Two-year clinical outcomes of drug-coated balloon angioplasty and angiographic predictors of restenosis among patients with de novo femoropopliteal lesions.

OBJECTIVES: We analyzed the 2-year clinical outcomes of patients with de novo femoropopliteal (FP) lesions who underwent drug-coated balloon (DCB) angioplasty and the angiographic predictors of restenosis. METHODS: This single-center, retrospective, and observational study evaluated 129 de novo FP lesions treated with DCB angioplasty without bailout stenting. Clinical outcomes and risk factors for loss of primary patency were analyzed using univariate and multivariate Cox proportional hazards regression models. RESULTS: The participants were aged 48-93 (mean: 73.6 ± 9.8) years, and 31% were women. Approximately 33% of the patients were receiving regular dialysis, and 35% of the affected limbs had critical ischemia. The mean lesion length was 132 ± 96 mm, and the mean reference vessel diameter (RVD) was 4.7 ± 0.8 mm. Forty-three (33%) limbs had chronic total occlusion of the target artery segment. Fifty-seven (44%) and 72 (56%) lesions were treated with DCB angioplasty using IN.PACT Admiral and Lutonix, respectively. The primary patency and amputation-free survival at 2 years were 59.3% and 89.5%, respectively. RVD was found to be an independent predictor of loss of primary patency. Based on the receiver operating characteristic analysis, an RVD of 4.2 mm was the best predictor of loss of primary patency at 2 years. CONCLUSIONS: The short-term clinical outcome of DCB angioplasty for de novo FP lesions was acceptable. Moreover, an RVD of <4.2 mm was an independent predictor of restenosis after DCB angioplasty.

Scoring model to predict low image quality of drug-eluting stent evaluated by computed tomography coronary angiography.

Evaluation of in-stent restenosis (ISR) by computed tomography coronary angiography (CTCA) is less invasive but often impossible. We aimed to create a scoring model for predicting which drug-eluting stents (DES) cannot be evaluated with CTCA. We enrolled 757 consecutive implanted DES assessed with CTCA. Non-diagnostic evaluation was defined as poor/not evaluative by two different observers. These stents were randomly divided into a derivation (n = 379) and validation (n = 378) group. In the derivation group, we assessed predictors using logistic regression analysis and created a scoring model that would stratify non-diagnostic evaluation of DES-ISR. The validity of this scoring model was evaluated in the validation group using receiver-operating characteristic analysis. The percentage of non-diagnostic stents was 19/21% in the derivation/validation group (p = 0.71). Non-diagnostic evaluation was independently associated with implanted stent diameter (2.25-2.5. vs. 2.5-3 vs. > 3.0 mm), severe calcification, stent-in-stent lesion, and type of DES (stainless vs. CoCr vs. PtCr) in the derivation group. The predicting system of implanted DES non-diagnostic by CTCA (PIDENT) for non-diagnostic evaluation, including these four baseline factors, was derived (C-statistic = 0.86 in derivation group, cutoff: 8 points). The PIDENT score had a high predictive value for non-diagnostic DES in the validation model (C-statistic = 0.87, sensitivity 86%, specificity 74%, cutoff 8 points, p < 0.001). The PIDENT score, consisting of baseline characteristics including implanted stent diameter, severe calcification, stent-in-stent lesion, and type of DES, could identify non-diagnostic evaluation of DES-ISR with CTCA. The PIDENT score was valuable in reducing nonevaluable and meaningless CTCA for DES-ISR.

Successfully Managed Access-Site Complication Was Not Associated With Worse Outcome After Percutaneous Transfemoral Transcatheter Aortic Valve Implantation: Up-to-Date Insights From the OCEAN-TAVI Registry.

