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Objectives: This study aimed to clarify the relationship between 43-kDa TAR DNA-binding protein (TDP-43) pathology and spinal cord anterior horn motor neuron (AHMN) atrophy in sporadic amyotrophic lateral sclerosis (SALS)., Methods: Eight patients with SALS and 12 controls were included in this study. Formalin-fixed specimens of lumbar spinal cord samples were paraffin-embedded and sectioned at the level of the fourth lumbar spinal cord with a 4 μm thickness. Using a microscope, the long diameters of the neurons with nucleoli were measured in spinal AHMNs stained with an anti-SMI-32 antibody. AHMNs were divided into medial and lateral nuclei for statistical analysis. We also used previously reported data to measure the long diameter of AHMNs with initial TDP-43 pathology, in which TDP-43 was present both in the nucleus and cytoplasm., Results: The long diameter of the lumbar spinal AHMNs in patients with SALS was smaller in the medial nucleus (42.54 ± 9.33 μm, n = 24) and the lateral nucleus (49.41 ± 13.86 μm, n = 129) than in controls (medial nucleus: 55.84 ± 13.49 μm, n = 85, p < 0.001; lateral nucleus: 62.39 ± 13.29 μm, n = 756, p < 0.001, Mann-Whitney U test). All 21 motor neurons with initial TDP-43 pathology were in the lateral nucleus, and their long diameter (67.60 ± 18.3 μm, p = 0.352) was not significantly different from that of controls., Conclusion: Motor neuron atrophy in SALS does not occur during the initial stages of TDP-43 pathology, and TDP-43 pathology is already advanced in the atrophied motor neurons., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bowen's disease (BD), also known as squamous cell carcinoma (SCC) in situ, is a precancerous skin condition that can potentially progress to invasive tumors. Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor typically found in sun-exposed areas of elderly Caucasians. The coexistence of BD and MCC is extremely rare, particularly when MCC is located in subcutaneous tissue rather than its typical epidermal or dermal layers. This case report presents an unusual instance of BD coexisting with subcutaneous MCC on the dorsum of the hand in an elderly Japanese male. An 87-year-old Japanese male with over 30 years of sun exposure presented with a progressively enlarging red tumor on the dorsum of his left hand. A biopsy confirmed BD, and the tumor was excised with a 5 mm margin followed by skin grafting. Histopathological examination revealed subcutaneous MCC along with BD, with MCC cells forming small nests in the dermal papillary layer. Immunohistochemistry showed positive staining for synaptophysin and CK20 in a perinuclear dot pattern, confirming the MCC diagnosis. Given the patient's advanced age and the absence of positive surgical margins, a watch-and-wait approach was adopted. The patient has been under close outpatient monitoring, and no recurrence has been observed after six months. This case highlights the rarity of subcutaneous MCC coexisting with BD, with only a few reported cases of such coexistence. The unusual subcutaneous presentation and the presence of multiple micro-nodules instead of large atypical cell clusters suggest an early-stage MCC beneath BD. The pathogenesis of this coexistence remains unclear but raises important questions regarding the relationship between sun exposure and viral factors like Merkel cell polyomavirus (MCPyV), which was not tested in this case. The findings underscore the need for comprehensive diagnostic evaluation when encountering complex or atypical skin lesions. This report emphasizes the rarity of subcutaneous MCC coexisting with BD and underscores the importance of comprehensive diagnostic assessment in unusual cases. Further research is warranted to better understand the underlying mechanisms and to guide optimal management strategies for such rare and challenging presentations., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ishihara et al.)

Patients with amyotrophic lateral sclerosis (ALS) do not develop oculomotor disturbances and vesicorectal dysfunction until end-stage disease owing to the survival of certain motor neurons (MNs), including oculomotor neurons and MNs within Onuf's nucleus. In sporadic ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated editing of GluA2 mRNA at the Q/R site is compromised in lower MNs. We previously developed genetically modified mice with a conditional knockout of ADAR2 in cholinergic neurons (ADAR2 flox/flox /VAChT-Cre, Fast; AR2). These mice displayed slow and progressive lower motor neuron death with TAR DNA-binding protein 43 (TDP-43) pathology, attributable to insufficient editing at the GluA2 Q/R site due to ADAR2 deficiency. MN death was more common in fast-fatigable MNs owing to differential vulnerability under conditions of ADAR2 deficiency. Although facial and hypoglossal nerves were impaired in AR2 mice, cell death did not occur within the oculomotor nerve nucleus, as observed in patients with sporadic ALS. Since the basis for avoiding cystorectal damage in ALS is unknown, we compared the features of Onuf's nucleus MNs in 12-month-old AR2 mice with those in age-matched wild-type mice. Although the number of MNs was not significantly lower in AR2 mice, the neurons exhibited a shrunken morphology and TDP-43 pathology. Onuf's nucleus MNs could survive in an ADAR2-deficient state and mainly included fast fatigue-resistant (FR) and slow (S) MNs. In summary, FR and S MNs show increased resilience to ADAR2 deficiency, potentially participating in an important neuronal death avoidance mechanism in ALS., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Myxomas, when they manifest in the paranasal sinuses and/or maxillae of infants, are classified as sinonasal myxomas (SNMs). We present a case of SNM in the maxilla of a 15-month-old infant. Following the initial surgical intervention, the patient unfortunately experienced a recurrence of the condition. However, a subsequent surgery employing marginal excision was performed, and since then, no further recurrence has been reported. SNM exhibits consistent clinical features and histological characteristics that are distinct from those of odontogenic myxomas. Furthermore, in this case, immunohistochemical staining was positive for β-catenin, whereas odontogenic myxomas are generally negative for β-catenin staining. Another study reported that SNMs share genetic mutations with desmoid tumors, which are not observed in odontogenic myxomas. This suggests that this entity is distinct from odontogenic myxomas, leading us to propose that it may indeed represent a separate disease entity. This fact may lead to the reclassification of the disease and, ultimately, to changes in treatment strategies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kashiwagi et al.)

