Long-term outcomes of spine surgery in dialysis patients, focusing on activities of daily living, life expectancy, and the risk factors for postoperative mortality.

BACKGROUND: Because of the high incidence of major perioperative adverse events, spine surgery in dialysis patients should be recommended carefully after consideration of its risks and benefits. However, the benefits of spine surgery in dialysis patients remain unclear because of the lack of long-term outcomes. The purpose of this study is to elucidate the long-term outcomes of spine surgery in dialysis patients, focusing on activities of daily living (ADLs), life expectancy, and risk factors for postoperative mortality. METHODS: Data for 65 dialysis patients who underwent spine surgery at our institution and were followed up for a mean duration of 6.2 years were retrospectively reviewed. ADLs, number of surgeries, and survival times were recorded. The postoperative survival rate was calculated using the Kaplan-Meier method, and risk factors for postoperative mortality were investigated using a generalized Wilcoxon test and multivariate Cox proportional-hazards model. RESULTS: Compared with preoperative ADLs, ADLs significantly improved at discharge after surgery and at the final follow-up. However, 16 of the 65 patients (24.6%) underwent multiple surgeries, and 34 (52.3%) died during the follow-up period. Kaplan-Meier analysis revealed that the survival rate after spine surgery was 95.4% at 1 year, 86.2% at 3 years, 69.6% at 5 years, 59.7% at 7 years, and 28.7% at 10 years, and the overall median survival time was 99 months. Multivariate Cox regression analysis showed that a dialysis period of ≥10 years was a significant risk factor. CONCLUSIONS: Spine surgery in dialysis patients improved and maintained ADLs in the long term and did not shorten life expectancy. However, dialysis patients undergoing spine surgery require multiple surgeries more frequently, and a dialysis period of ≥10 years is a significant risk factor for postoperative mortality.

[Autologous stem cell transplantation after pola-BR regimen as a salvage therapy in relapsed diffuse large B-cell lymphoma].

A 57-year-old male patient with relapsed/refractory diffuse large B-cell lymphoma received 4 courses of Pola-BR (polatuzumab vedotin-bendamustine-rituximab). After treatment, stem cell collection with G-CSF and plerixafor successfully yielded 4.2×106 cells/kg of CD34-positive cells. The patient underwent autologous peripheral hematopoietic stem cell transplantation. Neutrophil engraftment was achieved on day 12 and the patient was followed up without progression. In this case, stem cell mobilization with G-CSF and plerixafor was effective even in patients who had received chemotherapy including bendamustine, which is known to sometimes complicate stem cell collection. Although bendamustine should generally be avoided in cases where stem cell collection is planned, there are cases in which the decision to perform transplantation is made after chemotherapy including bendamustine. We have reported a case in which we were able to perform stem cell collection after pola-BR regimen.

Lewy Body Disease Primate Model with α-Synuclein Propagation from the Olfactory Bulb.

BACKGROUND: Lewy body diseases (LBDs), which are pathologically defined as the presence of intraneuronal α-synuclein (α-Syn) inclusions called Lewy bodies, encompass Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies. Autopsy studies have shown that the olfactory bulb (OB) is one of the regions where Lewy pathology develops and initiates its spread in the brain. OBJECTIVE: This study aims to clarify how Lewy pathology spreads from the OB and affects brain functions using nonhuman primates. METHODS: We inoculated α-Syn preformed fibrils into the unilateral OBs of common marmosets (Callithrix jacchus) and performed pathological analyses, manganese-enhanced magnetic resonance imaging, and 18 F-fluoro-2-deoxy-d-glucose positron emission tomography up to 6 months postinoculation. RESULTS: Severe α-Syn pathology was observed within the olfactory pathway and limbic system, while mild α-Syn pathology was seen in a wide range of brain regions, including the substantia nigra pars compacta, locus coeruleus, and even dorsal motor nucleus of the vagus nerve. The brain imaging analyses showed reduction in volume of the OB and progressive glucose hypometabolism in widespread brain regions, including the occipital lobe, and extended beyond the pathologically affected regions. CONCLUSIONS: We generated a novel nonhuman primate LBD model with α-Syn propagation from the OB. This model suggests that α-Syn propagation from the OB is related to OB atrophy and cerebral glucose hypometabolism in LBDs. © 2022 International Parkinson and Movement Disorder Society.