BACKGROUND: Access-site complications during transfemoral transcatheter aortic valve implantation (TF-TAVI) cause serious issues in the future, if unresolved, but the best strategies to manage these complications remains unclear. This study aimed to comprehensively assess access-site complications during percutaneous TF-TAVI in terms of their management. METHODS: Using the prospective, multicentre, observational registry OCEAN (Optimized Transcatheter Valvular Intervention), 1497 patients who underwent percutaneous TF-TAVI between October 2013 and May 2017 were identified. The incidence, predictors, temporal changes, and prognosis of access-site complications along with its treatment strategy and re-intervention rate were evaluated. RESULTS: Access-site complications occurred in 105 patients (7.0%) and was predicted with lower body-mass-index (OR, 0.94; 95% CI; 0.89-0.99; p = 0.03) and higher sheath-to-femoral-artery-ratio (OR, 1.12; 95% CI, 1.03-1.24; p < 0.002). The incidence of access-site complications declined over time, irrespective of the increasing number of percutaneous TF-TAVI cases. Access-site complications were treated by conservative therapy (n = 19, 18%), interventional procedures (n = 42, 40%), rescue surgical repair (SR) (n = 10, 10%), and primary SR (n = 34, 32%). The severity of complications differed but the re-intervention rate was similar among 4 groups (p = 0.46). Re-intervention was not needed, except for a case of common femoral artery stenosis/occlusion induced by ProGlide. The need for all SRs decreased annually. Access-site complications were not associated with 30 days- and 1 year-survival rate. CONCLUSIONS: The incidence of access-site complications was not low but has declined annually. Access-site complications are not related to worse outcomes after successful management. Interventional procedure is acceptable as the first-line strategy to treat access-site complications.

Scoring Model to Predict Major Amputation in Patients With Chronic Limb-Threatening Ischemia at Wound, Ischemia, and Foot Infection Clinical Stage 4 After Endovascular Therapy.

PURPOSE: We investigated the predictors of major amputation (MA) at 1 year and prepared a scoring model to stratify the clinical outcomes of chronic limb-threatening ischemia (CLTI) patients at wound, ischemia, and foot infection (WIfI) clinical stage 4 after endovascular therapy (EVT). MATERIALS AND METHODS: This study was a retrospective, observational study performed at a single center. A total of 353 CLTI patients (390 limbs) were treated with EVT between April 2007 and December 2016. Among these, limbs at WIfI clinical stages 1, 2, and 3 were excluded, and 194 limbs at WIfI clinical stage 4 (49.7%) were enrolled. The primary endpoint was major amputation (MA) free rate at 1 year. Predictors of MA at 1 year was evaluated by Cox proportional hazard analysis. RESULTS: At 1 year, the incidence of MA was 18.0% (35 limbs). Cox proportional hazard analysis revealed that hemodialysis (hazard ratio [HR] 2.63; 95% confidence interval [CI], 1.24-5.58; p=0.012), fI3 (HR 2.54; 95% CI, 1.28-5.06; p=0.008), toe wounds (HR 0.29; 95% CI, 0.094-0.88; p=0.029), and visible blood flow to the wound (HR 0.43; 95% CI, 0.21-0.89; p=0.023) were associated with MA. We assigned 1 point for positive predictors of MA, hemodialysis, and fI3; 1 point was deducted for negative predictors of MA, toe wounds, and visible blood flow to the wound. A score of -2 or -1, was defined as the low-risk group, 0 was defined as the intermediate-risk group, and +1 or +2 were defined as the high-risk group. At 1 year, MA free rate, wound healing rate, and amputation-free survival rate were stratified according to a scoring model. MA free rate was 96.6% in low-risk, 72.4% in intermediate-risk, and 67.3% in high-risk (p<0.001); wound healing rate was 67.8% in low-risk, 27.6% in intermediate-risk, and 4.1% in high-risk (p<0.001); amputation-free survival rate was 65.3% in low-risk, 44.8% in intermediate-risk, and 18.4% in high-risk (p<0.001). CONCLUSIONS: The scoring model based on the predictors of MA stratified clinical outcomes in CLTI patients at WIfI clinical stage 4.

Influence of polyvascular disease on clinical outcome in patients undergoing transcatheter aortic valve implantation via transfemoral access.