Wheelchair cushions are recommended to be used with wheelchair and can protect the buttocks from pain and injury by relieving interface pressure for wheelchair users. However, further investigations are required for proper use in response to the development of new types of wheelchair cushions. The objective of this study was to evaluate physical characteristics of wheelchair cushions by comparing pressure redistributing effects of four types of cushions. The participants were 16 healthy adults who consented to participate in this study. A pressure mapping system (CONFORMat, Nitta Corp.) was used for the measurements. Pressure at ischium was measured immediately after the stabilization of the sitting posture and 10 minutes after. The pressure at ischium significantly decreased with any wheelchair cushions (P < 0.01). A significant negative correlation between body mass index and pressure at ischium was observed without a wheelchair cushion (r = - 0.70), however, the correlation disappeared upon use of a wheelchair cushion. The pressure at ischium increased over time with cushions of urethane, air, and urethane-air hybrid while that with the 3D thermoplastic elastomer cushion did not, and the change in the pressure was statistically less than that in other cushions (P < 0.01). Use of wheelchair cushions was effective in redistribution of the pressure at ischium, and the overtime change in the pressure depends on the type of used cushions.

Objective: It is generally believed that the decremental response in repetitive nerve stimulation (RNS) stabilizes at the fourth or fifth response. We have a preliminary impression that the decremental response approaches a plateau earlier in proximal muscles than in distal muscles. We investigated the speed of the completion of the decremental response in different muscles., Methods: The "decrement completion ratio (DCR)" in the second or third response (DCR2 or DCR3) was defined as the ratio of the decremental percentage of the second or third response to that of the fourth response. Patients showing more than 10% decremental response both in the abductor pollicis (APB) and deltoid muscles were retrospectively extracted from our EMG database. The DCR2 and DCR3 were compared between two muscles in patients with myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS)., Results: Identified subjects consisted of 11patients with MG and 11 patients with ALS. Multiple regression analysis revealed that only the difference of muscle influenced on DCR2 and DCR3, with no contribution from the different disorder (MG or ALS) or the initial amplitude of the compound muscle action potential (CMAP). Both DCR2 and DCR3 were significantly higher in deltoid than in APB. In ALS, the normalized CMAP amplitude was not different between APB and deltoid whereas the decremental percentage was significantly higher in deltoid, suggesting a lower safety factor of the neuromuscular transmission in proximal muscles., Conclusions: The decremental response completed more rapidly in deltoid than in APB which may be related to the lower safety factor also documented by this study., Significance: Unexpected early completion of the decrement such as at the second response in RNS is not a technical error but may be an extreme of the rapid completion in deltoid, a proximal muscle., (© 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Objective: The relationship between the healing time of pressure ulcers (PUs) and wound cleaning frequency among older people in homecare settings was investigated., Method: This single-centre, prospective cohort study was conducted from April 2018 to March 2019. Patients who used home-visit nursing services, had National Pressure Ulcer Advisory Panel classification stage 2 PUs, and had their wounds cleaned at least twice a week were enrolled in the study. Wound cleaning was performed using tap water and a weakly acidic cleanser. Participants were divided into two groups, determined by the frequency of wound cleaning (twice weekly versus ≥3 times weekly). Duration of PU healing and the increase in care insurance premiums were compared in both groups., Results: A total of 12 patients were included in the study. The mean healing period of PUs cleaned ≥3 times per week (65.3±24.8 days) was significantly shorter than that of PUs cleaned twice a week (102.6±19.2 days; p<0.05). Furthermore, the increase in care insurance premiums for PUs cleaned ≥3 times per week (¥122,497±105,660 Yen per six months) was significantly lower than that for PUs cleaned twice a week (¥238,116±60,428 per six months) (p<0.05)., Conclusion: Our results suggest that frequent cleaning of PUs by health professionals in homecare settings not only shorten PU healing period but also reduces care insurance premiums for PU care.

This report highlights two cases of surgical site infections (SSIs) caused by Mycobacterium fortuitum (Mf) following abdominal mesh implantation. The first case involved an 83-year-old male experiencing non-healing erythema and wounds post-operation, which persisted despite multiple treatments, until effective management was achieved with targeted antibiotics after Mf identification. The second case concerned a female patient with a gynecological postoperative hernia, where Mf was quickly detected following SSI onset three weeks after surgery. Prompt mesh removal and appropriate antibiotic treatment led to a rapid and full recovery. These cases emphasize the importance of early detection and intervention in managing Mf infections effectively, illustrating how the timing of diagnosis can significantly influence treatment outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tsuchiya et al.)

A 31-year-old man with neurofibromatosis type 1 (NF-1) had undergone resection of a malignant peripheral nerve sheath tumor (MPNST) on the buttock 3 months previously. He subsequently underwent mechanical thrombectomy for a hyperacute left middle cerebral artery embolism. Histopathologically, the emboli comprised neurofilament-positive pleomorphic tumor cells with geographic necrosis and conspicuous mitosis and were identified as MPNST. The patient died of respiratory failure due to lung MPNST metastasis on day 15 of hospitalization. To our knowledge, this is the first report of a spontaneous cerebral embolism due to MPNST in a NF-1 patient.

