Bone marrow-derived fibroblast migration via periostin causes irreversible arthrogenic contracture after joint immobilization.

Joint contracture causes distressing permanent mobility disorder due to trauma, arthritis, and aging, with no effective treatment available. A principal and irreversible cause of joint contracture has been regarded as the development of joint capsule fibrosis. However, the molecular mechanisms underlying contracture remain unclear. We established a mouse model of knee joint contracture, revealing that fibrosis in joint capsules causes irreversible contracture. RNA-sequencing of contracture capsules demonstrated a marked enrichment of the genes involved in the extracellular region, particularly periostin (Postn). Three-dimensional magnetic resonance imaging and immunohistological analysis of contracture patients revealed posterior joint capsule thickening with abundant type I collagen (Col1a2) and POSTN in humans. Col1a2-GFPTG ; Postn-/- mice and chimeric mice with Col1a2-GFPTG ; tdTomatoTG bone marrow showed fibrosis in joint capsules caused by bone marrow-derived fibroblasts, and POSTN promoted the migration of bone marrow-derived fibroblasts, contributing to fibrosis and contracture. Conversely, POSTN-neutralizing antibody attenuated contracture exacerbation. Our findings identified POSTN as a key inducer of fibroblast migration that exacerbates capsule fibrosis, providing a potential therapeutic strategy for joint contracture.

Temporal dynamics of gait function in acute cervical spinal cord injury.

BACKGROUND: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. METHODS: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2-4 months, 4-6 months, and 6-8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. RESULTS: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. CONCLUSIONS: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Effects of combined test dose and therapeutic drug monitoring strategy in exposure-directed busulfan.

Although exposure-directed busulfan (BU) dosing can improve allogeneic hematopoietic stem cell transplantation outcomes, there is still large variability in BU exposure with test dose alone due to changes in BU clearance caused by drug interactions. We conducted a single-arm phase II trial using the combined test dose and therapeutic drug monitoring strategy (PK-guided group) and compared the outcomes with an external historical cohort receiving a fixed-dose (fixed-dose group). The first eight and second eight doses were adjusted based on the area under the blood concentration-time curve (AUC) of the test and first doses, respectively, targeting a total AUC of 82.1 mg·h/L. All patients received either BU and cyclophosphamide conditioning (BU/CY) or fludarabine (FLU)-containing conditioning. The BU clearance at the first dose decreased more in patients receiving FLU than in those receiving BU/CY; however, BU clearance also declined over time in patients who received BU/CY. The simulated total AUC (sAUC) with test dose only was significantly higher in patients who received FLU than in those who received BU/CY, but sAUC with the combined strategy was comparable. The 100-day progression-free survival was 85.5% (95% confidence interval [CI]: 71.9-92.8%), and was not inferior to that in the fixed-dose group. For the FLU-containing regimens, the PK-guided group showed decreased relapse (0.0% vs. 26.9%, p = 0.03), and favorable overall survival (75.1% vs. 57.0%, p = 0.07) at 1 year. The combined strategy effectively controlled the BU exposure close to the target levels, potentially improving efficacy, especially in patients receiving the FLU-containing regimen. Clinical evaluation of efficacy of dose-modified intravenous busulfan in allogeneic hematopoietic stem cell transplantation for hematological malignancy (#UMIN000014077, June 15th, 2014).

Syntheses and Biological Activities of Danicalipin A Derivatives.

Synthesis of three derivatives of danicalipin A, tetrachloride, trisulfate and a fluorescent probe was achieved through Wittig reaction strategy. Toxicity of the derivatives against brine shrimp (Artemia salina) as also investigated to provide useful information for the biological activity; i) less chloride derivative showed similar toxicity to danicalipin A, ii) the amphiphilic property, a characteristic feature of danicalipin A, was crucial because trisulfate considerably decreased the toxicity and iii) fluorescent derivative kept brine shrimp toxicity of danicalipin A.

Long-term outcomes and central nervous system relapse in extranodal natural killer/T-cell lymphoma.

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.

Predicting motor function recovery in cervical spinal cord injury-induced complete paralysis with reflex response.

