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1.
Dtsch Med Wochenschr ; 149(10): 569-578, 2024 May.
Article in German | MEDLINE | ID: mdl-38657596

ABSTRACT

The first patients positive for SARS-CoV-2 were registered in December 2019. In March 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a global pandemic, the beginning of a worldwide health crisis that revealed numerous medical challenges for healthcare systems and pandemic emergency strategies.Among these challenges, mucormycosis, a typically rare fungal infection, gained global attention. With an average global incidence of about 2 per 1 million people, mucormycosis is considered a very rare disease, an opportunistic infection mostly affecting the lungs or skin and soft tissues in immunocompromised patients. Poorly controlled diabetes mellitus is one of the leading risk factors for rhino-orbital mucormycosis. Countries with a high prevalence of diabetes and limited healthcare resources have higher mucormycosis rates, with India and Pakistan being among the nations with particularly high incidences.During the second wave of the COVID-19 pandemic in India, mucormycosis rates surged dramatically within a few weeks, with over 47,500 cases of COVID-19-associated mucormycosis (CAM) reported between May and August 2021. Mucormycosis is characterized by a high mortality rate of up to 90%, especially when the diagnosis is delayed, and treatment commences late. There were concerns about a potentially global threat.In this article, we explore the risk factors and mechanisms leading to this viral-fungal coinfection. We present global distribution patterns, clinical presentation, and challenges in the diagnosis and treatment of COVID-19-associated mucormycosis.


Subject(s)
COVID-19 , Mucormycosis , Humans , COVID-19/epidemiology , COVID-19/complications , Mucormycosis/epidemiology , Mucormycosis/diagnosis , Mucormycosis/therapy , Risk Factors , SARS-CoV-2 , Antifungal Agents/therapeutic use , Pandemics
2.
Mycopathologia ; 189(2): 25, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38466469

ABSTRACT

The European Confederation of Medical Mycology (ECMM), formed due to the surge in invasive fungal infections (IFI), initiated the Excellence Centers program in 2016 to guide stakeholders to leading medical mycology sites. This report focuses on the Cologne ECMM Excellence Center, recognized with Diamond status for active global involvement in 2017. The center offers free consultation via email and phone, responding within 24 h for life-threatening IFI, collecting data on origin, pathogens, infection details, and more. Over two years, 189 requests were received globally, predominantly from Germany (85%), mainly involving Aspergillus spp., Mucorales, and Candida spp. Fungal mixed infections occurred in 4% of cases. The center's service effectively addresses IFI challenges, advocating for a comprehensive study encompassing all ECMM Excellence Centers to enhance global mycological care. Proactive expansion of consultancy platforms is crucial, with future analyses needed to assess expert advice's impact on patient outcomes.


Subject(s)
Invasive Fungal Infections , Mycoses , Humans , Mycology , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Mycoses/drug therapy , Aspergillus , Referral and Consultation , Antifungal Agents/therapeutic use
3.
J Antimicrob Chemother ; 77(10): 2850-2858, 2022 09 30.
Article in English | MEDLINE | ID: mdl-35929089

ABSTRACT

BACKGROUND: Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients. OBJECTIVES: To analyse clinical presentation, predisposing factors, treatment and outcome of Trichoderma infections. METHODS: A systematic literature review was conducted for published cases of invasive Trichoderma infection in PubMed until December 2021 and by reviewing the included studies' references. Cases from the FungiScope® registry were added to a combined analysis. RESULTS: We identified 50 invasive infections due to Trichoderma species, including 11 in the FungiScope® registry. The main underlying conditions were haematological malignancies in 19 and continuous ambulatory peritoneal dialysis (CAPD) in 10 cases. The most prevalent infection sites were lung (42%) and peritoneum (22%). Systemic antifungal therapy was administered in 42 cases (84%), mostly amphotericin B (n = 27, lipid-based formulation 13/27) and voriconazole in 15 cases (30%). Surgical interventions were performed in 13 cases (26%). Overall mortality was 48% (n = 24) and highest for allogeneic HSCT and solid organ transplantation (SOT) recipients [80% (4/5) and 77% (7/9), respectively]. In patients treated with amphotericin B, voriconazole and caspofungin, mortality was 55% (15/27), 46% (7/15) and 28% (2/7), respectively. Three out of four patients treated with a combination therapy of voriconazole and caspofungin survived. CONCLUSIONS: Despite treatment with antifungal therapies and surgery, invasive Trichoderma infections are life-threatening complications in immunocompromised patients, especially after HSCT and SOT. In addition, Trichoderma spp. mainly affect the lungs in patients with haematological malignancies and the peritoneum in CAPD patients.


