Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study

Objective: This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA). Materials and Methods: Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h. Results: Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05). Conclusion: Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.

Evaluation of electrocardiographic markers of cardiac arrhythmic events and their correlation with cardiac iron overload in patients with ß-thalassemia major.

Iron overload is associated with an increased risk of atrial and ventricular arrhythmias. Data regarding the relationship between electrocardiographic parameters of atrial depolarisation and ventricular repolarisation with cardiac T2* MRI are scarce. Therefore, we aimed to investigate these electrocardiographic parameters and their relationship with cardiac T2* value in patients with ß-thalassemia major. In this prospective study, 52 patients with ß-thalassemia major and 52 age- and gender-matched healthy patients were included. Electrocardiographic measurements of QT, T peak to end interval, and P wave intervals were performed by one cardiologist who was blind to patients' data. All patients underwent MRI for cardiac T2* evaluation. Cardiac T2* scores less than 20 ms were considered as iron overload. P wave dispersion, QTc interval, and the dispersions of QT and QTc were significantly prolonged in ß-thalassemia major patients compared to controls. Interestingly, we found prolonged P waves, QT and T peak to end dispersions, T peak to end intervals, and increased T peak to end/QT ratios in patients with T2* greater than 20 ms. No significant correlation was observed between electrocardiographic parameters and cardiac T2* values and plasma ferritin levels. In conclusion, our study demonstrated that atrial depolarisation and ventricular repolarisation parameters are affected in ß-thalassemia major patients and that these parameters are not correlated with cardiac iron load.

Subacute Venous Infarct Mimicking Cerebral Metastasis in 18F-FDG PET/CT.

A 68-year-old woman with colon carcinoma was referred to F-FDG PET/CT imaging for staging. In addition to primary tumor involvement, PET/CT demonstrated focal FDG uptake in the right temporal lobe suggestive of primary brain tumor or metastasis. To delineate the lesion, a brain MRI scan showed sigmoid sinus thrombosis and vasogenic edema in the right temporal lobe. The patient presented a history of right-sided headache that began 1 week before the PET/CT. Neurological examination and MRI findings were concluded as subacute venous infarct due to sigmoid sinus thrombosis and that is a potential cause for false-positive FDG uptake on PET/CT.

68Ga-PSMA-11 PET/CT in Newly Diagnosed Prostate Adenocarcinoma.

INTRODUCTION: Prostate-specific membrane antigen (PSMA) ligand PET/CT is an emerging modality to detect the metastatic disease, especially in intermediate- and high-risk prostate cancer (PCa). In this study, we analyzed the contribution of Ga-PSMA-11 PET/CT in staging and therapy management of newly diagnosed PCa. MATERIALS AND METHODS: A total of 78 patients with biopsy-proven PCa who were referred for Ga-PSMA-11 PET/CT for primary staging were retrospectively analyzed. The patients were divided into risk groups according to the D'Amico risk stratification criteria. All of the patients had undergone pelvic MRI, and 65 patients had bone scintigraphy also. The findings of Ga-PSMA-11 PET/CT were compared with these conventional imaging (CI) methods for staging of the disease. The relations between SUVmax of the primary tumors and Gleason scores (GSs), prostate-specific antigen (PSA) levels, and metastatic extent of the disease were analyzed. RESULTS: Of 78 patients, 5 patients were in low-risk group, 18 patients were in intermediate-risk group, and 55 patients were in high-risk group. Metastatic disease was found in 40 (51.2%) of 78 patients in Ga-PSMA-11 PET/CT. Ten patients had regional lymph node metastases, and 30 patients had distant metastases. Ga-PSMA-11 PET/CT changed the staging in 44 (56.4%) of 78 patients compared with CI. There was significant difference between the SUVmax of the tumors with GSs of 6 and 7 compared with GSs of 8, 9, and 10 (P = 0.003). The SUVmax were significantly different between the patients with no metastasis (n = 38) and patients with regional lymph node metastases or distant metastases (n = 40; 16.1 ± 10.9, 28.7 ± 25.8, P = 0.003, respectively). There was significant difference between the SUVmax of patients with PSA level less than 10 ng/mL compared with patients with PSA level of 10 or greater and less than 20 ng/mL and PSA 20 ng/mL or greater (P = 0.009). A weak correlation between PSA and primary tumor SUVmax was also found (r = 0.21). CONCLUSIONS: Ga-PSMA-11 PET/CT is an important imaging modality for primary evaluation of newly diagnosed PCa changing the disease stage substantially. Also the SUVmax of the primary tumor has a relation with GS, metastatic extent of disease, and PSA levels defining the prognosis.

PET/CT in the Diagnosis and Workup of Sarcoidosis: Focus on Atypical Manifestations.

