Genotype-phenotype analyses of Iranian patients with hemophilia B (Leyden -) and hemophilia B (Leyden +): A single-center study.

BACKGROUND: There is a high prevalence of inherited bleeding disorders in Iran, such as hemophilia A (HA) and hemophilia B (HB). This study aimed to analyze the molecular and clinical profiles of patients with HB. METHODS: A single-center study was conducted among patients with severe HB between March 20, 2000, and June 31, 2023. The polymerase chain reaction (PCR) amplification was used for all of the major regions, such as the promoter, the exons, the adjacent intronic regions, and the untranslated regions of the F9 gene. Finally, Sanger sequencing was performed on the PCR products. RESULTS: A total of 111 HB patients (17 with HB [Leyden +] and 94 with HB [Leyden -]) were enrolled in this study. Among 94 patients with HB (Leyden -), 59 (62.8 %) had missense, 21 (22.3 %) had nonsense, and 8 (8.5 %) had frameshift mutations. Moreover, the most frequent pathogenic variant in HB (Leyden +) was c.-17 A>G in this study. CONCLUSION: The results of this study confirm that HB is caused by a wide range of molecular defects in Iran. Thus, by knowing the genotypes and phenotypes, we would be able to stratify the patients which is important in terms of their management and outcome.

Falling and rising in the vortex of cancer: children's adaptation with cancer: a qualitative study.

BACKGROUND: Cancer is a considerable health problem worldwide and the second leading cause of death in children. It has many physical, psychological, and social consequences for children and their families. The ability to adapt to cancer plays a vital role in the recovery and quality of life of affected children. This study aimed to explain the adaptation of children with cancer to their disease. METHODS: This qualitative study adopted the directed content analysis approach based on the Roy nursing model. The participants were nine children with cancer aged 6-18 years old, five family members, four nurses, one doctor, one teacher, and two charity association members, recruited by purposive sampling method. The information was collected via individual semi-structured interviews, a focus group discussion, and field notes. The data were analyzed simultaneously with data collection using the Elo and Kyngäs method. The study rigor was ensured based on the Guba and Lincoln criteria. FINDINGS: Of the four categories of physical challenges, fragile self-concept, the difficulty of role transition, and disruption of the path to independence, the theme of Falling and rising in the cancer vortex was abstracted. CONCLUSION: Based on the Roy model, the children in the present study were at the compensatory level of adaptation. This research demonstrates that the adaptation of children being treated for cancer is fragile and not constant. With each hospitalization and exacerbation of the disease, they made efforts to adapt to their disease using regulatory and cognitive subsystems. Paying attention to different stimulants and the effects of support systems on physical challenges, fragile self-concept, difficult role transition, and disruption of the path to independence for each child, as well as providing individualized care for these children, can help their adaptation to and healthy transition from the vortex of cancer. The Roy adaptation model was helpful and efficient for elucidating the adaptation of children with cancer. Providing care for children by healthcare specialists, especially nurses, should be theory-based and individualized.

Evolution of neuroimaging findings in angioinvasive cerebral aspergillosis in a pediatric patient with leukemia during long-term observation.

The central nervous system is one of the most common sites of aspergillosis involvement in immunocompromised people, just after sinopulmonary infections. Neuroimaging modalities are crucial for the diagnosis of cerebral aspergillosis (CA). Here, we describe a rare case of concurrent mixed aspergillosis infection with Aspergillus fumigatus and Aspergillus niger in a 2-year-old leukemic boy. The first neuroimaging finding, which was followed by focal seizures, was recognized as extensive cerebral hemorrhage in the absence of thrombocytopenia and coagulopathy. As the patient survived for more than 4 months after diagnosis, we were able to perform a neuroimaging evaluation during long-term observation. In serial neuroimaging studies, a secondary fungal abscess was observed at the site of hemorrhagic infarctions. Finally, the patient died from bacterial sepsis. In this case study, we try to categorize the neuroimaging findings of CA into distinct phases to better understand how CA changes over time.

Bleeding disorder of unknown cause: Results from Iranian study.