STUDY DESIGN: A retrospective clinical study. OBJECTIVE: To elucidate the usefulness of the patellar tendon reflex (PTR), bulbocavernosus reflex (BCR), and plantar response (PR) as factors in the prognostic prediction of motor function in complete paralysis due to cervical spinal cord injuries (CSCIs) at the acute phase. SETTING: Department of Orthopedic Surgery, Spinal Injuries Center, Japan. METHODS: 99 patients assessed as the American Spinal Injury Association Impairment Scale (AIS) grade A (AIS A) were included in this study. The PTR, BCR, and PR were evaluated respectively as positive or negative at the time of injury. We classified the patients into two groups based on their neurological recovery at 3 months after injury: "recovered" group was defined as AIS C, D, or E; "non-recovered" group was defined as AIS A or B. RESULTS: Eight patients demonstrated positive PTR, while 91 demonstrated negative. Three out of eight patients with positive PTR (37.5%) were R group, while 83 out of 91 patients with negative PTR (91.2%) were N group. A significant difference was observed (p = 0.043). For BCR, no significant difference was observed (p > 0.05). Twenty-six patients demonstrated positive PTR, while 73 demonstrated negative. Nine out of twenty-six patients with positive PR (34.6%) were R group, while 71 out of 73 patients with negative PR (97.3%) were N group. A significant difference was observed (p = 0.000068). CONCLUSION: The PTR and PR are useful for poor prognostic prediction of motor function in CSCI at the acute phase.

Traumatic cervical spinal cord injury after cervical laminoplasty for ossification of posterior longitudinal ligament: a case series.

STUDY DESIGN: A retrospective review of a case series of five participants. OBJECTIVE: To elucidate the effects of post-cervical laminoplasty on the clinical pathophysiology of traumatic CSCI. Cervical laminoplasty has been widely performed with good results in individuals for cervical myelopathy. However, no reports have thus far referred to the incidence of traumatic cervical spinal cord injury (CSCI) after previous history of cervical laminoplasty. SETTING: Spinal Injuries Center, Japan. METHODS: From 2008 to 2017, 999 cervical myelopathy individuals were treated by cervical laminoplasty in our institution. Of these, only five participants were subsequently emergency transported to our institution caused by traumatic CSCI. The pathology of five participants were cervical ossification of posterior longitudinal ligament (C-OPLL). The changes of cervical sagittal range of motion (ROM) and the morphology of OPLL were radiologically evaluated. Moreover, the mechanism of injury, the level of injury, and neurological evaluations were discussed. RESULTS: All of the participants demonstrated ankylosed cervical spine due to developing OPLL and spontaneous bony facet and laminar fusion on post-laminoplasty. A significant difference in cervical ROM was observed between pre-laminoplasty and 6 months post-laminoplasty (p = 0.0065). Three participants were extension injury and the other two were flexion injury. CONCLUSIONS: All of the five traumatic CSCI participants had a history of previous cervical laminoplasty for C-OPLL. Cervical laminoplasty for C-OPLL might lead to cervical spine with rigidity and ankylosing due to developing OPLL and bony facet and laminar fusion, and might have a risk for traumatic CSCI.

First dose-ranging study of remimazolam in Japanese patients undergoing gastrointestinal endoscopy: Phase II investigator-initiated clinical trial.

OBJECTIVES: Remimazolam, an ultra-short-acting benzodiazepine, has been used for procedural sedation in the United States. We conducted an investigator-initiated clinical trial to determine the appropriate dose of remimazolam required for sedation during gastrointestinal endoscopy in Japanese subjects. METHODS: In this single-center, open-label, uncontrolled, phase II trial, a three-stage cohort investigated the appropriate initial and additional doses of remimazolam required for gastrointestinal endoscopy. This study was designed with advice from the Pharmaceuticals and Medical Devices Agency. The initial and additional doses were 2 mg and 1 mg/dose, 3 mg and 1 mg/dose, and 5 mg and 2 mg/dose in cohorts 1, 2, and 3, respectively. Each cohort included 10 cases of upper gastrointestinal endoscopy and colonoscopy. The primary end-point was the success rate of sedation during gastrointestinal endoscopy. RESULTS: Sedation was successful in all gastrointestinal endoscopies in cohorts 1 and 2. In cohort 1, sedation was achieved in five (25.0%) and 10 (50.0%) participants with the initial dose and total dose (initial dose + additional dose ≤ the initial dose of the next cohort), respectively, before endoscopy. In cohort 2, sedation was achieved in 11 (55.0%) and 18 (90.0%) participants with the initial dose and total dose, respectively, before endoscopy. No patient in either cohort lost consciousness or required flumazenil or manual ventilation. CONCLUSION: Initial and additional doses of 3 mg and 1 mg/dose of remimazolam, respectively, were shown to be effective and safe for sedation during gastrointestinal endoscopy in Japanese patients.

[Diagnostic Neuroradiology in Head Injury].