BACKGROUND: The influence of polyvascular disease (PVD) on the short- and long-term clinical outcomes of patients undergoing transcatheter aortic valve implantation via trans-femoral access (TF-TAVI) has not been fully elucidated. METHODS: A total of 2167 patients from the Optimized CathEter vAlvular iNtervention-TAVI (OCEAN-TAVI) registry who underwent TF-TAVI was studied. PVD was defined as the presence of at least two of the following vascular bed (VB) diseases: concomitant coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral artery disease (PAD). RESULTS: Patients with PVD (288 patients, 13.3%) had a higher incidence of in-hospital complications, such as AKI (16.3% vs. 7.0%, p<0.01) and disabling stroke (3.5% vs. 1.2%, p<0.01) than patients without PVD. These complications caused higher rates of procedural mortality (4.5% vs. 2.0%, p<0.01). PVD increased the risk of the 2-year rate of cardiovascular death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.04-2.50; p<0.05); however, non-cardiovascular death, myocardial infarction, or ischemic stroke was not associated with PVD. Worsening heart failure (4.6% vs. 1.1%, p<0.01) was the main cause of cardiovascular death among patients with PVD. In a sub-analysis, compared with patients with AS alone, those with 2 VB diseases (CAD+PAD; adjusted HR, 1.93; 95% CI, 1.06-3.53; p<0.05) and 3 VB diseases (CAD+CVD+PAD; adjusted HR, 2.61; 95% CI, 1.21-5.62; p<0.05) had a higher risk of 2-year cardiovascular death. CONCLUSIONS: The increased prevalence of concomitant atherosclerotic VB diseases before TF-TAVI may increase the rates of in-hospital complications and 2-year cardiovascular death. Given the higher rate of mortality in patients with PVD undergoing TF-TAVI, future studies focusing on medical therapy are needed to reduce long-term cardiovascular events in this high-risk subset.

Bedside Electrophysiological Study Using a Temporary Pacemaker May Predict Recurrence of Atrioventricular Block After Transcatheter Aortic Valve Replacement.

High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However, some patients with HAVB/CHB recover with time. The results of electrophysiological studies (EPSs) using permanent pacemaker implantation (PPI) in patients with suspicious HAVB/CHB are considered controversial.This study aimed to evaluate whether HAVB/CHB induction at the bedside using a temporary pacemaker can predict recurrence in patients who had recovered from HAVB/CHB after TAVR.We enrolled a total of 11 patients who had recovered from HAVB/CHB and evaluated their electrophysiology using right ventricular pacing and/or procainamide administration.HAVB/CHB induction was positive. Three patients tested positive for HAVB/CHB, whereas 8 tested negative. The ejection fraction and the interval between HAVB/CHB onset and EPS were found to be significant. HAVB/CHB positive patients underwent PPI. A patient with a balloon-expandable valve tested positive just before recovery of CHB, but tested negative 5 days later and was included in the negative group. The 4 patients who tested negative received a cardiovascular implantable electric device (CIED). We observed HAVB/CHB in 2 patients who had previously tested positive after 3 months. Among those who tested negative, those with CIED had no HAVB/CHB, and others showed neither HAVB/CHB on electrocardiogram nor experienced syncope or sudden death.Our EPS revealed that HAVB/CHB induction may predict HAVB/CHB recurrence after TAVR. Valve type and EPS timing may affect the results.

ULSOSEAL Technique: A Unique Technique to Achieve Hemostasis Using ExoSeal in High-Risk Patients after Common Femoral Artery Puncture.

This study aimed to assess the safety and feasibility of the ULtrasound-guided uSe Of exoSEAL technique (ULSOSEAL technique) in patients at a high risk of complications following the use of ExoSeal. ExoSeal is a novel, completely extravascular hemostatic device that can treat punctures of the common femoral artery; however, it is not preferable for use in cases that require hemostasis of complex puncture sites. From November 2019 to August 2020, the ULSOSEAL technique was performed in 35 patients with implanted stents (6 patients, 17%), severe calcification (32 patients, 91%), and plaque (7 patients, 20%) around the puncture site; the presence of these conditions is usually undesirable when using ExoSeal. The antegrade approach was used in 22 patients (71%). The size of the ExoSeal used was 5 Fr (13 patients, 37%), 6 Fr (21 patients, 60%), and 7 Fr (1 patient, 2%). Technical success was achieved in 34 patients (97%), while ExoSeal malfunction occurred in 1 patient. There was no incidence of vessel occlusion, pseudoaneurysm, arteriovenous fistula, infection, and secondary bleeding. One patient developed a hematoma (>5 cm in size); however, it occurred before the use of ExoSeal due to side leakage from the inserted sheath. The ULSOSEAL technique was safe and feasible for hemostasis in patients who were considered unsuitable for the ExoSeal device.

Vascular Response after Directional Coronary Atherectomy for Left Main Bifurcation Lesion.

