Risk factors and management of intraprocedural rupture during coil embolization of unruptured intracranial aneurysms: role of balloon guiding catheter.

Introduction: Intraprocedural rupture (IPR) is a serious complication of endovascular coil embolization of unruptured intracranial aneurysms (UIAs). Although outcomes after IPR are poor, methods to prevent subsequent neurological deterioration have not yet been investigated. We evaluated the risk factors and management strategies for IPR, particularly the role of balloon guiding catheters (BGCs) in rapid hemostasis. Methods: We retrospectively reviewed all UIA cases treated with coil embolization at three institutions between 2003 and 2021, focusing on preoperative radiological data, operative details, and outcomes. Results: In total, 2,172 aneurysms were treated in 2026 patients. Of these, 19 aneurysms in 19 patients (0.8%) ruptured during the procedure. Multivariate analysis revealed that aneurysms with a bleb (OR: 3.03, 95% CI: 1.21 to 7.57, p = 0.017), small neck size (OR: 0.56, 95% CI: 0.37 to 0.85, p = 0.007), and aneurysms in the posterior communicating artery (PcomA) (OR: 4.92, 95% CI: 1.19 to 20.18, p = 0.027) and anterior communicating artery (AcomA) (OR: 12.08, 95% CI: 2.99 to 48.79, p < 0.001) compared with the internal carotid artery without PcomA were significantly associated with IPR. The incidence of IPR was similar between the non-BGC and BGC groups (0.9% vs. 0.8%, p = 0.822); however, leveraging BGC was significantly associated with lower morbidity and mortality rates after IPR (0% vs. 44%, p = 0.033). Discussion: The incidence of IPR was relatively low. A bleb, small aneurysm neck, and location on PcomA and AcomA are independent risk factors for IPR. The use of BGC may prevent fatal clinical deterioration and achieve better clinical outcomes in patients with IPR.

Intermediate catheter use is associated with complete occlusion and dense packing in coil embolization of unruptured cerebral aneurysms: a propensity score matched study.

BACKGROUND: An intermediate catheter (IMC) can improve the maneuverability and stability of the microcatheter. OBJECTIVE: To investigate the efficacy and safety of using an IMC in triaxial systems for coil embolization of unruptured cerebral aneurysms (UCAs). METHODS: A total of 2430 consecutive saccular UCAs (2259 patients) that underwent initial coil embolization at three institutions between November 2003 and May 2023 were retrospectively reviewed. Patients were classified into two groups: with IMC (IMC(+)) and without IMC (IMC(-)). To investigate whether IMC use increased the rate of complete occlusion and the packing density, a propensity score-matched analysis was used to control for clinical, anatomical, and procedural features. RESULTS: Ultimately, 595 (24.5%) coil embolization used an IMC. Propensity score matching was successful for 424 paired IMC(+) and IMC(-) aneurysms. Compared with the IMC(-) group, the IMC(+) group had significantly higher rate of Raymond-Roy Occlusion Classification class 1 immediately after treatment (30.0% vs 20.8%, P=0.003) and at 6 months (28.8% vs 20.0%, P=0.004) and a higher volume embolization ratio (27.2% (SD 6.5%) vs 25.9% (SD 6.2%), P=0.003). Re-treatment rates were not significantly different between the two groups (0.7% vs 0.2%, P=0.624). No significant differences in the incidences of ischemic and hemorrhagic complications and IMC-related parent artery dissection were found between the two groups. CONCLUSION: Use of IMCs in triaxial systems can provide effective and safe support in coil embolization of UCAs because complete occlusion and dense coil packing can be achieved without increased complications.

Histological transition from minimal change disease to THSD7A-associated membranous nephropathy in a patient receiving long-term steroid treatment: A case report.