Sarcoidosis is a multisystem disease characterized by the formation of noncaseating granulomas. Lung and intrathoracic lymph nodes are classic sites of involvement; however, sarcoidosis can affect any site in the body. The clinical course is extremely variable, and the imaging features are diverse and dependent on the affected site, degree of inflammation, and treatment the patient receives. Atypical manifestations and imaging findings can make diagnosis and/or management challenging. In addition, assessment of treatment response can be difficult in the setting of chronic disease. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is sensitive for assessment of the inflammatory activity of sarcoidosis in any organ. Although FDG PET/CT is not included in the standard workup for sarcoidosis, there has been growing evidence that supports the value of this examination in guiding diagnosis and management. FDG PET/CT may be especially useful for assessing reversible granuloma, treatment response, disease extent, occult disease, and cardiac or osseous sarcoidosis, and determining the most suitable biopsy site. Capability to image the entire body during a single examination is advantageous in cases of systemic disease such as sarcoidosis. The authors review the use of FDG PET/CT, providing up-to-date evidence and describing various cases of sarcoidosis in which FDG PET/CT has an important role in diagnosis and/or management. They also discuss the usefulness of FDG PET/CT in cases of selective manifestations of sarcoidosis. ©RSNA, 2018.

Comparison of day 3 and day 5 thyroglobulin results after thyrogen injection in differentiated thyroid cancer patients.

BACKGROUND: It is necessary to stimulate serum thyroid-stimulating hormone (TSH) levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH) for radioactive iodine (RAI) therapy. Thyrotropin alfa (Thyrogen) has many advantages over THW. Radiation dose to laboratory staff while drawing blood for tests on the day 5 is one of the disadvantages of preferring Thyrogen. Our aim was to compare day 3 and day 5 blood test results after Thyrogen injections. MATERIAL AND METHOD: In our study, Thyrogen was preferred in 32 differentiated thyroid cancer patients with a mean age of 50.5 ± 12.3 years. Thyrogen was injected on day 1 and day 2 intramuscularly in all patients before I-131 was given on day 3. A total of 22 patients received 5 mCi RAI for ablation control scintigraphy and 10 patients received 100-250 mCi RAI for ablation or therapy (high-dose group). Blood tests were performed on day 3 and day 5 after Thyrogen injections. RESULTS: Mean TSH level was 98.1 mg/dl for day 3 and 29.5 mg/dl for day 5. In the diagnostic group, thyroglobulin (Tg) and anti-Tg levels were nearly the same on day 3 and day 5. In the therapy group, day 5 Tg levels were higher than day 3. CONCLUSION: After Thyrogen injection of two consecutive days, blood sampling might be enough on day 3. Day 5 blood sampling may not be necessary routinely for radiation protection of laboratory staff. For the diagnostic group, if Tg and anti-Tg is normal then 5 mCi imaging may not be necessary.

Lacrimal gland uptake on F-18 florbetapir amyloid positron emission tomography scan.

In 2012, the Food and Drug Administration (FDA) approved the use of F-18 florbetapir to estimate ß-amyloid neuritic plaque density when indicated. A normal scan will show increased radiotracer uptake in the white matter. Mild uptake in salivary glands, skin, muscles, and bones is considered normal. Being a new and infrequently performed study, familiarity with normal biodistribution and variants is important. We hereby present 2 cases with F-18 florbetapir uptake in lacrimal glands. Patients had no symptoms or known systemic conditions to explain this uptake. We speculate that lacrimal gland uptake of F-18 florbetapir could represent a normal variant.

Clinical, pathological and (18)F-FDG PET/CT findings in synchronous primary vaginal and endometrial cancers.

Synchronous primary gynecologic malignancies are infrequently seen. In this report, we describe the clinical, pathological and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) findings of a patient with synchronous primary vaginal and endometrial cancers. To our knowledge, this is the first such case described in the literature.

Diagnostic value of F-18 FDG PET/CT in patients with spondylodiscitis: Is dual time point imaging time worthy?

PURPOSE: In this retrospective study, we aimed to investigate the value of FDG-PET/CT in the diagnosis of spondylodiscitis (SD), the significance of dual time point imaging (DTPI) for SD diagnosis and the worth of SUVmax data for distinguishing tuberculous vs. non-tuberculous SD. MATERIALS AND METHODS: 32 patients with suspected SD were scanned with FDG-PET/CT. For quantitative analysis maximum standardized uptake value (SUVmax) of the lesion area was measured. Nineteen patients had DTPI of FDG-PET/CT. The final diagnoses were achieved by histopathological, microbiological, and clinical results. RESULTS: Specific pathogens were isolated in 21 patients; other patients were accepted as nonspecific bacterial SD. In all patients, FDG-PET/CT results were compatible with SD diagnosis. The SUVmax data for tuberculous and non-tuberculous SD and DTPI results were statistically insignificant. CONCLUSION: FDG-PET/CT is a successful modality for SD diagnosis; additionally, DTPI protocol for FDG-PET/CT in SD diagnosis and SUVmax data for differentiation between non-tbc SD and tbc SD are useless.

Congenital amegakaryocytic thrombocytopenia: three case reports from patients with different clinical diagnoses and somatic abnormalities.