BACKGROUND: Definite diagnosis of patients with mild to moderate bleeding is challenging. Some studies reported that even more than 50% of their patients remained undiagnosed which is classified as a Bleeding disorder of unknown cause (BDUC). This study aims to document the clinical characteristics and proportion of patients with BDUC in the Iranian Comprehensive Hemophilia Care Center (ICHCC) one of the referral centers for diagnosis of congenital bleeding disorder in Iran. METHODS: This study was conducted on 397 patients who were referred with a bleeding manifestation to ICHCC from 2019 to 2022. Demographic and laboratory data were documented for all patients. Bleeding questionnaires including ISTH-Bleeding Assessment tool (ISTH-BAT) and the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 (MCMDM-1 (ISTH-BAT, MCMDM-1, and the Pictorial Bleeding Assessment Chart (PBLAC) were filled out for all patients. The data were analyzed by the statistical package for social science (SPSS version 22, SPSS, Chicago, Illinois, USA). RESULTS: BDUC was diagnosed in 200 patients and 197 patients reached the final diagnosis. Hemophilia, von Willebrand disease (VWD), factor (F) VII deficiency, and platelet functional disorders (PFDs) were confirmed in 54, 49, 34, and 15 of the patients, respectively. No significant difference was found in bleeding scores between patients with BDUC and those with confirmed disease. In contrast, after setting cut-off (ISTH-BAT for males ≥ 4 and females ≥ 6 and MCMDM-1 for males ≥ 3 and females ≥ 5) clinically significant difference was found. There was no association between having a positive consanguineous marriage and setting a diagnosis; however, significant associations were seen for having a positive family history of bleeding. Age (OR =0.977, 95% CI.965-0.989), gender (BDUC female, 151/200; final diagnosis female, 95/197) (OR=3.3, 95% CI 2.16-5.06), family history (OR = 3.19, 95% CI 1.99-5.11), and consanguineous marriage (OR=1.59, 95% CI 1.03-2.45) were considered as a risk factor for categorizing the patients with BDUC or final diagnosis. CONCLUSION: The findings are mainly in line with previous studies about BDUC patients. The large number of patients with BDUC underlines the incompleteness of available routine laboratory tests and shows the necessity of progress in the development of reliable diagnostic tools to identify underlying bleeding disorders.

Antibody waning after immunosuppressive chemotherapy and immunomodulators, re-immunization considerations in pediatric patients with malignancy and chronic immune thrombocytopenic purpura.

INTRODUCTION: Immunosuppressive chemotherapy increase the risk of vaccine-preventable infectious diseases in children; nevertheless, chemotherapy may result in delay or miss updated immunization schedules. The predictable antibody waning after incomplete primary immunization series may be intensified at the end of chemotherapy. This study aimed to investigate post-chemotherapy vaccine immunity waning at the end of immunosuppressive therapy in children with malignancy and hematologic disorders. MATERIALS AND METHODS: Children with malignancies and hematologic disorders including chronic immune thrombocytopenic purpura (ITP) younger than 18 years old were enrolled from September 2015 to August 2019. Eligible patients who completed their treatment protocol for at least 6 months were recruited. The patient information, including sex, age at the date of diagnosis, number of chemotherapy sessions, underlying disease, and vaccination history, was taken by chart review using predefined questionnaires. The patient's blood samples were obtained, and serum IgG antibody titer checked against diphtheria, tetanus, hepatitis B virus (HBV), mumps, measles, and rubella (MMR) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: 110 children receiving immunosuppressive chemotherapy were recruited. Forty-four (40%) of the children tested were girls and 66 (60%) were boys. The mean age of patients was 5.5 years with a range of 2 to 13 years. Of 110 studied children, 27.3% were seronegative for all antibodies. On average, patients undergo 19 episodes of chemotherapy. The mean chemotherapy sessions were significantly greater in children who were seronegative for all tested antibodies (mean: 36.2, 95% CI 33.16 to 39.24, p-value < 0.001). No statistically significant differences were observed regarding the patient's sex and age between the seropositive and seronegative groups (p-value 0.513 and 0.060, respectively). Based on Poisson regression model analysis, the female gender was associated with 37% lower odds of seronegativity (incidence rate ratio (IIR): 0.63; [95% conf. interval: 0.39 to 1.01, p-value: 0.55]), while chemotherapy sessions 30 or more was associated with significant odds of seronegativity for all tested vaccines (IIR: 25.41; [95% conf. interval: 6.42 to 100.57, p-value < 0.001]). CONCLUSION: Our results reemphasized planned catchup immunization in children undergoing immunosuppressive chemotherapy for malignancy, especially against tetanus, diphtheria, and hepatitis B at least 6 months after the end of chemotherapy sessions.