RATIONALE: A predominant Th2 immune response is suggested in the pathogenesis of both minimal change disease (MCD) and membranous nephropathy (MN); however, consecutive development of the 2 diseases in a patient is extremely rare. PATIENT CONCERN: A Japanese man, who developed nephrotic syndrome in his 50s and was diagnosed with MCD by renal biopsy, experienced a relapse of proteinuria approximately 3 years later during long-term steroid treatment. Since the proteinuria was resistant to increase in steroid dosage, repeat renal biopsy was performed, which revealed a small amount of glomerular subepithelial immune deposits containing immunoglobulin (Ig)G (dominantly IgG4). Immunostaining for thrombospondin-type-1-domain-containing-7A (THSD7A) was positive on the glomerular capillary walls, whereas that for other causative antigens of MN, such as phospholipase A2 receptor or neural epidermal growth factor-like 1 protein, was negative. Detailed examination found no associated condition, including malignancies and allergic diseases. DIAGNOSIS: The diagnosis of THSD7A-associated idiopathic MN was made. INTERVENTIONS AND OUTCOMES: He received further increased dose of steroids. Thereafter he maintained clinical improvement because his urinary protein level was decreased. LESSONS: The present case suggested that histological transition from MCD to MN is possible and repeat biopsy would be crucial for accurate diagnosis.

IMbrave150: Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: An Exploratory Analysis of the Phase III Study.

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) stage B disease. Methods: Patients with systemic treatment-naive unresectable HCC and Child-Pugh class A liver function were randomized 2:1 to receive 1,200 mg of atezolizumab plus 15 mg/kg of bevacizumab or 400 mg of sorafenib. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in the BCLC stage B subgroup. Patients in this analysis had BCLC stage B disease at baseline per electronic case report form. Secondary efficacy endpoints included the objective response rate (ORR) and change in the sum of longest diameters (SLD) of target lesions from baseline per IRF RECIST 1.1 and modified RECIST (mRECIST) for HCC. Results: Of 501 enrolled patients, 74 (15%) had BCLC stage B disease at baseline (atezolizumab + bevacizumab, n = 49; sorafenib, n = 24). For this group, median follow-up was 19.7 months. A trend toward improved OS and PFS per IRF RECIST 1.1 was observed with atezolizumab + bevacizumab versus sorafenib (OS: hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.29, 1.34; PFS: HR: 0.64; 95% CI: 0.36, 1.12). ORRs per IRF RECIST 1.1 and HCC mRECIST were 43% and 50% with atezolizumab + bevacizumab and 26% and 30% with sorafenib, respectively. Percentage change in SLD of target lesions from baseline per IRF RECIST 1.1 and HCC mRECIST showed durable responses with atezolizumab + bevacizumab treatment. Safety data were consistent with known profiles of atezolizumab and bevacizumab, as seen in the overall study population. Discussion/Conclusion: Efficacy benefits were observed with atezolizumab + bevacizumab in patients with baseline BCLC stage B disease, consistent with the intention-to-treat population.

Spontaneous shrinkage of vestibular schwannoma with the recovery of impaired hearing: A case report and literature review.

Background: Sporadically occurring vestibular schwannomas (VSs) are the most frequent tumors in the cerebellopontine cistern and internal meatus and are commonly associated with hearing loss. These tumors have demonstrated spontaneous shrinkage rates of 0-22%; however, the relationship between tumor shrinkage and changes in hearing remains unclear. Case Description: We report a case of a 51-year-old woman with a diagnosis of a left-sided VS and accompanying moderate hearing loss. The patient was treated with a conservative approach for 3 years, and the tumor showed a regression along with an improvement in her hearing ability during the yearly follow-ups. Conclusion: The spontaneous shrinkage of a VS along with an associated improvement in hearing is a rare phenomenon. Our case study may support that the "wait and scan" approach is an alternative option for patients with VS and moderate hearing loss. Further investigations are needed to understand spontaneous VS regression and hearing changes.

Enhancement of antitumor immune response by radiation therapy combined with dual immune checkpoint inhibitor in a metastatic model of HER2-positive murine tumor.

