Demographic Traits, Clinical Status, and Comorbidities of Patients With Thromboangiitis Obliterans in Japan.

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

Neurotropin® accelerates peripheral nerve regeneration in a rat sciatic nerve crush injury model.

BACKGROUND: Peripheral nerve injuries are common and serious conditions. The effect of Neurotropin® (NTP), a nonprotein extract derived from the inflamed skin of rabbits inoculated with vaccinia virus, on peripheral nerve regeneration has not been fully elucidated. However, it has analgesic properties via the activation of descending pain inhibitory systems. Therefore, the current study aimed to determine the effects of NTP on peripheral nerve regeneration. METHODS: We examined axonal outgrowth of dorsal root ganglion (DRG) neurons using immunocytochemistry in vitro. In addition, nerve regeneration was evaluated functionally, electrophysiologically, and histologically in a rat sciatic nerve crush injury model in vivo. Furthermore, gene expression of neurotrophic factors in the injured sciatic nerves and DRGs was evaluated. RESULTS: In the dorsal root ganglion neurons in vitro, NTP promoted axonal outgrowth at a concentration of 10 mNU/mL. Moreover, the systemic administration of NTP contributed to the recovery of motor and sensory function at 2 weeks, and of sensory function, nerve conduction velocity, terminal latency, and axon-remyelination 4 weeks after sciatic nerve injury. In the gene expression assessment, insulin-like growth factor 1 and vascular endothelial growth factor expressions were increased in the injured sciatic nerve 2 days postoperatively. CONCLUSIONS: Therefore, NTP might be effective in not only treating chronic pain but also promoting peripheral nerve regeneration after injury.

Cubitus varus deformity following paediatric supracondylar humeral fracture remodelling predominantly in the sagittal direction: A three-dimensional analysis of eighty-six cases.

PURPOSE: Three-dimensional (3D) capacity for remodelling in cubitus varus deformity (CVD) after paediatric supracondylar humeral fractures (PSHFs) remains unelucidated. This study investigated remodelling patterns after PSHFs by examining 3D deformity distribution over time after injury. METHODS: Computed tomography (CT) data of 86 patients with CVD after PSHFs were analysed. The 3D deformity angles in the sagittal, coronal, and axial directions were assessed and correlated with the duration between the age at injury and CT evaluation. For the subgroup analysis, we performed the same correlation analysis in a younger (< 8 years old) and an older group (≥ 8 years old); we categorized the duration into early (< 2 years), middle (≥ 2 to < 5 years), and late periods (≥ 5 years) and compared the deformity angles of each direction among the three groups. RESULTS: Sagittal deformity showed a moderate correlation with the duration of deformity (r = -0.54; P < 0.001), while coronal and axial deformities showed a negligible correlation. Sagittal deformity showed moderate correlations with the duration in the younger group (r = -0.62; P < 0.001) and weak correlations in the older group (r = -0.37; P = 0.091). In the sagittal direction, the deformity angle in the early period was significantly larger than those in the mid and late periods (P < 0.001). However, there were no significant differences among the three groups in the coronal and axial directions. CONCLUSION: Sagittal deformities in CVDs are capable of remodelling, especially in the early period and at a younger age, whereas coronal and axial deformities are less likely to undergo remodelling.

Endothelial mechanisms for inactivation of inflammation-induced hyperpermeability.