The 4th edition of the Guidelines for Treatment and Management of Head Injury by the Japan Society of Neurotraumatology newly published a three-step evaluation method for CT, indications for repeat CT, cancer risk associated with radiation exposure, and preparation of examination guidelines for reduction of radiation exposure. This manuscript describes how to proceed with diagnostic imaging of head injuries and the new items. The important points are as follows: •CT is the first-step diagnostic imaging method in the acute phase. •Initial CT assesses the presence or absence of intracranial hemorrhage requiring emergency craniotomy. •It is necessary to perform repeat CT to assess secondary injury. •For minor head injuries, the indication for CT should be determined by confirming neurological concomitant symptoms considering radiation exposure.

A prediction model of functional outcome at 6 months using clinical findings of a person with traumatic spinal cord injury at 1 month after injury.

STUDY DESIGN: Retrospective statistical analysis of database. OBJECTIVES: Prediction of the Spinal Cord Independence Measure version III Total Score (SCIM-TS) at 6 months after injury based on physical findings at 1 month after injury is an important index for rehabilitation approach in the recovery phase. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: The study participants were selected from patients with traumatic spinal cord injuries who were registered in the Japan Single Center Study for Spinal Cord Injury Data Base (JSSCI-DB) of the Japan Spinal Injuries Center specializing in spine and spinal cord injuries. Of the 534 participants registered with the JSSCI-DB between January 2012 and October 2018, we retrospectively extracted 137 participants for 6 months after injury, and these participants were included in this study. RESULTS: According to multiple regression analysis, SCIM-TS at 6 months after injury could be predicted based on only six variables, i.e., age at injury, three key muscles (C6 wrist extensors, C8 finger flexors, and L3 knee extensors), and two mobility assessments (WISCI and SCIM-item13) (Adjusted R-Squared: 0.83). These six independent variables were significant factors reflecting SCIM-TS at 6 months. CONCLUSIONS: In rehabilitation after traumatic spinal cord injuries, a simple and reliable prognostic model can help accurately predict the achievable activity of daily living competency to set a goal. In addition, if the procedure is simple, evaluation can be completed in a short period of time, and the physical burden on both treating staff and patients can be reduced.

The time course of dysphagia following traumatic cervical spinal cord injury: a prospective cohort study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To elucidate serial changes in dysphagia and elucidate the critical period for dysphagia following acute traumatic cervical spinal cord injury (CSCI). SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: We prospectively examined individuals with acute traumatic CSCI admitted within 2 weeks after injury. Severity of dysphagia was evaluated using both the dysphagia severity scale (DSS) and functional oral intake scale (FOIS) at 2 weeks, 1 month, 2 months, and 3 months after injury. Condition of oral intake before injury was assessed by history taking. American Spinal Injury Association (ASIA) impairment scale grade and motor scores were also assessed at the same timepoints, and the correlation between dysphagia and paresis was analyzed. RESULTS: Sixty-five individuals with CSCI were assessed consecutively for 3 months after injury. Swallowing function, evaluated using both the DSS and FOIS, was significantly decreased at 2 weeks after injury, but significantly improved thereafter. Significant correlations between severity of dysphagia (DSS and FOIS scores) and motor scores were found at 2 weeks after injury (rs = 0.66 and 0.61; p < 0.001 and p < 0.001, respectively), indicating that individuals with lower motor scores had more severe swallowing dysfunction. CONCLUSIONS: Dysphagia occurred immediately after injury, but gradually improved over time. Individuals with more severe paralysis had significantly more severe dysphagia. Special attention for dysphagia should be paid to individuals with severe paralysis in acute phase.

The beneficial aspects of spasticity in relation to ambulatory ability in mice with spinal cord injury.

STUDY DESIGN: Experimental study with mice. OBJECTIVES: Spasticity is a common complication after spinal cord injury (SCI) and has detrimental aspects, such as persistent pain and involuntary muscle spasms. This study aimed to assess the influence of antispastic therapy on locomotor function after SCI. SETTING: University-based laboratory in Fukuoka, Japan. METHODS: A mouse model of spasticity was developed by producing incomplete SCI at the 9th thoracic level. At 8 weeks after SCI, an antispastic drug, baclofen, was intraperitoneally administered to six injured and two sham-operated mice. The severity of spasticity was evaluated by the modified Ashworth scoring (MAS) system, and locomotor function was evaluated by the Basso-Beattie-Bresnahan (BBB) scale/Basso mouse score (BMS). RESULTS: The administration of baclofen significantly improved spasticity in the SCI mice and the mean MAS decreased to from 6.2 to 2.8. However, at the same time, it significantly exacerbated the locomotor dysfunction of the SCI mice and the mean BMS decreased from 4.7 to 2.3. The time-course of the changes in locomotor function coincided with the time-course of the spasticity score. We also confirmed that the administration of baclofen was not associated with any changes in either locomotor function or spasticity of the sham-operated control mice. CONCLUSIONS: Our results suggest that spasticity has a certain beneficial effect on ambulation ability. It is important to note that antispastic treatments may be associated with a risk of impairing the preserved function of chronic SCI patients.