AIMS: To evaluate the vascular response after directional coronary atherectomy (DCA) for left main (LM) bifurcation lesion. METHODS: This study was a retrospective, single-center study enrolling 31 patients who underwent stentless therapy using DCA followed by drug-coated balloon (DCB) angioplasty for LM bifurcation lesion. We compared intravascular ultrasound (IVUS) findings before and after DCA. RESULTS: After DCA, the lumen and vessel areas significantly increased, whereas the plaque area (PA) and %PA were significantly reduced. When the lesions were divided into small vessel and large vessel groups using the median value of the vessel area, the maximum balloon pressure of the DCA catheter was greater in the large vessel group. Changes in the lumen and vessel areas were also significantly greater in the large vessel group. On the other hand, the changes in PA and %PA were similar between groups. CONCLUSIONS: The main vascular responses associated with lumen enlargement after DCA were plaque reduction and vessel expansion. Contribution of vessel expansion to lumen enlargement was larger than the effect of plaque reduction in large vessel lesions.

Additional debulking efficacy of low-speed rotational atherectomy after high-speed rotational atherectomy for calcified coronary lesion.

We aimed to evaluate the additional debulking efficacy of low-speed rotational atherectomy (RA) after high-speed RA by using intravascular imaging. A total of 22 severe calcified coronary lesions in 19 patients (age, 74 ± 10 years; 74% male) were retrospectively analyzed. All of these lesions underwent RA under optical coherence tomography (OCT) or optical frequency domain imaging (OFDI) guidance. At first, we performed high-speed RA with 220,000 rpm until the reduction of rotational speed disappeared; then, low-speed RA with 120,000 rpm using the same burr size was performed. OCT or OFDI was performed after both high-speed and low-speed RAs, and the minimum lumen area were compared. The initial and final burr sizes of high-speed RA were 1.5 (1.5-1.75) and 1.75 (1.5-2.0) mm, respectively. The number of sessions, total duration time, and maximum decreased rotational speed during high-speed RA were 11 ± 5 times, 113 ± 47 s, and 4000 (3000-5000) rpm, respectively. During low-speed RA, the number of sessions, total duration time, and maximum reduction of rotational speed were 3 ± 1 times, 32 ± 11 s, and 1000 (0-2000) rpm, respectively. The minimum lumen area was similar between after high-speed and after low-speed RA [2.61 ± 1.03 mm2 (after high-speed RA) vs. 2.65 ± 1.00 mm2 (after low-speed RA); P = 0.91]. Additional low-speed RA immediately after sufficient debulking by high-speed RA was not associated with increased lumen enlargement. There was no clinical efficacy of low-speed RA after high-speed RA.

Use of the orbital atherectomy system backed up with the guide-extension catheter for a severely tortuous calcified coronary lesion.

A 68-year-old man was scheduled to undergo percutaneous coronary intervention for in-stent total occlusion of the severely tortuous right coronary artery. Intravascular ultrasound revealed heavy in-stent calcification. Lesion atherectomy was required; however, severe proximal vessel tortuosity was detected. We introduced a 7-Fr guide-extension catheter beyond the severely tortuous part and performed rotational atherectomy with a 1.5 mm burr. However, the balloon could not expand; therefore, we changed to an orbital atherectomy system. Subsequently, the balloon successfully expanded, and intravascular ultrasound revealed an enlarged lumen. Severe proximal vessel tortuosity limits the use of atherectomy devices; however, a guide-extension catheter delivers the atherectomy device beyond the tortuosity. The delivery of the orbital atherectomy system inside the guide-extension catheter is easy due to its low profile; the debulking effect increases with the number of passes and rotational speed. This strategy is a useful option for treating severe calcified lesions with proximal vessel tortuosity.

Sustained drug retention after paclitaxel-coated balloon angioplasty for superficial femoral artery disease: Follow-up intravascular imaging.

A 63 year-old woman with claudication underwent endovascular therapy for diffuse stenosis of the right superficial femoral artery in our hospital. We performed paclitaxel-coated balloon angioplasty using the IN.PACT™ Admiral™ and achieved acceptable results. After 42 days, we performed follow-up optical frequency domain imaging for the right superficial femoral artery lesion treated with paclitaxel-coated balloon and observed several high-intensity regions with attenuation on the lumen surface. Sustained drug availability is a notable characteristic of paclitaxel-coated balloon. To the best of our knowledge, this is the first report on the visualization of sustained drug retention on the lumen surface using follow-up optical frequency domain imaging after paclitaxel-coated balloon angioplasty in a human patient with superficial femoral artery disease.

Peripartum Iliac Arterial Aneurysm and Rupture in a Patient with Vascular Ehlers-Danlos Syndrome Diagnosed by Next-Generation Sequencing.

