A screw position change at an early postoperative stage preceding the subsequent occurrence of screw loosening.

PURPOSE: The authors recently proposed the novel radiologic assessment method to measure chronological screw position changes precisely. The aim of this study was to predict the late occurrence of screw loosening, which was diagnosed by the radiographic lucent zone, by evaluating screw position changes at an early postoperative stage using the novel method. METHODS: Forty-three patients who underwent thoracolumbar screw fixation and follow-up computed tomography (CT) scans on the day, between 1 and 5 weeks, and at more than 6 months after surgery were retrospectively evaluated. Screw images were generated from CT data. Screw position changes were evaluated by superposing screw images on the day and between 1 and 5 weeks after surgery. Screw loosening was diagnosed by the radiographic lucent zone on CT images at 6 months or later post-surgery, and patients were classified into screw loosening and non-loosening groups. The early screw position changes were compared between the two groups. RESULTS: Significant differences in early screw position changes were found between the screw loosening and non-loosening groups in Mann-Whitney U test (p = 0.001). On the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve was 0.791, and the best cutoff value of early screw position change for the prediction of screw loosening was 0.83 mm with a sensitivity of 64.0% and a specificity of 88.9%. CONCLUSION: We calculated a cutoff value of the screw position changes at an early postoperative stage for the prediction of subsequent development of screw loosening with the radiographic lucent zone.

Computational Fluid Dynamics for Cerebral Aneurysms in Clinical Settings.

Hemodynamics is thought to play an important role in the pathogenesis of cerebral aneurysms and recent development of computer technology makes it possible to simulate blood flow using high-resolution 3D images within several hours. A lot of studies of computational fluid dynamics (CFD) for cerebral aneurysms were reported; therefore, application of CFD for cerebral aneurysms in clinical settings is reviewed in this article.CFD for cerebral aneurysms using a patient-specific geometry model was first reported in 2003 and it has been revealing that hemodynamics brings a certain contribution to understanding aneurysm pathology, including initiation, growth and rupture. Based on the knowledge of the state-of-the-art techniques, this review treats the decision-making process for using CFD in several clinical settings. We introduce our CFD procedure using digital imaging and communication in medicine (DICOM) datasets of 3D CT angiography or 3D rotational angiography. In addition, we review rupture status, hyperplastic remodeling of aneurysm wall, and recurrence of coiled aneurysms using the hemodynamic parameters such as wall shear stress (WSS), oscillatory shear index (OSI), aneurysmal inflow rate coefficient (AIRC), and residual flow volume (RFV).

Safety of bronchoscopy in patients with malignant hematologic disorders.

BACKGROUND: Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. METHODS: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. RESULTS: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09-0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18-25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14-0.73, p = 0.01). CONCLUSIONS: Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient's procedural tolerance and lower complications.

Association of the Emergence of Acyclovir-Resistant Herpes Simplex Virus Type 1 With Prognosis in Hematopoietic Stem Cell Transplantation Patients.

Background: Antiviral-resistant herpes simplex virus type 1 (HSV-1) has been recognized as an emerging clinical problem among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A prospective observational study was conducted at a hematological center over a 2-year period. Oropharyngeal swab samples were serially collected each week from 1 week before and up to 100 days after HSCT and were tested for virus isolation. The HSV-1 isolates were tested for sensitivity to acyclovir (ACV). The prognosis of patients with ACV-resistant (ACVr) HSV-1 and the genetic background of the ACVr HSV-1 isolates were assessed. Results: Herpes simplex virus type 1 was isolated in 39 of 268 (15%) HSCT patients within 100 days after transplantation. Acyclovir-resistant HSV-1 emerged in 11 of these 39 patients (28%). The 100-day death rates of HSCT patients without HSV-1 shedding, those with only ACV-sensitive HSV-1 shedding, and those with ACVr HSV-1 shedding were 31%, 39%, and 64%, respectively. Patients with HSV-1, including ACVr HSV-1, shedding showed a significantly higher mortality rate. Relapsed malignancies were a significant risk factor for the emergence of ACVr HSV-1. Acyclovir resistance was attributable to viral thymidine kinase and DNA polymerase mutations in 6 and 5 patients, respectively. Conclusions: Herpes simplex virus type 1, including ACVr HSV-1, shedding was associated with poorer outcome in HSCT patients, even if HSV disease did not always occur. Patients with relapsed malignancies were at especially high risk for the emergence of ACVr HSV-1.