How much time is necessary to confirm the diagnosis of permanent complete cervical spinal cord injury?

STUDY DESIGN: Retrospective chart audits. OBJECTIVE: To investigate the optimal timing at which permanent complete cervical spinal cord injury (CSCI) can be confirmed when evaluating paralysis caused by traumatic CSCI. SETTING: Department of Orthopedic Surgery, Spinal Injuries Center, Japan. METHODS: Two-hundred and three patients with CSCI that was classified with an American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A (AIS A) within 72 h of the initial diagnosis of traumatic CSCI were included in the present study. Neurological data from the time of the initial diagnosis to 1 year after the injury were extracted. The number of those with recovery from AIS A and changes of AIS in the recovery were examined. RESULTS: Thirty-five of 203 (17%) patients whose injuries were initially classified with an AIS A showed recovery from AIS A. Thirty-four of 35 (97%) patients showed recovery from AIS A within 8 weeks after injury. CONCLUSION: If CSCI patients with AIS A have not recovered by 8 weeks, the likelihood that they will recover from AIS A is marginal. However, this conversely means that we must consider the possibility that a patient with a traumatic CSCI classified with an AIS A may still show recovery from AIS A within the first 8 weeks after injury.

[Successful treatment with enzyme replacement therapy for pelvic fragile fracture in an elderly case of type I Gaucher's disease].

A 76-year-old male with lower-limb weakness was admitted to our hospital where thrombocytopenia and anemia were noticed. CT showed massive splenomegaly and multiple nodules inside the spleen. Bone marrow examination showed an increase of macrophages with large cytoplasm. Suspected of splenic lymphoma, the patient underwent splenectomy. Spleen specimens were histologically analyzed and suggested the probability of Gaucher's disease (GD). Leukocyte glucocerebrosidase (GBA) enzyme activity had decreased to 1.25 nmol/mg, and mutation analysis of GBA revealed two missense variants, p.D448H (D409H), p.L483P (L444P), which confirmed the diagnosis of type I GD. Fourteen months after splenectomy, he developed right buttock pain, and pelvic magnetic resonance imaging showed a fragile right pubic and pelvic fracture. We initiated injection of imiglucerase as enzyme replacement therapy (ERT) and administered bisphosphonate. His symptoms gradually improved without surgical treatment. In addition, thrombocytopenia and anemia also improved, and angiotensin-converting enzyme levels decreased. Type I GD should be considered a differential diagnosis of giant splenomegaly and thrombocytopenia, even in the elderly. ERT or substrate reduction therapy should be administrated to GD patients, while paying attention to the development of bone lesions.

Clinical Implications of t(11;14) in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

Conventional cytogenetic analyses and fluorescent in situ hybridization (FISH) are helpful for stratifying patients with multiple myeloma (MM) into high-risk [t(4;14), t(14;16), and/or del 17p] and standard-risk [t(11;14)] categories. However, the prognosis of patients with MM treated with autologous stem cell transplantation (ASCT) stratified according to these categories remains unclear. This retrospective observational study analyzed 97 patients with MM who received a single, planned ASCT after treatment with 200 mg/m2 melphalan between 2001 and 2011. The patients were grouped according to chromosomal abnormality, including t(11;14) (n = 45), t(4;14) (n = 31), del 17p (n = 10), t(11;14) with del 17p (n = 7), and t(4;14) with del 17p (n = 4). Median overall survival (OS) of the t(11;14) group (64.1 months) was not significantly different from that of the t(4;14) group (not reached), but it was significantly longer than that of the del 17p group (23.0 months; P = .002). G-banding revealed that the median OS of the t(11;14) group with additional chromosomal abnormalities (ACAs) (46.2 months) was significantly shorter than that of the t(11;14) group without ACAs (not reached; P = .005) and the t(4;14) group (not reached; P = .010). These findings highlight the importance of G-banding in patients with t(11;14) MM.