Microvascular hyperpermeability is a hallmark of inflammation. Many negative effects of hyperpermeability are due to its persistence beyond what is required for preserving organ function. Therefore, we propose that targeted therapeutic approaches focusing on mechanisms that terminate hyperpermeability would avoid the negative effects of prolonged hyperpermeability while retaining its short-term beneficial effects. We tested the hypothesis that inflammatory agonist signaling leads to hyperpermeability and initiates a delayed cascade of cAMP-dependent pathways that causes inactivation of hyperpermeability. We applied platelet-activating factor (PAF) and vascular endothelial growth factor (VEGF) to induce hyperpermeability. We used an Epac1 agonist to selectively stimulate exchange protein activated by cAMP (Epac1) and promote inactivation of hyperpermeability. Stimulation of Epac1 inactivated agonist-induced hyperpermeability in the mouse cremaster muscle and in human microvascular endothelial cells (HMVECs). PAF induced nitric oxide (NO) production and hyperpermeability within 1 min and NO-dependent increased cAMP concentration in about 15-20 min in HMVECs. PAF triggered phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in a NO-dependent manner. Epac1 stimulation promoted cytosol-to-membrane eNOS translocation in HMVECs and in myocardial microvascular endothelial (MyEnd) cells from wild-type mice, but not in MyEnd cells from VASP knockout mice. We demonstrate that PAF and VEGF cause hyperpermeability and stimulate the cAMP/Epac1 pathway to inactivate agonist-induced endothelial/microvascular hyperpermeability. Inactivation involves VASP-assisted translocation of eNOS from the cytosol to the endothelial cell membrane. We demonstrate that hyperpermeability is a self-limiting process, whose timed inactivation is an intrinsic property of the microvascular endothelium that maintains vascular homeostasis in response to inflammatory conditions.NEW & NOTEWORTHY Termination of microvascular hyperpermeability has been so far accepted to be a passive result of the removal of the applied proinflammatory agonists. We provide in vivo and in vitro evidence that 1) inactivation of hyperpermeability is an actively regulated process, 2) proinflammatory agonists (PAF and VEGF) stimulate microvascular hyperpermeability and initiate endothelial mechanisms that terminate hyperpermeability, and 3) eNOS location-translocation is critical in the activation-inactivation cascade of endothelial hyperpermeability.

Association of simple renal cysts to aneurysm sac shrinkage in true thoracic aortic aneurysms after thoracic endovascular aortic repair.

BACKGROUND: An increased prevalence of thoracic aortic aneurysms (TAA) has been demonstrated in patients with simple renal cysts (SRC); patients with SRC have a less elastic aortic wall than those without SRC. The purpose of this study was to evaluate aneurysm sac shrinkage after thoracic endovascular aortic repair (TEVAR) for true TAA in patients with and without SRC. METHODS: One hundred three patients with true aneurysms of the thoracic aorta who underwent TEVAR at our university hospital from November 2013 to December 2021 were included in this study. Aneurysm sac size was compared between that on baseline preoperative computed tomography and that on postoperative computed tomography scans at 1 year. A change in aneurysm sac size ≥5 mm was considered to be significant, whether due to expansion or shrinkage. RESULTS: The patients were divided into two groups: those with SRC (46 patients [45%]) and those without SRC (57 patients [55%]). At 1 year, there was a significant difference in the proportion of aneurysm sac shrinkage between patients with SRC and those without SRC (23.9% vs 59.6%; P < .001). Patients with SRC showed significantly less aneurysm sac shrinkage than those without SRC (-1.8 ± 5.6 mm vs -5.1 ± 6.6 mm; P = .009). Univariable and multivariable analyses showed that the initial sac diameter (odds ratio, 1.08; 95% confidence interval, 1.03-1.14; P = .002) and the presence of SRC (odds ratio, 0.15; 95% confidence interval, 0.06-0.40; P < .001) were positively and negatively associated with aneurysm sac shrinkage after TEVAR, respectively. CONCLUSIONS: The presence of a SRC was independently associated with failure of aneurysm sac shrinkage after TEVAR for true TAA. This suggests that the presence of a SRC may be a predictor for the failure of aneurysm sac shrinkage after TEVAR.

Association of High-Sensitivity C-Reactive Protein With Aneurysm Sac Shrinkage in Patients Undergoing Endovascular Abdominal Aneurysm Repair.