Successful Treatment of Pulmonary Mucormycosis Caused by Cunninghamella bertholletiae with High-Dose Liposomal Amphotericin B (10 mg/kg/day) Followed by a Lobectomy in Cord Blood Transplant Recipients.

Infection caused by Cunninghamella bertholletiae carries one of the highest mortality rates among mucormycosis, and there are no reported cases that survived from the infection in allogeneic hematopoietic stem cell transplantation recipients occurring before neutrophil engraftment. Here, we present two cases of pulmonary mucormycosis caused by C. bertholletiae occurring before neutrophil engraftment after cord blood transplantation. Both were successfully treated with high-dose liposomal amphotericin B (10 mg/kg/day) combined with micafungin, which was then followed by neutrophil recovery, reduction in immunosuppressive agents, and a subsequent lobectomy. The intensive antifungal therapy immediately administered upon suspicion of mucormycosis greatly suppressed the infection in its early stage and was well tolerated despite its prolonged administration and simultaneous use of nephrotoxic agents after transplantation. Although the synergic effect of micafungin remains unclear, these cases highlight the importance of prompt administration of high-dose lipid polyene when suspecting mucormycosis in highly immunocompromised patients, which enables subsequent diagnostic and therapeutic interventions, resulting in a favorable outcome.

A Novel Reduced-Toxicity Myeloablative Conditioning Regimen Using Full-Dose Busulfan, Fludarabine, and Melphalan for Single Cord Blood Transplantation Provides Durable Engraftment and Remission in Nonremission Myeloid Malignancies.

A pilot study of a novel, reduced-toxicity, myeloablative conditioning regimen using intravenous busulfan 12.8 mg/kg, fludarabine 180 mg/m(2), and melphalan 80 mg/m(2) for single cord blood transplantation (CBT) was conducted at our institution. Fifty-one patients with myeloid malignancies not in remission were included in this study. Their median age was 59 years (range, 19 to 70 years), with a median hematopoietic cell transplantation-specific comorbidity index score of 3. With a median observation period of 39.6 months (range, 24.3 to 90.8 months) among the survivors, overall survival and progression-free survival at 2 years were both 54.9%. Forty-six of 51 achieved neutrophil engraftment at a median of 19.5 days (range, 13 to 38 days) after transplantation, with a cumulative incidence of 90.2%. No patient developed graft rejection in this study. All patients who achieved engraftment showed hematological complete remission with complete donor chimerism. Eleven patients relapsed at a median of 4.9 months (range, .5 to 26.7 months). Cumulative incidences of nonrelapse mortality (NRM) at 100 days and 2 years were 11.8% and 25.5%, respectively. In conclusion, the present results show that the novel conditioning regimen for single CBT provided durable engraftment and remission with acceptable NRM leading to excellent survival, even for a relatively older population with myeloid malignancies not in remission.

[Distribution of Pain and Numbness in Patients with Cervical Spine Disorders].

PURPOSE: To elucidate the distribution of improved pain and numbness after cervical decompression surgery in patients with cervical spine disorders. METHODS: This study included 4 men and 5 women aged 45 to 71 years(mean 58 years)presenting with radiculopathy and 50 men and 17 women aged 35 to 88 years(mean 66 years)presenting with myelopathy. RESULTS: All 9 patients with radiculopathy presented with neck pain, and 3 presented with cervical angina. Among the patients with myelopathy, 2 presented with headache, 2 with onion-skin facial pain, 29 with neck pain, 8 with truncal pain, 7 with low back pain, 4 with numbness below the T4 dermatomal area, 1 with penile pain, 61 with arm pain, 49 with leg pain, and 2 without pain or numbness. Patients with myelopathy presenting with preoperative neck and arm pain had significantly better recovery rates compared to patients without such pain. CONCLUSION: Patients with cervical spine disorders present with pain and numbness in various areas. Preoperative neck pain and arm pain are indicators for better recovery in patients with myelopathy.

Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies.

The impact of anti-HLA antibodies, except for donor-specific anti-HLA-A, -B, -DRB1 antibodies, on engraftment was retrospectively evaluated in 175 single cord blood transplantations (CBT). Patients and donors had been typed at HLA-A, -B, and -DRB1 antigens, and anti-HLA antibodies had been screened before transplantation to avoid the use of cord blood (CB) units with corresponding antigens. The median age was 59 (range, 17 to 74) years. Overall, 61% were male, 89% had high-risk disease status, 77% received myeloablative conditioning regimens, and over 80% were heavily transfused patients. Sixty-nine of the 175 (39.4%) were positive for anti-HLA antibodies. Thirty-nine patients had antibodies only against HLA-A, -B, or -DRB1, 13 had antibodies only against HLA-C, -DP, -DQ, or -DRB3/4/5, and 17 had antibodies both against HLA-C, -DP, -DQ, or -DRB3/4/5 and against HLA-A, -B, or -DRB1. Because CB units had not been typed at HLA-C, -DP, -DQ, or -DRB3/4/5, it was possible that antibodies against them were unrecognized donor-specific antibodies. Patients with antibodies only against HLA-A, -B, or -DRB1 showed comparable neutrophil engraftment rates to those without antibodies (89.7% versus 83%, P = .65), whereas patients having antibodies against C, DP, DQ, or -DRB3/4/5 showed lower engraftment rate (66.7%, P = .12), which became statistically significant in a subgroup of HLA-mismatched donor-recipient pairs (50%, P = .01). Our results demonstrated that the presence of donor nonspecific anti-HLA-A, -B, -DRB1 antibodies had no significant influence on engraftment, whereas anti-HLA-C, -DP, -DQ, or -DRB3/4/5 antibodies adversely affect engraftment, possibly because of unrecognized donor-specific anti-HLA antibodies against them, especially in HLA-mismatched CBT.

[Herpes simplex virus type 2 fulminant hepatitis after umbilical cord blood transplantation for acute myeloid leukemia].

This report describes a 41-year-old patient, who developed herpes simplex virus type 2 (HSV-2)-hepatitis after umbilical cord blood transplantation (CBT). The patient had received allogeneic bone marrow transplantation from an unrelated donor for acute myeloid leukemia (AML) not in remission. AML relapsed 18 months after the first transplantation, and CBT was performed. AML relapsed again 5 months later and the patient was given chemotherapy. Although there was no active chronic graft-versus-host disease, liver dysfunction appeared, and one week later, progressed to acute liver failure. Viral screening of blood by PCR including hepatitis B and C viruses, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 and HSV-2 revealed elevation of HSV-2 (2.34 × 104 copies/ml). We diagnosed the patient as having HSV-2 acute hepatitis, and initiated treatment with antiviral drugs (acyclovir, foscarnet) and plasma exchange. However, liver functions deteriorated rapidly, and the patient died on day 6 after the onset of acute liver failure. Although HSV hepatitis is very rare after allogeneic stem cell transplantation, it is rapidly progressive and associated with a high mortality rate. Thus, early diagnosis with prompt antiviral intervention is recommended.

Ibuprofen Would Be the First-Line Nonsteroidal Anti-inflammatory Drug for Polymyalgia Rheumatica: A Case Series of Five Patients.

The primary treatment of choice for polymyalgia rheumatica (PMR) is corticosteroids, which are better avoided for elderly patients susceptible to PMR. The cases of five patients cured with only a small dosage of 600 mg/day ibuprofen without steroids or methotrexate are reported. Their clinical features were compared with those of the 26 PMR patients who had steroids and/or methotrexate in addition to ibuprofen. PMR was diagnosed based on the 2015 EULAR/ACR criteria. They were all females aged 73-80. They all had no giant cell arteritis or autoantibodies. Nonsteroidal anti-inflammatory drugs (NSAIDs) other than ibuprofen had not worked in four cases; for the one, ibuprofen was the first NSAID. Their serum CRP levels were 1.57-12.8 mg/dL at ibuprofen introduction. Colchicine was co-administered in two patients. At the next visit three to seven days after ibuprofen introduction, they all showed a clear recovery with a CRP level decrease. Ibuprofen tapering was started within three months, and no relapse was until two to five years' follow-up. Comparison with the 26 patients who had additional steroid and/or methotrexate showed that the disease duration until ibuprofen introduction was statistically significantly shorter in the five patients (1.40±0.65 vs 3.28±2.98 months). Ibuprofen would be the first-line drug for PMR, and its earliest use would be beneficial.