Striatal-Inoculation of α-Synuclein Preformed Fibrils Aggravated the Phenotypes of REM Sleep without Atonia in A53T BAC-SNCA Transgenic Mice.

Accumulation of α-synuclein (α-syn) is the pathological hallmark of α-synucleinopathy. Rapid eye movement (REM) sleep behavior disorder (RBD) is a pivotal manifestation of α-synucleinopathy including Parkinson's disease (PD). RBD is clinically confirmed by REM sleep without atonia (RWA) in polysomnography. To accurately characterize RWA preceding RBD and their underlying α-syn pathology, we inoculated α-syn preformed fibrils (PFFs) into the striatum of A53T human α-syn BAC transgenic (A53T BAC-SNCA Tg) mice which exhibit RBD-like phenotypes with RWA. RWA phenotypes were aggravated by PFFs-inoculation in A53T BAC-SNCA Tg mice at 1 month after inoculation, in which prominent α-syn pathology in the pedunculopontine nucleus (PPN) was observed. The intensity of RWA phenotype could be dependent on the severity of the underlying α-syn pathology.

α-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson's disease model.

Parkinson's disease is one of the most common movement disorders and is characterized by dopaminergic cell loss and the accumulation of pathological α-synuclein, but its precise pathogenetic mechanisms remain elusive. To develop disease-modifying therapies for Parkinson's disease, an animal model that recapitulates the pathology and symptoms of the disease, especially in the prodromal stage, is indispensable. As subjects with α-synuclein gene (SNCA) multiplication as well as point mutations develop familial Parkinson's disease and a genome-wide association study in Parkinson's disease has identified SNCA as a risk gene for Parkinson's disease, the increased expression of α-synuclein is closely associated with the aetiology of Parkinson's disease. In this study we generated bacterial artificial chromosome transgenic mice harbouring SNCA and its gene expression regulatory regions in order to maintain the native expression pattern of α-synuclein. Furthermore, to enhance the pathological properties of α-synuclein, we inserted into SNCA an A53T mutation, two single-nucleotide polymorphisms identified in a genome-wide association study in Parkinson's disease and a Rep1 polymorphism, all of which are causal of familial Parkinson's disease or increase the risk of sporadic Parkinson's disease. These A53T SNCA bacterial artificial chromosome transgenic mice showed an expression pattern of human α-synuclein very similar to that of endogenous mouse α-synuclein. They expressed truncated, oligomeric and proteinase K-resistant phosphorylated forms of α-synuclein in the regions that are specifically affected in Parkinson's disease and/or dementia with Lewy bodies, including the olfactory bulb, cerebral cortex, striatum and substantia nigra. Surprisingly, these mice exhibited rapid eye movement (REM) sleep without atonia, which is a key feature of REM sleep behaviour disorder, at as early as 5 months of age. Consistent with this observation, the REM sleep-regulating neuronal populations in the lower brainstem, including the sublaterodorsal tegmental nucleus, nuclei in the ventromedial medullary reticular formation and the pedunculopontine nuclei, expressed phosphorylated α-synuclein. In addition, they also showed hyposmia at 9 months of age, which is consistent with the significant accumulation of phosphorylated α-synuclein in the olfactory bulb. The dopaminergic neurons in the substantia nigra pars compacta degenerated, and their number was decreased in an age-dependent manner by up to 17.1% at 18 months of age compared to wild-type, although the mice did not show any related locomotor dysfunction. In conclusion, we created a novel mouse model of prodromal Parkinson's disease that showed RBD-like behaviour and hyposmia without motor symptoms.

Factors affecting postoperative activities of daily living in patients with osteoporotic vertebral collapse with neurological deficits.