Cutaneous diphtheria complicated oncologic reconstruction surgery in osteosarcoma.

Diphtheria is an uncommon bacterial infection of the upper respiratory tract. We described a surgical site infection in a young adolescent female on maintenance chemotherapy. Corynebacterium diphtheriae was recovered from the wound, and she was treated with antibiotics and antitoxin. Cutaneous diphtheria should be considered in immunocompromised patients receiving chemotherapy.

Clinical Manifestations and Therapeutic Findings of the Children with Glucose-6-Phosphate Dehydrogenase Deficiency Presenting Favism.

AIM: Favism is characterized as acute anemia, due to Glucose-6-phosphate dehydrogenase (G6PD) deficiency as a result of fava beans intake. It is associated with paleness, jaundice, and hemoglobinuria. In this study, signs, symptoms and therapeutic findings of the patients with hemolysis due to G6PD deficiency were investigated in Shahid Madani Hospital of Khorramabad, Lorestan. METHODS: This is a single-center cross-sectional descriptive study that was conducted on all children with G6PD deficiency-induced hemolysis. RESULTS: 308 children (64.3% male and 35.7% female) were included in this study. The most common complaint was jaundice (82.5%) and the most common cause of hemolysis was the intake of fava bean (85.7%). 68% of the children were treated with hydration/fluid therapy. Blood transfusion was conducted in 36.36% of the cases and the mean of blood administered was 18.9 cc/kg. CONCLUSION: In this study, hydration therapy was performed in most of the children presenting favism. Also, the incorrect calculation of the amount of blood needed for transfusion increased the frequency of blood transfusions and prolonged hospitalization time.

Serum Concentrations of Vitamin D, Calcium, Phosphorus and Trace Minerals in Adults and Children with Haemophilia A: Association with Disease Severity, Quality of Life, Joint Health and Functional Status.

Background : To investigate the serum levels of 25(OH)D and minerals in adults and children with haemophilia A, and the possible association of these factors with Pediatric Haemophilia/Haemophilia Activities List (PedHAL/HAL), Haemophilia Joint Health Score (HJHS) and Haemophilia-specific quality of life (QoL) index this case-control study was conducted. Materials and Methods: Eighty five haemophilia A patients (HP) registered in Hemophilia Society of Lorestan province were recruited. Along with HP, sex and age matched healthy controls (HCs) were recruited. Linear regression was used to evaluate the possible relation between biochemical factors and other variables. One-way analysis of variance (ANOVA) was used to compare the biochemical factors between three or more independent groups. Results: Results indicated that serum zinc, phosphorus and magnesium were significantly lower, whereas, serum level of alkaline phosphatase (ALP) was statistically higher in HP compared with HCs. Other biochemical factors including calcium and parathyroid hormone (PTH) were not different between groups. Serum 25(OH) D was lower only in children with haemophilia and not in adults. Percentage of subjects who were vitamin D deficient was higher in HP vs. HCs (57.6% vs. 35.3%), and also this rate was higher in children with haemophilia vs. adults (77.8% vs. 48.3%). Lower serum concentrations of assessed minerals and vitamin D were associated with lower physical activity, poor QoL and worst joint health, and these associations were stronger in children. Conclusion: Present study indicated that serum levels of vitamin D and minerals were low in HP, and these low levels were associated with poor QoL, lower physical activity and worst joint health.

