytic lymphoma.

A Case of Subcutaneous Granuloma Annulare (SGA) in the Scalp of a Child: Histological Findings.

Subcutaneous granuloma annulare is type of granuloma annulare which usually occurs in children. Scalp involvement is rare. The authors report a 3-year-old girl with subcutaneous granuloma annulare confirmed by imaging and histologic findings. No treatment was provided. The patient was followed for 6 months with no considerable complications.

Leukocytoclastic vasculitis in a patient with ankylosing spondylitis: A case report.

Key Clinical Message: Although the concurrent occurrence of vasculitis with AS is uncommon, when patients diagnosed with AS exhibit symptoms including skin petechiae, purpura, abdominal discomfort, malaise, elevated ESR, and reduced complement levels, vigilant monitoring for vasculitis is advisable following the exclusion of secondary vasculitis triggers such as malignancies, infections, and pharmaceutical agents. Abstract: The primary characteristic of ankylosing spondylitis (AS) involves inflammation occurring within the sacroiliac joint and the spine, leading to destruction and eventual ankylosis. A notably infrequent complication associated with AS is vasculitis, with limited reports linking AS to vasculitis. This case study documents a 48-year-old male, diagnosed with HLA-B27-positive AS for the past 15 years, who developed abdominal pain and skin lesions following the cessation of his medication on his own. Subsequent clinical evaluations identified leukocytoclastic vasculitis (LCV) related to AS after excluding all other potential causes of LCV, including drug-related sources, cancer, hepatitis B and C viruses, Henoch-Schönlein purpura (HSP), and IgA nephropathy.

Primary adrenal mantle cell lymphoma mimicking a non-functional retroperitoneal paraganglioma.

Key Clinical Message: Patients presenting with abdominal pain and retroperitoneal mass in radiographic images may be in the early stages of primary adrenal mantle cell lymphoma, which requires histological studies for a definite diagnosis. Abstract: This report presents a 37-year-old woman complaining of ambiguous abdominal pain, with imaging findings revealing a retroperitoneal abdominal mass on the left side of the aorta, and a possible diagnosis of non-functional retroperitoneal paraganglioma. Total laparoscopic excision was performed. Surprisingly, histological examinations revealed features in favor of mantle cell lymphoma.

Castleman disease presenting as lymphadenopathy in a female with systemic lupus erythematosus: A rare case report.

Castleman disease is an infrequent disease that affects the lymph nodes and related tissues. The condition may manifest with lymphadenopathy, characterized by the enlargement of the lymph nodes, alongside additional symptoms such as high fever, nocturnal sweating, exhaustion, and loss of body mass. The diagnosis of Castleman disease typically entails a multifaceted approach that includes a physical examination, imaging modalities, and a biopsy of the lymph nodes that are affected. The selection of treatment modalities is contingent upon the classification and extent of the disease. Systemic lupus erythematosus (SLE) has been identified as a potential risk factor for the development of lymphoma, a condition that may manifest with lymphadenopathy resembling Castleman disease. Hence, it is crucial for individuals diagnosed with SLE and exhibiting lymphadenopathy to undergo a comprehensive assessment to exclude the possibility of any other associated disease. Although lymphadenopathy is a common symptom shared by both Castleman illness and SLE, these diseases have distinct etiologies and are treated in different ways. Seeking advice from a healthcare practitioner is crucial in order to obtain an accurate diagnosis and effective treatment. A 39-year-old female patient with a history of SLE since 18 years ago and lupus nephritis since 6 years ago which treated with Mycophenolic Acid 2 g daily, Hydroxychloroquine 400 mg daily, and low doses of Prednisolone. Also, Mycophenolic Acid has discontinued for her 5 months ago due to the reduction of proteinuria and the control of the disease. Although the association of Castleman Disease with SLE is infrequent, establishing a connection between them could prove advantageous in the treatment and etiology of diseases.

TTP-like syndrome and its relationship with complement activation in critically ill patients with COVID-19: A cross-sectional study.