Introduction: A higher levodopa dose is a risk factor for motor complications in Parkinson's disease (PD). Istradefylline (IST) is used as adjunctive treatment to levodopa in PD patients with off episodes, but its impact on levodopa dose titration remains unclear. The objective of this study was to investigate the effect of IST on levodopa dose escalation in PD patients with wearing-off., Methods: This was a multicenter, open-label, randomized, parallel-group controlled study (ISTRA ADJUST PD) in which PD patients experiencing wearing-off (n = 114) who were receiving levodopa 300-400 mg/day were randomized to receive IST or no IST (control). Levodopa dose was escalated according to clinical severity. The primary endpoint was cumulative additional levodopa dose, and secondary endpoints were changes in symptom rating scales, motor activity determined by a wearable device, and safety outcomes., Results: The cumulative additional levodopa dose throughout 37 weeks and dose increase over 36 weeks were significantly lower in the IST group than in the control group (both p < 0.0001). The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I and device-evaluated motor activities improved significantly from baseline to 36 weeks in the IST group only (all p < 0.05). Other secondary endpoints were comparable between the groups. Adverse drug reactions (ADRs) occurred in 28.8% and 13.2% of patients in the IST and control groups, respectively, with no serious ADRs in either group., Conclusion: IST treatment reduced levodopa dose escalation in PD patients, resulting in less cumulative levodopa use. Adjunctive IST may improve motor function more objectively than increased levodopa dose in patients with PD., Trial Registration: Japan Registry of Clinical Trials: jRCTs031180248., (© 2024. The Author(s).)

It is unclear whether normal human skin tissue or abnormal scarring are photoreceptive. Therefore, this study investigated photosensitivity in normal skin tissue and hypertrophic scars. The expression of opsins, which are photoreceptor proteins, in normal dermal fibroblasts (NDFs) and hypertrophic scar fibroblasts (HSFs) was examined. After exposure to blue light (BL), changes in the expression levels of αSMA and clock-related genes, specifically PER2 and BMAL1 , were examined in both fibroblast types. Opsins were expressed in both fibroblast types, with OPN3 exhibiting the highest expression levels. After peripheral circadian rhythm disruption, BL induced rhythm formation in NDFs. In contrast, although HSFs showed changes in clock-related gene expression levels, no distinct rhythm formation was observed. The expression level of αSMA was significantly higher in HSFs and decreased to the same level as that in NDFs upon BL exposure. When OPN3 knocked-down HSFs were exposed to BL, the reduction in αSMA expression was inhibited. This study showed that BL exposure directly triggers peripheral circadian synchronization in NDFs but not in HSFs. OPN3-mediated BL exposure inhibited HSFs. Although the current results did not elucidate the relationship between peripheral circadian rhythms and hypertrophic scars, they show that BL can be applied for the prevention and treatment of hypertrophic scars and keloids.

Chronic limb-threatening ischemia (CLTI) is associated with a short-term risk of limb loss. Multidisciplinary teams are often involved in CLTI treatment; however, in Asian countries, multidisciplinary teams that include podiatrists specializing in foot wounds and vascular surgeons who can perform distal bypass surgery are lacking. We investigated predictive factors for limb salvage and foot ulcer recurrence in patients with CLTI treated by a Japanese single-center intensive multidisciplinary team over 6 years. We retrospectively investigated 84 patients with CLTI and foot ulcers who had undergone revascularization and wound treatment between October 2013 and December 2019. Following postrevascularization treatment, including undertaking minor amputations, the healing rate was 77.8%, and the average wound healing time was 75 ± 68 days. To achieve adequate blood supply, 17.7% of patients were treated using a combination of endovascular revascularization and bypass surgeries. Thirty-three (44%) patients had wound recurrence and there was wound recurrence within 6 months in 58.9% of these patients. Multivariate logistic regression analysis showed that postrevascularization skin perfusion pressure was significantly associated with wound healing (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.033-1.243, P  = .0078). Diabetes mellitus (OR 9.72, 95% CI 1.855-50.937, P  = .0071), and heart disease (OR 3.51, 95% CI 1.052-11.693, P  = .0411) were significantly associated with wound recurrence ( P  < .05). Treatment within a single-center intensive multidisciplinary team resulted in good patient outcomes. Our study indicates that the revascularization endpoint of CLTI treatment should be marked by attainment of adequate blood supply and wound healing. The timing of revascularization and debridement is of utmost importance for the successful treatment of CLTI wounds., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Venous malformations (VMs) are histopathologically benign but can greatly impair patients' quality of life. Screlothprapy is known to be effective in improving symptoms without a scar, but surgical resection of residual lesions is sometimes necessary due to inadequate reduction. However, there is no consensus on what criteria should be used to consider switching to surgical treatment, and individualized decisions must be made for each case. To investigate the factors that contribute to the lack of efficacy of sclerotherapy in reducing lesions and how to predict this, the authors performed a retrospective clinical imaging and histopathological study of 6 cases of labial vein malformations treated with sclerotherapy and 3 cases without sclerotherapy. Clinical image investigations are based on magnetic resonance imaging before and after sclerotherapy. The authors found a significant decrease in the percentage of cystic components in the total lesion of VMs after sclerotherapy. Histopathological investigations are based on resected VMs with or without sclerotherapy. Elastica van Gieson stains suggested a significant increase in fibrotic tissue inside VMs treated with sclerotherapy compared with those without. In conclusion, magnetic resonance imaging signal changes inside the VMs after sclerotherapy was observed, and it may reflect fibrosis of the tissue. These changes in the VMs after sclerotherapy may reduce the effect of sclerotherapy on tissue reduction should be considered., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