Outcomes of allogeneic stem cell transplantation for DLBCL: a multi-center study from the Kyoto Stem Cell Transplantation Group.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) has been considered as a potentially curative treatment option for refractory or relapsed diffuse large B cell lymphoma (DLBCL) patients. However, there is little information available, especially for Japanese patients and in cord blood transplantation (CBT). We aimed to determine treatment outcomes of allo-SCT for DLBCL in the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group. Sixty-eight DLBCL patients who underwent their first allo-SCT between 2003 and 2016 were included. The median time from diagnosis to transplantation was 13.5 months. Thirty-one patients were in CR/PR at transplantation. Twenty-seven patients underwent CBT. The median follow-up for survivors was 44.2 months. Four-year overall survival (OS) and relapse-free survival (RFS) rates were 23% (95% CI, 13-35%) and 20% (95% CI, 11-31%), respectively. Cumulative incidences of non-relapse mortality and relapse were 23% and 57%, respectively. Patients in CR/PR at allo-SCT had better OS (4-year, 46% vs 4%, P < 0.001) and RFS (4-year, 36% vs 7%, P = 0.005). The source of the stem cell did not significantly affect OS (4-year, bone marrow vs cord blood vs peripheral blood, 28.6% vs 27.2% vs 6.5%, P = 0.193). In multivariate analysis, non-remission status at SCT associated with inferior OS and RFS. Duration from diagnosis to transplantation of less than 1 year associated with inferior RFS. Allo-SCT, including CBT, may be a promising therapeutic modality for DLBCL patients who have good disease control at transplantation.

Improved prognosis of extranodal NK/T cell lymphoma, nasal type of nasal origin but not extranasal origin.

Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.

The EQ-5D-5L in patients admitted to a hospital in Japan with recent spinal cord injury: a descriptive study.

STUDY DESIGN: Descriptive study. OBJECTIVE: To demonstrate Euro Quality of Life 5-dimensional 5-level (EQ-5D-5L) by severity level at the acute stage and discharge in patients with traumatic spinal cord injury (SCI). SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: Patients with traumatic SCI who completed the EQ-5D-5L instrument at the acute stage and discharge were divided into four groups according to severity (severity group G1; C1-C4 ASIA Impairment Scale (AIS) A, B, and C, G2; C5-C8 AIS A, B, and C, G3; T1-S5 AIS A, B, and C, G4; all AIS D). All data were extracted from the Japan single-center study for spinal cord injury database (JSSCI-DB). RESULTS: Data were collected from 139 individuals at the acute stage and 164 individuals at discharge. In the comparison of utility score by severity in acute stage and discharge, G3 was significantly higher in discharge (0.325 versus 0.580). Utility scores by degree of severity were significantly higher in group G4 than those of G1, G2, and G3 at the acute stage. Utility scores at discharge were significantly higher in groups G3 and G4 than in G1, and there was a significant difference between groups G4 and G2. CONCLUSIONS: At each stage, the utility scores of group G4 were significantly higher than those of groups G1 and G2. Altogether, the utility scores for hospitalized patients with traumatic SCI that were indicated in this study will serve as basic data that can be used while performing spinal regeneration medical procedures in the future.

Relationship between changes in regional cerebral blood volume and oxygenation and changes in cardiac output and systemic vascular resistance during spinal anesthesia in women undergoing cesarean section.

PURPOSE: The decrease in maternal regional cerebral blood volume (rCBV) and oxygenation (rCBO) during spinal anesthesia for cesarean section depends on the severity of hypotension. We examined the relationships between changes in the systemic circulatory parameters, cardiac output (CO) and systemic vascular resistance (SVR), and rCBV and rCBO after induction of spinal anesthesia, evaluated by near-infrared spectroscopy (NIRS) and an arterial pressure-based cardiac output monitoring system (APCOs). METHODS: Seventeen patients undergoing elective cesarean section under spinal anesthesia were monitored every 1 min for mean arterial pressure (MAP), heart rate (HR), end-tidal carbon dioxide (EtCO2) and oxygen saturation (SpO2), and at 20 s intervals for CO, SVR, concentrations of oxy-hemoglobin (Hb), deoxy-Hb, total-Hb, and tissue oxygenation index (TOI), until 15 min after the intrathecal injection of bupivacaine. We investigated changes in the parameters from baseline and evaluated correlations between the changes in total-Hb and TOI and changes in CO and SVR, respectively, at the same timepoints. RESULTS: Oxy-Hb, total-Hb, TOI, and SVR significantly decreased and HR significantly increased with a decrease in MAP (P < 0.01). Deoxy-Hb, CO, SpO2, and EtCO2 levels did not change from baseline. There were statistically significant, although weak, positive correlations between both total-Hb and TOI with SVR (total-Hb; r = 0.18, P < 0.01, TOI; r = 0.38, P < 0.01). CONCLUSION: The decreases in both rCBV and rCBO after induction of spinal anesthesia for cesarean section are probably dependent on the decrease in SVR due to spinal anesthesia.

Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs.