Evaluation of childhood malignancies presenting with musculoskeletal manifestations from two different divisions: a multicenter study.

BACKGROUND: The aim of the study was to evaluate the approaches of pediatric rheumatologists and pediatric hematologists to patients with similar musculoskeletal (MSK) complaints and to highlight the differences that general pediatricians should consider when referring patients to these specialties. METHODS: This is a cross-sectional study involving the patients who applied to pediatric rheumatology centers with MSK complaints and were diagnosed with malignancy, as well as patients who were followed up in pediatric hematology centers with a malignancy diagnosis, and had MSK complaints at the time of admission. RESULTS: A total of 142 patients were enrolled in the study. Of these patients, 83 (58.4%) applied to pediatric rheumatology centers, and 59 (41.6%) applied to pediatric hematology centers. Acute lymphoblastic leukemia (ALL) was the most common diagnosis among the patients who applied to both centers, with 80 cases (56.3%). The median age of diagnosis was 87 (interquartile range, IQR: 48-140) months. The most common preliminary diagnosis in pediatric rheumatology centers was juvenile idiopathic arthritis (JIA), with 37 cases (44.5%). MSK involvement was mainly seen as arthralgia, and bone pain. While arthralgia (92.7%) was the most common complaint in rheumatology centers, bone pain (88.1%) was more common in hematology centers. The most frequently involved joints were the knee (62.9%), ankle (25.9%), hip (25%), and wrist (14%). The most common laboratory abnormalities were high lactate dehydrogenase (LDH), high C-reactive protein (CRP), anemia, and high erythrocyte sedimentation rate (ESR). Thrombocytopenia, neutropenia, and high LDH were statistically significantly more frequent in patients admitted to hematology centers than in patients admitted to rheumatology centers (p < 0.001, p=0.014, p=0.028, respectively). Patients who applied to rheumatology clinics were found to have statistically significantly higher CRP levels (p=0.032). CONCLUSIONS: Malignancies may present with only MSK system complaints in childhood. Therefore, malignancies should be included in the differential diagnosis of patients presenting with MSK complaints.

Late Relapse in Neuroblastoma: Case Report and Review of the Literature.

BACKGROUND: Neuroblastoma is the most common extra-cranial solid tumor in children. The survival rate of relapsed/refractory neuroblastoma is dismal. Late recurrence may occur rarely. CASE PRESENTATION: We have, herein, presented a case with stage IV neuroblastoma who relapsed after 11 years and had a subsequent relapse after 15 years from the initial diagnosis, and reviewed cases with late relapsed (after >5 years) neuroblastoma in the literature. The case presented with recurrent disease at the T7 vertebra after 11 years from the initial diagnosis. The patient received surgery, chemotherapy, MIBG treatment, and antiGD2 combined with chemotherapy, and had a further local recurrence in the paravertebral area of the removed T7 vertebra after three years. The patient was operated, received anti-GD2 combined with chemotherapy, and is still alive with no symptoms for 19 months after the last relapse. CONCLUSION: There is not a well-established treatment regimen for the majority of these patients. MIBG treatment and antiGD2 combined with chemotherapy may be promising options for relapsed/ refractory neuroblastoma.

Acute complications observed during intensive chemotherapy in pediatric patients with acute lymphoblastic leukemia: Single-center experience.

OBJECTIVE: In childhood acute lymphoblastic leukemia (ALL), very promising results were obtained thanks to the developments in treatment strategies in recent years. However, acute complications during treatment continue to be the important causes of mortality and morbidity. In this study, acute complications that develop during the treatment of ALL in childhood were evaluated. METHODS: Medical records of 47 patients treated according to (ALL Intercontinental Berlin-Frankfurt-Münster) 2009 protocol between 2016 and 2021 were evaluated retrospectively. RESULTS: Of 47 patients, 28 (59.6%) were male and 19 (40.4%) were female. The mean age at diagnosis was 5.9±4.2 years. Forty-four patients (93.6%) were pre-B cell ALL, 3 patients (6.4%) were pre-T cell ALL. Of 47 patients, 9 (19.1%) were high risk, 32 (68.1%) were intermediate risk, and 6 (12.8%) were standard risk. Acute complications developed in 38 patients (80.8%). Among these complications, infectious complications are the most common and these were followed by gastrointestinal complications, drug-related reactions, thrombotic, neurological, and endocrine/metabolic complications, respectively. CONCLUSION: In terms of complications that may develop, the threshold of suspicion should be kept low, and patients should be treated with the same medical team in fully equipped centers with a multidisciplinary approach. Inpatient treatment strategies should be applied especially in the early stages of treatment. The importance of inpatient treatment strategy, especially in the early stages of treatment, is emphasized.