We report the case of a 40-year-old woman, with endometriosis, who presented with a history of foot drop and cyclic sensory disturbance of the right lower limb. She was initially diagnosed with lumbar disc herniation. Neurological examination revealed muscle weakness and sensory disturbance associated with the right sciatic nerve. Nerve conduction studies revealed a low amplitude sensory nerve action potential in the right superficial fibular and sural nerves. Pelvic magnetic resonance imaging revealed an endometriotic cyst in the right ovary, and an endometriotic lesion extending from the right ovary, pelvis, and the right sciatic nerve. Though her symptoms moderately improved with hormonal therapy, the foot drop remained. Our case and previous reports suggest that endometriosis with sciatic neuropathy shows cyclic neurological symptoms during menstruation, with a higher incidence on the right extremity. This case highlights that endometriosis should be considered as a potential differential diagnosis in women of reproductive age with sciatic nerve dysfunction. Its cyclic neurological manifestations should be investigated.

High plantar pressure is a risk factor for diabetic foot ulcers, and it is known that restriction of ankle dorsiflexion range of motion (ROM) causes high plantar pressure. Stretching is a non-invasive and general means to improve ROM; however, the effect of stretching on the ROM and plantar pressure has not been clarified in patients with diabetes mellitus. We aimed to study the effects of intermittent weight-bearing stretching on ankle dorsiflexion ROM and plantar pressure during gait in patients with diabetes mellitus. Seven patients with diabetes mellitus participated, and their triceps surae was stretched using weight-bearing stretching with a stretch board. Five minutes of stretching was performed 4 times with a rest interval of 30 s. Ankle dorsiflexion ROM was measured with the knee flexed and extended. Peak pressure and pressure-time integral during gait were measured and calculated for the rearfoot, midfoot, forefoot, and total plantar surface before and after stretching. Ankle dorsiflexion ROM with the knee extended or bent increased significantly after stretching ( P <  .05). Peak pressure and the pressure-time integral decreased significantly, especially in the forefoot ( P <  .01), and these also decreased significantly in the total plantar surface ( P <  .05). The duration of foot-flat decreased after stretching ( P <  .05). Weight-bearing stretching improved ankle dorsiflexion ROM and reduced plantar pressure during gait. These results suggest that weight-bearing calf stretching may be an effective means to prevent and treat diabetic foot ulcers.

This secondary analysis study aimed to detect individual variables that influence the efficacy of monophasic pulsed microcurrent on pressure injury healing. Eleven patients with pressure injuries showing delayed healing underwent a microcurrent stimulation period and a placebo period. We analyzed the correlation between the individual variables and the following three outcomes using monophasic pulsed microcurrent: the wound reduction rate in the electrical stimulation period, the reduction rate in the placebo period, and the difference between these two reduction rates. Furthermore, the patients were divided into two groups, one with a wound reduction rate of more than 10% and the other with less than 10%, and the relationship between each variable was compared. As a result, the wound reduction rate in the electrical stimulation period and the difference in the reduction rate between the two periods showed significant positive correlations with patients' body mass index. In addition, a significant difference was observed in the body mass index between subjects with a reduction rate of 10% or higher and those with a reduction rate of less than 10%. This study found a correlation between the effect of monophasic pulsed microcurrent for pressure injury healing and the level of patients' body mass index.

Rehabilitation is usually provided to patients with chronic foot wounds (CFWs) after surgery. This study aimed to assess whether early postoperative rehabilitation could maintain walking independence in hospitalized patients with CFWs. This single-blind, randomized clinical trial was performed between September 10, 2018 and March 2019, involving 60 patients who underwent both surgical procedures and rehabilitation. Participants were randomly allocated into the early rehabilitation (EG, n = 30) or the control (CG, n = 30) groups. EG received early rehabilitation immediately after surgery, while CG received late rehabilitation after wound closure. Both groups received rehabilitation sessions 5 times per week until discharge. The primary outcome was walking independence, measured via Functional Independence Measure (FIM)-gait scores. Secondary outcomes included health-related quality of life (HRQoL) using EuroQol 5 dimensions 5-level (EQ-5D-5L) and the presence of rehabilitation-related adverse events, including dehiscence of wounds and falls. Differences in intervention timing effects were analyzed using nonparametric split-plot factorial design analysis, including Fisher's exact test, Mann-Whitney U test, and Wilcoxon signed-rank test ( P  < .05). Out of the 60 participants, 53 patients completed the discharge follow up. Three participants (10.0%) from the EG and 4 (13.3%) from the CG dropped out due to postoperative complications unrelated to rehabilitation intervention. No rehabilitation-related adverse events were found. Participants in the EG maintained greater FIM-gait scores during hospitalization than the CG (difference, -1; P  = .0001), with a difference of 0 ( P  = .109) at discharge. EQ-5D-5L significantly improved in both groups (EG: difference, 0.13 [ P  = .014], CG: difference, 0.17 [ P  = .0074]). The EG intervention was associated more with maintaining walking independence at discharge than CG intervention. Postoperative rehabilitation improved HRQoL without adverse events, indicating that clinicians should recommend early rehabilitation for patients with CFW to enhance walking independence.