Surgical treatment of osteoporotic vertebral collapse (OVC) with neurological deficits presents significant clinical challenges because some patients have fragile bones and often have medical comorbidities, which affect the severity of osteoporosis. We hypothesized that clinical results of surgery in these patients depend on the extent of medical comorbidities that induce secondary osteoporosis. The aim of this study is to examine the effects of medical history and comorbidities on surgical outcomes for these patients, along with the factors that predict postoperative function in activities of daily living (ADL). We retrospectively reviewed data for 88 patients with OVC and neurological deficits who underwent surgery. We assessed clinical results regarding neurological deficits and function in ADL. The presence or absence of comorbidities responsible for secondary osteoporosis and treatments or medical events that affect bone metabolism were examined. We performed statistical analysis to examine prognostic factors for postoperative function in ADL. Of 88 patients, the distributions of comorbidities, treatment, and events in medical history were as follows: hypertension, 57 patients (64.8%); chronic kidney disease (CKD) stage 3 or 4, 32 (36.4%); diabetes mellitus, 16 (18.2%); liver dysfunction, 11 (12.5%); cardiovascular disease, 10 (11.4%); rheumatoid arthritis, 9 (10.2%); and glucocorticoid intake, 8 (9.1%). Twenty-five patients (28.4%) represented poor postoperative ADL (chair-bound or bed-bound), and 11 of 25 patients with poor postoperative ADL represented full neurological recovery. Multivariate analysis revealed decreased estimated glomerular filtration rate (odds ratio 0.96; 95% confidence interval 0.93-0.99; p = 0.005) and a high serum alkaline phosphatase (ALP) level (odds ratio 1.01; 95% CI 1.00-1.02; p = 0.01) were strong predictive factors for poor postoperative function in ADL. The majority of patients with poor postoperative function in ADL had advanced CKD with a disorder of bone metabolism as well as bone fragility.

Neurological manifestations of thoracic myelopathy.

INTRODUCTION: Investigation of preoperative manifestations of thoracic myelopathy in a large population has not been reported. The aim of this study was to identify symptoms specific to anatomical pathology or compressed segments in thoracic myelopathy through investigation of preoperative manifestations. MATERIALS AND METHODS: Subjects were 205 patients [143 men, 62 women; mean age, 62.2 (range 21-87 years)] with thoracic myelopathy who underwent surgery at our affiliate institutions from 2000 to 2011. The disease distribution included ossification of the ligamentum flavum (OLF) in 106 patients, ossification of the posterior longitudinal ligament (OPLL) in 17, OLF with OPLL in 17, intervertebral disc herniation (IDH) in 23, OLF with IDH in 3, and spondylosis in 39. We assessed (1) initial and preoperative complaints, (2) neurological findings, (3) Japanese Orthopaedic Association scores (JOA, full score, 11 points), (4) the compressed segments, and (5) preoperative duration. Multivariate analyses were performed to examine potential relationships between preoperative manifestations and anatomical pathology or compressed segments. RESULTS: The multivariate analyses revealed relationships between lower limb muscle weakness and T10/11 anterior compression; lower limb pain and T11/12 anterior compression; low back pain and T11/12 compression; and hyporeflexia in the patellar tendon reflex/foot drop and T12/L1 anterior compression. CONCLUSION: This study elucidated symptoms specific to anatomical pathology or compressed segments in thoracic myelopathy. These relationships can be helpful in the initial investigation of thoracic diseases, although additional measures such as MRI or CT are necessary for definitive diagnosis.

Mid-Term Results of Single-Level Posterior Lumbar Interbody Fusion in Patients with Pelvic Incidence Minus Lumbar Lordosis Mismatch.

BACKGROUND: Recent literature suggests that sagittal imbalance is a risk factor for adjacent segment disease following fusion surgery. This study explored the influence of pelvic incidence minus lumbar lordosis (PI-LL) mismatch on the mid-term results and reoperation rate after single-level posterior lumbar interbody fusion (PLIF). METHODS: The participants of this study included 253 patients (80 men and 173 women; mean age 68.2 years) who underwent L4-5 single-segment PLIF. Preoperative PI-LL mismatch was defined as a PI-LL of 30° or greater. The patients were divided into 2 groups according to the presence or absence of PI-LL mismatch (PI-LL mismatch group; group M, Control group; group C), and the clinical outcomes and radiographic parameters were compared. RESULTS: Of the 253 cases, 25 were classified in group M and 228 in group C. The Japanese Orthopaedic Association score at 5 years postoperatively was 23.0 ± 3.6 in group M and 23.5 ± 5.1 in group C, and the recovery rate was 66.2 ± 32.6% in group M and 64.6 ± 21.4% in group C and there was no significant difference in the recovery rate between the 2 groups. All radiographic parameters except sacral slope were significantly worse in group M. One patient (4.3%) in Group M and 18 patients (7.8%) in Group C required revision surgery at 2.4 years (range 0.0-5.0) and there was no significant difference in the revision rate between the 2 groups. CONCLUSIONS: The mid-term results of L4-5 single-level PLIF were compared with and without PI-LL mismatch, with the threshold defined as 30°; however, there were no significant differences in both the Japanese Orthopaedic Association recovery and reoperation rates between the 2 groups.