PURPOSE: The factors associated with aneurysm sac shrinkage after endovascular aneurysm repair (EVAR) are not well established. As inflammation is implicated in aneurysm pathophysiology, we hypothesized that high-sensitivity C-reactive protein (hsCRP) was associated with aneurysm sac shrinkage after EVAR and compared the preoperative level of hsCRP between patients with and without postoperative aneurysm sac shrinkage after EVAR. METHODS: From November 2013 to April 2019, 143 patients undergoing EVAR using Gore C3 Excluder (W. L. Gore & Associates, Inc, Flagstaff, Arizona) at our university hospital were included in this study. Aneurysm sac size was compared between that on baseline preoperative computed tomography (CT) and that on postoperative CT scans. A change in aneurysm sac size ≥5 mm was considered to be significant, whether due to enlargement or shrinkage. RESULTS: Aneurysm sac size showed a significant decrease from 50.6 ± 9.8 mm to 47.1 ± 10.3 mm at 1 year. At 1 year postoperatively, aneurysm sac shrinkage (≥5 mm) was observed in 48 patients (34%), a stable aneurysm sac was noted in 93 patients (65%), and aneurysm sac enlargement was noted in 2 patients (1.4%). The mean preoperative hsCRP was 0.33 ± 0.54 mg/dL. Univariable analysis showed that preoperative hsCRP (p=0.029) and the presence of a renal cyst (p=0.002) were associated with aneurysm sac shrinkage. Multivariable analysis showed that preoperative hsCRP [>0.19mg/dL] (odds ratio [OR] = 0.22; 95% confidence interval [CI] = 0.05-0.96; p=0.042), and the presence of a renal cyst (OR = 0.31; 95% CI = 0.15-0.67; p=0.002) were independent risk factors for aneurysm sac shrinkage after EVAR. CONCLUSIONS: The level of preoperative hsCRP was independently associated with aneurysm sac shrinkage after EVAR in patients with abdominal aortic aneurysms. These data suggest that the high level of hsCRP can be a negative predictor for aneurysm sac shrinkage after EVAR.

Simple renal cyst and its association with sac shrinkage after endovascular aneurysm repair for abdominal aortic aneurysms.

OBJECTIVE: Patients with abdominal aortic aneurysm (AAA) frequently have simple renal cyst (SRC), a common manifestation of connective tissue degeneration. This study aimed to determine whether SRC is a risk factor for failure of sac shrinkage after endovascular aneurysm repair (EVAR). METHODS: Between October 2013 and May 2017, there were 155 consecutive patients with an infrarenal AAA or a common iliac artery aneurysm who underwent EVAR with the GORE C3 Excluder (W. L. Gore & Associates, Flagstaff, Ariz) at Tokyo Medical University Hospital. All these patients were registered in a prospectively maintained database. Any kidney lesion >5 mm in diameter, with no evidence of contrast enhancement or septation and with low attenuation, was defined as SRC. A change in sac size of >5 mm from baseline was considered significant. The patients were divided into those with SRC and those without SRC, and sac shrinkage at 1 year and 2 years was compared. The presence of SRC was assessed with respect to being a risk factor for failure of sac shrinkage at 1 year using univariate and multivariable logistic regression analysis. RESULTS: The patients were divided into two groups: those with SRC (92 patients [59.0%]) and those without SRC (63 patients [41.0%]). At 1 year and 2 years, significant differences were observed in the proportion of sac shrinkage between patients with SRC and those without SRC (19.2% vs 42.4% [P = .003] and 19.6% vs 53.3% [P = .001], respectively). Patients with SRC showed significantly less sac shrinkage than those without SRC at 1 year and 2 years (-2.0 ± 5.5 mm vs -4.4 ± 6.2 mm [P = .002] and -1.8 ± 6.3 mm vs -6.4 ± 8.6 mm [P = .005], respectively). Multivariable analysis demonstrated that SRC (odds ratio, 0.28; 95% confidence interval, 0.12-0.63; P = .002) and initial sac size (odds ratio, 1.05; 95% confidence interval, 1.01-1.09; P = .027) were positive and negative risk factors for sac shrinkage, respectively. CONCLUSIONS: The presence of SRC is a risk factor for failure of sac shrinkage after EVAR. This suggests that AAA in patients with SRC has a more degenerated wall than in those without SRC. The property of the aneurysm wall may be associated with sac shrinkage after EVAR.

