The c.1243T>C mutation in the PROC gene is linked with inherited protein C deficiency and severe purpura fulminans.

Purpura fulminans is a severe coagulation disorder that often leads to death in neonates. Mutations in the protein C (PROC) gene can cause protein C deficiency, leading to this disorder. This study aimed to investigate a family with a history of coagulopathies, particularly those related to protein C deficiency. The primary objective was to identify any genetic mutations in the PROC gene responsible for the coagulopathies. The study focused on a male neonate with purpura fulminans who ultimately died at 2 months of age. The patient had low protein C activity levels (6%). The entire PROC gene of the patient and his family was analyzed using next-generation sequencing to identify any genetic mutations. Segregation analysis was conducted to determine if the mutation followed an autosomal dominant inheritance pattern. In silico analysis was also conducted to evaluate the pathogenicity of the identified mutation. Analysis revealed a novel homozygous c.1243T>G variant PROC gene. The mutation resulted in a Phe415Val substitution. The mutation was found in at least three generations of the family. Carrier family members had lower protein C activity levels than wild-type homozygotes. Additionally, the mutation may account for the observed reduction in protein C enzyme activity.

P53, CK20, and FGFR3 Overexpression is Associated with the Characteristics of Urothelial Cell Carcinoma of the Bladder

OBJECTIVES: The aim of this study was to investigate the association between the overexpression of tumor protein (P53), cytokeratin 20 (CK20), fibroblast growth factor receptor 3 (FGFR3), biomarkers and the grading, prognosis, heterogeneity, and relapse tendency of urothelial cell carcinomas (UCCs) of the bladder. METHODS: A cross-sectional study was conducted using 413 samples of Iranian patients diagnosed with UCC of the bladder. The tissue microarray technique was used to evaluate the patterns of tumor tissue. Two pathologists scored tissue staining using a semi-quantitative scoring system. RESULTS: The results showed that P53 was a predictor of a high-grade pattern (the area under the curve (AUC)=0.620) with a best cut-off value of 95.0 using the receiver operating characteristic (ROC) curve. CK20 was another predictor of a high-grade pattern (AUC=0.745) with a best cut-off value of 15. However, the overexpression of both biomarkers was not associated with a heterogeneous pattern and could not predict tumor-associated death or relapse. The heterogeneous (odds ratio (OR)=4.535, p-value=0.001) and non-papillary (OR= 6.363, p-value= 0.001) patterns were effective predictors of tumor recurrence among all baseline variables, including patient and tumor characteristics. FGFR3 was positive in all specimens and was not a valuable biomarker for differentiating patterns. None of the variables predicted tumor prognosis. CONCLUSION: The study findings indicate that the intensity and percentage of cell staining for P53 and CK20 in the UCC of the bladder can aid in differentiating the grading patterns. The tendency of tumor relapse can be predicted by demonstrating heterogeneous and non-papillary patterns.

Impact of Imatinib on reducing the painful crisis in patients with sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is a common hemoglobinopathy worldwide that causes painful crises and hospitalization of patients. These attacks decrease survival and cause chronic end-organ damage in these patients. HYPOTHESIS: For this reason, finding new treatment approaches could be helpful. METHOD: In this study, Imatinib was applied as a mast cell inhibitor to reduce pain crises in these patients. Seven patients resistant to hydroxyurea and folic acid treatment and who had at least four painful crises per year with hospitalization were enrolled in this study with treatment with Imatinib (100 mg, twice daily). Subsequently, the number and duration of hospitalizations, analgesic requirement, the severity of chronic pain, and changes in the hematological parameters of these patients were evaluated before and after the treatment. RESULTS: The data showed that the total number of hospitalizations and the entire duration of hospitalizations were reduced 16 times after treatment with Imatinib, without apparent changes in hematological parameters. Also, the demand for pethidine, tramadol, and nonsteroidal anti-inflammatory drugs (NSAIDs) was reduced in all patients. The average reduction in chronic pain was over 70%. CONCLUSION: This study demonstrates that treatment with Imatinib in patients with SCD or sickle cell anemia (SCA) may be a suitable therapeutic option for reducing painful crises.