Computational fluid dynamics for predicting the growth of small unruptured cerebral aneurysms.

OBJECTIVE: Larger cerebral aneurysms are more likely to enlarge, but even small aneurysms can grow. The aim of this study was to investigate the hemodynamic characteristics regarding the growth of small aneurysms using computational fluid dynamics (CFD). METHODS: The authors analyzed 185 patients with 215 unruptured cerebral aneurysms with a maximum diameter of 3-5 mm, registered in a multicenter prospective observational study of unruptured aneurysms (Systematic Multicenter Study of Unruptured Cerebral Aneurysms Based on Rheological Technique at Mie) from January 2013 to February 2022. Based on findings on repeated images, aneurysms were divided into a stable group (182 aneurysms) and a growth group (33 aneurysms). The authors developed the high shear concentration ratio (HSCR), in which high wall shear stress (HWSS) was defined as a value of 110% of the time-averaged wall shear stress of the dome. High shear area (HSA) was defined as the area with values above HWSS, and the ratio of the HSA to the surface area of the dome was defined as the HSA ratio (HSAR). They also created the flow concentration ratio (FCR) to measure the concentration of the inflow jet. Multivariate logistic regression analysis was performed to determine morphological variables and hemodynamic parameters that independently characterized the risk of growth. RESULTS: The growth group had a significantly higher projection ratio (0.74 vs 0.67, p = 0.04) and volume-to-ostium area ratio (1.72 vs 1.44, p = 0.02). Regarding the hemodynamic parameters, the growth group had significantly higher HSCR (6.39 vs 4.98, p < 0.001), lower HSAR (0.28 vs 0.33, p < 0.001), and lower FCR (0.61 vs 0.67, p = 0.005). In multivariate analyses, higher HSCR was significantly associated with growth (OR 0.81, 95% CI 7.06 e-1 to 9.36 e-1; p = 0.004). CONCLUSIONS: HSCR may be a useful hemodynamic parameter to predict the growth of small unruptured cerebral aneurysms.

Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia.

We retrospectively analyzed 12 consecutive adult severe aplastic anemia patients who received unrelated umbilical cord blood transplantation after a reduced-intensity conditioning regimen (RI-UCBT). The conditioning regimen consisted of 125 mg/m² fludarabine, 80 mg/m² melphalan, and 4 Gy of total body irradiation. The median infused total nucleated cell number and CD34(+) cell number were 2.50 × 107/kg and 0.76 × 105/kg, respectively. Eleven of the 12 patients achieved primary neutrophil and platelet engraftment. All patients who achieved engraftment had complete hematologic recovery with complete donor chimerism, except for one patient who developed late graft failure 3 years after RI-UCBT. Two of the 12 patients died of idiopathic pneumonia syndrome, and the remaining 10 patients are alive, having survived for a median of 36 months. Our encouraging results indicate that RI-UCBT may become a viable therapeutic option for adult severe aplastic anemia patients who lack suitable human leukocyte antigen-matched donors and fail immunosuppressive therapy.

Successful engraftment after reduced-intensity umbilical cord blood transplantation for myelofibrosis.

Although allogeneic hematopoietic stem cell transplantation has recently been applied to patients with myelofibrosis with reproducible engraftment and resolution of marrow fibrosis, no data describe the outcomes of umbilical cord blood transplantation. We describe 14 patients with primary (n = 1) and secondary myelofibrosis (n = 13) who underwent reduced-intensity umbilical cord blood transplantation. Conditioning regimens included fludarabine and graft-versus-host disease prophylaxis composed cyclosporine/tacrolimus alone (n = 6) or a combination of tacrolimus and mycophenolate mofetil (n = 8). Thirteen patients achieved neutrophil engraftment at a median of 23 days. The cumulative incidence of neutrophil and platelet engraftment was 92.9% at day 60 and 42.9% at day 100, respectively. Posttransplantation chimerism analysis showed full donor type in all patients at a median of 14 days. The use of umbilical cord blood could be feasible even for patients with severe marrow fibrosis, from the viewpoint of donor cell engraftment.