PURPOSE: Treatments for metastatic human epidermal growth factor receptor 2 (HER2)-positive tumors are improving but remain inadequate. We investigated activating antitumor immune response by combining radiation therapy with immune checkpoint inhibitors using mouse tumors overexpressing HER2, a pivotal driver oncogenic antigen, to develop new immunotherapies for metastatic HER2-positive tumors. MATERIALS AND METHODS: NT2.5 cells were inoculated into the two mammary fat pads of FVB/N mice, which were divided into four groups: no treatment (Non), anti-PD-1 and anti-CTLA4 antibodies (P1C4), irradiation of the large tumor (Rad), and combination (R + P1C4) groups. Tumor growth, immunostaining of tumor-infiltrating lymphocytes, and the proportion of HER2-tumor antigen-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were analyzed. RESULTS: In the Rad group, unirradiated and irradiated tumors shrank after treatment. Besides the directly irradiated tumors, the unirradiated tumors in the R + P1C4 group shrank the most. In the unirradiated tumors, CD8-positive T cells and FOXP3-positive T cells accumulated significantly more in the R + P1C4 group than in the P1C4 and the Rad groups (all p < 0.001). CD4-positive helper T cells accumulated significantly more in the R + P1C4 group than in the Rad group (p < 0.05), but this was not significantly different from the P1C4 group. HER2-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were significantly increased in the R + P1C4 group compared to the P1C4 and Rad groups (all p < 0.0001). CONCLUSION: Irradiation of HER2-positive tumors induced an antitumor immune effect against the unirradiated tumor, which was enhanced by the combined use of immune checkpoint inhibitors and was mediated by enhanced recruitment of HER2-tumor antigen-specific cytotoxic T lymphocytes at the tumor site in an HER2-positive mouse tumor model. Harnessing the distant antitumor immune response induced by the combination of radiation therapy and immune checkpoint inhibitors could be a promising treatment strategy for metastatic HER2-positive tumors.

Synthesis and Properties of Aromatic-Terminated Diacetylene Organogelators and Their Application to Photopatterning of Polydiacetylenes.

A series of simply structured diacetylene-diamide-based gelators (DAGs) with aromatic terminals were synthesized, and their gelation and subsequent photopolymerization abilities were analyzed. DAGs with an adequate spacer length (n) and tolyl terminals (DA-Tn) interacted with aromatic solvents, such as benzene and xylenes, at elevated temperatures. During the subsequent cooling process, the DAGs interacted with each other through CH-π interactions at their terminal positions. They also formed one-dimensional hydrogen bonding arrays through secondary amides, leading to stable organogels. These gels polymerized into π-conjugated polydiacetylenes (PDAs) under ultraviolet irradiation. In the p-xylene gels of DA-Tn, the spacer length exerted characteristic odd-even effects on the photopolymerization rates over a certain range (n = 3-6), which can be explained by periodic changes in the uniformity of the molecular packing modes. When the gelling solvent was changed to cyclohexane, the gelation and photopolymerization abilities were greatly improved because the DA-Tn gel networks became highly crystallized and transparent to ultraviolet light (254 nm). The ultimate conversion to PDA from DA-T8/cyclohexane gels was 45.2 wt %. Applying photolithographic techniques to the DAG with excellent photopolymerizability in the film state, we successfully fabricated microscale photopatterns of PDA. We also established a convenient removal process (development process) of DA monomers in unexposed areas. The resulting PDA patterns were quite stable to ambient light stimuli.

Effective Control of Brain Metastases Irrespective of Distance from Isocenter in Single-isocenter Multitarget Stereotactic Radiosurgery.