Subject(s)
Hematologic Neoplasms , Trichoderma , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Caspofungin , Hematologic Neoplasms/complications , Humans , Registries , Voriconazole/therapeutic use
4.
J Clin Lipidol ; 15(5): 690-698, 2021.
Article in English | MEDLINE | ID: mdl-34304999

ABSTRACT

BACKGROUND: Sitosterolemia is a rare lipid disorder caused by mutations in adenosine triphosphate-binding cassette genes (ABCG) 5 and 8. OBJECTIVE: To evaluate the phenotypic/genotypic features of sitosterolemia in a group of Turkish patients. METHODS: Seven probands with unexplained hematologic abnormalities and their 13 relatives were enrolled. Sterol levels were measured by gas chromatography and genetic studies were performed using Sanger sequencing. Individuals were diagnosed with sitosterolemia if they were found to have frankly elevated sitosterol level >15 µg/mL and/or pathogenic variants of the ABCG5/ABCG8. RESULTS: The seven probands and their six relatives  were diagnosed with frank sitosterolemia, and all these patients had hematologic abnormalities. The remaining seven relatives were asymptomatic heterozygous carriers. Three novel variants in the ABCG5 gene (c.161G>A, c.1375C>T, IVS10-1G>T), one novel variant in the ABCG8 gene (c.1762G>C) and one known variant in the ABCG5 gene (c.1336 C>T) were identified. No variant was identified in one case. The mean sitosterol level was significantly higher and mean platelet count was significantly lower in patients with homozygous variants compared to heterozygous variants (p<0.05, for all). Diets low in plant sterols were recommended for 13 symptomatic cases. Four homozygotes received ezetimibe, and their splenomegaly, anemia, and thrombocytopenia completely resolved except one. CONCLUSION: The five pathogenic variants identified in this study indicate the genetic heterogeneity of sitosterolemia in Turkish population. Patients with unexplained hematologic abnormalities (specifically macrothrombocytopenia) should have their sterol level measured as initial testing. Ezetimibe can be a good choice for sitosterolemia.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics , Hypercholesterolemia/blood , Hypercholesterolemia/genetics , Intestinal Diseases/blood , Intestinal Diseases/genetics , Lipid Metabolism, Inborn Errors/blood , Lipid Metabolism, Inborn Errors/genetics , Lipoproteins/genetics , Mutation , Phytosterols/adverse effects , Sitosterols/blood , Adolescent , Adult , Biomarkers/blood , Child , Child, Preschool , Chromatography, Gas , Female , Genotype , Heterozygote , Humans , Hypercholesterolemia/diagnosis , Intestinal Diseases/diagnosis , Lipid Metabolism, Inborn Errors/diagnosis , Male , Middle Aged , Phenotype , Phytosterols/blood , Phytosterols/genetics , Sequence Analysis, DNA/methods , Turkey , Young Adult
5.
J Antimicrob Chemother ; 76(6): 1593-1603, 2021 05 12.
Article in English | MEDLINE | ID: mdl-33599275

ABSTRACT

OBJECTIVES: To provide a basis for clinical management decisions in Purpureocillium lilacinum infection. METHODS: Unpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed. RESULTS: We identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22). CONCLUSIONS: P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.


Subject(s)
Paecilomyces , Amphotericin B , Antifungal Agents/therapeutic use , Humans , Hypocreales , Microbial Sensitivity Tests , Voriconazole
6.
Emerg Infect Dis ; 27(4): 1077-1086, 2021.
Article in English | MEDLINE | ID: mdl-33539721

ABSTRACT

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.


Subject(s)
Aspergillus fumigatus/isolation & purification , COVID-19 , Intensive Care Units/statistics & numerical data , Pulmonary Aspergillosis , Voriconazole/therapeutic use , Aged , Antifungal Agents/therapeutic use , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Incidence , International Cooperation , Male , Outcome and Process Assessment, Health Care , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/mortality , Registries , Respiration, Artificial/methods , Risk Factors , SARS-CoV-2/isolation & purification
7.
J Antimicrob Chemother ; 76(3): 765-774, 2021 02 11.
Article in English | MEDLINE | ID: mdl-33254240