Metronomic Chemotherapy for Children in Low- and Middle-Income Countries: Survey of Current Practices and Opinions of Pediatric Oncologists.

PURPOSE: Low- and middle-income countries (LMICs) experience the burden of 80% of new childhood cancer cases worldwide, with cure rates as low as 10% in some countries. Metronomics combines frequent administrations of low-dose chemotherapy with drug repurposing, which consists of using already-approved drugs for new medical applications. With wide availability, limited costs, and little infrastructure needs, metronomics can be part of constraint-adapted regimens in these resource-limited settings-with the understanding that metronomics shall not be a substitute for standard treatments when available and doable. Our study aims to describe the experience, practices, opinions, and needs in metronomics of physicians working in LMICs. METHODS: An online questionnaire was sent to more than 1,200 physicians in pediatric oncology networks in LMICs. Items included the type of center, physician's demographics, experience in pediatric oncology, and experience with current knowledge of metronomics. Opinions and perspectives were explored using multiple-answer and open questions. RESULTS: Of physicians, 17% responded. Of respondents, 54.9% declared that they had already used a metronomic regimen. The most frequently cited repositioned drugs were celecoxib (44%) followed by propranolol and valproic acid (17%). Respondents highlighted the advantages of outpatient use (20%) and expected low toxicity (24%). In considering the drawbacks of metronomics, 47% of responses highlighted the lack of scientific evidence or guidelines, 33% the availability or affordability of drugs, and 18% the problem of acceptance or compliance. Of physicians, 79% believed that use of metronomics will spread in LMICs in the near future and 98% of them were willing to participate in international metronomic protocols or registries. CONCLUSION: Metronomics is already used in LMICs and is a potential answer to unmet needs in pediatric oncology. There is room for improvement in the availability of drugs and a necessity to develop collaborative protocols and research to generate level A evidence.

Expression of antiapoptotic proteins livin and survivin in pediatric AML patients, as prognostic markers.

OBJECTIVE: Survivin and livin are highly expressed in various malignancies and their expression levels may be related to unfavorable prognosis. The aim was to investigate the relationships of these two markers with some prognostic factors and with survival of the children with acute myeloid leukemia (AML). METHODS: Livin and survivin expression was investigated quantitatively by immunohistochemistry staining technique in 43 primary formalin-fixed, paraffin-embedded bone marrow blocks in pediatric age group (<18 years). RESULTS: Both survivin and livin were expressed in 81.4% of AML patients. Livin expression showed significant positive association with high level of primary WBC (p = .002). Survivin expression showed significant positive correlations with risk of relapse (p ≤ .001) and high level of primary WBC (p = .003). The relationship of overall survival (OS) of the patients with livin and survivin expression, were investigated separately in disease subtypes. Significant association was observed between survivin expression and shorter OS regardless of subtypes including acute promyelocytic (APL) (p = .01) and nonacute promyelocytic leukemia (non-APL) (p = .008). Also, significant association of livin expression with shorter OS was detected, but only in APL subgroup (p = .046). Nevertheless, in Cox regression model after adjusting for disease subtypes, stage and cytogenetics; survivin and livin showed no significant association with OS (p > .05). CONCLUSION: Livin and survivin showed significant associations with some poor prognostic factors of AML. Although survivin in both subtypes and livin in non APL subtype, showed a significant relationship with shorter OS, none of them was determined as independent prognostic factors. Further studies with larger sample size are suggested.

Hypo-pigmented mycosis fungoides is a rare malignancy in pediatrics.

Hypopigmented mycosis fungoides (HMF) is an uncommon form of cutaneous T-cell lymphoma. It can be seen in children and is usually mistaken for eczema, vitiligo, or progressive macular hypomelanosis, clinically and histopathologically. We present a boy with HMF confirmed by histopathology. The patient had a course with slow clinical progression without Sezary syndrome.

Colonic basidiobolomycosis with liver involvement masquerading as gastrointestinal lymphoma: a case report and literature review.