Background: The covid-19 disease has caused many deaths worldwide since December 2019. Many thromboembolic events, such as VTE and TTP, have been reported since the beginning of this pandemic. Considering the prominent role of complement in developing TTP and TTP-like syndrome in recent studies, this study aimed to assess the prevalence of TTP-like syndrome and its relationship with complement activity in critically ill patients with COVID-19. Method: This study was conducted on 77 COVID-19 patients admitted to the ICU wards of Tabriz Imam Reza hospital from March to June 2021. TTP-like syndrome was diagnosed using a blood specimen for evidence of thrombocytopenia, microangiopathic hemolysis (low hemoglobin, increased LDH level, schistocytes in a peripheral blood smear, and negative direct agglutination test), and end-organ injury, including acute kidney injury or neurological deficit. ADAMTS 13 activity levels could not be achieved owing to logistic issues; therefore, we could not accurately diagnose TTP and TTP-like syndrome based on ADAMTS 13 levels, so to increase the accuracy of diagnosis, we have included people with classical pentad evidence in the TTP-like syndrome group. Complement parameters, including C3, C4, and CH50, were measured. Result: Seven cases of TTP-like syndrome were diagnosed using the previously mentioned criteria, which stands for 9.1% of the study population. Compared with patients without TTP-like syndrome, C3 was significantly lower in patients with TTP-like syndrome (p-value = 0.014), and C4 and CH50 demonstrated insignificant differences between the two groups (p-value = 0.46, p-value = 0.75). Conclusion: Our study showed that the TTP-like syndrome was present in a significant percentage of critically ill patients with COVID-19. Lower C3 levels in TTP-like syndrome-diagnosed patients can indicate complement activation as one of the influential factors in initiating TTP-like syndrome in COVID-19 patients. More studies are recommended to clarify the exact mechanism to achieve adequate therapeutic methods and better manage the disease and its complications.

Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients.

OBJECTIVES: Epigenetic alterations like methylation of tumor suppressor genes or oncogenes, in respiratory epithelium have been associated with lung cancer. Hypermethylation of genes promoter is an epigenetic event, and is responsible to tumor suppressor genes inactivation as well as oncogenes activation. This study aimed to assess the role of methylation status in promoter of RASSF1 and ATIC genes their potential implication in the pathogenesis of lung tumor in Iranian patients. METHODS: In this study, we collected 100 tissue samples (50 lung cancer tissues and 50 adjacent non-cancerous lung tissues) from Iranian lung cancer patients. The genomic DNA was extracted, and methylation status of both RASSF1 and ATIC genes was investigated by methylation-sensitive high-resolution melting (MS-HRM) assay technique and Real-Time PCR. Cancer Genome Atlas (TCGA) dataset was also analyzed for further validation of the gene's methylation. RESULTS: Methylation of RASSF1 gene promoter was significantly higher in lung tumor tissues. However, promoter methylation levels of ATIC gene was significantly lower in lung tumor tissues. These results were additionally confirmed by TCGA analysis. Promoter methylation of both RASSF1 and ATIC genes was significantly associated with lymph node metastasis, and clinical stage of lung cancer. The receiver operating characteristic (ROC) curve analysis indicated a high accuracy of promoter methylation in these genes as a diagnostic biomarker for lung cancer. CONCLUSIONS: Methylation levels of both RASSF1 and ATIC genes promoters were associated with lung cancer pathogenesis in Iranian population, and may be a suitable biomarker for diagnosis and prognosis of lung cancer in early stage of tumorigenesis.

Responsible enzymes for metabolizing vitamin D in patients with acute leukemia and the relationship with treatment outcomes: a case-control study.

Anti-cancer properties of vitamin D have been reported in studies. The aim of this study was to evaluate the expression of some key enzymes involved in vitamin D metabolism and the serum levels of related proteins. Fifty-four patients with acute myeloid leukemia (AML) and 55 eligible individuals were studied as the control group. The expression of VDR, CYP27B1, and CYP24A1 genes was measured. Serum levels of related proteins were quantified. The association between the studied variables and treatment outcomes: duration of fever and neutropenia, length of hospital stay, achievement of complete remission and overall survival has been investigated. Expression of CYP24A1 gene and serum levels of CYP27B1 and CYP24A1 proteins were significantly higher in the patient group. CYP24A1 gene expression, its blood concentrations and serum levels of CYP27B1 were significantly higher in the AML group. Vitamin D status and key enzymes did not show a strong change in AML patients neither did associate with treatment outcomes except CYP24A1.

Rosai-Dorfman disease presenting with solitary liver mass without lymphadenopathy: A case report.

Rosai-Dorfman disease (RDD), as a lymphoproliferative disorder with unknown etiology, is commonly identified with systemic clinical manifestations in various organs. In this case study, RDD occurrence was reported with an exceedingly liver mass.

Synchronous gallbladder squamous cell carcinoma and adenocarcinoma, both as primary tumors in one patient.

INTRODUCTION: Synchronous primary carcinomas of gallbladder are extremely rare. In this paper, we report a case of double primary carcinomas in gallbladder CASE REPORT: A 65 year old male was admitted to the hospital for surgical removal of gallbladder, which was diagnosed as cholecystitis in ultrasonography. Macroscopic examination disclosed a single whitish mass in gallbladder neck and another distinct mass in the fundus as wall thickening. Pathologic findings revealed squamous cell carcinoma of the neck and adenocarcinoma in the fundus. DISCUSSION: This study represents an example of misdiagnosis. Being cautious is mandatory in order to manage the patient properly. CONCLUSION: Synchronous primary carcinomas of gallbladder are rare. However this diagnosis should be taken into account in patients with cholecystitis features in order to seeking for the best surgical approach.