ABSTRACT

OBJECTIVES: To provide a basis for clinical management decisions in Paecilomyces variotii infection. METHODS: Unpublished cases of invasive P. variotii infection from the FungiScope® registry and all cases reported in the literature were analysed. RESULTS: We identified 59 cases with P. variotii infection. Main baseline factors were presence of indwelling devices in 29 cases (49.2%), particularly peritoneal catheters (33.9%) and prosthetic heart valves (10.2%), haematological or oncological diseases in 19 (32.2%), major surgery in 11 (18.6%), and diabetes mellitus in 10 cases (16.9%). The most prevalent infection sites were peritoneum (n = 20, 33.3%) and lungs (n = 16, 27.1%). Pain and fever were frequent (n = 35, 59.3% and n = 33, 55.9%, respectively). Diagnosis was established by culture in 58 cases (98.3%). P. variotii caused breakthrough infection in 8 patients. Systemic antifungals were given in 52 patients (88.1%). Amphotericin B was administered in 39, itraconazole in 15, and posaconazole in 8 patients. Clinical isolates were frequently resistant to voriconazole, whereas the above-mentioned antifungals showed good in vitro activity. Infections of the blood and CNS caused high mortality. Overall mortality was 28.8% and death was attributed to P. variotii in 10 cases. CONCLUSIONS: P. variotii causes life-threatening infections, especially in immunocompromised and critically ill patients with indwelling devices. Patients undergoing peritoneal dialysis are at particular risk. Multidisciplinary management is paramount, including molecular techniques for diagnosis and treatment with efficacious systemic antifungals. Amphotericin B, itraconazole and posaconazole are regarded as treatments of choice. Combination with flucytosine may be considered. Surgical debridement and removal of indwelling devices facilitate favourable outcome.


Subject(s)
Mycoses , Paecilomyces , Antifungal Agents/therapeutic use , Byssochlamys , Humans , Mycoses/drug therapy , Mycoses/epidemiology , Registries , Voriconazole
8.
Mycoses ; 63(10): 1060-1068, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32485012

ABSTRACT

BACKGROUND: Regional differences in the underlying causes, manifestations and treatment of mucormycosis have been noted in studies covering Europe, Asia and South America. OBJECTIVES: To review cases of mucormycosis across the Middle East and North Africa (MENA) region in order to identify epidemiological, treatment and outcome trends in this region. PATIENTS/METHODS: Cases of proven or probable invasive mucormycosis from the region were identified from the FungiScope® database and the medical literature. For each case, information on underlying condition, site of infection, pathogenic species, therapeutic intervention, type of antifungal therapy and outcome were analysed. RESULTS: We identified 310 cases of mucormycosis in the MENA region. The number of reported cases increased by decade from 23 before 1990 to 127 in the 2010s. In this region, the most common underlying conditions associated with mucormycosis were diabetes mellitus (49.7%) and conditions associated with immunosuppression (46.5%). The majority of patients received treatment with antifungals (93.5%), with a large proportion treated with both antifungals and surgery (70.6%). Overall mortality rates decreased from 47.8% before 1990 to 32.3% in the 2010s. CONCLUSIONS: The number of reported cases of mucormycosis in the MENA region has risen over the past few decades, in line with increases in the number of patients with underlying conditions associated with this infection. Although the majority of patients received treatment with antifungal therapies and/or surgery, the associated mortality rate remains high and there is a clear need for more effective prevention and treatment strategies in the MENA region.


Subject(s)
Mucormycosis , Africa, Northern/epidemiology , Antifungal Agents/therapeutic use , Diabetes Complications , Humans , Immunosuppression Therapy , Middle East/epidemiology , Mortality , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Mucormycosis/pathology , Mucormycosis/surgery , Registries , Risk Factors
9.
Mycoses ; 63(3): 265-274, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31769549

ABSTRACT

BACKGROUND: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi. OBJECTIVES: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection. PATIENTS/METHODS: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope® registry and all reported cases from a literature were included. RESULTS: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9). CONCLUSION: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency.