Development of patient-reported outcome for adult spinal deformity: validation study.

Adult spinal deformity (ASD) is a complex condition that combines scoliosis, kyphosis, pain, and postoperative range of motion limitation. The lack of a scale that can successfully capture this complex condition is a clinical challenge. We aimed to develop a disease-specific scale for ASD. The study included 106 patients (mean age; 68 years, 89 women) with ASD. We selected 29 questions that could be useful in assessing ASD and asked the patients to answer them. The factor analysis found two factors: the main symptom and the collateral symptom. The main symptom consisted of 10 questions and assessed activity of daily living (ADL), pain, and appearance. The collateral symptom consisted of five questions to assess ADL due to range of motion limitation. Cronbach's alpha was 0.90 and 0.84, respectively. The Spearman's correlation coefficient between the change of main symptom and satisfaction was 0.48 (p < 0.001). The effect size of Cohen's d for comparison between preoperative and postoperative scores was 1.09 in the main symptom and 0.65 in the collateral symptom. In conclusion, we have developed a validated disease-specific scale for ASD that can simultaneously evaluate the benefits and limitations of ASD surgery with enough responsiveness in clinical practice.

Allotype analysis to distinguish the origin of varicella-zoster virus immunoglobulin G after allogeneic stem cell transplantation.

Varicella-zoster virus (VZV) reactivation is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Although previous studies have revealed that cellular immunity is important for suppressing reactivation, the role of humoral immunity against VZV has been poorly evaluated. We analyzed inherited polymorphisms in the immunoglobulin G (IgG) heavy chain constant regions of 50 HSCT recipient-donor pairs to distinguish donor-derived and recipient-derived antibodies. Twelve pairs were informative regarding the origin of IgG, since either the donors (n = 3) or recipients (n = 9) were homozygous null for the IgG1m(f) allotype. In these 9 homozygous-null recipients, allotype-specific IgG against VZV were measured by enzyme-linked immunosorbent assay and compared with measles-IgG. All 9 homozygous-null recipients were monitored for more than 1 year after HSCT, with (n = 4, localized zoster) or without (n = 5) clinical VZV disease. In 3 patients with VZV disease, donor-derived IgG against VZV was elevated between 500 to 700 days after HSCT after the episode of VZV disease. In 1 patient who suffered from VZV disease just before HSCT, donor-derived VZV IgG was elevated within 3 months after HSCT. On the other hand, 2 patients who received reduced-intensity conditioning (RIC) transplantation from an IgG1m(f) null donor maintained recipient-derived IgG against VZV for more than 1 year, whereas it was decreased within 3 months in 1 recipient who received conventional conditioning. In conclusion, the production of anti-VZV IgG by recipient plasma cells persists long after RIC. In patients without symptomatic VZV reactivation, donor-derived anti-VZV IgG did not reach titers comparable to those measured in healthy virus carriers.

Association between serum high-molecular-weight adiponectin level and the severity of chronic graft-versus-host disease in allogeneic stem cell transplantation recipients.

Recently, a growing body of evidence has suggested that adiponectin, which is secreted by adipose tissues, plays a critical role in obesity-related and autoimmune diseases. We compared the concentrations of adiponectin among 26 normal subjects and 34 allogeneic stem cell transplantation recipients. The concentrations of adiponectin were significantly higher in recipients with chronic graft-versus-host disease (cGVHD) than those in subjects without cGVHD (21.7 ± 11.0 vs 9.1 ± 6.1 µg/mL in females, P < .001; and 10.1 ± 6.8 vs 4.3 ± 2.9 µg/mL in males, P = .003). Multivariate analysis revealed that a higher concentration of adiponectin was associated with female sex (ß-coefficient 8.2, P < .0001) and the severity of cGVHD (ß-coefficient 6.6, 12.7, and 15.6, P < .01, each for mild, moderate, and severe cGVHD, respectively). In addition, adiponectin levels increased as cGVHD progressed, decreased as cGVHD improved, and did not change with stable cGVHD. In conclusion, adiponectin was associated with the severity of cGVHD and might play a role in the pathophysiology of cGVHD.