The congenital amegakaryocytic thrombocytopenia (CAMT) is a syndrome characterized by preservation of granulocytic and erythroid cells during genesis, with a gradual or progressive decrease in the number of megakaryocytic series of cells in the bone marrow. At later times, most patients develop aplastic anemia. It is important to rule out specific causes of thrombocytopenia that develop in the early stages of CAMT. Typically, there are no specific somatic abnormalities that accompany this deadly disease. Here we present three CAMT cases that presented with different clinical diagnoses, with various physical anomalies in two of those cases. The first patient was examined because of a cytomegalovirus infection. The second patient had been referred with a suspected neonatal alloimmune thrombocytopenia, whereas the third patient presented with chronic immune thrombocytopenic purpura. Subsequently, all three patients were diagnosed with CAMT. Two of the patients had physical anomalies. In particular, the first patient had a duplex urinary system. To our knowledge, this is the first patient with CAMT to have a duplicated collecting sysem. The second patient had a secundum atrial septal defect, an atypical facial appearance, and growth retardation. Since CAMT could also be observed outside the neonatal period, the differential diagnosis for thrombocytopenia should be considered for all age groups. Moreover, it should be considered that CAMT may also be accompanied with somatic abnormalities.

A single center's experience with Candida parapsilosis related long-term central venous access device infections: the port removal decision and its outcomes.

Pediatric cancer patients have an increased risk of potentially life-threatening fungal infections such as Candida parapsilosis, associated with long-term CVADs. The Infectious Diseases Society of America (IDSA) guidelines on Candida catheter-related bloodstream infections recommend systemic antifungal therapy and catheter removal. In this study, we focused on our experience with antifungal failure due to totally implanted catheter-associated C. parapsilosis bloodstream infections. We investigated cases leading to port removal in pediatric malignancy patients and the associated patient outcomes. In the first phase of the study, a retrospective chart review was performed to collect patient information, including primary disease; time from hospitalization to port-related candidemia; antifungal drug choice; and the time at which port removal occurred. During the second phase, antifungal susceptibility tests for C. parapsilosis were performed in our microbiology laboratory. All patients had fevers and were neutropenic at the time of candidemia diagnosis. The mean duration between the first isolation of Candida parapsilosis from the port samples to the port removal was 9.75 ± 5.29 days for 11 patients. Patient fevers lasted for a mean time of 16.22 ± 6.51 days. The median recovery duration from fever after CVC removal was four days (range 2-12 days). The median duration for achieving negative blood cultures, following antifungal treatment was 18 days (range 10-27 days). Our data favored the removal of catheters in the presence of ongoing fever, as suggested by the guidelines, independent of the chosen antifungal treatment. Future studies with large samples are needed to evaluate the effects of catheter removal on mortality rates and patient outcomes.

Higher expression of the novel gene upregulated gene 4 in two acute lymphoblastic leukemia patients with poor prednisolone response.

Elucidation of the molecular mechanisms of leukemogenesis is important for a better understanding of the prognosis of acute lymphoblastic leukemia (ALL). Studies have shown that the expression of upregulated gene 4 (URG4), which promotes cell growth and survival, is increased in different types of carcinomas including hepatocellular carcinoma, gastric cancer and osteosarcoma. Similarly, higher expression of URG4 and cyclin D1 gene might promote proliferation of the blast cells by causing escape from the G1 checkpoint and entry into the S phase. This study reports the high expression level of URG4 in 2 high-risk ALL patients for the first time in the literature. In conclusion, the higher expression of URG4 in our 2 patients suggests that URG4 might be involved in leukemogenesis. Future studies with a large number of high-risk ALL patients and cell culture studies are needed to demonstrate the exact role of URG4 in leukemogenesis.

Rhabdomyolysis due to Escherichia coli sepsis in three pediatric patients with acute lymphoblastic leukemia.

Rhabdomyolysis with myoglobinuria is an uncommon complication of bacterial sepsis. The authors describe three pediatric acute lymphoblastic leukemia patients who developed rhabdomyolysis during a neutropenic sepsis episode due to Escherichia coli. All of the patients needed hemodynamic supportive treatment because of septic shock. Broad-spectrum antibiotics, alkalinization, and intravenous fluid therapy was given. One patient with renal insufficiency died, despite aggressive treatment. Muscle pain and dark urine color should alert physicians to the possibility of rhabdomyolysis in immunocompromised patients with sepsis. Early and appropriate treatment is critical in these patients to prevent renal failure and shock, and for a better outcome.

Skin and muscle involvement as presenting symptoms in four children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and polyserositis. It is the most frequent periodic fever syndrome. In FMF, sterile peritonitis, pleuritis and arthritis are frequently seen in addition to recurrent febrile attacks. Skin and muscle involvement is less common. Here, we report four patients presented with skin lesions or myalgia. Most striking findings in those patients are the absence of other major criteria for FMF and dominancy of skin lesions or myalgia. All four patients had MEFV gene mutations on both alleles. In patients with erysipelas-like lesions or erythema nodosum along with arthritis/arthralgia or recurrent myalgia, FMF should be kept in mind.