Vascular Ehlers-Danlos syndrome (vEDS), a genetic disorder caused by mutations in procollagen type III gene (COL3A1), may lead to fatal vascular complication during peripartum period because of the arterial fragility. We experienced a case of vEDS with peripartum life-threatening arterial rapture diagnosed by next-generation sequencing (NGS) and successfully treated the vascular complications. A 25-year-old female in pregnancy at 34 weeks had sudden and acute pain in the left lower abdomen. After successful delivery, her computed tomography scan showed a dissecting aneurysm of the left common iliac artery (CIA). Four days after delivery, she presented in hemorrhagic shock induced by arterial rupture in the CIA. Since her clinical presentations inferred vEDS even in the absence of familial history, we performed NGS-based genetic screening for inherited connective tissue disorders including vEDS with informed consent. Even though we started intensive medication, her iliac aneurysm was progressively enlarging within 3 weeks. After an urgent molecular diagnosis for vEDS (a splice-site mutation), cautious endovascular therapy for her CIA aneurysm was successfully performed. This is the first report for pretreatment molecular diagnosis of vEDS using NGS in an emergent situation of severe vascular complications.

Oxidative imbalance in idiopathic renal hypouricemia.

An important complication of idiopathic renal hypouricemia is exercise-induced acute renal failure (ARF). The most plausible explanation for this complication is that decreased antioxidant potential leads to kidney injury by reactive oxygen species (ROS). We demonstrated this oxidative imbalance by a concomitant assessment of ROS production and antioxidant system capability in a 15- year-old girl with idiopathic renal hypouricemia caused by a mutation in the urate transporter (URAT1) gene. Her serum level of ROS increased with decreasing antioxidant potential capacity soon after the initiation of anaerobic stress due to treadmill exercise. Thereafter, serum levels of ROS and antioxidant potential showed a parallel course, returning to the baseline values at 240 min after exercise. Some patients with idiopathic renal hypouricemia demonstrate oxidative imbalance soon after exercise with a predisposition to exercise-induced acute renal failure. Antioxidant properties may alter this imbalance by augmenting the antioxidant activity.

Functional analysis of JAK3 mutations in transient myeloproliferative disorder and acute megakaryoblastic leukaemia accompanying Down syndrome.

JAK3 mutations have been reported in transient myeloproliferative disorder (TMD) as well as in acute megakaryoblastic leukaemia of Down syndrome (DS-AMKL). However, functional consequences of the JAK3 mutations in TMD patients remain undetermined. To further understand how JAK3 mutations are involved in the development and/or progression of leukaemia in Down syndrome, additional TMD patients and the DS-AMKL cell line MGS were screened for JAK3 mutations, and we examined whether each JAK3 mutation is an activating mutation. JAK3 mutations were not detected in 10 TMD samples that had not previously been studied. Together with our previous report we detected JAK3 mutations in one in 11 TMD patients. Furthermore, this study showed for the first time that a TMD patient-derived JAK3 mutation (JAK3(I87T)), as well as two novel JAK3 mutations (JAK3(Q501H) and JAK3(R657Q)) identified in an MGS cell line, were activating mutations. Treatment of MGS cells and Ba/F3 cells expressing the JAK3 mutants with JAK3 inhibitors significantly decreased their growth and viability. These results suggest that the JAK3 activating mutation is an early event during leukaemogenesis in Down syndrome, and they provide proof-of-principle evidence that JAK3 inhibitors would have therapeutic effects on TMD and DS-AMKL patients carrying activating JAK3 mutations.

Outcome of non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation from family donors in children and adolescents.

Non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (SCT) from family members has been reported, but its effectiveness and safety are not fully known. In this study, we examined the outcomes of 83 children and adolescents with nonmalignant (n = 11) or malignant (n = 72) disorders who underwent SCT mismatched at 2 or 3 HLA loci, either from the mother (n = 56), a noninherited maternal antigen (NIMA)-mismatched sibling (n = 14), or the father/a noninherited paternal antigen (NIPA)-mismatched sibling (n = 13). Engraftment was satisfactory. Severe (grade III-IV) acute graft-versushost disease (GVHD) was noted only in malignant disease, with an incidence of 21 of 64 evaluable patients. GVHD prophylaxis with a combination of tacrolimus and methotrexate was significantly associated with a lower risk of severe acute GVHD, compared with other types of prophylaxis (P = .04). Nine of 11 patients with nonmalignant disease and 29 of 72 patients with malignant disease were alive at a median follow-up of 26 months (range, 4-57 months). Outcomes were not significantly different among the 3 donor groups (mother versus NIMA-mismatched sibling versus father/NIPA-mismatched sibling) for the malignancy disorders. Our results indicate that non-T-cell-depleted HLA-haploidentical SCT may be feasible, with appropriate GVHD prophylaxis, for young recipients who lack immediate access to a conventional stem cell source.

