Shakiba Hassanzadeh

Hypogammaglobulinemia without B-cells is a subgroup of inborn errors of immunity (IEI) which is characterized by a significant decline in all serum immunoglobulin isotypes, coupled with a pronounced reduction or absence of B-cells. Approximately 80 to 90% of individuals exhibit genetic variations in Bruton’s agammaglobulinemia tyrosine kinase (BTK), whereas a minority of cases, around 5–10%, are autosomal recessive agammaglobulinemia (ARA). Very few cases are grouped into distinct subcategories. We evaluated phenotypically and genetically 27 patients from 13 distinct families with hypogammaglobinemia and no B-cells. Genetic analysis was performed via whole-exome and Sanger sequencing. The most prevalent genetic cause was mutations in BTK. Three novel mutations in the BTK gene include c.115 T > C (p. Tyr39His), c.685-686insTTAC (p.Asn229llefs5), and c.163delT (p.Ser55GlnfsTer2). Our three ARA patients include a novel homozygous stop-gain mutation in the immunoglobulin heavy constant Mu chain (IGHM) gene, a novel frameshift mutation of the B-cell antigen receptor complex-associated protein (CD79A) gene, a novel bi-allelic stop-gain mutation in the transcription factor 3 (TCF3) gene. Three patients with agammaglobulinemia have an autosomal dominant inheritance pattern, which includes a missense variant in PIK3CD, a novel missense variant in PIK3R1 and a homozygous silent mutation in the phosphoinositide-3-kinase regulatory subunit (RASGRP1) gene. This study broadens the genetic spectrum of hypogammaglobulinemia without B-cells and presented a few novel variants within the Iranian community, which may also have implications in other Middle Eastern populations. Notably, disease control was better in the second affected family member in families with multiple cases.

Infection with the SARS-CoV-2 virus causes coronavirus disease 2019 (COVID-19). COVID-19 usually affects the lungs but may also involve other organs such as the heart. We report a case of a para-cardiac mass in a previously healthy 45-year-old male who developed persistent dyspnea following SARS-CoV-2 infection. The patient underwent cardiac surgery since the mass was attached to the pericardium and was causing constrictive pericarditis. The pathology report indicated an inflammatory pattern for the mass. Based on the authors' knowledge there has been no previous report of developing a para-cardiac inflammatory mass after SARS-CoV-2 infection. This report aimed to increase awareness regarding the possibility of developing a para-cardiac inflammatory mass following COVID-19.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive that was first described in 2014. It is a monogenic disease that is caused by loss-of-function variants in the ADA2 gene. DADA2 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 (TNF)-inhibitors. We aimed to give 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.

Background. Acquired factor VIII (FVIII) deficiency or acquired hemophilia A (AHA) is very uncommon in children. Patients with AHA usually present with abnormal or unexpected bleeding which may be life-threatening. These patients usually have unexplained, prolonged, and isolated activated partial thromboplastin time (aPTT). Consequently, FVIII activity should be immediately evaluated. Bleeding prevention is important in patients with AHA.Case report. We present a case of a previously healthy 13-year-old female who presented with intramuscular hematoma, soft tissue hemorrhage, and epistaxis who was eventually diagnosed with AHA.Conclusion. To our knowledge, the present report is one of the few reported cases of an Asian patient that was diagnosed with acquired hemophilia A at a young age.

Background. SCC of the gallbladder is characterized by more rapid and invasive growth with infiltration of the adjacent organs and less spread to the lymph nodes compared to adenocarcinoma of the gallbladder. It is a rare neoplasm that accounts for 1.4–12.7 % of gallbladder tumors. SCC of the gallbladder has a poor prognosis. symptoms usually appear later when the disease has progressed and the malignancy has reached advanced stages. therefore, usually, the patients expire soon following the diagnosis. the etiology of the SCC of the gallbladder is complex and is mostly associated with gallstones. Case description. We report a case of a 56-year-old man that had been suffering from colicky abdominal pain in the right upper quadrant for about two weeks before his admission. He did not have nausea, vomiting, shortness of breath, fever, lack of appetite, or weight loss. after evaluation, a diagnosis of acute cholecystitis was established and antibiotic therapy was initiated. However, he did not respond to medical therapy and underwent surgery. A tumor mass was detected during surgery. therefore, cholecystectomy and extended right hepatectomy were performed. The pathological evaluation of the biopsy specimen revealed squamous cell carcinoma. consequently, he underwent radiotherapy and chemotherapy and was followed up for two years. He acquired complete tumor remission. Conclusion. The present case highlights the requirement of considering further investigation on the histogenesis of SCC of the gallbladder.

COVID-19 (novel coronavirus disease 2019), caused by the SARS-CoV-2 virus, has various clinical manifestations and several pathogenic pathways. Although several therapeutic options have been used to control COVID-19, none of these medications have been proven to be a definitive cure. Transmembrane serine protease 2 (TMPRSS2) is a protease that has a key role in the entry of SARS-CoV-2 into host cells. Following the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptors of the host cells, TMPRSS2 processes and activates the S protein on the epithelial cells. As a result, the membranes of the virus and host cell fuse. Bromhexine is a specific TMPRSS2 inhibitor that potentially inhibits the infectivity cycle of SARS-CoV-2. Moreover, several clinical trials are evaluating the efficacy of bromhexine in COVID-19 patients. The findings of these studies have shown that bromhexine is effective in improving the clinical outcomes of COVID-19 and has prophylactic effects by inhibiting TMPRSS2 and viral penetration into the host cells. Bromhexine alone cannot cure all of the symptoms of SARS-CoV-2 infection. However, it could be an effective addition to control and prevent the disease progression along with other drugs that are used to treat COVID-19. Further studies are required to investigate the efficacy of bromhexine in COVID-19.

Coronavirus disease‐19 (COVID‐19) vaccines are massively administered globally and some adverse events, such as myocarditis, are being reported. Most of the reported cases of post‐vaccination myocarditis have occurred following mRNA vaccinations. However, there have also been recent reports of myocarditis following adenovirus vector vaccinations. We present a case of a 32‐year‐old female patient who developed myocarditis following the administration of the first dose of the AstraZeneca vaccine. The patient developed inappropriate exertional tachycardia and exertional dyspnea from Day 3 and was diagnosed with myocarditis by subsequent echocardiography about 3 months later. We are unable to confirm a direct association between myocarditis and AstraZeneca vaccination. However, we would like to increase awareness regarding the possibility of developing myocarditis following AstraZeneca vaccination.

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. Init...

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.

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.