Clinical and Morphological Outcomes in Endovascular Aortic Repair of Abdominal Aortic Aneurysm Using GORE C3 EXCLUDER: Comparison between Patients Treated within and Outside Instructions for Use.

BACKGROUND: The goals of this study were to evaluate mid-term outcome in endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) using a GORE C3 EXCLUDER and compare results between patients treated within and outside the instructions for use (IFU). METHODS: Over a 3-year period spanning October 2013 to September 2016, consecutive patients undergoing EVAR for AAA using the C3 EXCLUDER at Tokyo Medical University Hospital were registered on a prospectively maintained database. The data thus obtained were retrospectively analyzed. RESULTS: A total of 109 AAA patients underwent EVAR using the C3 EXCLUDER. The median follow-up duration was 729 days (interquartile range, 542-1,069 days). Technical success was achieved in 98.2% of cases. Adjunctive, unplanned proximal cuff-extender implantation was required in 8 patients (9.2%). Of the total number, 29 (24.8%) were categorized as being treated outside the IFU. No significant difference was observed in freedom from overall mortality or aneurysm-related mortality between patients treated within and outside the IFU. Freedom from reintervention tended to be lower in patients treated outside the IFU. There was aneurysm sac shrinkage (≥5 mm) in 30.3% and 39.1%; stable aneurysm sac in 69.7% and 56.3%; and aneurysm sac expansion (≥5 mm) in 0% and 4.7% of cases at 1 and 2 years, respectively. No significant difference was observed in aneurysm sac shrinkage between patients treated within and outside the IFU. CONCLUSIONS: The C3 EXCLUDER showed good clinical performance and aneurysm sac shrinkage, regardless of whether the patient was treated within or outside the IFU. The results suggest, however, that in those treated outside the IFU, precise planning, careful operative procedure, and subsequent follow-up are required to obtain short-term and mid- to long-term success in EVAR for AAA using the C3 EXCLUDER.

Assessment of the effects of switching oral bisphosphonates to denosumab or daily teriparatide in patients with rheumatoid arthritis.

The aim of this observational, non-randomized study was to clarify the unknown effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily teriparatide (TPTD) in patients with rheumatoid arthritis (RA). The characteristics of the 194 female patients included in the study were 183 postmenopausal, age 65.9 years, lumbar spine (LS) T score -1.8, femoral neck (FN) T score -2.3, dose and rate of taking oral prednisolone (3.6 mg/day) 75.8%, and prior BP treatment duration 40.0 months. The patients were allocated to (1) the BP-continue group (n = 80), (2) the switch-to-DMAb group (n = 74), or (3) the switch-to-TPTD group (n = 40). After 18 months, the increase in bone mineral density (BMD) was significantly greater in the switch-to-DMAb group than in the BP-continue group (LS 5.2 vs 2.3%, P < 0.01; FN 3.8 vs 0.0%, P < 0.01) and in the switch-to-TPTD group than in the BP-continue group (LS 9.0 vs 2.3%, P < 0.001; FN 4.9 vs 0.0%, P < 0.01). Moreover, the switch-to-TPTD group showed a higher LS BMD (P < 0.05) and trabecular bone score (TBS) (2.1 vs -0.7%; P < 0.05) increase than the switch-to-DMAb group. Clinical fracture incidence during this period was 8.8% in the BP-continue group, 4.1% in the switch-to-DMAb group, and 2.5% in the switch-to-TPTD group. Both the switch-to-DMAb group and the switch-to-TPTD group showed significant increases in LS and FN BMD, and the switch-to-TPTD group showed a higher increase in TBS compared to the BP-continue group at 18 months. Switching BPs to DMAb or TPTD in female RA may provide some useful osteoporosis treatment options.

Neurotropin® Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model.