Posterior Communicating Artery-incorporated Internal Carotid-Posterior Communicating Artery Aneurysms Prone to Recur After Coil Embolization.

OBJECTIVE: The objective was to clarify predisposing factors of recurrence after coil embolization for internal carotid-posterior communicating artery (IC-Pcom) aneurysms. METHODS: The medical records were retrospectively reviewed and patients harboring IC-Pcom aneurysms treated with coil embolization between June 2004 and June 2020 were identified. Aneurysms whose 3-dimensional images were available, whose initial treatment was performed during the study period, and whose follow-up term was more than 1 year were included. Information of the patients, the aneurysms and Pcoms, the initial treatment, and angiographic outcomes were collected. The IC-Pcom aneurysms were divided into Pcom-incorporated when their neck mainly rode on the Pcom or non-Pcom-incorporated when their neck mainly rode on the internal carotid artery or the classification was equivocal. Relationship between these factors and recurrence was analyzed. RESULTS: Fifty-seven IC-Pcom aneurysms from 55 patients were recruited. Fifteen of the 57 aneurysms were categorized into Pcom-incorporated. Eighteen of the 57 aneurysms recurred. Mean follow-up term was 74.3 months and mean duration between the initial treatment and recurrence was 47.9 months. On univariate analyses, ruptured (P = 0.004), fetal-type Pcom (P = 0.002), and Pcom-incorporated (P < 0.001) were significantly correlated with recurrence. Multivariate analysis demonstrated that Pcom-incorporated aneurysms were significantly associated with recurrence (P < 0.001) along with ruptured (P = 0.027). Kaplan-Meier estimate demonstrated that cumulative recurrence-free rate was significantly lower in Pcom-incorporated aneurysms compared with non-Pcom-incorporated aneurysms (log-rank P < 0.001). CONCLUSIONS: Pcom-incorporated IC-Pcom aneurysms were susceptible to recur after coil embolization, especially when ruptured and the incorporated Pcom was fetal-type.

Impact of Body Mass Index on 5-Year Survival Rates in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Cancer survival is associated with body mass index (BMI). However, the impact of patients' baseline characteristics on allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes remains unclear. This study aimed to examine the baseline clinical factors associated with 5-year survival rates in patients undergoing allo-HSCT. Material and Methods: This was a retrospective exploratory observational study. Patients (n = 113, 52 women; average age: 55 years) who underwent allo-HSCT at the Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, between January 2008 and March 2015, were included in the present study. Results: Patients with low BMI (<18.5 kg/m2) had significantly lower 5-year survival rates than those with normal (18.5-24.9 kg/m2) and high (⩾25.0 kg/m2) BMI. The 5-year survival rate was poorer for patients with sarcopenia (41.5%) than that for those without sarcopenia prior to allo-HSCT (P = .05). The 5-year survival rate was poorer for patients with geriatric nutritional risk index (GNRI < 98) (34.5%) than that for those without GNRI prior to allo-HSCT (P < .01). Conclusions: Low BMI before allo-HCST pre-treatment was a predictor of 5-year survival rates in this study. Patients undergoing allo-HSCT may require nutritional interventions during pre-treatment to reduce the risk of sarcopenia and GNRI (<98), which affects their survival rates.

Examination of a nutritional treatment pathway according to pretreatment health status and stress levels of patients undergoing hematopoietic stem cell transplantation.