Basidiobolomycosis is an unusual fungal skin infection that rarely involves the gastrointestinal tract. This study reported a 5-year-old boy with gastrointestinal basidiobolomycosis that had been misdiagnosed as gastrointestinal lymphoma. He was treated by surgical resection and a combination of posaconazole and amphotericin B deoxycholate with an acceptable response and no recurrence.

Colonic basidiobolomycosis with liver involvement masquerading as gastrointestinal lymphoma: a case report and literature review

Abstract Basidiobolomycosis is an unusual fungal skin infection that rarely involves the gastrointestinal tract. This study reported a 5-year-old boy with gastrointestinal basidiobolomycosis that had been misdiagnosed as gastrointestinal lymphoma. He was treated by surgical resection and a combination of posaconazole and amphotericin B deoxycholate with an acceptable response and no recurrence.

Comparison Effect of Intravenous Ketamine with Pethidine for Analgesia and Sedation during Bone Marrow Procedures in Oncologic Children: A Randomized, Double-Blinded, Crossover Trial.

Background: Children suffering from cancer always require pain relief and reduce anxiety when undergoing painful procedures. The aim of this study is to compare the effect of pethedine and ketamine administration in cancer-diagnosed children undergoing bone marrow aspiration and biopsy procedures. Subjects and Methods: A randomized, double-blinded, crossover trial was carried out on 57 children undergoing painful procedures (bone marrow aspiration/biopsy). Patients were randomly assigned in a double-blinded fashion to receive either intravenous pethedine (1 mg/kg/dose) or ketamine (1 mg/kg/dose), respectively. The effectiveness of the drug was measured utilizing three parameters; perception of procedural pain with Wong-Baker Faces Pain Rating Scale and Richmond Agitation-Sedation Scale (RASS), hemodynamic changes and respiration and the frequency of vomiting nausea score. Results: Additionally, hemodynamic stability and pain control were significantly better in the patients receiving ketamine (p<0.05, at 0, 15, 30 min). Nausea and vomiting were more frequent in Group K than in Group M but there were no significant differences. No serious complications were observed. Conclusion: This study showed that intravenous ketamine generated a superior clinical effect in decreased pain. Ketamine may also be recommended as a reasonable option before oncology procedures in children suffering from cancer.

Current strategies against invasive fungal infections in patients with aplastic anemia, strong power and weak weapon, a case report and review of literature.

We report an 18 year old boy with Aplastic anemia complicated by serious fungal rhinosinusitis. Despite prompt treatment and early repeated surgical debridements, he died after about more than 6 weeks of hard challenges with fungal infections. Current strategies against invasive fungal infections (IFIs) in patients with Aplastic anemia may be inadequate for the management of serious complications. Antifungal prophylaxis is highly recommended in pre-transplant period for severe form of Aplastic anemia.

A case report of simultaneous occurrence of Wilms tumor and acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most and Wilms tumor is the sixth most common malignancy in childhood. Genetic changes in WT1 or WT2 in Wilms tumor and a wide range of chromosomal mutations are reported in ALL that may predispose them to other congenital anomalies especially in Wilms tumor patients. Hospitalized patient was a 3-year-old girl with high-grade fever, petechia, and solid abdominal mass. The patient had anemia, thrombocytopenia, and leukocytosis in her initial homogram, and a large renal mass originated from left kidney in abdominal imagings. Bone marrow aspiration revealed ALL, and simultaneous kidney biopsy uncovered her Wilms tumor. Leukemia and Wilms tumor are 2 independent malignancies but occurred together in this patient. It is reasonable to investigate cellular and genetic relation of these 2 independent malignancies.

Cyclosporine in the treatment of a case of fulminant and refractory acute disseminated encephalomyelitis.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare, monophasic, demyelinating disease of the CNS which sometimes could be refractory to traditional treatment. CASE PRESENTATION: We present a case of fulminant ADEM which is treated with combination of corticosteroid, intravenous immunoglobulin and cyclosporine. CONCLUSION: Immunosuppressive agents such as cyclosporine may be effective especially in fulminant form of the disease.