Neurotropin® (NTP), a non-protein extract of inflamed rabbit skin inoculated with vaccinia virus, is clinically used for the treatment of neuropathic pain in Japan and China, although its effect on peripheral nerve regeneration remains to be elucidated. The purpose of this study was to investigate the effects of NTP on Schwann cells (SCs) in vitro and in vivo, which play an important role in peripheral nerve regeneration. In SCs, NTP upregulated protein kinase B (AKT) activity and Krox20 and downregulated extracellular signal-regulated kinase1/2 activity under both growth and differentiation conditions, enhanced the expression of myelin basic protein and protein zero under the differentiation condition. In a co-culture of dorsal root ganglion neurons and SCs, NTP accelerated myelination of SCs. To further investigate the influence of NTP on SCs in vivo, lysophosphatidylcholine was injected into the rat sciatic nerve, leading to the focal demyelination. After demyelination, NTP was administered systemically with an osmotic pump for one week. NTP improved the ratio of myelinated axons and motor, sensory, and electrophysiological function. These findings reveal novel effects of NTP on SCs differentiation in vitro and in vivo, and indicate NTP as a promising treatment option for peripheral nerve injuries and demyelinating diseases.

Administration of Oxygen Ultra-Fine Bubbles Improves Nerve Dysfunction in a Rat Sciatic Nerve Crush Injury Model.

Ultra-fine bubbles (<200 nm in diameter) have several unique properties and have been tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUBs) on a sciatic nerve crush injury (SNC) model rats. Rats were intraperitoneally injected with 1.5 mL saline, OUBs diluted in saline, or nitrogen ultra-fine bubbles (NUBs) diluted in saline three times per week for 4 weeks in four groups: (1) control, (sham operation + saline); (2) SNC, (crush + saline); (3) SNC+OUB, (crush + OUB-saline); (4) SNC+NUB, (crush + NUB-saline). The effects of the OUBs on dorsal root ganglion (DRG) neurons and Schwann cells (SCs) were examined by serial dilution of OUB medium in vitro. Sciatic functional index, paw withdrawal thresholds, nerve conduction velocity, and myelinated axons were significantly decreased in the SNC group compared to the control group; these parameters were significantly improved in the SNC+OUB group, although NUB treatment did not affect these parameters. In vitro, OUBs significantly promoted neurite outgrowth in DRG neurons by activating AKT signaling and SC proliferation by activating ERK1/2 and JNK/c-JUN signaling. OUBs may improve nerve dysfunction in SNC rats by promoting neurite outgrowth in DRG neurons and SC proliferation.

Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis.

The aim of this 12-month, retrospective study was to compare the effects of denosumab (DMAb; 60 mg subcutaneously every 6 months) plus native vitamin D (VD) (cholecalciferol) combination therapy with DMAb plus active VD analog (alfacalcidol) combination therapy in patients with postmenopausal osteoporosis. Patients [N = 127; mean age 75.6 years (range 58-93 years); 28 treatment-naïve patients, 59 patients treated with oral bisphosphonate therapy, 40 patients treated with teriparatide daily] were allocated to either (1) the DMAb plus native VD group (n = 60; cholecalciferol, 10 µg, plus calcium, 610 mg/day; 13 treatment-naïve patients, 28 patients treated with oral bisphosphonate therapy, and 19 patients treated with teriparatide daily) or (2) the DMAb plus active VD group [n = 67; alfacalcidol, 0.8 ± 0.0 µg, plus calcium, 99.2 ± 8.5 mg/day; 15 treatment-naïve patients, 31 patients treated with oral bisphosphonate therapy, and 21 patients treated with teriparatide daily) on the basis of each physician's decision. Changes in bone mineral density (BMD), serum bone turnover marker levels, and fracture incidence were monitored every 6 months. There were no significant differences in baseline age, BMD, bone turnover marker levels, and prior treatments between the two groups. After 12 months, compared with the DMAb plus native VD group, the DMAb plus active VD group showed similar increases in the BMD of the lumbar spine (6.4% vs 6.5%) and total hip (3.3% vs 3.4%), but significantly greater increases in the BMD of the femoral neck (1.0% vs 4.9%, P < 0.001) and the distal part of the forearm (third of radius) (-0.8% vs 3.9%, P < 0.01). These tendencies were similar regardless of the differences in the prior treatments. The rates of decrease of bone turnover marker levels were similar for tartrate-resistant acid phosphatase isoform 5b (-49.0% vs -49.0%), procollagen type I N-terminal propeptide (-45.9% vs -49.3%), and undercarboxylated osteocalcin (-56.0  vs -66.5%), whereas serum intact parathyroid hormone levels were significantly lower in the DMAb plus active VD group (47.6 pg/mL vs 30.4 pg/mL, P < 0.001). The rate of hypocalcemia was 1.7% in the DMAb plus native VD group and 1.5% in the DMAb plus active VD group, and the rate of clinical fracture incidence was 8.3% in the DMAb plus native VD group and 4.5% in the DMAb plus active VD group, with no significant difference between the groups. DMAb with active VD combination therapy may be a more effective treatment option than DMAb with native VD combination therapy in terms of increasing BMD of the femoral neck and distal part of the forearm and also maintaining serum intact parathyroid hormone at lower levels.