Subject(s)
Antifungal Agents/therapeutic use , Communicable Diseases, Emerging/epidemiology , Eurotiales/pathogenicity , Invasive Fungal Infections/epidemiology , Mycoses/epidemiology , Adolescent , Adult , Antifungal Agents/pharmacology , Canada/epidemiology , Communicable Diseases, Emerging/drug therapy , Communicable Diseases, Emerging/microbiology , Communicable Diseases, Emerging/mortality , Cough , Dyspnea , Europe/epidemiology , Eurotiales/drug effects , Female , Hematologic Diseases/complications , Humans , Immunocompromised Host , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/mortality , Japan/epidemiology , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/epidemiology , Lung Diseases, Fungal/microbiology , Lung Diseases, Fungal/mortality , Male , Microbial Sensitivity Tests , Middle Aged , Mycoses/drug therapy , Mycoses/microbiology , Mycoses/mortality , Registries , Risk Factors , United States/epidemiology , Young Adult
10.
Pediatr Blood Cancer ; 66(5): e27636, 2019 05.
Article in English | MEDLINE | ID: mdl-30706992

ABSTRACT

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.


Subject(s)
Emigration and Immigration/statistics & numerical data , Hospitalization/statistics & numerical data , Refugees/statistics & numerical data , Socioeconomic Factors , beta-Thalassemia/epidemiology , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Demography , Female , Follow-Up Studies , Humans , Infant , Male , Prevalence , Prognosis , Survival Rate , Turkey/epidemiology , Young Adult , beta-Thalassemia/therapy
11.
J Pediatr Hematol Oncol ; 40(5): 355-359, 2018 07.
Article in English | MEDLINE | ID: mdl-29746437

ABSTRACT

Inherited metabolic diseases are pathologic conditions that generally develop as a result of impairment of the production or breakdown of protein, carbohydrate, and fatty acids. Early determination of hematological findings has a positive effect on the prognosis of metabolic diseases. Three hundred eighteen patients who were being followed-up within the previous 6 months at Department of Pediatric Nutrition and Metabolism, Gazi University, Turkey, were included in the study. The hematological findings were classified under 7 main groups: anemia of chronic disease, iron deficiency anemia, vitamin B12 deficiency anemia, hemophagocytosis, leukocytosis, and thrombocytosis. Nine hundred twenty-two hematological examinations of the 319 patients were included in the study, and 283 hematological findings were determined, 127 anemia of chronic disease, 81 iron deficiency anemia, 56 cytopenia, and 4 vitamin B12 deficiency anemia. Leukocytosis (n=1), thrombocytosis (n=5), and hemophagocytosis (n=9) were also observed. It was determined that, although anemia of chronic disease and nutritional anemia are the most common hematological findings, these may be diagnosed late, whereas neutropenia, thrombocytopenia, pancytopenia, and hemostasis disorders may be diagnosed earlier. Our study is the most comprehensive one in the literature, and we think it would positively contribute to the monitoring and prognosis of congenital metabolic diseases.


Subject(s)
Hematologic Diseases/epidemiology , Hematologic Diseases/etiology , Metabolism, Inborn Errors/complications , Metabolism, Inborn Errors/epidemiology , Adolescent , Adult , Child , Child, Preschool , Chronic Disease , Female , Humans , Infant , Male , Middle Aged
12.
Hematology ; 23(8): 542-548, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29318945

ABSTRACT

OBJECTIVES: Iron deficiency is common in obese children although the underlying mechanism is unclear. The aim of this study was to investigate the associations between iron parameters, leptin, hepcidin and adiponectin levels in obese children. METHODS: A total of 237 children, ranging in age from 5 to 18 years, 180 with primary obesity and 57 healthy children and adolescents, were enrolled. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, leptin, hepcidin and adiponectin levels were studied. RESULTS: White blood cell and platelet count, iron-binding capacity, high-sensitive C-reactive protein, leptin and hepcidin values in the obese group were higher than those of the control group (p < 0.001, p = 0.002, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). However, mean corpuscular volume, adiponectin and transferrin saturation values in the obese group were lower than in the control group (p = 0.026, p = 0.003, and p < 0.001, respectively). No significant differences were found in terms of hemoglobin, serum ferritin, iron and IL-6 levels. CONCLUSIONS: Our study suggests that hepcidin levels do not contribute to the development of iron deficiency anemia in pediatric obese individuals.


Subject(s)
Anemia, Iron-Deficiency/blood , Hepcidins/blood , Iron/blood , Obesity/blood , Adolescent , Blood Cell Count , Blood Proteins/metabolism , Child , Child, Preschool , Female , Humans , Male
13.
J Pediatr Hematol Oncol ; 39(6): 458-462, 2017 08.
Article in English | MEDLINE | ID: mdl-28697165

ABSTRACT

Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.


Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Cytochrome P-450 CYP3A/genetics , Neoplasms/drug therapy , Neurotoxicity Syndromes/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Vincristine/adverse effects , Adolescent , Antineoplastic Agents, Phytogenic/therapeutic use , Case-Control Studies , Child , Child, Preschool , Dose-Response Relationship, Drug , Genotype , Humans , Infant , Neoplasms/complications , Neoplasms/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Turkey , Vincristine/therapeutic use
14.
Pediatr Hematol Oncol ; 33(3): 226-32, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27120435

ABSTRACT

Iron-refractory iron deficiency anemia (IRIDA) is a rarely diagnosed autosomal recessive disorder that presents with hypochromic, microcytic anemia due to mutations in TMPRSS6, which encodes matriptase-2. Contrary to classical iron deficiency anemia, serum hepcidin levels are found to be elevated in this disorder. Here, we report 5 cases from 4 unrelated families with inadequate response to iron therapy, who were consequently diagnosed as IRIDA. The mean age of the cases at diagnosis was 5.0 years (range: 0.7-11.3 years). All cases were either homozygous or compound heterozygous for missense or frameshift mutations in the TMPRSS6 gene, 2 of the mutations being novel (Cys410Ser and Leu689Pro). IRIDA should be considered in patients with findings of iron deficiency anemia unresponsive to oral iron therapy, whose serum ferritin levels are found normal or elevated.


Subject(s)
Anemia, Iron-Deficiency/genetics , Membrane Proteins/genetics , Mutation , Serine Endopeptidases/genetics , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/drug therapy , Child , Child, Preschool , Female , Ferritins/blood , Humans , Infant , Iron/therapeutic use , Male
16.
Clin Appl Thromb Hemost ; 21(6): 565-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-24563246

ABSTRACT

The diagnosis of mild bleeding disorders is not easy as most of the "healthy" individuals also report bleeding symptoms. In order to get a precise bleeding history, Pediatric Bleeding Questionnaire (PBQ) has been developed. In our study, Turkish children diagnosed with Von Willebrand disease (VWD), platelet function defect (PFD), and healthy children without any symptoms (control group 1) and healthy children with symptoms but found hemostatically normal (control group 2) were analyzed with PBQ. The cut off level for "positive bleeding score" was found to be ≥2 (area under the curve [AUC]: 0.785, 95% confidence interval [CI]: 0.718-0.852). The sensitivity, specificity, positive predictive value, and negative predictive value of PBQ to define VWD versus control group 1 was 100%, 97.4%, 96.4%, and 100%; VWD versus control group 2 was 100%, 53.1%, 64.3%, and 100%; PFD versus control group 1 was 93.3%, 53.1%, 73.7%, and 85%; and PFD versus control group 2 was 93.3%, 53.1%, 73.7%, and 85%, respectively.


Subject(s)
Hemorrhage/diagnosis , Surveys and Questionnaires , von Willebrand Diseases/diagnosis , Adolescent , Child , Child, Preschool , Female , Humans , Male , Turkey
17.
Turk Kardiyol Dern Ars ; 42(2): 154-60, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24643147

ABSTRACT

OBJECTIVES: P-wave and QT dispersion are increased and associated with atrial and ventricular arrhythmia and an increase in sudden death in a variety of diseases. This study aimed to investigate P-wave and QT dispersion in children with Eisenmenger syndrome (ES). STUDY DESIGN: The study group included 27 children (15 females, 12 males) with both congenital heart disease (CHD) and ES. The control group consisted of 30 children with CHD without pulmonary arterial hypertension. Electrocardiographic records were used to determine P-wave, QT, and corrected QT (QTc) dispersions. 24-hour (h) rhythm Holter was fitted in all patients. Atrial volumes, ventricular dimensions and tricuspid annular plane systolic excursion (TAPSE) were measured by echocardiography. RESULTS: There was no difference between groups with regard to age, sex, weight, and body surface area (p>0.05). Right atrial volume was significantly larger in the ES group than in the control group. P-wave, QT and QTc dispersions were higher in the patients with ES (50.10±11.12 vs. 26.32±8.90, p<0.001; 57.40±24.21 vs. 38.20±8.92 ms, p<0.001; and 78.20±16.02 vs. 56.52±13.92 ms, p<0.001, respectively). Ventricular and supraventricular ectopy were significantly more frequent in the ES group. Four patients (14.8%) in the study group had tachyarrhythmias during 24-h Holter monitoring. CONCLUSION: In our study, P-wave and QT dispersion were found to be greater in children with ES than in the healthy control subjects.