INTRODUCTION: This study aimed to validate hematopoietic stem cell transplantation (HSCT) treatment via a tailored nutritional pathway in myeloablative conditioning (MAC), determine its efficacy in terms of remission, and explore associations between clinical outcomes and nutritional indicators. METHODS: We included patients who underwent MAC for HSCT at the Shizuoka Cancer Center Stem Cell Transplantation between 2015 and 2019. We evaluated outcomes from the day before treatment initiation (transplant date: day 0) to day 42. RESULTS: Among the 40 MAC cases (participant characteristics: 20/40 males, mean age of 52 years, and mean body mass index of 21.9 kg/m2), we found that the percent loss of body weight and loss of skeletal muscle mass were correlated with the basal energy expenditure rate (BEE rate; r = 0.70, p<0.001 and r = 0.49, p<0.01, respectively). Based on the receiver operating characteristics curves, the cutoff value for the BEE rate in terms of weight loss was 1.1. Salivary amylase levels did not significantly change during the treatment course. Continuous variables, including oral caloric intake and performance status, showed statistically significant correlations with nutrition-related adverse events during treatment (r = -0.93, p<0.01 and r = 0.91, p<0.01, respectively). Skeletal muscle mass before treatment initiation was an independent predictive variable for reduced 2-year survival (p = 0.04). CONCLUSION: Our results support the validity of a safe nutritional pathway with a BEE rate of 1.1 for HSCT patients pretreated with MAC. Specifically, we found that this pathway could prevent weight loss in response to nutrition-related adverse events. Skeletal muscle mass before treatment was identified as an independent risk factor for reduced 2-year survival.

Impact of HLA disparity in the graft-versus-host direction on engraftment in adult patients receiving reduced-intensity cord blood transplantation.

Delayed engraftment or graft failure is one of the major complications after cord blood transplantation (CBT). To investigate factors impacting engraftment, we conducted a retrospective analysis of adult patients who underwent reduced-intensity CBT at our institute, in which preparative regimens mainly consisted of fludarabine, melphalan, and total body irradiation with graft-versus-host (GVH) disease prophylaxis using single calcineurin inhibitors. Among 152 evaluable patients, the cumulative incidence of neutrophil engraftment was 89%. High total nucleated cell and CD34(+) cell dose were associated with the faster speed and higher probability of engraftment. In addition, the degree of human leukocyte antigen (HLA) mismatch in the GVH direction was inversely associated with engraftment kinetics, whereas no statistically significant association was observed with the degree of HLA mismatch in the host-versus-graft direction. Similarly, the number of HLA class I antigens mismatched in the GVH direction, but not in the host-versus-graft direction, showed a negative correlation with engraftment kinetics. HLA disparity did not have significant impact on the development of GVH disease or survival. This result indicates the significant role of HLA disparity in the GVH direction in the successful engraftment, raising the novel mechanism responsible for graft failure in CBT.

[Optimal therapeutic concentration of tacrolimus in adult patients undergoing reduced-intensity cord blood transplantation].

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.

A case presenting as fatal subarachnoid hemorrhage due to segmental arterial mediolysis associated with Crohn's disease.

BACKGROUND: Segmental arterial mediolysis (SAM) is a rare arterial pathology and can cause rupture or dissection of the intracranial arterial wall. The etiology is unveiled, but vasospastic stimuli such as migraine are considered as a possible cause of SAM. We present the first case of subarachnoid hemorrhage (SAH) due to SAM associated with Crohn's disease and migraine, and discuss the possible contribution of Crohn's disease to the development of SAM besides migraine. CASE DESCRIPTION: A 33-year-old man with Crohn's disease, which had been treated with adalimumab, repeatedly underwent 3-tesla magnetic resonance (MR) imaging and angiography for severe headache due to migraine and the subsequent development of fatigue in the left arm and both legs. At 7 months after the last MR imaging studies showing no abnormalities, he had a sudden onset of severe SAH, which was caused by rupture or dissection of the terminal portion in the right internal carotid artery. As his brain-stem reflexes were absent, the patient was conservatively treated and died 6 days after the ictus. By postmortem histopathological examination, SAM was diagnosed as the cause of SAH. Vasa vasorum was also observed around the rupture point. CONCLUSIONS: Our case suggests that: 1) the formation of vasa vasorum may be an antecedent pathology for vessel rupture of the fragile arterial wall affected by SAM, and 2) vasospastic nature of both Crohn's disease and migraine may contribute to the development of intracranial SAM.