Any Concern About Delays in the Diagnosis of Childhood Cancers During the COVID-19 Pandemic?

OBJECTIVE: The lockdown precautions during the COVID-19 pandemic led to concerns about the delayed diagnosis of malignancies. This study aimed to compare the duration of complaints at home and the presence of metastasis at diagnosis during the pre-pandemic and pandemic period in children with cancer. MATERIALS AND METHODS: All children diagnosed with cancer and followed up in our clinic between 2017 and 2022 were included. Patients with a diagnosis of acute/chronic leukemia were excluded. Age, gender, cancer type, duration of complaints, and presence of metastasis at diagnosis of the children were recorded. The duration of complaints and presence of metastasis at diagnosis were compared statistically before and after March 11, 2020, the start point of the COVID-19 pandemic in our country. RESULTS: A total of 161 patients diagnosed with cancer were analyzed retrospectively; 61% of patients were males and 39% were females. These patients were diagnosed with brain tumors (23.6%), lymphomas (23%), neuroblastoma (13.7%), rhabdomyosarcomas (10.6%), Ewing's sarcoma (4.3%), osteosarcoma (3.7%), Wilm's tumor (3.7%), and germ cell tumors (3.1%). The duration of complaint was longer during the pandemic than before the pandemic (median: 45 days vs. 30 days) (P < .05). The presence of metastases at diagnosis was 45.3% in the prepandemic period, while it was 40% during the pandemic with no statistical difference (P > .5). CONCLUSION: We concluded that the duration of complaint before diagnosis was longer during the pandemic, while this delay did not affect the metastasis rate at diagnosis in children with cancer. The high rates of distant metastases in newly diagnosed patients both before and during the pandemic suggest that more studies are needed to diagnose these patients earlier.

How do the threshold values used in the decision on red blood cell and platelet transfusions comply with the guidelines?

OBJECTIVE: Blood transfusion is life-saving medical practice with significant risks. National and international guidelines have been established for indications related to blood use and threshold values for transfusions. In this study, we aimed to determine the erythrocyte and thrombocyte transfusion rates in surgical, internal, and emergency clinics in our hospital and to compare the threshold values before erythrocyte and platelet (PLT) transfusion among the clinics. METHODS: Red blood cell (RBC) and PLT transfusions in our hospital between January 2019 and June 2019 were retrospectively analyzed. Clinics were divided into three groups: surgical clinics, internal clinics, and emergency clinic. Demographic characteristics, pre-transfusion hemoglobin (Hb), and PLT values of patients were recorded. Data were analyzed statistically. RESULTS: During the 6-month study period, 5179 patients were transfused in 24,924 patients and the transfusion rate was 21%. In this period, a total of 14,518 units of blood products including 8369 units RBC suspension and 1390 units PLT suspension were transfused. The mean age of the patient was 50.32±28.88 years and the female/male ratio was 1.11. The most RBC transfusions were performed in the general internal medicine service in internal clinics and gynecology in surgical clinics. The most PLT transfusions were performed in the general medicine service in internal clinics and pediatric cardiovascular surgery in surgical clinics. ES transfusions were performed in the emergency medicine clinic with the lowest mean Hb value (Hb: 8.07±1.84 g/dl) and in the surgical clinics with the highest mean Hb value (Hb: 9.29±1.46 g/dl). TS transfusions were performed in internal clinics with the lowest mean PLT value (PLT: 44030±44075/mm3), while the highest mean PLT value (PLT: 97140±75782/mm3) was performed in surgical clinics. CONCLUSION: It was observed that threshold values in particular for PLT transfusions in our hospital were above the guideline recommendations. Our results suggest that the knowledge level of physicians about transfusion limits and practices should be increased.

Use of granulocyte transfusion in early period in life-threatening infections of pediatric hematology and oncology patients: A single-center experience.

Despite all the developments in medicine, infections continue to be one of the most important causes of mortality in pediatric hematology and oncology patients. The more severe the degree of neutropenia develops after intensive chemotherapy in cancer patients, and the longer the neutropenia duration, the higher the risk of infection. Granulocyte transfusion (GT) is used as supportive therapy in cases where the bone marrow needs time to recover in invasive bacterial or fungal infections along with severe neutropenia. The patients who had granulocyte transfusions in our clinic between June 2019 and June 2020 were reviewed retrospectively. A total of 15 units of granulocyte concentrate were used in 11 febrile neutropenia attacks of 9 patients. The demographic characteristics of the patients and features belonging to the period of GT were recorded. In our study, the clinical response rate after GT was 90.9 %, while the hematological response rate was 40 %. Most of the patients were treated succesfully, the mortality rate was 9%. We think that the most critical factor for success with GTs is determining the neutropenic patient in particular with a combination of high-risk malignancy and acute life-threatening infection for using GT. Also, early use of GT in those patients who do not recover despite appropriate antimicrobial and supportive treatment may contribute to improvement of the clinical conditon in a shorter period of time and reduction of repeated GTs.