Clinical and genetic analyses of presumed Shwachman-Diamond syndrome in Japan.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities. SBDS was identified as a causative gene for SDS in 2003, and genetic analyses of SDS have been performed. We performed genetic analysis of 13 Japanese patients with presumed SDS and found that 10 of them had SBDS mutations. Most patients had recurrent mutations (181-184TA-->CT and 258+2T-->C); however, 2 patients had unique mutations (259-1G-->A and 428C-->G). Although genetic analysis is useful for definitive diagnosis and for genetic counseling of SDS patients and families, SDS appears to be a genetically heterogeneous disorder. In addition, presumed SDS patients without SBDS mutations may be included in other disorders.

Malignant rhabdoid tumor of the liver: case report and literature review.

A case of malignant rhabdoid tumor (MRT) occurring as a primary hepatic neoplasm in a 12-month-old Japanese female infant is presented. The patient had a slight fever for 2 weeks and presented with a palpable mass in her left hypochondrial region. After admission, the hepatic artery was embolized due to intra-abdominal hemorrhage arising from the tumor. The patient received chemotherapy with cisplatin, cyclophosphamide and adriacin. Despite treatment, the patient developed dyspnea, pancytopenia and disseminated intravascular coagulation. Rupture of the tumor resulted in death within 3 weeks. A limited abdominal autopsy revealed that the liver weighed 1240 g and was occupied by multiple hemorrhagic and/or necrotic tumor nodules. Histologically, neoplastic cells had an abundant eosinophilic cytoplasm containing paranuclear inclusions, and vesicular nuclei with a centrally located prominent nucleolus. Ultrastructurally, the cytoplasmic inclusions were composed of whorled filaments measuring 10 nm. Immunohistochemically, almost all of the neoplastic cells were positive for vimentin and cytokeratins (CK) 8 and 18, some were positive for CK 7 and 19, while none were positive for CK 1, 10, 13-17 and 20. The tumor cells did not express desmin, myoglobin, and alpha-fetoprotein. We found 18 cases of MRT of the liver published in English language literature and then, adding the present case, we summarized the 19 cases. Hepatic MRT is an uncommon neoplasm. However, it should be considered in the differential diagnosis of an aggressive liver neoplasm in childhood.

A case of primary Ewing's sarcoma of the occipital bone presenting with obstructive hydrocephalus.

BACKGROUND: Ewing's sarcomas account for approximately 10% of primary malignant bone tumors. While most of the primary Ewing's sarcomas occur in the long bones, pelvis, or ribs, approximately 1-6% of these sarcomas arise in the skull. We found approximately 50 cases of Ewing's sarcoma of the calvarium reported in our search of the literature. Of these, 36 cases were reported in detail. CASE REPORT AND DISCUSSION: In this article we describe a rare case of primary Ewing's sarcoma of the occipital bone presenting with acute obstructive hydrocephalus and review the literature.

The effect of thrombopoietin on erythroid progenitors in Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a rare congenital red blood cell aplasia. Usually, erythropoiesis in vitro is defective, and decreased numbers of erythroid progenitors are found in colony assays performed with bone marrow cells. Recently, some investigators showed that thrombopoietin (TPO) also works on common multipotent progenitor cells and stimulates erythropoiesis. We examined the effect of TPO together with erythropoietin (EPO), stem cell factor (SCF), and/or interleukin-3 (IL-3) on erythroid burst-forming units (BFU-E) of bone marrow nonadherent mononuclear cells from 2 patients with DBA using a serum-free culture system. Very few BFU-E appeared in cultures containing EPO alone. Adding IL-3, SCF, or both to cultures containing EPO induced an increase in the number of BFU-E. When TPO was added to cultures containing EPO and IL-3, SCF, or both, the number of BFU-E further increased. Especially in patient 2, BFU-E formation was grossly equal to that in normal controls. We conclude that TPO enhances bone marrow erythropoiesis in patients with DBA in the presence of EPO and SCF and/or IL-3. The data raise the possibility of the combination of TPO and SCF as a therapeutic agent in DBA.