Toxic Skin Reactions Should Be Differentiated from Allergic Reactions to Chemotherapeutic Drugs in Children: A Case Series and Review of the Literature.

Background: Chemotherapeutic drugs can lead to a wide spectrum of cutaneous findings, ranging from nonimmune toxic reactions to severe immune-mediated hypersensitivity reactions. The aim of this study was to evaluate the clinical, histopathological features, and prognosis of toxic skin reactions to chemotherapeutic drugs and to compare them with characteristics of immune-mediated reactions in children with malignancies. Methods: The medical records of all children with cancer who experienced skin reactions after chemotherapy administration and diagnosed as a toxic skin reaction between 2010 and 2022 were retrospectively analyzed. The diagnosis was re-evaluated and differentiated from other similar disorders by using clinical manifestations, photodocumentation, and histopathological findings. Results: A total of 17 children aged 2-17 years were involved: toxic erythema of chemotherapy (TEC) in 14 children, methotrexate-induced epidermal necrosis in 2 children, and toxic epidermal necrolysis (TEN)-like TEC in 1 child. The most commonly implicated drug was methotrexate. Most patients recovered rapidly after drug cessation and supportive measures. In 10 of the 17 patients, reintroduction of the culprit chemotherapeutic drug at reduced doses or increased dosage intervals was possible without any recurrence. Six patients could not receive further doses since they deceased due to sepsis and other complications. Conclusions: Cutaneous toxic eruptions to chemotherapeutic drugs may present with a severe phenotype resembling Stevens-Johnson syndrome/TEN. An accurate diagnosis prevents potentially harmful therapeutic interventions, withholding of chemotherapy, and erroneous assignment of drug allergies.

Thromboprophylaxis in pediatric patients with earthquake-related crush syndrome: a single centre experience.

PURPOSE: Injuries increase the risk of venous thromboembolism (VTE). However, the literature on the management of anticoagulant therapy in pediatric patients with crush injury is limited. In this study, we aimed to share our experience about anticoagulant thromboprophylaxis in pediatric patients with earthquake-related crush syndrome. METHODS: This study included patients who were evaluated for VTE risk after the Turkey-Syria earthquake in 2023. Since there is no specific pediatric guideline for the prevention of VTE in trauma patients, risk assessment for VTE and decision for thromboprophylaxis was made by adapting the guideline for the prevention of perioperative VTE in adolescent patients. RESULTS: Forty-nine patients [25 males and 24 females] with earthquake-related crush syndrome had participated in the study. The median age of the patients was 13.5 (8.8-15.5) years. Seven patients (14.6%) who had no risk factors for thrombosis were considered to be at low risk and did not receive thromboprophylaxis. Thirteen patients (27.1%) with one risk factor for thrombosis were considered to be at moderate risk and 28 patients (58.3%) with two or more risk factors for thrombosis were considered to be at high risk. Moderate-risk patients (n = 8) and high-risk patients aged < 13 years (n = 11) received prophylactic enoxaparin if they could not be mobilized early, while all high-risk patients aged ≥ 13 years (n = 13) received prophylactic enoxaparin. CONCLUSION: With the decision-making algorithm for thyromboprophylaxis we used, we observed a VTE rate of 2.1% in pediatric patients with earthquake-related crush syndrome.

Evaluation of Intestinal Microbiota in Children With Sickle Cell Disease.