Hemophagocytic Lymphohistiocytosis Related to Tuberculosis Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, albeit potentially fatal, condition in which fever, hepatosplenomegaly, and cytopenia predominate the clinical picture. Although it may be primary, it may also develop secondary to various etiologies. Herein, we aimed to report a patient who was diagnosed with pulmonary tuberculosis, developed fever and cytopenia during follow-up, and received immunomodulatory therapy together with antituberculosis therapy for the diagnosis of HLH. Sequencing of PRF1 showed heterozygous mutation. Although primary HLH has been detected in infants and children, genetic mutation of genes should be considered a differential diagnosis of HLH even in the adolescent. HOW TO CITE THIS ARTICLE: Erdogan S, Çakir D, Bozkurt T, Karakayali B, Kalin S, Koç B, et al. Hemophagocytic Lymphohistiocytosis Related to Tuberculosis Disease. Indian J Crit Care Med 2020;24(1):63-65.

Testis Involvement in Neuroblastoma: Report of 3 Cases in the Turkish Pediatric Oncology Group-Neuroblastoma Study and Review of the Literature.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. Primary and secondary testicular involvement is extremely uncommon in neuroblastoma. PROCEDURE: All children with neuroblastoma treated with the Turkish Pediatric Oncology Group (TPOG)-Neuroblastoma (NB) Study and who had testis involvement either at diagnosis or at relapse were retrospectively evaluated. A review of all cases with neuroblastoma and testis involvement in the literature was done. RESULTS: There were 3 children with NB documented to have involvement of the testis, 2 at diagnosis, 1 at recurrence, within the 559 cases (0.5%) treated with the Turkish Pediatric Oncology Group (TPOG)-Neuroblastoma Protocol. All had advanced stage. Two were infants. A total of 57 cases of testicular or paratesticular neuroblastoma have been reported in children, and most cases represent metastases as in the 3 cases in our series. CONCLUSIONS: Neuroblastoma should be considered in the differential diagnosis of testicular mass and work-up for neuroblastoma should be done before orchiectomy. Scrotal ultrasonography should be used as the first diagnostic tool and abdominal ultrasonography shall be done additionally. Testis examination should be performed at diagnosis and regularly during follow-up for boys diagnosed with neuroblastoma. Testes may be sanctuary sites when neuroblastoma is metastatic, as is the case in leukemia.

Treatment of plasminogen deficiency patients with fresh frozen plasma.

Congenital plasminogen (Plg) deficiency leads to the development of ligneous membranes on mucosal surfaces. Here, we report our experience with local and intravenous fresh frozen plasma (FFP). We retrospectively reviewed medical files of 17 patients and their eight first-degree relatives. Conjunctivitis was the main complaint. Thirteen patients were treated both with intravenous and conjunctival FFP. Venous thrombosis did not develop in any. Genetic evaluation revealed heterogeneous mutations as well as polymorphisms. Diagnosis and treatment of Plg deficiency is challenging; topical and intravenous FFP may be an alternative treatment.

Homozygous protein C deficiency presenting as neonatal purpura fulminans: management with fresh frozen plasma, low molecular weight heparin and protein C concentrate.

Purpura fulminans in neonates is a rapidly progressive thrombotic disorder manifesting as hemorrhagic skin infarction and disseminated intravascular coagulation. Being inherited in an autosomal dominant manner, it is a medical emergency. Clinical presentations of patients may vary depending on the genetic mutations. Retinal and intracranial hemorrhages are the worst clinical scenarios with persistent morbidity. During acute phase, fresh frozen plasma, protein C concentrates and anticoagulant therapy should be administered rapidly. Here we report a patient with homozygous protein C deficiency.

Breast Metastases in Children and Adolescents With Rhabdomyosarcoma: A Large Single-Institution Experience and Literature Review.