BACKGROUND/AIM: Few previous studies have evaluated the effectiveness of single-isocenter multitarget (SIMT) stereotactic radiosurgery (SRS) in clinical practice. PATIENTS AND METHODS: Gross tumor volumes of 113 metastases in 13 patients were measured by contrast-enhanced magnetic resonance imaging. Prescribed doses were set at 20-24 Gy. Based on tumor reduction rates (TRRs) measured before and after SIMT SRS, tumor shrinkage effect was categorized into four grades; almost disappeared: TRR=1, decreased: 0.3≤TRR<1, stable: -0.2

A Series of Bisamide-Substituted Diacetylenes Exhibiting a Terminal Alkyl Odd/Even Parity Effect on Mechanoactivated Photopolymerization.

Diacetylene derivatives exhibit solid-state polymerization to polydiacetylene initiated by UV light or γ-ray irradiation. The activation of the photopolymerization relies on the monomer diynes arrangement. Recently, it has been demonstrated that the first mechanoresponsive bisamide substituted diacetylenes (DAs) show dramatic switching from light-inert to light-reactive states at a given pressure. The origin of this unique phenomenon was apparently related to the pressure-sensitive crystalline transition in DAs, but the molecular mechanism remains elusive. To obtain more insight, herein a series of DAs with varying terminal alkyl spacer length is presented, and their molecular structural effect on the intermolecular hydrogen bonding and steric repulsion is examined. In pristine states, even-parity DAs were inactive upon UV irradiation (λ=254 nm) unless external pressure was applied. By contrast, odd-parity DAs were easily polymerized upon UV irradiation without pressure application. However, the pressure-induced crystalline phase transition exhibiting photopolymerization was valid for all DAs regardless of their alkyl spacer length. A systematic investigation revealed that the terminal alkyl spacer length, especially its odd/even parity plays a key role in determining the intrinsic intermolecular hydrogen-bonding nature of DA crystals and the resultant molecular packing. In addition, the relevant thermochromic behavior was also observed from photopolymerized polydiacetylenes.

Comparison of Clinical Outcomes After Stent-Assisted Coiling with 3 Types of Self-Expanding Laser-Cut Stents in Patients with Wide-Necked Intracranial Aneurysms.

OBJECTIVE: We report the clinical outcomes of stent-assisted coiling for wide-necked intracranial aneurysms using 3 low-profile laser-cut stents and compare the results according to stent type. METHODS: All patients treated with stent-assisted coiling for their intracranial aneurysms at our hospital between July 2010 and September 2019 were reviewed. We selected patients with Enterprise, Neuroform EZ, or Neuroform Atlas stents who underwent imaging follow-up and investigated aneurysm and stent features, stent-related complications, recanalization, and retreatment rates. We compared the retreatment risk among the patients treated with the 3 stent types using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: We evaluated 364 consecutive cases (103 Enterprise, 105 Neuroform EZ, and 156 Neuroform Atlas stents). Neuroform Atlas was more frequently used in distal vessels: 8 (7.8%) Enterprise, 2 (1.9%) Neuroform EZ, and 41 (26.3%) Neuroform Atlas cases, respectively. The median follow-up durations were 6.49, 4.91, and 1.24 years for the Enterprise, Neuroform EZ, and Neuroform Atlas cases, respectively, and retreatment was performed in 11 (10.1%), 9 (8.6%), and 6 (3.8%) cases. In the first 2 years of follow-up, the estimated retreatment risk ratios for Neuroform EZ and Neuroform Atlas with Enterprise as reference were 0.63 (95% confidence interval, 0.24-1.65; P = 0.35) and 0.54 (95% confidence interval, 0.18-1.59; P = 0.26), respectively. CONCLUSIONS: Neuroform Atlas stents were more frequently deployed in small-caliber vessels compared with the other 2 types of stents. The complication rate and retreatment risk until at least 1 year after the aneurysm treatment appeared to be similar for the 3 stent types.

Prediction of radiation pneumonitis using dose-volume histogram parameters with high attenuation in two types of cancer: A retrospective study.