This study aimed to elucidate the vasodilatory effects and cytotoxicity of various vasodilators used as antispasmodic agents during microsurgical anastomosis. Rat smooth muscle cells (RSMCs) and human coronary artery endothelial cells (HCAECs) were used to investigate the physiological concentrations and cytotoxicity of various vasodilators (lidocaine, papaverine, nitroglycerin, phentolamine, and orciprenaline). Using a wire myograph system, we determined the vasodilatory effects of each drug in rat abdominal aortic sections at the concentration resulting in maximal vasodilation as well as at the surrounding concentrations 10 min after administration. Maximal vasodilation effect 10 min after administration was achieved at the following concentrations: lidocaine, 35 mM; papaverine, 0.18 mM; nitroglycerin, 0.022 mM; phentolamine, 0.11 mM; olprinone, 0.004 mM. The IC 50 for lidocaine, papaverine, and nitroglycerin was measured in rat abdominal aortic sections, as well as in RSMCs after 30 min and in HCAECs after 10 min. Phentolamine and olprinone showed no cytotoxicity towards RSMCs or HCAECs. The concentrations of the various drugs required to achieve vasodilation were lower than the reported clinical concentrations. Lidocaine, papaverine, and nitroglycerin showed cytotoxicity, even at lower concentrations than those reported clinically. Phentolamine and olprinone show antispasmodic effects without cytotoxicity, making them useful candidates for local administration as antispasmodics.

Background and Purpose: To clarify the effect of perampanel (PER) on sporadic amyotrophic lateral sclerosis (sALS) progression, the relationship between the changes in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores and serum PER concentrations was investigated., Methods: 12 patients with sALS from our hospital who agreed to participate and completed the PER for sALS randomized phase 2 study were included. After completing the study, we retrospectively obtained serum PER concentration data from the patients. Based on their mean PER concentrations, we divided the patients who had been taking PER into two groups: four patients with a mean PER concentration of ≥400 ng/mL were assigned to the H group, and three with a mean PER concentration of <400 ng/mL were assigned to the L group. The control group consisted of five patients who had been taking a placebo. We obtained the ALSFRS-R scores of each patient at 36 and 48 weeks after randomization. The differences in ALSFRS-R scores at baseline (0 weeks) and each subsequent week were used in the analysis., Results: At 48 weeks, there were no differences in the degree of deterioration of the bulbar, upper and lower limb, and respiratory ALSFRS-R subscores and total ALSFRS-R score. However, at 36 weeks, the bulbar subscore was significantly lower in the H group than in the control group ( p =0.032)., Conclusions: Because high PER concentrations may exacerbate bulbar symptoms in patients with sALS, serum PER measurements may be beneficial when patients with sALS are taking PER., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

Background: Dropped head syndrome (DHS) is a rare specific abnormal posture known to develop in Parkinson's disease (PD). This case series study aimed to characterize DHS by analyzing the characteristics of sagittal spinopelvic alignment in patients with PD/DHS., Methods: The study included eight patients with PD/DHS (men = 3, women = 5; mean age, 68.1 ± 6.4 years). Sagittal spinopelvic alignment was evaluated using 10 parameters on whole-spine lateral radiographs., Results: The time from the onset of PD to that of DHS varied among the patients from 0 to 15.3 years. In three patients, DHS appeared before the diagnosis of PD. The severity of motor symptoms at DHS onset varied from modified Hoehn and Yahr stage 1 to 4 among the patients. Although the spinopelvic parameters differed among PD/DHS individuals, all patients exhibited cervical kyphosis (cervical lordosis < 0˚). In patients with a larger T1 slope and greater thoracic kyphosis, anterocollis tended to be more severe. According to the assessment of the sagittal vertical axis (SVA), half of the patients showed a positive SVA (SVA ≥ 0 mm), whereas the other half showed a negative SVA (SVA < 0 mm)., Conclusion: DHS appeared regardless of the duration or severity of PD. Although all patients with PD/DHS exhibited cervical kyphosis, the C7 plumb line was shifted anteriorly in half of the patients and posteriorly in the other half., (© 2023. The Author(s).)

For a long time, ex vivo-expanded peripheral-blood-derived γδT cell (PBγδT)-based immunotherapy has been attractive, and clinical trials have been undertaken. However, the difficulty in expanding cytotoxic γδT cells to an adequate number has been a major limitation to the efficacy of treatment in most cases. We successfully re-generated γδT cells from γδT cell-derived human induced pluripotent stem cells (iPSCs). The iPSC-derived γδT cells (iγδTs) killed several cancer types in a major histocompatibility complex (MHC)-unrestricted manner. Single-cell RNA sequencing (scRNA-seq) revealed that the iγδTs were identical to a minor subset of PBγδTs. Compared with a major subset of PBγδTs, the iγδTs showed a distinctive gene expression pattern: lower CD2, CD5, and antigen-presenting genes; higher CD7, KIT, and natural killer (NK) cell markers. The iγδTs expressed granzyme B and perforin but not interferon gamma (IFNγ). Our data provide a new source for γδT cell-based immunotherapy without quantitative limitation., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Artificial intelligence (AI) in medical care can raise diagnosis accuracy and improve its uniformity. This study developed a diagnostic imaging system for chronic wounds that can be used in medically underpopulated areas. The image identification algorithm searches for patterns and makes decisions based on information obtained from pixels rather than images. Images of 50 patients with pressure sores treated at Kobe University Hospital were examined. The algorithm determined the presence of necrosis with a significant difference ( p = 3.39 × 10 -5 ). A threshold value was created with a luminance difference of 50 for the group with necrosis of 5% or more black pixels. In the no-necrosis group with less than 5% black pixels, the threshold value was created with a brightness difference of 100. The "shallow wounds" were distributed below 100, whereas the "deep wounds" were distributed above 100. When the algorithm was applied to 24 images of 23 new cases, there was 100% agreement between the specialist and the algorithm regarding the presence of necrotic tissue and wound depth evaluation. The algorithm identifies the necrotic tissue and wound depth without requiring a large amount of data, making it suitable for application to future AI diagnosis systems for chronic wounds.