Deficiency of adenosine deaminase 2: a challenging differential diagnosis of polyarteritis nodosa.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disorder that was first described in 2014. It is a monogenic disease that is caused by loss-of-function variants in the ADA2 gene. Deficiency of adenosine deaminase 2 involves small- and medium-sized vessels and its clinical presentations include polyarteritis nodosa (PAN)-like features such as livedoid rash, early-onset stroke, hypogammaglobulinemia, hematological abnormalities, and systemic inflammation. Early diagnosis and treatment of DADA2 are crucial as the clinical features could be potentially life-threatening but might be treatable. The first-line treatment of choice in DADA2 is tumor necrosis factor α inhibitors. We aimed to provide an overview of the known pathophysiology, clinical presentations, diagnosis, and treatment of DADA2. A clearer knowledge of DADA2 may help to better diagnose, manage, and improve the clinical outcome of DADA2 patients. However, further studies are required to investigate the genotype-phenotype associations and exact pathophysiology of DADA2.

Late side effects of cancer treatment in childhood cancer survivors.

INTRODUCTION: Childhood cancers are usually treated with chemotherapy and radiation. Therefore, understanding the late side effects of such treatments is important to improve the quality of life in childhood cancer survivors. The present study aimed to investigate the late complications of treatments in childhood cancer survivors. METHODS: This study is a retrospective descriptive study. A total number of 93 cases were enrolled in this study. These cases had a history of childhood cancer documented in their medical records at the Shafa Hospital, Ahvaz, Iran. The age range was 5.9-21.3 years and included 62 males and 31 female patients. RESULTS: Many of the patients at this hospital with childhood cancer had experienced chemotherapy side effects as well as late effects of cancer therapy. Hypothyroidism is a late complication of therapy in thoracic cancers and head/neck tumors with relative frequencies of 23.1% and 12.5%, respectively. Scoliosis was observed in the patients undergoing the ABVD + COPP and 8/1 regimens with relative frequencies of 4% and 50%, respectively. Lower growth percentiles were also late side effects of cancer therapy. The highest relative frequency of growth retardation was observed in the <5 age group (46.7%). Restrictive lung changes had an overall relative frequency of 6.5% in male patients with all types of tumors. Sensorineural hearing loss was observed in patients with leukemia and Hodgkin lymphoma with relative frequencies of 8.7% and 24.0, respectively. CONCLUSION: The occurrence of most side effects could be decreased through early diagnosis, dose adjustment of some drugs, and preventative measures.

Renal cell carcinoma: an overview of the epidemiology, diagnosis, and treatment.

Renal cell carcinoma (RCC) is the most common type of urogenital cancer. It has a mortality rate of 30-40% and is more commonly seen in men than women. In addition to gender, other risk factors of RCC include obesity, hypertension, smoking, and chronic kidney disease. Following the improvements in diagnostic tests, such as CT and MRI imaging, the incidence of patients diagnosed with RCC has rapidly increased over the past decades. The most common type of RCC, based on histological and molecular subtypes, is clear cell carcinoma which occurs frequently due to mutations in the VHL gene. Nephron-sparing surgery is a selective technique to maintain kidneys in patients while radical nephrectomy and partial nephrectomy are used to remove small tumors. In addition to surgical approaches, adjuvant therapy and targeted therapy are applied in patients with metastatic RCC. In this review, we give an overview of the most recent research on RCC which would help physicians to better manage patients with RCC.

Comparing the Efficacy and Side Effects of Intravenous Ibuprofen and Acetaminophen in Pain Control Following Laparoscopic Cholecystectomy.

BACKGROUND: The importance of using effective postoperative analgesia is widely accepted. Systemic opioids are the gold standard for reducing severe pain after surgery, but the side effects have limited the use of adequate doses. We aimed to evaluate the effect of adding intravenous acetaminophen and intravenous ibuprofen to fentanyl on patient-controlled analgesia. METHODS: In this randomized clinical trial study in Ardabil city hospital at 2019, 90 patients undergoing elective laparoscopic cholecystectomy were randomly divided into three groups. The control group (n=30) received normal saline, the acetaminophen group (n=30) received 1g intravenous acetaminophen, and the ibuprofen group (n=30) received 800 mg intravenous ibuprofen. All patients received a pain control by intravenous pump containing fentanyl (15µ/ml). The drugs were injected intravenously after surgery. Shoulder and abdominal pain scores, sedation rate, nausea and vomiting, satisfaction, and the doses of fentanyl and meperidine were recorded in SPSS software within 24 h after surgery. RESULTS: The mean abdominal pain scores in ibuprofen (3.02) and acetaminophen (2.89) groups were not significantly different (P=0.719) but were significantly lower than in the control group (5.10) (P<0.001). The severity of shoulder pain, nausea and vomiting, sedation, and fentanyl intake were not significantly different in the ibuprofen and acetaminophen groups but were significantly lower than in the control group. CONCLUSION: The use of both intravenous acetaminophen and ibuprofen in pain control after surgery can reduce the need for opioid use. Acetaminophen can also be a suitable alternative for postoperative pain control in patients that are unable to use NSAIDs.

Cytomegalovirus colitis in a child with leukemia: a case report.

A 17-month-old boy with a known case of T-cell acute lymphoblastic leukemia was admitted to the authors' hospital because of blood-streaked diarrhea a week after his last chemotherapy session. Initially, he was treated with supportive care and an empiric regimen for opportunistic causes of diarrhea; however, this was not effective. Eventually, evaluation of his stool with PCR showed positivity for cytomegalovirus. Consequently, he responded dramatically to treatment with ganciclovir. Although cytomegalovirus colitis is rare, a few case reports suggest cytomegalovirus as a possible cause of colitis in children with leukemia, which can be fatal and should be considered as a differential diagnosis.

COVID-19-induced immune thrombocytopenic purpura; Immunopathogenesis and clinical implications.

Following the outbreak of the COVID-19 pandemic, millions of people around the world have been affected with SARS-CoV-2 infection. In addition to the typical symptoms, thrombotic events, lymphopenia, and thrombocytopenia have been reported in COVID-19 patients. Immune thrombocytopenic purpura (ITP) is one of the thrombotic events that occur in some COVID-19 patients. Hyperinflammation, cytokine storms, and immune dysregulation in some patients are the cause to the main COVID-19 complications such as ALI (acute lung injury), acute respiratory distress syndrome (ARDS), and multiple organ failure. Disruption in the differentiation of T-cells, enhanced differentiation of Th17 and Th1, cell death (pyroptosis), hyper-inflammation and dysfunction of inflammatory neutrophils and macrophages, and hyperactivity of NLRP3-inflammasome are among the important factors that may be the cause to COVID-19-induced ITP. This study aimed to give an overview of the findings on the immunopathogenesis of ITP and COVID-19-induced ITP. Further studies are required to better understand the exact immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders.

Subcutaneous panniculitis-like T-cell lymphoma in a young girl presenting with periorbital edema and fever: A case report.

Subcutaneous panniculitis-like T-cell lymphoma is a rare and highly malignant extra-nodal lymphoma. It has a wide range of clinical presentations (such as periorbital swelling as in our case) and should be considered in the differential diagnosis of systemic lupus erythematosus, especially in children.

Radiographic Features of the Maxillofacial Anomalies in Beta-Thalassemia Major: With New View.

BACKGROUND: Beta- thalassemia major causes the basic skeletal changes due to ineffective erythropoiesis in suffering patients. The aim of the study was to determine the frequency of maxillo-facial anomalies and the hemoglobin and ferritin levels in patients with beta-thalassemia major compared to the healthy control group. METHODS: The present study was performed on 72 beta- thalassemia major patients and 70 healthy control group in Ahvaz, Southwest Iran, from Jan 2014 to Mar 2015. Panoramic radiographs were taken using a standard procedure. The frequency of abnormalities including enlargement of bone marrow spaces, small maxillary sinuses, thickness of inferior mandibular cortex, prominent antegonial notch, absence of inferior alveolar canal and thin lamina dura, were determined by two Oral and Maxillofacial Radiologist. We also paid to identification of the relationship between abnormalities frequency and hemoglobin and ferritin levels during previous 6 months in thalassemia patients. RESULTS: The mean age of case and control groups was 18.6±7.25 and 17 ± 6. 55 yr, respectively. The frequency of abnormalities in the case and control groups was as follows, enlargement of bone marrow spaces [69 (95.8%) vs 3 (4.3%)], small maxillary sinuses [45 (62.5%) vs 1(1.4%)], reduced thickness of inferior mandibular cortex [21(29.2%) vs 6 (8.6%)], prominent antegonial notch [10 (13.9%) vs 2 (2.9%)], absence of inferior alveolar canal [68(94.4%) vs 41(58.6%)] and thin lamina dura [40 (55.6%) vs 5 (7.1%)]. CONCLUSION: The all above mentioned abnormalities in patients with beta-thalassemia major was higher than the control group. Moreover, the frequency of maxillo-facial abnormalities decreased by increasing hemoglobin and decreasing ferritin.

Inferior Part of Rectus Abdominis Muscle Flap Outcomes after Abdominoperineal Resection: A Case Series Pilot Study.

BACKGROUND: The standard surgical treatment for low rectal cancer is abdominoperineal resection (APR). Comparing to primary closure, immediate flap reconstruction has shown to have good outcomes. We aimed to assess the inferior rectus abdominis muscle flap complications after APR surgery, a new method of reconstruction. METHODS: This study was conducted from 2014 to 2016 in a single center in Firoozgar Hospital, Tehran, Iran. Eighteen patients who underwent pelvic floor closure with inferior part of abdominis rectus musculofascial flap were included enrolled. The sampling method used in this study was census. All patients had distal rectoanal malignancies. A checklist including age, gender, tumor location, complications after surgery, tumor type, length of hospital stay, length of operation, neoadjuvant chemotherapy and neoadjuvant radiotherapy history was filled for all patients. RESULTS: Among 18 participants, 27.8% were female. The mean age of participants was 58.28 ± 17.86 yr (minimum of 19 and the maximum of 89 yr). The pathology of the tumor in all but one of the cases was adenocarcinoma (94.4%). The overall complication rate after surgery was 27.8%. In total, 80% received neoadjuvant chemoradiotherapy. In 12 months follow-up 2 patients needed reoperation. CONCLUSION: Inferior part of rectus abdominis muscle flap was a reliable and comparable means of reconstruction after APR surgery with low rate of complications and mortality.

Effect of White Tea (Camellia sinensis) Extract on Skin Wound Healing Process in Rats.

BACKGROUND: White tea (Camellia sinensis) has anti-inflammatory and antioxidant properties and a protective effect against wrinkles, sunburn and UV damages on the skin. Thus, we aimed to evaluate the effect of white tea extract on the healing process of skin wounds in rats. METHODS: This study was done in the Research Center of Shahrekord University of Medical Sciences, Shahrekord, Iran in 2019. Excisional skin wounds were created on five groups of healthy male Wistar rats (200-250 g, n=21) including control group, Eucerin-treated group, white tea 5% ointment (Eucerin) treated group, gel-treated group, white tea 5% gel treated group. Treatment was begun on day 1 and repeated every day at the same time until day 15. Pathologic samples were taken on days 4, 7 and 15 for histopathological examinations. Kruskal-Wallis test was used to analyze data by SPSS. Statistical significance was defined as P<0.05. RESULTS: Wound closure rate of control group was more than other groups on day 4 (P<0.05). On day 7, reepithelisation and granulation tissue of control group were more than white tea 5% ointment-treated and its inflammation was less than others (P<0.05). Neo-vascularization of white tea 5% ointment-treated group was more than control group on days 4 and 15 (P<0.05). On day 4, intact mast cells of control group were more than white tea treated groups (P<0.05). Degranulated mast cells of white tea 5% gel treated group was significantly (P<0.05) more than control group on days 4 and 15. CONCLUSION: Five percent white tea extract could not help the skin wound healing process.

Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?

Chloroquine and hydroxychloroquine belong to the aminoquinoline drugs. Studies revealed that chloroquine and hydroxychloroquine shows antagonism activity against COVID-19 under laboratory conditions. ARDS and ALI are conditions that occur in patients with COVID-19 as the main pathological complications of cytokine storm. Inflammasomes play a key role in the pathogenesis of many diseases associated with destructive inflammation. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The possible role of NLRP3 inflammasome inhibitors in the treatment of COVID-19 has been considered. We surveyed the potential inhibitory effect of chloroquine and hydroxychloroquine on inflammasome. Studies indicate that one of the possible anti-inflammatory mechanisms of chloroquine and hydroxychloroquine is inhibition of the activity of NLRP3 inflammasome.