The constraint values of dose-volume histogram (DVH) parameters for radiation pneumonitis (RP) prediction have not been uniform in previous studies. We compared the differences between conventional DVH parameters and DVH parameters with high attenuation volume (HAV) in CT imaging in both esophageal cancer and lung cancer patients to determine the most suitable DVH parameters in predicting RP onset. Seventy-seven and 72 patients who underwent radiation therapy for lung cancer and esophageal cancer, respectively, were retrospectively assessed. RP was valued according to the Common Terminology Criteria for Adverse Events. We quantified HAV with quantitative computed tomography analysis. We compared conventional DVH parameters and DVH parameters with HAV in both groups of patients. Then, the thresholds of DVH parameters that predicted symptomatic RP and the differences in threshold of DVH parameters between lung cancer and esophageal cancer patient groups were compared. The predictive performance of DVH parameters for symptomatic RP was compared using the area under the receiver operating characteristic curve. Mean lung dose, HAV30% (the proportion of the lung with HAV receiving ≥30 Gy), and HAV20% were the top three parameters in lung cancer, while HAV10%, HAV5%, and V10 (the percentage of lung volume receiving 10 Gy or more) were the top three in esophageal cancer. By comparing the differences in the threshold for parameters predicting RP between the two cancers, we saw that HAV30% retained the same value in both cancers. DVH parameters with HAV showed narrow differences in the threshold between the two cancer patient groups compared to conventional DVH parameters. DVH parameters with HAV may have higher commonality than conventional DVH parameters in both patient groups tested.

Preoperative Light Transmission Aggregometry Values Predict for Thromboembolic Complications After Stent-Assisted Coil Embolization.

OBJECTIVE: Risk control of thromboembolic complications (TECs) during stent-assisted coil embolization (SACE) for unruptured intracranial aneurysms (UIAs) is crucial for satisfactory treatment outcomes. We retrospectively evaluated the data from our cohort of SACE for UIAs to analyze the role of anatomical, clinical, and stent type-related factors to determine the optimal preoperative values of light transmission aggregometry (LTA) for TEC prevention. METHODS: From July 2015 to May 2018, we retrospectively analyzed the data from 132 patients with SACE-treated UIAs at our hospital. Data regarding the aneurysm location, maximum diameter, stent type used, preoperative LTA value, and ischemic and hemorrhagic complications were collected. Aspirin 100 mg and clopidogrel 75 mg were started 7 days before surgery, with a "boost" dose (an additional 75 mg of clopidogrel for an LTA value >60%) added after August 2016 to address clopidogrel resistance. After multivariate analysis, we developed our original combined parameter termed the thromboembolic predictor (TEP). Receiver operating characteristic (ROC) analysis for TEP and each significant variable was performed. RESULTS: TECs were confirmed in 5 of the 132 patients (3.8%) and hemorrhagic complications in 9 of the 132 patients (6.8%). From the multivariate analysis results, the LTA value and maximum diameter were chosen as significant variables and included in the TEP. ROC analysis of the LTA value revealed a sensitivity and specificity of 0.866 and 0.600, respectively (area under the curve, 0.747), with a cutoff of 62%. TEP permitted the establishment of an optimal LTA value according to the aneurysm maximum diameter to predict for TECs. The complication rate for the Neuroform EZ, Enterprise, Neuroform Atlas, and LVIS stents was 2.9%, 10.5%, 1.4%, and 14.3%, respectively. CONCLUSIONS: The preoperative LTA value contributes to the prediction of TECs after SACE for UIAs. The TEP (relating the LTA cutoff to aneurysm size) allows for improved antiplatelet therapy adjustment before SACE to reduce TECs.

[Chronic Encapsulated Intracerebral Hematoma Associated with Arteriovenous Malformation, Shrinking after Feeder Embolization with Clinical Improvement:A Case Report].

Chronic encapsulated intracerebral hematoma(CEIH)with arteriovenous malformation(AVM)is rare. We report a case of CEIH shrinking after feeder embolization for AVM. A 60-year-old man experiencing headaches for 2 weeks was admitted to our hospital due to intracerebral hematoma detected by MRI. The hematoma was shown as a low-density mass lesion on CT scans. Angiography and enhanced MRI showed an AVM in the right temporal lobe associated with the CEIH. Mild disturbance of consciousness and headaches gradually worsened, as the CEIH grew. Before AVM resection, feeder embolization was performed. On the day after the embolization, symptoms improved and the CEIH shrunk in size. A week following the embolization, the AVM including the partial hematoma capsule was resected without neurological deficit. Previous literature showed similarities between CEIH and chronic subdural hematoma(CSDH)in clinical features and pathological findings of the capsule. This case indicated that feeder embolization might be a treatment option for CEIH with AVM, such as embolization of middle meningeal artery for intractable CSDH.

Pressure-Induced Transition of Bisamide-Substituted Diacetylene Crystals from Nonphotopolymerizable to Photopolymerizable State.

Mechanoresponsive diacetylenes (DAs) exhibiting a transition of crystalline orientation from light-inert to light-active state upon applied force are reported. Amide units are introduced to DAs where hydrogen bonding is utilized to control intermolecular interactions. Application of external pressure (2-150 MPa) to DAs results in an emergence of new crystal phases with changing the d-spacing which possibly reduces the reaction barrier. Accordingly, the dramatic crystalline transition from "perfectly off" to "on" state to undergo the light-induced topochemical polymerization of bulk DA crystals is obtained. Subsequent UV irradiation at a wavelength of 254 nm enables the polymerization of the pressed region, changing its color from white to blue which suggests the selective formation of polydiacetylene (PDA) polymorphs. In addition, by utilizing the mechanoresponsive crystallinity with low-enough activation pressure, a new strategy for PDA patterning is demonstrated based on the selective transfer of information by means of force to a DA film. This phenomenon can be applicable to a new nanoimprinting technique where no mechanical deformation of resist materials but phase transition is induced by the mold.

Multistage "Hybrid" (Open and Endovascular) Surgical Treatment of Vertebral Artery-Thrombosed Giant Aneurysm by Trapping and Thrombectomy.

BACKGROUND: Surgical treatment of vertebral artery (VA)-thrombosed giant aneurysms requires achieving both obliteration of the parent artery to prevent bleeding and dome thrombectomy to relieve the brain stem from mass effect. To secure both proximal and distal control of complex VA aneurysms, the contralateral approach to the aneurysm might be a useful alternative, as previously described. We successfully treated a case of VA-thrombosed giant aneurysm in a new, original way by combining craniotomy (ipsilateral and contralateral) and the endovascular technique. CASE DESCRIPTION: A 48-year-old man presented with a thrombosed giant aneurysm of the right VA compressing the brain stem. Treatment consisted of endovascular proximal ligation of the VA followed by 2-staged craniotomy for complete trapping of the aneurysm and intra-aneurysmal thrombectomy. The VA distal to the aneurysm was obliterated via contralateral craniotomy as only that provided adequate working space. Finally, intra-aneurysmal partial thrombectomy was performed through an ipsilateral craniotomy, which also made possible the obliteration of the eventually dangerous remaining vasa vasorum and additional proximal ligation of the VA. CONCLUSIONS: Based on pathologic and surgical anatomical characteristics, a combination of an endovascular procedure with 2-staged craniotomy for complete trapping, thrombectomy, and vasa vasorum obliteration could be considered a feasible way to treat VA-thrombosed giant aneurysms located ventral to the brain stem and have their distal neck portions/patent vessel beyond the midline toward the contralateral side.

Exclusion of emphysematous lung from dose-volume estimates of risk improves prediction of radiation pneumonitis.