BACKGROUND AND AIMS: Sickle cell disease (SCD) is a chronic hemolytic anemia that may be life-threatening due to multisystemic effects. Identification of the factors which affect the pathophysiology of the disease is important in reducing mortality and morbidity. This study aimed to determine gut microbial diversity in children and adolescents with SCA compared with healthy volunteers and to evaluate the clinical impact of microbiota. MATERIALS AND METHODS: The study included 34 children and young adolescents with SCD and 41 healthy volunteer participants. The microbiome was assessed by 16S rRNA sequencing in stool samples. Laboratory parameters of all participants, such as complete blood count and C-reactive protein values and clinical characteristics of SCD patients, were determined and compared, as well as clinical conditions of the patients, such as vascular occlusive crisis and/or acute chest syndrome, frequency of transfusions, intake of penicillin, hydroxyurea, and chelation therapy were recorded. RESULTS: White blood cell count, hemoglobin, immature granulocyte and C-reactive protein levels were significantly higher in the patient group ( P <0.05). Microbiota analysis revealed 3 different clusters among subjects; controls and 2 clusters in the SCD patients (patient G1 and G2 groups). Bacteroides spp. were more prevalent, while Dialester spp. and Prevotella spp. were less prevalent in SCD compared with controls ( t =2.142, P <0.05). Patient G2 (n=9) had a higher prevalence of Bacteroides and a lower prevalence of Prevotella than patient G1 (n=25). CONCLUSION: In our study, there was a difference between SCD patients and the control group, while 2 different microbiota profiles were encountered in SCD patients. This difference between the microbiota of the patients was not found to affect the clinical picture (such as vascular occlusive crisis, acute chest syndrome).

A feasibility study of risk prediction modelling for vasoocclusive crisis in children with sickle cell disease.

BACKGROUND: The availability of a selection of biomarkers that includes information about disease risk is very important in the treatment of sickle cell disease (SCD). We used the predictiveness curve (PC), which classifies diseased individuals according to low- and high-risk thresholds, for this purpose. Our aim was to define this new statistical method and to determine the biomarkers that predict vaso-occlusive crisis (VOC) in children with SCD to guide preventive treatment. METHODS: Thirty-eight pediatric patients with SCD were included in this feasibility study. Leucocytes (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and YKL-40 were studied in patients with VOC and without VOC. The patient group with a low or high risk of VOC was assessed using the PC. Risk prediction and classification performance were evaluated using the PC and receiver operating characteristic (ROC) curve. RESULTS: According to the PC, patients with a high risk of VOC could be detected via TNF-α, IL-6, and WBC, and TNF-α was the best risk prediction marker (TPF = 0.67). CONCLUSIONS: The PC provides disease risk information by comparing more than one biomarker and can thereby help clinicians determine appropriate preventive treatments. This is the first study to evaluate biomarkers to predict VOC risk in SCD patients.

Impact of injectable chitosan cryogel microspherescaffolds on differentiation and proliferation of adiposederived mesenchymal stem cells into fat cells.

Difficulty in the clinical practice of stem cell therapy is often experienced in achieving desired target tissue cell differentiation and migration of stem cells to other tissue compartments where they are destroyed or die. This study was performed to evaluate if mesenchymal stem cells (MSCs) may differentiate into desired cell types when injected after combined with an injectable cryogel scaffold and to investigate if this scaffold may help in preventing cells from passing into different tissue compartments. MSCs were obtained from fat tissue of the rabbits as autografts and nuclei and cytoplasms of these cells were labeled with BrdU and PKH26. In Group 1, only-scaffold; in Group 2, only-MSCs; and in Group 3, combined stem cell/scaffold were injected to the right malar area of the rabbits. At postoperative 3 weeks, volumes of the injected areas were calculated by computer-tomography scans and histopathological evaluation was performed. The increase in the volume of the right malar areas was more in Group 3. In histopathological evaluation, chitosan cryogel microspheres were observed microscopically within the tissue and the scaffold was only partially degraded. Normal tissue form was seen in Group 2. Cells differentiated morphologically into fat cells were detected in Groups 2 and 3. Injectable chitosan cryogel microspheres were used in vivo for the first time in this study. As it was demonstrated to be useful in carrying MSCs to the reconstructed area, help cell differentiation to desired cells and prevent migration to other tissue compartments, it may be used for reconstructive purposes in the future.

Investigation of the relationship between periodontal and systemic inflammation in children with Sickle Cell Disease: A case- control study.