Partial foot amputation (PFA) is generally planned to minimize the amputation level; nonetheless, the effect of PFA levels on gait independence in amputees remains unclear. This study aimed to investigate the impact of PFA levels of the forefoot on gait independence in patients with chronic lower extremity (LE) wounds. This multicenter retrospective cohort study included 232 hospitalized Japanese patients treated and rehabilitated for chronic LE wounds. A multivariate analysis based on PFA levels was conducted for gait independence at discharge, with age and comorbidities as independent variables. Patients with Lisfranc amputation had significantly less independent gait than patients with more distal amputation and those without amputation (<22% vs >40%; P  = .027; Fisher's exact test). Logistic regression analysis revealed that Lisfranc amputation (odds ratio [OR]: 0.257, P  = .047), age (OR: 0.559, P  = .043), and chronic limb-threatening ischemia (OR: 0.450, P  = .010) were independent factors associated with gait independence. Additionally, the regression model confirmed discrimination performance using the C index (0.691, P  < .001) with receiver operating characteristic analysis. In patients with chronic LE wounds undergoing PFA, Lisfranc amputation was negatively associated with gait independence.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective degeneration of motor neurons (MNs). In the MNs of patients with ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated RNA editing of GluA2 mRNA at the Q/R site is profoundly deficient. In genetically modified mice (ADAR2 flox/flox /VAChT-Cre.Fast; AR2), the selective knockout of ADAR2 in cholinergic neurons induced progressive loss of lower MNs. MNs exhibiting an age-related increase in abnormal TDP-43 localization and reduced ADAR2 immunoreactivity are localized in the lateral areas of the anterior horns (AHs) in aged wild-type mice. However, the patterns in the AHs of AR2 mice remain unknown. In this study, we investigated whether similar degeneration is observed in AR2 mice. We compared the number of astrocytes and MNs in the lateral and medial AHs of the lumbar spinal cord of 12-month-old AR2 mice with age-matched wild-type mice. The number of MNs significantly decreased in both the lateral and medial areas in AR2 mice AHs, particularly in the former. The number of reactive astrocytes increased significantly in the lateral areas of the AHs of AR2 mice. In conclusion, stronger activation of astrocytes with reduction of MNs in the ADAR2 deficiency-related lateral area increases in AR2 mice AHs. Fast fatigable MNs are expected to be present in the lateral area of the AHs. We found that MN death is more common in the lateral area of AHs associated with FF MNs due to differences in vulnerability to MN under ADAR2 deficiency., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Abdominal incisional hernia is a complication of the rectus abdominis myocutaneous (RAMC) flap harvest. This study aimed to compare the incidence of abdominal incisional hernia and donor-site closure time between absorbable barbed continuous (ABC) and non-absorbable non-barbed interrupted (nAnBI) methods., Methods: This study included 145 patients who underwent free RAMC flap reconstruction after head and neck cancer surgery at Kobe University Hospital between January 2012 and March 2020. The nAnBI method was selected between January 2012 and August 2016, and the ABC method was selected between September 2016 and March 2020. The incidence of abdominal incisional hernia and the average time required for donor-site closure were compared between the two groups., Results: Of the 145 patients surveyed, 116 (57 and 59 in the nAnBI and ABC groups, respectively) were followed-up for at least 90 days after the surgery. The incidence rates of abdominal incisional hernia were 0% and 5.1% (n = 3) in the nAnBI and ABC groups, respectively, with no significant differences ( p = 0.244). The average donor-site closure times were 127.6 and 111.3 minutes in the nAnBI and ABC groups, respectively, with no significant differences ( p = 0.122)., Conclusions: No significant differences in the incidence of abdominal incisional hernia and donor-site closure time were observed between the nAnBI and ABC groups. However, there was a tendency for increased hernia occurrence and shorter wound closure time in the ABC group. A randomized prospective multicenter study is warranted to validate our findings of the ABC method., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

High plantar flexor moment and limited ankle mobility are known to cause high plantar pressure under the forefoot. Stretching is an effective physical therapy for the limited ankle range of motion (ROM), and electrical stimulation is used to regulate the activity of antagonistic muscle via the action of reciprocal inhibition. Additionally, stretching paired with electrical stimulation has been reported to improve the limited ROM significantly. This study aims to investigate the influences of stretching on triceps surae (STR), electrical stimulation to tibialis anterior (ES), and the combination (ES+STR) on the ROM, kinematic parameters, and plantar pressure distribution during gait in patients with diabetes mellitus. Planter pressure and other parameters were measured before and after the intervention of ES, STR, ES+STR, or the rest sitting on the bed (CON) for 10 min. Pressure time integral under the medial forefoot decreased in the ES+STR compared to CON ( P < .05). Interestingly, ES+STR increased passive and dynamic ROM on ankle dorsiflexion during gait and increased the lateral center of pressure excursion ( P < .05). Furthermore, these changes were followed by decreased contact duration under the medial forefoot ( P < .05). The combined therapy improves ankle mobility during gait and reduces the contact duration and the plantar pressure under the medial forefoot in patients with diabetes mellitus.