BACKGROUND: The risk factors for radiation pneumonitis (RP) in patients with chronic obstructive pulmonary disease (COPD) are unclear. Mean lung dose (MLD) and percentage of irradiated lung volume are common predictors of RP, but the most accurate dosimetric parameter has not been established. We hypothesized that the total lung volume irradiated without emphysema would influence the onset of RP. METHODS: We retrospectively evaluated 100 patients who received radiotherapy for lung cancer. RP was graded according to the Common Terminology Criteria for Adverse Events (version 4.03). We quantified low attenuation volume (LAV) using quantitative computed tomography analysis. The association between RP and traditional dosimetric parameters including MLD, volume of the lung receiving a dose of ≥2 Gy, ≥ 5 Gy, ≥ 10 Gy, ≥ 20 Gy, and ≥30 Gy, and counterpart measurements of the lung without LAV, were analyzed by logistic regression. We compared each dosimetric parameter for RP using multiple predictive performance measures including area under the receiver operating characteristic curve (AUC) and integrated discrimination improvement (IDI). RESULTS: Of 100 patients, RP of Grades 1, 2, 3, 4, and 5 was diagnosed in 24, 12, 13, 1, and 1 patients, respectively. Compared with traditional dosimetric parameters, counterpart measurements without LAV improved risk prediction of symptomatic RP. The ratio of the lung without LAV receiving ≥30 Gy to the total lung volume without LAV most accurately predicted symptomatic RP (AUC, 0.894; IDI, 0.064). CONCLUSION: Irradiated lung volume without LAV predicted RP more accurately than traditional dosimetric parameters.

Speed ratio but cabin temperature positively correlated with increased heart rates among professional drivers during car races.

OBJECTIVES: The present study measures heart rate (HR) on a number of professional race-car drivers during actual car races through annual seasons to test hypotheses that faster relative speed and higher cabin temperature would induce higher HR. METHODS: Heart rates in fifteen male drivers (31.2 ± 5.5 years old) were obtained by chest-strap sensors during official-professional 13 races. Average HR was calculated while the driver was racing from the start to the end of each race. RESULTS: The average HR during races was 164.5 ± 15.1 beats min-1 and the average amount of time each driver spent driving per race was 54.2 ± 13.7 min. Average HR significantly and positively correlated with mean speed ratio (P < 0.001), but not with the average cabin temperatures (P = 0.533, range 25.6-41.8 °C) by the multiple linear regression analysis. Both average HR and mean speed ratio were significantly lower under wet, than dry conditions (151.9 ± 16.5 vs. 168.3 ± 12.5 beats min-1, 86.9 ± 4.4 vs. 93.4 ± 1.5 %). CONCLUSIONS: The cardiovascular system of drivers is considerably stressed at extremely high HR. This high average HR positively correlated with mean speed ratio, suggesting that faster driving speed would induce greater cardiovascular stress to professional drivers during actual races. However, contrary to our hypothesis, cabin temperature was not significantly correlated with average HR. It is speculated that direct body cooling systems used in this professional race category work well against increases in HR by thermal stress under the temperature range found herein.

The relationship between widespread changes in gravity and cerebral blood flow.

OBJECTIVES: We investigated the dose-effect relationship between wide changes in gravity from 0 to 2.0 Gz (Δ0.5 Gz) and cerebral blood flow (CBF), to test our hypothesis that CBF has a linear relationship with levels of gravity. SUBJECTS AND METHODS: Ten healthy seated men were exposed to 0, 0.5, 1.0, 1.5, and 2.0 Gz for 21 min, by using a tilt chair and a short-arm human centrifuge. Steady-state CBF velocity (CBFV) in the middle cerebral artery by transcranial Doppler ultrasonography, mean arterial pressure (MAP) at the heart level (MAPHeart), heart rate, stroke volume, cardiac output and respiratory conditions were obtained for the last 6 min at each gravity level. Then, MAP in the middle cerebral artery (MAPMCA), reflecting cerebral perfusion pressure, was estimated. RESULTS: Steady-state CBFV decreased stepwise from 0.5 to 2.0 Gz. Steady-state heart rate, stroke volume, estimated MAPMCA and end-tidal carbon dioxide pressure (ETCO2) also changed stepwise from hypogravity to hypergravity. On the other hand, steady-state MAPHeart and cardiac output did not change significantly. Steady-state CBFV positively and linearly correlated with estimated MAPMCA and ETCO2 in most subjects. CONCLUSION: The present study demonstrated stepwise gravity-induced changes in steady-state CBFV from 0.5 to 2.0 Gz despite unchanged steady-state MAPHeart. The combined effects of reduced MAPMCA and ETCO2 likely led to stepwise decreases in CBFV. We caution that a mild increase in gravity from 0 to 2.0 Gz reduces CBF, even if arterial blood pressure at the heart level is maintained.