Comparison of the efficacy of peripheral blood stem cell mobilization using G-CSF alone from healthy donors and patients with hematologic malignancies.

Peripheral blood stem cell (PBSC) collection using granulocyte colony-stimulating factor (G-CSF) alone is superior to the combination of chemotherapy and G-CSF in terms of low morbidity, short duration of mobilization and low cost. We retrospectively compared the results of PBSC collection using G-CSF alone in 11 patients with malignant lymphoma (ML), 23 patients with plasma cell neoplasms (PCN) and 48 healthy donors. The geometric mean number of CD34(+) cells/kg obtained on the first day of collection was 0.99 × 10(6)/kg in ML patients, 2.26 × 10(6)/kg in PCN patients, and 3.36 × 10(6)/kg in healthy donors. The probability of collecting at least 1 × 10(6)/kg CD34(+) cells/kg during a single course of apheresis was 90.9% in ML patients, 95.7% in PCN patients, and 100% in healthy donors. In a multiple regression analysis of the CD34(+) cell yields on the first day of apheresis, we identified disease, the baseline white blood cell count (WBC), platelet count, and lactate dehydrogenase as independent significant variables. Particularly, disease was strongly associated with the CD34(+) cell yield, probably due to the difference in the number of previous chemotherapy cycles. In conclusion, the minimal dose of CD34(+) cells for autologous transplantation was collected in almost all patients with hematological malignancies. However, patients who have received repeated cycles of chemotherapy, such as patients with ML, and those who have low WBC counts and/or platelet counts may be at higher risk for poor mobilization.

Surgical outcomes of posterior thoracic interbody fusion for thoracic disc herniations.

INTRODUCTION: Surgical strategy for thoracic disc herniation (TDH) remains controversial. We have performed posterior thoracic interbody fusion (PTIF) by bilateral total facetectomies with pedicle screw fixation. The objectives of this retrospective study are to demonstrate the surgical outcomes of PTIF for TDH. MATERIALS AND METHODS: We enrolled 11 patients who underwent PTIF for myelopathy due to TDH and were followed for at least 1 year. The mean age at surgery was 55.2 years and the average period of follow-up was 4.3 years. The levels of operation were T10-T11 in three cases, T12-L1 in three, and T2-T3, T3-T4, T9-T10, T11-T12, and T10-T12 in one case, respectively. The pre- and postoperative clinical status was evaluated according to the modified Frankel grade and the Japanese Orthopaedic Association (JOA) score modified for thoracic myelopathy. Additionally, postoperative complications were assessed. Local kyphosis at the operated segment and status of fusion were evaluated using plain radiographs and computed tomography. RESULTS: Improvement of at least one modified Frankel grade was observed in all but one patient. Average pre- and postoperative JOA scores were 4.9 and 8.8 points, respectively. The average recovery rate was 61%. Bony union was observed in ten cases. One patient's postsurgical outcome resulted in pseudoarthrosis, which required revision surgery due to kyphosis deterioration. Cerebrospinal fluid leakage was observed in one patient postoperatively with neither neurological deficit nor evidence of infection. CONCLUSION: PTIF has produced satisfactory outcomes for myelopathy due to TDH. Therefore, PTIF is one of the surgical treatments of choice for patients with TDH causing myelopathy.

Surgical treatment for osteoporotic vertebral collapse with neurological deficits: retrospective comparative study of three procedures--anterior surgery versus posterior spinal shorting osteotomy versus posterior spinal fusion using vertebroplasty.