Introduction: Post-sternotomy surgical site infection (SSI) is a serious complication of cardiovascular surgery. Here, we proposed a new clinical classification and reconstructive strategy for this condition., Methods: A retrospective study based on medical records was performed on 100 consecutive cases requiring wound management by plastic surgeons for post-sternotomy SSI at Kobe University Hospital between January 2009 and December 2021. We classified 100 cases into four categories according to the anatomical invasiveness of the infection (type 1, superficial SSI; type 2, sternal osteomyelitis; type 3, mediastinitis; and type 4, aortic graft infection). The standard treatment plan comprised initial debridement, negative pressure wound therapy with continuous irrigation, and reconstructive surgery. Reconstructive methods and their outcomes (in-hospital mortality rate, follow-up period, and infection recurrence rate) were investigated for each SSI category., Results: There were nine SSI cases in type 1, 28 in type 2, 25 in type 3, and 38 in type 4. The pectoralis major (PM) muscle advancement flap was mainly selected in types 1 and 2 (100 and 70.4%, respectively), while the omental flap or latissimus dorsi (LD) myocutaneous flaps were mainly selected in types 3 and 4 (77.3 and 81.8%, respectively) for reconstructive surgery. The in-hospital mortality rates for types 1, 2, 3, 4 were 44.4, 3.6, 12.0, and 15.8%, respectively. The mean follow-up periods for types 1, 2, 3, 4 were 542.8, 1514.5, 1154.5, and 831.1 days, respectively. Infection recurrence rates for types 1, 2, 3, 4 were 0, 11.5, 13.3, and 19.2%, respectively. All of these recurrent cases, except for 4 cases of type 4 that required surgical intervention, were treated with conservative wound management., Conclusion: A volume-rich flap (omental or LD flap) was required to fill the dead space after debridement in mediastinitis (type 3) or aortic graft infection (type 4), whereas superficial SSI (type 1) or sternal osteomyelitis (type 2) received a less-invasive flap (PM muscle advancement flap). Our new classification method was based on the anatomical invasiveness of the infection, providing both a simple and easy diagnosis and definitive treatment strategy., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

In general, it is common knowledge that people's feelings are reflected in their voice and facial expressions. This research work focuses on developing techniques for diagnosing depression based on acoustic properties of the voice. In this study, we developed a composite index of vocal acoustic properties that can be used for depression detection. Voice recordings were collected from patients undergoing outpatient treatment for major depressive disorder at a hospital or clinic following a physician's diagnosis. Numerous features were extracted from the collected audio data using openSMILE software. Furthermore, qualitatively similar features were combined using principal component analysis. The resulting components were incorporated as parameters in a logistic regression based classifier, which achieved a diagnostic accuracy of ~90% on the training set and ~80% on the test set. Lastly, the proposed metric could serve as a new measure for evaluation of major depressive disorder.

Background: Freezing of gait (FOG) is an important symptom that can impair activities of daily living in patients with Parkinson's disease (PD). However, its pathogenic mechanism is largely unknown. The aim of the present study was to elucidate the clinical characteristics of newly diagnosed and levodopa-naïve patients with PD who present with FOG., Methods: A total of 53 patients with untreated PD (29 men and 24 women) within 2 years of disease onset were included in the study. Using item 3 of the Freezing of Gait Questionnaire (FOG-Q), patients were classified as "freezers" and "nonfreezers" and compared for cognitive function, depressive symptoms, apathy, olfactory function, motor severity, gait parameters, and daily physical activity. We also assessed the relationship between FOG severity (total score of items 3-6 on the FOG-Q) and various clinical parameters., Results: The FOG was reported by 8 (15%) patients with PD. The Apathy Scale score ( p =0.018), Modified Hoehn and Yahr stage ( p < 0.001), Unified Parkinson's Disease Rating Scale part III score ( p < 0.001), and postural instability and gait disorder score ( p < 0.001) were significantly higher, and the mean gait acceleration amplitude ( p =0.006) was significantly lower in freezers compared to that in nonfreezers. However, there was no significant correlation between FOG severity and these clinical parameters. There was also no significant difference in cognitive function, depressive symptoms, and olfactory function between the two groups. Daily physical activity was significantly lower in freezers than that in nonfreezers., Conclusions: Since FOG develops soon after PD onset, the study findings suggest that the FOG might be associated with the severity of apathy, motor symptoms, and in particular, gait disturbance., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Hiroo Terashi et al.)

Aim: Maintaining functional status through revascularization is a major goal in patients with chronic limb-threatening ischemia (CLTI). Nevertheless, there is a lack of clarity on the impact of revascularization on mobility over time. This study examined ambulatory status over time after revascularization and predictors of ambulation loss in CLTI patients., Methods: We used a clinical database established by the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia study, a prospective, multicentre, observational study including patients with CLTI. The primary endpoint was mobility over time., Results: Of the 381 patients, the ambulatory proportion at baseline was 71%. The proportion gradually decreased, finally reaching 40% at 36 months. In non-ambulatory patients at revasacularisation, approximately 20-40% of patients achieved ambulation. Multivariate analysis confirmed that age, impaired mobility before CLTI onset and at revascularization, renal failure on dialysis, and WIfI clinical stage 4 were positively associated with ambulation loss at either specific or all time points, whereas male sex and surgical reconstruction were inversely associated with the outcomes at specific time points., Conclusion: Mobility in the overall population gradually decreased, whereas the number of deceased patients increased. Advanced age, impaired mobility before CLTI onset and at revascularization, renal failure on dialysis, and WIfI stage 4 were associated with ambulation loss at almost all points after revascularization.