Three-dimensional corrective osteotomy for cubitus varus deformity using patient-matched instruments.

Background: Various methods of two or three-dimensional (3D) corrective osteotomy for cubitus varus deformity have been reported. However, whether 3D correction of cubitus varus deformity is necessary is controversial because of technical difficulties and surgical complications. This study introduced 3D simulations and printing technology for corrective osteotomy against cubitus varus deformities. Moreover, recent studies on the application of these technologies were reviewed. Methods: The amount of 3D deformity was calculated based on the difference in 3D shape between the affected side and the contralateral normal side. Patient-matched instruments were created to perform the actual surgery as simulated. Further, a 3D corrective osteotomy was performed using patient-matched instruments for cubitus varus deformity in pediatric and adolescent patients. The humerus-elbow-wrist angle, tilting angle, and elbow ranges of motion were evaluated. Results: Humerus-elbow-wrist angle and tilting angle were corrected from -21° to 14° and from 30° to 43°, respectively, in the pediatric patient and from -18° to 10° and from 20° to 40°, respectively, in the adolescent patient. The elbow flexion and extension angles changed from 130° to 140° and from 20° to 10°, respectively, in the pediatric patient and from 120° to 130° and from 15° to 0°, respectively, in the adolescent patient. Conclusion: The 3D computer simulations and the use of patient-matched instruments for cubitus varus deformity are reliable and can facilitate an accurate and safe correction. These technologies can simplify the complexity of 3D surgical procedures and contribute to the standardization of treatment for cubitus varus deformity.

Acceptable range of forearm deformity derived from relation to three-dimensional analysis and clinical impairments.

This study aimed to investigate deformity patterns that cause clinical impairments and determine the acceptable range of deformity in the treatment of forearm diaphyseal fractures. A three-dimensional (3D) deformity analysis based on computed bone models was performed on 39 patients with malunited diaphyseal both-bone forearm fractures to investigate the 3D deformity patterns of the radius and ulna at the fracture location and the relationship between 3D deformity and clinical impairments. Clinical impairments were evaluated using forearm motion deficit. Cutoff values of forearm deformities were calculated by performing receiver operating characteristic analysis using the deformity angle and the limited forearm rotation range of motion (less than 50° of pronation or supination) resulting in activities of daily living (ADL) impairment as variables. The extension, varus, and pronation deformities most commonly occurred in the radius, whereas the extension deformity was commonly observed in the ulna. A positive correlation was observed between pronation deficit and extension deformity of the radius (R = 0.41) and between supination deficit and pronation deformity of the ulna (R = 0.44). In contrast, a negative correlation was observed between pronation deficit and pronation deformity of the radius (R = -0.44) and between pronation deficit and pronation deformity of the ulna (R = -0.51). To minimize ADL impairment, radial extension deformity should be <18.4°, radial rotation deformity <12.8°, and ulnar rotation deformity <16.6°. The deformities in the sagittal and axial planes of the radius and in the axial plane of the ulna were responsible for the limited forearm rotation.