PURPOSE: In general, osteoporotic vertebral collapse (OVC) with neurological deficits requires sufficient decompression of neural tissues to restore function level in activities of daily living (ADL). However, it remains unclear as to which procedure provides better neurological recovery. The primary purpose of this study was to compare neurological recovery among three typical procedures for OVC with neurological deficits. Secondary purpose was to compare postoperative ADL function. METHODS: We retrospectively reviewed data for 88 patients (29 men and 59 women) with OVC and neurological deficits who underwent surgery. Three typical kinds of surgical procedures with different decompression methods were used: (1) anterior direct neural decompression and reconstruction (AR group: 27 patients), (2) posterior spinal shorting osteotomy with direct neural decompression (PS group: 36 patients), and (3) posterior indirect neural decompression and short-segment spinal fusion combined with vertebroplasty (VP group: 25 patients). We examined clinical results regarding neurological deficits and function level in ADL and radiological results. RESULTS: The mean improvement rates for neurological deficits and ADL function level were 60.1 and 55.0%, respectively. There were no significant differences among three groups in improvement rates for neurological deficits or ADL function level. The VP group had a significantly lower estimated mean blood loss (338 mL) and mean duration of surgery (229 min) than both the AR and PS groups (p < 0.001). CONCLUSION: Direct neural decompression is not always necessary, and the majority of patients can be treated with a less-invasive procedure such as short-segment posterior spinal fusion with indirect decompression combined with vertebroplasty. The high-priority issue is careful evaluation of patients' general health and osteoporosis severity, so that the surgeon can choose the procedure best suited for each patient.

Spinopelvic sagittal realignment and incidence of adjacent segment disease after single-segment posterior lumbar inter-body fusion using 12° lordotic cages-a 2-year prospective cohort study.

Background: The importance of spinopelvic sagittal alignment for adjacent segment disease (ASD) after lumbar fusion surgery has been reported. However, no longitudinal cohort studies have determined the extent to which segmental alignment and spinopelvic global alignment can be achieved using 12° lordotic cages in posterior lumbar inter-body fusion (PLIF) and the extent to which the development of ASD can be prevented. The purpose of this study was to analyze changes in segmental and spinopelvic sagittal alignment after single-segment PLIF with 12° lordotic cages, to clarify the relationship between changes in segmental and spinopelvic sagittal alignment, and to report the incidence of ASD at 2 years postoperatively. Methods: Subjects in this 2-year prospective longitudinal cohort study were 28 patients who had undergone L4/5 PLIF using 12° lordotic cages. Incidence of operative ASD (O-ASD) was evaluated as clinical outcomes. Radiological measurements were examined preoperatively and at 3 months, 1 year and 2 years postoperatively. The following radiographic spinopelvic parameters were measured: segmental lordosis (SL) at L4/5; sagittal vertical axis (SVA); T1 pelvic angle (TPA); thoracic kyphosis (TK); lumbar lordosis (LL); sacral slope (SS); pelvic tilt (PT); and pelvic incidence (PI). With respect to radiological outcomes, changes in SL (ΔSL) and spinopelvic parameters and the incidence of radiological ASD (R-ASD) were evaluated. Correlations of ΔSL and changes in other spinopelvic parameters (ΔSVA, ΔTPA, ΔTK, ΔLL, ΔSS, ΔPT, and ΔPI-LL) between preoperatively and 3 months postoperatively were examined. Results: The follow-up rate was 100% (n=28) at 1 year postoperatively and 96.4% (n=27) at 2 years postoperatively. No cases of O-ASD were seen during 2 years of follow-up. Significant realignment was observed and maintained at 2 years postoperatively in almost all spinopelvic sagittal parameters (SL, SVA, TPA, LL, PT, PI-LL). Regarding the correlation between ΔSL and other parameters, significant correlations were detected with ΔSVA (r=-0.37, P<0.05) and ΔLL (r=0.538, P<0.01). Three cases (11.1%) showed R-ASD at 2 years postoperatively. Conclusions: PLIF with 12° lordotic cages for L4 degenerative spondylolisthesis improved SL and global sagittal realignment, and achieved satisfactory clinical outcomes with a low incidence of ASD during 2 years of follow-up.

Management of Antithrombotic Drugs before Elective Spine Surgery: A Nationwide Web-Based Questionnaire Survey in Japan.