Mixed-phenotype acute leukemia characteristics: first report from Iran.

Mixed-phenotype acute leukemia (MPAL) is the infrequent type of acute leukemia characterized by immunophenotypic and/or cytochemical features of both lineages, but the diagnosis of this disease still is a challenge. In this study, we analyzed immunophenotyping, cytochemistry and frequency of MPAL patients to better diagnosis of MPAL characteristics according to WHO 2016 criteria for the first time in Iran. In this retrospective study, 27 patients were diagnosed as MPAL based on WHO 2016 criteria during 2014-2017. Flow cytometric immunophenotyping was performed on PB and BM samples evaluation of different CD marker expressions in MPAL subsets. RT-PCR was performed for the analyses of BCR/ABL1 fusion in MPAL subsets. Among 27 cases, (70.4%) 19 cases were B + My, (22.22%) 6 cases were T + My, and 2 cases (7.40%) were B + T + My. CD34, CD19, HLA-DR, TdT, CD22, iMPO were positive in majority of B + My cases. CD45, iMPO, iCD3, CD7, CD2 and CD5 were positive in majority of T + My cases. HLA-DR, TdT, CD10, CD22, iCD79a, iMPO, CD45, iCD3, CD7, CD3, CD2, CD5 were positive in majority of B + T + My cases. BCR/ABL1 fusion was positive for 3 cases (11.1%) of p190 fusion and 2 cases (7.4%) of p210 fusion in B + My cases. WHO 2016 criteria are the current standard for diagnosing MPAL. Also, evaluation of TdT, CD2, CD5, CD7 expressions by flow cytometry in EGIL criteria is useful for the better diagnosis of MPAL subsets. In addition, evaluation of BCR/ABL1 and MLL rearrangements in patients should be part of standard work-up in MPAL.

Cervical osteochondroma with neurological symptoms: literature review and a case report.

INTRODUCTION: Osteochondromas are common benign tumors of bone and spinal involvement is uncommon. Solitary spinal osteochondromas may produce a wide variety of symptoms depending on their location and relationship to adjacent neural structures. CASE PRESENTATION: Herein, we present a case of solitary osteochondroma arising from the posterior arch of C1, causing left-sided ascending numbness and paresthesia and difficulty walking. The lesion was totally resected through a posterior approach. Histopathological examination confirmed the diagnosis of benign osteochondroma. DISCUSSION: Spinal cord compression is uncommon in spinal osteochondromas because in most cases the tumor grows out of the spinal column. To prevent neurological compromise, complete surgical removal is mandatory when an intraspinal osteochondroma with cord compression is diagnosed, which also helps to prevent recurrence. Our literature review of similar cases indicates that despite the old belief that C2 is the most commonly involved vertebra for osteochondromas, C1 is actually the most commonly involved vertebra in the cervical region.

Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

BACKGROUND: Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. MATERIALS AND METHODS: Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. RESULTS: There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. CONCLUSION: Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

Gender Differences in Clinical Presentations of Cystic Fibrosis Patients in Azeri Turkish Population.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder with several clinical presentations. This study was undertaken in the Azeri Turkish population in Iran, to investigate gender differences in the age at onset and diagnosis, age of death, and duration of illness of CF. METHODS: The data of 331 CF patients from 2001 to 2015 was surveyed. Parameters including age, sex, ΔF508 mutation, age at onset, age at diagnosis, age of death and clinical presentations were evaluated for both sexes, using descriptive analysis. The association of gender with these variables was studied using logistic regression, chi-square test and Mann-Whitney U test by SPSS version 18. Odds ratio with a confidence interval of 95% and p≤0.05 was considered statistically significant. RESULTS: The study included 191 males (57.7%) and 140 females (42.3%), all showing statistically significant difference (p<0.001). Age duration differed between genders. Male and female patients were further under 9 and 4 years, respectively. The occurrence of ΔF508 mutation was 0.51 times more in females than in males. Age, diagnosis and sex were closely associated: males were diagnosed at a significantly later age than females (p=0.05). While this compression performed based on clinical presentations, males with respiratory disease had a later median age at diagnosis than females at lifespan (p=0.001). The risk of infertility in males was approximately two times greater than in females (p=0.02). CONCLUSION: These findings indicate gender differences in CF patients. Future studies are needed to establish other differences and evaluate the causes for the gender variations.