Periodontal diseases are chronic inflammatory diseases and tissue destruction increases with oxidative stress in periodontal tissues. Periodontal diseases are associated with systemic diseases such as diabetes, cardio-vascular diseases and rheumatoid arthritis by means of systemic inflammation. Sickle cell disease (SCD) is a chronic inflammatory disease in which vaso-occlusive crisis and endothelial dysfunction are present. It is not known whether the chronic systemic inflammation seen in SCD affect periodontal tissues. The aim of this study was to investigate the relationship between periodontal and systemic inflammation in children with SCD. Forty-three children with SCD and 43 healthy children were included in the study. Physical, dental and periodontal statuses were examined, blood and saliva samples were taken. Levels of pro-inflammatory and oxidative stress mediators in serum and saliva were evaluated. The periodontal findings of the groups were similar. The majority of the subjects in both groups had gingival inflammation. In SCD group, significantly higher serum high sensitive C-reactive protein (Hs-CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, total oxidant status (TOS), nitric oxide (NO) and salivary IL-6 were observed (p < 0.05). There were positive correlations between salivary IL-6 levels and serum Hs-CRP levels (r = 0.303, p < 0.05). In addition; it was determined that salivary IL-6, TNF-α and NO levels were increased 3-6 times in children with a history of painful crisis or acute chest syndrome compared to children who had never had a painful crisis or acute chest syndrome. Although, observed oral health status was similar in both groups, salivary cytokine levels were increased in children with SCD. The higher salivary cytokine levels may be associated with chronic systemic inflammation and vaso-occlusion observed in children with SCD.

Evaluation of Ocular Complications by Using Optical Coherence Tomography in Children With Sickle Cell Disease Eye Findings in Children With Sickle Cell Disease.

OBJECTIVE: The aim of this study was to compare optical coherence tomography (OCT) findings in pediatric patients with sickle cell disease (SCD) and healthy individuals and to investigate associations between these data and the patients' systemic findings. MATERIALS AND METHODS: The study included 108 eyes of 54 patients with SCD with no visual symptoms and a control group consisting of 110 eyes of 55 healthy subjects with no systemic or ocular pathology. After best-corrected visual acuity assessment, the study participants underwent a complete ophthalmologic examination including intraocular pressure. After examination and pupil dilation induced with 1% tropicamide, 9×9 mm macular sections were obtained with spectral-domain OCT. The macular sections were evaluated according to Early Treatment Diabetic Retinopathy Study (ETDRS) map and internal and external retinal thicknesses were measured using the software included in the OCT device. RESULTS: The patient group showed significantly more foveal flattening, temporal thinning, and vascular tortuosity than the control group (P<0.0001 for all). Foveal width was significantly greater in the patient group (1592.39±175.56 µm) compared with the control group (1391.01±175.56 µm) (P<0.0001), whereas foveal depth was significantly lower in the patient group (121.15±26.83 µm) than in the control group (146.1±12.25 µm) (P<0.0001). The mean total retinal thickness was 253.53±22.31 µm in the patient group and 261.03±18.48 µm in the control group (P=0.007). Similarly, central retinal thickness was significantly lower in the patient group (219.35±10.53 µm) compared with the control group (235.32±12.51 µm) (P<0.0001). DISCUSSION: Our study shows that pediatric patients with SCD may have subclinical retinal involvement and that temporal thinning, in particular, is an important OCT finding. This strongly suggests that OCT imaging would be a beneficial addition to routine ophthalmologic examination in the diagnosis and follow-up of this patient group.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM).

OBJECTIVES: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. METHODS: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. RESULTS: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention.

OBJECTIVE: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. MATERIALS AND METHODS: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with ß-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). RESULTS: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all ß-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. CONCLUSION: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.

Short-cut diagnostic tool in cystinosis: Bone marrow aspiration.

BACKGROUND: Cystinosis is a rare metabolic genetic disorder caused by a mutation in cystinosin lysosomal cystine transporter (CTNS). The diagnosis of nephropathic cystinosis (NC) is made by observing corneal cystine crystals and/or measuring the cystine content of leukocytes. CTNS mutation analysis confirms the diagnosis of cystinosis, but leukocyte cystine measurement and CTNS analysis have not been widely available, and cystine crystals in the cornea may not be apparent in the first months of life. Cystine crystal deposition can be seen in the bone marrow earlier than corneal deposition, in patients with NC. METHODS: Ten patients with cystinosis diagnosis were enrolled in the study. Medical records were reviewed retrospectively to collect demographic and clinical data such as age at diagnosis, disease presentation, parental consanguinity, family history, corneal cystine deposition, leukocyte cystine level, bone marrow cystine deposition, presence of renal failure, follow-up time and prognosis. RESULTS: Cystine crystals were seen in all of the patients' fresh bone marrow aspiration samples. Eight patients had corneal cystine deposition. Leukocyte cystine measurement could have been performed in four patients who had come from another center. Complications such as pulmonary hypertension and idiopathic intracranial hypertension (IIH) were observed in two patients. CONCLUSIONS: Bone marrow aspiration might be an easy and short-cut diagnostic tool for NC especially when it is not possible to measure fibroblast cystine content. Additionally some rare complications such as pulmonary hypertension and IIH can be encountered during the course of NC.

Bilateral Subperiosteal Hematoma and Orbital Compression Syndrome in Sickle Cell Disease.

A 14-year-old boy with sickle cell disease presented with preseptal cellulitis findings as proptosis, eyelid edema, and hyperemia. His best corrected visual acuity in the right eye was 20/20 and 16/20 in the left eye. He had limited ductions in vertical and lateral gazes in both eyes. Bilateral venous tortuosity was observed in posterior segment examination. Orbital bone infarction and subperiosteal hematoma were seen in magnetic resonance imaging. He was diagnosed as having orbital compression syndrome secondary to vaso-occlusive crisis of sickle cell disease and was treated with intravenous ampicilin-sulbactam and methylprednisolone.

[Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery]. / Combinação de levobupivacaína em dose baixa e fentanil para raquianestesia em cirurgia anorretal.

BACKGROUND: The aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. METHODS: In this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5µg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25µg fentanyl. All the patients remained in the seated position for 5min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. RESULTS: Motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. CONCLUSION: Spinal saddle block using hyperbaric levobupivacaine with both 12.5µg and 25µg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position.

Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery / Combinação de levobupivacaína em dose baixa e fentanil para raquianestesia em cirurgia anorretal

BACKGROUND: the aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. METHODS: in this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5 mg hyperbaric levobupivacaine plus 12.5 µg fentanyl and in group II received intrathecal 2.5 mg hyperbaric levobupivacaine plus 25 µg fentanyl. All the patients remained in the seated position for 5 min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. RESULTS: motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p < 0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. CONCLUSION: spinal saddle block using hyperbaric levobupivacaine with both 12.5 µg and 25 µg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position.

JUSTIFICATIVA: O objetivo deste estudo foi investigar os efeitos da raquianestesia com o uso de duas doses diferentes de fentanil em combinação com dose baixa de levobupivacaína em cirurgia anorretal. MÉTODOS: Neste estudo prospectivo e duplo-cego, 52 pacientes com estado físico ASA I-II, programados para cirurgia eletiva anorretal, foram randomicamente alocados em dois grupos. Os pacientes do Grupo I receberam 2,5 mg de levobupivacaína hiperbárica mais 12,5 µg de fentanil por via intratecal e os do Grupo II receberam 2,5 mg de levobupivacaína hiperbárica mais 25 µg de fentanil por via intratecal. Todos permaneceram em posição sentada por cinco minutos após o término da raquianestesia. O bloqueio sensorial foi avaliado com o teste da picada de agulha e o bloqueio motor com a escala modificada de Bromage. RESULTADOS: O bloqueio motor não foi observado em ambos os grupos. O bloqueio sensorial limitou-se ao nível S2 no Grupo I e S1 no Grupo II. Nenhum dos pacientes precisou de analgésico suplementar durante a operação. O tempo de regressão de dois seguimentos foi menor no Grupo I em comparação com o Grupo II (p < 0,01). Um paciente do Grupo I e cinco do Grupo II apresentaram prurido. Os parâmetros hemodinâmicos permaneceram estáveis durante a cirurgia em ambos os grupos. CONCLUSÃO: O bloqueio espinhal em sela com o uso de levobupivacaína hiperbárica, tanto com 12,5 µg quanto com 25 µg de fentanil, proporciona boa qualidade de anestesia sem bloqueio motor para cirurgia anorretal em decúbito ventral.

Low-dose levobupivacaine plus fentanyl combination for spinal anesthesia in anorectal surgery.

BACKGROUND: the aim of this study was to investigate the effects of spinal anesthesia using two different doses of fentanyl combined with low-dose levobupivacaine in anorectal surgery. METHODS: in this prospective, double-blind study, 52 American Society of Anaesthesiologists I-II patients scheduled for elective anorectal surgery were randomized into two groups. The patients in group I received intrathecal 2.5mg hyperbaric levobupivacaine plus 12.5 µg fentanyl and in group II received intrathecal 2.5mg hyperbaric levobupivacaine plus 25 µg fentanyl. All the patients remained in the seated position for 5 min after completion of the spinal anesthesia. Sensory block was evaluated with pin-prick test and motor block was evaluated with a modified Bromage scale. RESULTS: motor block was not observed in both of the groups. The sensory block was limited to the S2 level in group I, and S1 level in group II. None of the patients required additional analgesics during the operation. Time to two-segment regression was shorter in group I compared with group II (p<0.01). One patient in group I and 5 patients in group II had pruritus. Hemodynamic parameters were stable during the operation in both of the groups. CONCLUSION: spinal saddle block using hyperbaric levobupivacaine with both 12.5 µg and 25 µg fentanyl provided good quality of anesthesia without motor block for anorectal surgery in the prone position.

Cystatin C, Beta2 Microglobulin, N-Acetyl-beta-D-glucosaminidase, Retinol-Binding Protein, and Endothelin 1 Levels in the Evaluation of Sickle Cell Disease Nephropathy.

OBJECTIVES: Renal involvement is common in sickle cell disease (SCD). Early demonstration of renal injury and commencement of appropriate treatment will increase survival and quality of life in these patients. We investigated renal manifestations in our pediatric and adult SCD patients and evaluated the role of cystatin C, Beta2 microglobulin (B2M), retinol-binding protein (RBP), N-acetyl-beta-D-glucosaminidase (NAG), and endothelin-1 (ET-1) to indicate renal damage. METHODS: The study involved 45 pediatric and 10 adult patients with SCD and 20 healthy children and 10 healthy adults as a control. All the patients were questioned for possible renal manifestations. 24-hour urine samples were collected and glomerular filtration rates (GFRs) were calculated by using creatinine (GFR(creatinine)), Schwartz formula (GFR(Schwartz)), and cystatin C (GFR(cystatin C)). Blood and urine samples were collected and serum cystatin C, urine B2M, RBP, NAG, and ET-1 levels were measured. RESULTS: Nocturnal enuresis and proteinuria were the most common renal manifestations in SCD patients. When the groups were compared in terms of GFR, GFR(creatinine) and GFR(Schwartz) levels were higher in group 1 and 2 patients than in control 1 and 2 patients (P < .05). Cystatin C, B2M, RBP, NAG, and ET-1 values were normal in both the patient and the control groups. However, B2M/creatinine levels were higher than 160 µg/mg creatinine levels in 10 patients. CONCLUSIONS: Serum cystatin C, urine NAG, RBP, and ET-1 levels were found to be insufficient for the evaluation of SCD nephropathy. Increased B2M/creatinie levels can be valuable in estimating possible glomerular and tubular damage in SCD.

Increase of serum fractalkine and fractalkine gene expression levels in sickle cell disease patients.

In the present study, we examined the role of fractalkine (Fkn), a member of the chemokine family, in the pathogenesis of sickle cell disease (SCD). Eighty-seven children with sickle cell disease and 55 healthy children were enrolled in the study. Complete blood counts, serum levels of C-reactive protein, tumor necrosis factor-α, interferon-γ and fractalkine, and gene expression levels of Fkn were investigated. Serum Fkn levels and Fkn gene expression values were significantly higher in the SCD group compared to control group (P < 0.05). The findings of elevated serum Fkn and Fkn gene expression in both vaso-occlusive crisis and stable forms of SCD suggest that this chemokine may be involved in the pathogenesis of inflammation observed in SCD. This study is the first to our knowledge to describe the relationship of Fkn and inflammation in SCD.

Tumor necrosis factor-superfamily 15 gene expression in patients with sickle cell disease.

OBJECTIVE: The aim of this study was to investigate the relation between tumor necrosis factor-superfamily 15 (TNFSF15) gene expression and clinical findings in children with sickle cell disease (SCD). MATERIALS AND METHODS: Forty-nine patients with SCD and 38 healthy controls were included in this study. TNFSF15 gene expression and plasma levels were analyzed. TNFSF15 gene expression was compared in subgroups considering the frequency of painful crises and acute chest syndrome (ACS). RESULTS: It was found that TNFSF15 gene expression was significantly higher in patients with SCD than the controls (p=0.001), whereas there was no significant difference between the patients with SCD and the control groups considering plasma levels of TNFSF15. TNFSF15 gene expression was also significantly higher in SCD patients with ACS (p=0.008). CONCLUSION: These findings suggest that TNFSF15 may have a role in the pathogenesis of SCD presenting with ACS. Further studies on larger groups are needed to determine the function of TNFSF15 in SCD patients with ACS and pulmonary hypertension. Analysis of TNFSF15 expression may also serve as a promising approach in ACS therapy.

A novel mutation of the transcobalamin II gene in an infant presenting with hemophagocytic lymphohistiocytosis.

Transcobalamin II (TC II) deficiency is a rare disorder of cobalamin (CBL, vitamin B12) metabolism that occurs due to mutations in transcobalamin gene (TCN2). Hemophagocytic lymphohistiocytosis (HLH) in contrast is a syndrome characterized by uncontrolled immune response with hyperinflammation. A 2-month-old male baby was admitted with complaints of fever, cough, diarrhea, and respiratory distress. The parents were first cousins. The baby exhibited five of the eight diagnostic criteria for HLH-2004 and was diagnosed as HLH. A second bone marrow aspiration demonstrated megaloblastic changes in the erythroid series. The patient's vitamin B12 level was normal; however, hyperhomocysteinemia was present. A genetic deficiency of TC II was suspected. The patient and his parents were tested for TCN2 mutation. He had a homozygote mutation that was not included in Human 'Gene Mutation Database Cardiff'. The patient was treated with intramuscular vitamin B12, which was followed by improvement in both clinical and laboratory findings. He was 12 months old at the time of this report, with normal physical and neuromotor development. In this case presenting with the clinical and laboratory findings of HLH, TC II deficiency was diagnosed. A new mutation was found that was not reported before. Potential causative mechanisms of HLH induced by defects of cobalamin synthesis merit further investigation.

Procalcitonin is more useful than C-reactive protein in differentiation of fever in patients with sickle cell disease.

This study aimed at evaluating the value of C-reactive protein (CRP) and procalcitonin (PCT) levels in the differential diagnosis of fever in patients with sickle cell disease (SCD). The study included 86 children with SCD (group 1) and 49 controls (group 2). During the study, the patients had 114 acute episodes or routine visits to the units. They were classified as having vasoocclusive crisis with fever (group 1A), vasoocclusive crisis without fever (group 1B), and no crisis or fever (steady state, group 1C). Only patients with crises were admitted to the hospital. Patients admitted to the hospital with various clinical signs and symptoms each and every time were included in groups 1A, 1B, and 1C. Thus, a total of 114 clinical episodes were analyzed. The mean CRP levels in the 3 patient groups were significantly higher than that in the group 2, and among the patient groups, the mean CRP was significantly higher in group 1A than the other groups. The mean CRP level in group 1A and group 1B was significantly higher than that in group 1C. There were no significant differences among the 3 SCD groups in terms of the median serum PCT level; however, the median PCT level in group 1A, group 1B, and group 1C patients was significantly higher than that in group 2 patients. These data indicate that vasoocclusive disease with or without fever apparently does not significantly increase PCT levels in relation to the baseline status of children with SCD, which in turn are clearly more elevated than PCT levels of control children.