Reproduction of forearm rotation dynamic using intensity-based biplane 2D-3D registration matching method.

This study aimed to reproduce and analyse the in vivo dynamic rotational motion of the forearm and to clarify forearm motion involvement and the anatomical function of the interosseous membrane (IOM). The dynamic forearm rotational motion of the radius and ulna was analysed in vivo using a novel image-matching method based on fluoroscopic and computed tomography images for intensity-based biplane two-dimensional-three-dimensional registration. Twenty upper limbs from 10 healthy volunteers were included in this study. The mean range of forearm rotation was 150 ± 26° for dominant hands and 151 ± 18° for non-dominant hands, with no significant difference observed between the two. The radius was most proximal to the maximum pronation relative to the ulna, moved distally toward 60% of the rotation range from maximum pronation, and again proximally toward supination. The mean axial translation of the radius relative to the ulna during forearm rotation was 1.8 ± 0.8 and 1.8 ± 0.9 mm for dominant and non-dominant hands, respectively. The lengths of the IOM components, excluding the central band (CB), changed rotation. The transverse CB length was maximal at approximately 50% of the rotation range from maximum pronation. Summarily, this study describes a detailed method for evaluating in vivo dynamic forearm motion and provides valuable insights into forearm kinematics and IOM function.

Impact of preoperative identification of the artery of Adamkiewicz on spinal cord injury after descending aortic and thoracoabdominal aortic repair.

Background: Some recent reports have demonstrated that preoperative Adamkiewicz artery (AKA) identification and its targeted reconstruction has provided satisfactory outcomes with respect to spinal cord protection. This paper investigates the impact of preoperative identification of the AKA on reducing the incidence of spinal cord injury (SCI) in open repair (OR) and endovascular repair (EVR) of descending thoracic aortic (dTA) and thoracoabdominal aortic aneurysm (TAA) repair. Methods: The clinical data of patients with dTA and TAA treated between 2011 and 2022 were investigated. A total of 256 patients comprising of 201 males and 55 females, with a mean age of 72.1±10.0 years, were included. OR was used in 102 patients and EVR in 154 patients whose distal landing zone was below T8, all of which needed preoperative identification of the AKA. Results: The AKA was identified in 207 (80.9%) patients, and was located in the level between T8 and T12 in 81.2%. In OR, the responsible arteries, including the identified AKA, were promptly reconstructed in 66 (64.7%) patients. In EVR, 65 (42.2%) patients had the AKA covered by an endovascular prosthesis. Deaths prior to 30 days occurred in seven (2.7%, four in OR and three in EVR) patients. In OR, SCI occurred in six (5.9%) patients including three (2.9%) with paraplegia and three (2.9%) with paraparesis, whereas in EVR ten (6.5%) patients had SCI, including two (1.3%) with paraplegia and eight (5.2%) with paraparesis. The incidence of SCI was significantly higher in patients with the AKA covered than those without it covered [13.8% (9 of 65) vs. 1.1% (1 of 89); P=0.002], whereas no significant differences were found between patients with or without the AKA reconstructed. Conclusions: Preoperative identification of the AKA was useful enough to determine treatment strategies with less likelihood of SCI in both OR and EVR for dTA and TAA pathologies.

Functional significance of cytosolic endothelial nitric-oxide synthase (eNOS): regulation of hyperpermeability.