Dose-Effect Relationship Between Mild Levels of Hypergravity and Autonomic Circulatory Regulation.

INTRODUCTION: The dose-effect relationships between different levels of hypergravity (>+1.0 Gz) and steady-state hemodynamic parameters have been reported in several studies. However, little has been reported on the dose-effect relationship between hypergravity levels and estimates of autonomic circulatory regulation, such as heart rate variability, arterial pressure variability, and spontaneous cardiac baroreflex sensitivity. We investigated dose-effect relationships between hypergravity levels from +1.0 Gz to +2.0 Gz (Δ0.5 Gz) and autonomic circulatory regulation to test our hypothesis that autonomic circulatory regulation has a linear relationship with hypergravity levels. METHODS: Using a short-arm human centrifuge, 10 healthy seated men were subjected to +1.0 Gz, +1.5 Gz, and +2.0 Gz hypergravity. We evaluated steady-state hemodynamic parameters and autonomic circulatory regulation indices. Heart rate variability, arterial pressure variability, and spontaneous cardiac baroreflex sensitivity between arterial pressure and R-R interval variabilities were assessed by spectral analysis, sequence analysis, and transfer function analysis. RESULTS: Steady-state heart rate, stroke volume, and sequence slope (indicating spontaneous cardiac baroreflex sensitivity in response to rapid changes in arterial pressure) showed linear correlations with increases in gravity (from +1.0 Gz to +2.0 Gz). On the other hand, steady-state cardiac output, steady-state systolic arterial pressure, and low-frequency power of diastolic arterial pressure (indicating peripheral vasomotor sympathetic activity) remained unchanged with gravity increases. CONCLUSION: Contrary to our hypothesis, the present study suggested that autonomic circulatory regulations show complex changes with hypergravity levels. Spontaneous cardiac baroreflex sensitivity reduces in a dose-dependent manner from +1.0 Gz to +2.0 Gz, whereas peripheral vasomotor sympathetic activity seems to be maintained.

Epstein-Barr virus-positive diffuse large B-cell lymphoma following acute myeloid leukemia: a common clonal origin indicated by chromosomal translocation t(3;4)(p25;q21).

Secondary non-Hodgkin lymphoma following acute myeloid leukemia (AML) is extremely rare. We here describe a unique case involving a patient who developed Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) during complete remission (CR) of AML. A 75-year-old Japanese man was initially diagnosed with AML with maturation (FAB M2), bearing chromosomal translocation t(3,4)(p25;q21). After intensive chemotherapy, bone marrow aspiration revealed normal karyotype, and he achieved CR. Six years and 4 months later, he was still in CR from AML, but developed DLBCL presenting in the terminal ileum. Cytogenetic analysis of the DLBCL cells showed the same translocation as the previous AML. The rearrangements of the immunoglobulin heavy chain genes of the two malignancies were examined using polymerase chain reaction amplification, and the rearrangement patterns were found to differ from each other. Our data thus suggest that, in the present case, the AML and DLBCL arose from a common progenitor cell, as indicated by the clonal abnormality t(3,4)(p25;q21), and that different immunoglobulin heavy chain gene rearrangements occurred during each course of clonal evolution.