INTRODUCTION: Breast metastasis is rare in childhood malignancies. Soft tissue sarcomas, especially rhabdomyosarcomas (RMS), and hematologic neoplasms, such as lymphomas, are the most common tumors that metastasize to the breast, albeit rare. MATERIALS AND METHODS: All cases with breast metastasis within a cohort of 200 RMS patients followed in our institution during 1990 to 2014 were assessed retrospectively and the literature was reviewed. RESULTS: There were 3 adolescent female patients with breast metastasis. All had alveolar histology. The primary tumors were in the parameningeal sites, extremities, and the perineum, respectively. Two patients had breast metastasis at diagnosis, and 1 during follow-up. In 1 breast lesion, there was a complete response to chemotherapy, and in another there was no response to chemotherapy, and the patient underwent radical mastectomy. In the third patient, there was partial response, and lesions progressed. All patients died with recurrent/progressive disease, 2 with no recurrence in the breast. In the English literature, there are 70 cases including our cases. All but 1 involve female patients, all adolescents, most have alveolar histology and poor prognosis. All had chemotherapy, whereas some had surgery and/or radiotherapy for local treatment. CONCLUSION: Breast metastasis should be considered in adolescent female patients with RMS. Optimal management is not clear. Besides chemotherapy, mastectomy and radiotherapy should be considered on a case basis.

Approach to the patient with neutropenia in childhood.

Neutrophils have an important role in host defense and acute inflammation. It is well known that susceptibility to infection increases when the neutrophil count is low. Neutropenia were classified as mild, moderate and severe according to the neutrophil counts, or acute and chronic depending on the duration of neutropenia, or congenital and acquired according to the mechanism. The patients with neutropenia are clinically different due to underlying mechanism, they have life- threatening infections or no infection may be observed. The most common cause of acquired neutropenia is viral infection, followed by drugs and autoimmune neutropenia. Congenital neutropenia are usually diagnosed by acute and life- threatening invasive bacterial and fungal infections. Immune system disorders and other systemic abnormalities may be accompanied or not. Recent years, novel single gen defects causing congenital neutropenia were defined through advanced genetic techniques. Molecular diagnosis is useful for risk stratification, choice of therapy and prognosis on follow- up. This review was prepared for pediatricians as a guide focused on approach neutropenia, which tests should be performed and when should be referred to a specialist.

Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The Istanbul Perspective.

OBJECTIVE: Alpha thalassemia syndromes are caused by mutations on one or more of the four α-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause α+-thalassemia, some cause (-20.5, MED, THAI, FIL) α0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. MATERIAL AND METHODS: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for α-thalassemia mutations by using the Vienna Lab α-Globlin StripAssay TM commercial kit. RESULTS: Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), α2 IVS1 (n=10 patients, 10.5%), α2 cd142 Hb Koya Dora (n=6 patients, 6.3%), α2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), α1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, α2 init cd and α2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had α-thalassemia triplication. In our study, three mutations (Hb Icaria, α1 cd14, α2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) were not determined in this study. CONCLUSION: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey should be created to screen the alpha thalassemia cost-effectively.

Delivery room blood pressure percentiles of healthy, singleton, liveborn neonates.

BACKGROUND: Arterial blood pressure (BP) is one of the four vital signs that reflect cardiovascular status in neonates. The present study aimed to obtain BP percentiles among healthy, singleton, liveborn neonates between 34 and 43 weeks of gestation who were less than 1 h old. METHODS: BP measurements were taken after birth in supine-positioned neonates in the delivery room using an oscillometric device. A total of 982 well-nourished neonates who did not require resuscitation, were not fetally malnourished, were not admitted to the neonatal intensive care unit and were without obvious congenital abnormalities were included in the study. RESULTS: Sex- and type-of-delivery-specific 5th and 95th percentiles BP measurements were obtained for gestation. Mean BP values for systolic, diastolic and mean of term neonates were 63.98 ± 12.29 mmHg, 38.34 ± 11.06 mmHg and 49.32 ± 11.33 mmHg, and late preterm neonates were 61.80 ± 12.46 mmHg, 33.17 ± 9.97 mmHg and 46.52 ± 10.8 mmHg, respectively. There were weak but significant correlations between birthweight, birth length and head circumference and systolic, diastolic and mean arterial BP values (r = 0.20, r = 0.15 and r = 0.20, respectively, P < 0.001). Neonates who were delivered vaginally had higher mean BP values for systolic, diastolic and mean than neonates delivered by cesarean section (P < 0.05). Female neonates had higher systolic BP values than male neonates (P < 0.05). CONCLUSION: Data presented in this study include sex- and delivery-mode-specific BP percentile curves using an oscillometric method and serve as a valuable reference for physicians in dealing with the management of singleton, liveborn late preterm and term newborns in the delivery room intensive care.