Subject(s)
Eisenmenger Complex/physiopathology , Adolescent , Arrhythmias, Cardiac/physiopathology , Child , Child, Preschool , Electrocardiography , Electrocardiography, Ambulatory , Female , Hemodynamics , Humans , Male , Retrospective Studies
18.
Turk J Pediatr ; 55(5): 479-84, 2013.
Article in English | MEDLINE | ID: mdl-24382527

ABSTRACT

Iron refractory iron deficiency anemia (IRIDA) is a recently described autosomal recessive disorder caused by mutations in TMPRSS6, the gene encoding matriptase-2. Patients have inappropriately high levels of hepcidin. Hypochromic microcytic anemia refractory to oral iron and only partially responsive to parenteral iron is the hallmark of this disorder. We report six patients from three unrelated families with mutations in the TMPRSS6 gene, with three of the four identified mutations being novel. Although response to oral iron in IRIDA patients has been reported rarely before, all of our five patients receiving oral iron and our one patient supplemented with vitamin C responded to therapy at least to some extent. We think that IRIDA should be considered in the differential diagnosis of patients with findings of iron deficiency anemia responding inadequately to oral iron, particularly in countries with a high rate of consanguineous marriages like Turkey.


Subject(s)
Abbreviations as Topic , Anemia, Iron-Deficiency/genetics , Membrane Proteins/genetics , Mutation , Serine Endopeptidases/genetics , Anemia, Iron-Deficiency/drug therapy , Child , Child, Preschool , Female , Humans , Iron/therapeutic use , Male
19.
Hum Exp Toxicol ; 30(11): 1751-60, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21393350

ABSTRACT

OBJECTIVE: The objective of the present study was to determine oxidant and antioxidant status in infants with hyperbilirubinemia and/or kernicterus and to find whether there is a relationship between bilirubin level and oxidant/antioxidant status. PATIENTS: The study includes 69 full-term newborns (neonates with hyperbilirubinemia needing phototherapy [Group 1, n = 36] and neonates with kernicterus [Group 2, n = 33]) and 25 age-matched healthy newborn. RESULTS: Plasma total antioxidant capacity (TAC) and serum total oxidant status (TOS) were significantly higher in Groups 1 and 2 than the control group. There was a significant difference between Group 1 and control cases for malondialdehyde (MDA; p < 0.001). Total free sulfhydryl group (TTHI) values were significantly elevated in Group 1 compared to Group 2 and control cases. Correlation analysis showed that the correlation between total bilirubin (TB) and TAC, TOS, MDA and oxidative stress index may be expressed by a quadratic curve. After phototherapy, a statistically significant increase in nitrite level was observed. CONCLUSION: We demonstrated that the relationship between serum TB and antioxidants and oxidative stress could be expressed by a quadratic correlation curve.


Subject(s)
Bilirubin/blood , Hyperbilirubinemia/blood , Kernicterus/blood , Oxidative Stress , Blood Cell Count , Case-Control Studies , Chromans/blood , Female , Humans , Hydrogen Peroxide/blood , Infant, Newborn , Male , Malondialdehyde/blood , Nitrates/blood , Nitrites/blood , Phototherapy , Sulfhydryl Compounds/blood
20.
J Child Neurol ; 26(1): 25-30, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20525941

ABSTRACT

The authors examined clinical outcome and cranial magnetic resonance imaging (MRI) findings in infants with hypoglycemia to determine the effects of hypoglycemia on the developing brain. A total of 110 infants with hypoglycemia were included in the study. Of the patients, 36 were females and 74 were males. The age of the infants was between 1 day and 22 months. Of the 110 infants, 47 were preterm neonates, 40 were term neonates, and 23 were older than 28 days. No difference in serum glucose level was noted between symptomatic and asymptomatic infants. The most common observed abnormal findings were hyperintense lesions, encephalomalacia, and cerebral atrophy. Abnormal MRI findings were found in 4% of preterm infants, in 32.5% of term infants, and in 43.5% of older infants. Abnormal MRI findings were statistically significantly more common in symptomatic infants than in asymptomatic infants. Of the infants, 45.5% of hypoglycemic infants had cerebral palsy and/or cerebral palsy plus epilepsy.


Subject(s)
Brain/pathology , Cerebral Palsy/etiology , Epilepsy/etiology , Hypoglycemia/complications , Hypoglycemia/pathology , Analysis of Variance , Cerebral Palsy/pathology , Epilepsy/pathology , Female , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , Treatment Outcome
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