Introduction: The number of patients on antithrombotic drugs for coronary heart disease or cerebrovascular disease has been increasing with the aging of society. We occasionally need to decide whether to continue or discontinue antithrombotic drugs before spine surgery. The purpose of this study is to understand the current perioperative management of antithrombotic drugs before elective spine surgery in Japan. Methods: In 2021, members of the Japanese Society for Spine Surgery and Related Research (JSSR) were asked to complete a web-based questionnaire survey that included items concerning the respondents' surgical experience, their policy regarding discontinuation or continuation of antithrombotic drugs, their reasons for decisions concerning the management of antithrombotic drugs, and their experience of perioperative complications related to the continuation or discontinuation of these drugs. Results: A total of 1,181 spine surgeons returned completed questionnaires, giving a response rate of 32.0%. JSSR board-certified spine surgeons comprised 75.1% of the respondents. Depending on the management policy regarding antithrombotic drugs for each comorbidity, approximately 73% of respondents discontinued these drugs before elective spine surgery, and about 80% also discontinued anticoagulants. Only 4%-5% of respondents reported continuing antiplatelet drugs, and 2.5% reported continuing anticoagulants. Among the respondents who discontinued antiplatelet drugs, 20.4% reported having encountered cerebral infarction and 3.7% reported encountering myocardial infarction; among those who discontinued anticoagulants, 13.6% reported encountering cerebral embolism and 5.4% reported encountering pulmonary embolism. However, among the respondents who continued antiplatelet drugs and those who continued anticoagulants, 26.3% and 27.2%, respectively, encountered an unexpected increase in intraoperative bleeding, and 10.3% and 8.7%, respectively, encountered postoperative spinal epidural hematoma requiring emergency surgery. Conclusions: Our findings indicate that, in principle, >70% of JSSR members discontinue antithrombotic drugs before elective spine surgery. However, those with a discontinuation policy have encountered thrombotic complications, while those with a continuation policy have encountered hemorrhagic complications.

Long-term persistence of limited HTLV-I Tax-specific cytotoxic T cell clones in a patient with adult T cell leukemia/lymphoma after allogeneic stem cell transplantation.

PURPOSE: Adult T cell leukemia/lymphoma (ATL) is a highly aggressive malignancy of T cells caused by human T cell lymphotropic virus type 1 (HTLV-1). Recent clinical studies have suggested that allogeneic stem cell transplantation (HSCT) improves the clinical course of ATL by harnessing a graft-versus-ATL effect, and that donor-derived HTLV-1 Tax-specific CD8(+) cytotoxic T cells (CTLs) contribute to the graft-versus-ATL effect after HSCT. However, little is known about the immunological characteristics of Tax-specific CTLs in ATL patients who underwent HSCT. METHODS: We serially analyzed frequencies, differentiation, functions and clonal dynamics of Tax-specific CTLs in paired samples of peripheral blood (PB) and bone marrow (BM) from an ATL patient after HSCT at the single-cell level. We used flowcytometric and single-cell T cell receptor (TCR) repertoire analysis methods without culture steps. RESULTS: Donor-derived Tax-specific CTLs effectively suppressed HTLV-1 replication in both PB and BM at least during chronic graft-versus-host disease after HSCT. Furthermore, Tax-specific CTLs had comparable properties between BM and PB, except for preferential accumulation in BM rather than PB. Tax-specific CTLs persistently existed as less-differentiated CD45RA(-)CCR7(-) effector memory CTLs based on predominant phenotypes of CD27(+), CD28(+/-) and CD57(+/-). Our approach using single-cell TCR repertoire analysis method showed highly restricted oligoclonal responses of Tax-specific CTLs, and TCR BV7- or BV30- expressing two predominant CTL clones persistently existed and maintained strong cytotoxic activities against HTLV-1 in both PB and BM over three years after HSCT. CONCLUSIONS: These findings about Tax-specific CTLs provide insights into future directions for studies on immunotherapy against ATL.

Clinical course of patients with aplastic anemia or myelodysplastic syndrome associated with persistent neutropenia.

Patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) often have persistent severe neutropenia and are susceptible to infectious complications. We retrospectively reviewed the clinical course of patients with AA or MDS who had neutropenia (neutrophil count < 500/µl) for more than 25 days. A total of 46 patients, 11 with AA and 35 with MDS, were included. Twenty-three patients had infectious events (IE), and the cumulative incidence of IE was 30% at 6 months and 51% at 1 year. The cumulative incidence of IE was 67% at 1 year in 30 patients who experienced very severe neutropenia of less than 200/µl. Overall survival in all patients was 76% at 6 months and 65% at 1 year. In a multivariate analysis, male sex, underlying diseases, and a neutrophil count of less than 200/µl as a time-dependent covariate significantly affected IE. In analyses that excluded patients with AA, male sex was the only factor. In conclusion, severe neutropenia was significantly associated with IE in patients with AA or MDS, and IE might be lethal. When we only considered patients with MDS, the neutrophil count alone could not be used to predict the prognosis.