Endothelial NOS (eNOS)-derived NO is a key factor in regulating microvascular permeability. We demonstrated previously that eNOS translocation from the plasma membrane to the cytosol is required for hyperpermeability. Herein, we tested the hypothesis that eNOS activation in the cytosol is necessary for agonist-induced hyperpermeability. To study the fundamental properties of endothelial cell monolayer permeability, we generated ECV-304 cells that stably express cDNA constructs targeting eNOS to the cytosol or plasma membrane. eNOS-transfected ECV-304 cells recapitulate the eNOS translocation and permeability properties of postcapillary venular endothelial cells (Sánchez, F. A., Rana, R., Kim, D. D., Iwahashi, T., Zheng, R., Lal, B. K., Gordon, D. M., Meininger, C. J., and Durán, W. N. (2009) Proc. Natl. Acad. Sci. U.S.A. 106, 6849-6853). We used platelet-activating factor (PAF) as a proinflammatory agonist. PAF activated eNOS by increasing phosphorylation of Ser-1177 and inducing dephosphorylation of Thr-495, increasing NO production, and elevating permeability to FITC-dextran 70 in monolayers of cells expressing wild-type and cytosolic eNOS. PAF failed to increase permeability to FITC-dextran 70 in monolayers of cells transfected with eNOS targeted to the plasma membrane. Interestingly, this occurred despite eNOS Ser-1177 phosphorylation and production of comparable amounts of NO. Our results demonstrate that the presence of eNOS in the cytosol is necessary for PAF-induced hyperpermeability. Our data provide new insights into the dynamics of eNOS and eNOS-derived NO in the process of inflammation.

Internalization of eNOS and NO delivery to subcellular targets determine agonist-induced hyperpermeability.

The molecular mechanisms of endothelial nitric oxide synthase (eNOS) regulation of microvascular permeability remain unresolved. Agonist-induced internalization may have a role in this process. We demonstrate here that internalization of eNOS is required to deliver NO to subcellular locations to increase endothelial monolayer permeability to macromolecules. Using dominant-negative mutants of dynamin-2 (dyn2K44A) and caveolin-1 (cav1Y14F), we show that anchoring eNOS-containing caveolae to plasma membrane inhibits hyperpermeability induced by platelet-activating factor (PAF), VEGF in ECV-CD8eNOSGFP (ECV-304 transfected cells) and postcapillary venular endothelial cells (CVEC). We also observed that anchoring caveolar eNOS to the plasma membrane uncouples eNOS phosphorylation at Ser-1177 from NO production. This dissociation occurred in a mutant- and cell-dependent way. PAF induced Ser-1177-eNOS phosphorylation in ECV-CD8eNOSGFP and CVEC transfected with dyn2K44A, but it dephosphorylated eNOS at Ser-1177 in CVEC transfected with cav1Y14F. Interestingly, dyn2K44A eliminated NO production, whereas cav1Y14F caused reduction in NO production in CVEC. NO production by cav1Y14F-transfected CVEC occurred in caveolae bound to the plasma membrane, and was ineffective in causing an increase in permeability. Our study demonstrates that eNOS internalization is required for agonist-induced hyperpermeability, and suggests that a mechanism by which eNOS is activated by phosphorylation at the plasma membrane and its endocytosis is required to deliver NO to subcellular targets to cause hyperpermeability.

Spinal Cord Ischemia in the Setting of Acute Type B Aortic Dissection: Successful Rescue with Thoracic Endovascular Aortic Repair.

We report 2 cases of successful thoracic endovascular aortic repair (TEVAR) for acute type B aortic dissection (ABAD) complicated with spinal cord ischemia (SCI). Case 1. A 70-year-old gentleman found with an uncomplicated ABAD with false lumen occluded, developed SCI shortly after admission during the initial medical management. Cerebrospinal fluid drainage (CSFD) was initiated followed by emergent TEVAR. SCI improved, and the patient was discharged. Case 2. A 52-year-old gentleman developed uncomplicated ABAD with patent false lumen. 5 hours after admission, he developed SCI during the initial medical management. Emergent TEVAR was performed followed by CSFD, and the SCI improved before discharge. These cases prompted us to address prompt TEVAR for primary entry closure and true lumen dilatation with postoperative hypertensive management to relieve the dynamic obstruction of the segmental arteries responsible for the compromised spinal cord circulation in complicated ABAD.