Abstract: This study aimed to analyze the Hess area ratio (HAR%) in cases of blowout fracture treated in our department and clarify the outline of eye movement disorders in blowout fractures. Patients who underwent surgery for orbital blowout fractures in our department were included. Fracture locations were classified into 5 types (A, outside floor; B, C, anterior and posterior floor; and D, E, anterior and posterior medial wall). The HAR% was compared before and after surgery in eligible cases. The relationship between the fracture location and preoperative HAR% was investigated using multiple regression analysis. The study involved 85 patients. Hess area ratio was higher postoperatively than preoperatively (70.75 ± 18.26 versus 90.06 ± 13.99, P  < 0.01). The postoperative HAR% tended to be higher when the iliac bones were compared to other materials; however, this difference was not significant (90.73 ± 12.91 versus 80.30 ± 17.81, P = 0.178). Fracture locations C and E significantly contributed to the prediction of HAR% as negative regression coefficients (P = 0.024 and 0.013, respectively). The posterior fracture area on both the orbital floor and medial wall contributed to the decrease in preoperative HAR%. This observation indicates that the reconstruction of the posterior region is extremely crucial., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Objectives: Tuning fork vibration sensation testing is widely used as a diagnostic test to detect diabetic neuropathy. However, evidence-based literature indicates that reliability between examiners is low. Attaching isosceles triangle diagrams on tuning forks lowers the discrepancy between examiners. This study aimed to analyze the relationship between vibration sensation measurement using an improved tuning fork and the presence of callus and wound development in patients with diabetic peripheral neuropathy., Methods: Participants included 56 general older adults and 52 patients with diabetic peripheral neuropathy. The methods included confirmation of the presence or absence of callus, range of motion of the ankle and the first metatarsophalangeal joint, vibratory sensitivity of the medial malleolus and the dorsal aspect of the first distal phalanx using an improved tuning fork, and touch-pressure sensitivity of the plantar aspect of the hallux. Patients with diabetic peripheral neuropathy were followed up for 3 years to check for the presence or absence of wounds., Results: When compared with the general older adults, the patients with diabetic peripheral neuropathy had significantly lower touch-pressure sensitivity ( p  < 0.01), vibratory sensitivity at the distal phalanx ( p  < 0.01) and medial malleolus ( p  < 0.01), ankle dorsiflexion range of motion ( p  < 0.01), and metatarsophalangeal joint extension range of motion ( p  < 0.01). The area under the receiver operating characteristic curve with callus formation was 0.93 for the medial malleolus and 0.96 for the distal phalanx, indicating that the accuracy of the distal phalanx was higher ( p  < 0.01) than the medial malleolus. According to the Cox proportional hazard analysis, the vibratory sensitivity of the distal phalanx was a significant risk factor for ulcer development ( p  < 0.05)., Conclusion: These findings suggest that the vibration sensation test, which we improved via the technique described in this study, is useful for predicting the occurrence of callus and ulcer., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Levodopa remains the most effective symptomatic treatment for Parkinson's disease (PD) more than 50 years after its clinical introduction. However, the onset of motor complications can limit pharmacological intervention with levodopa, which can be a challenge when treating PD patients. Clinical data suggest using the lowest possible levodopa dose to balance the risk/benefit. Istradefylline, an adenosine A 2A receptor antagonist indicated as an adjunctive treatment to levodopa-containing preparations in PD patients experiencing wearing off, is currently available in Japan and the US. Preclinical and preliminary clinical data suggested that adjunctive istradefylline may provide sustained antiparkinsonian benefits without a levodopa dose increase; however, available data on the impact of istradefylline on levodopa dose titration are limited. The ISTRA ADJUST PD study will evaluate the effect of adjunctive istradefylline on levodopa dosage titration in PD patients., Methods: This 37-week, multicenter, randomized, open-label, parallel-group controlled study in PD patients aged 30-84 years who are experiencing the wearing-off phenomenon despite receiving levodopa-containing medications ≥ 3 times daily (daily dose 300-400 mg) began in February 2019 and will continue until February 2022. Enrollment is planned to attain 100 evaluable patients for the efficacy analyses. Patients will receive adjunctive istradefylline (20 mg/day, increasing to 40 mg/day) or the control in a 1:1 ratio, stratified by age, levodopa equivalent dose, and presence/absence of dyskinesia. During the study, the levodopa dose will be increased according to symptom severity. The primary study endpoint is the comparison of the cumulative additional dose of levodopa-containing medications during the treatment period between the adjunctive istradefylline and control groups. Secondary endpoints include changes in efficacy rating scales and safety outcomes., Discussion: This study aims to clarify whether adjunctive istradefylline can reduce the cumulative additional dose of levodopa-containing medications in PD patients experiencing the wearing-off phenomenon, and lower the risk of levodopa-associated complications. It is anticipated that data from ISTRA ADJUST PD will help inform future clinical decision-making for patients with PD in the real-world setting., Trial Registration: Japan Registry of Clinical Trials, jRCTs031180248 ; registered 12 March 2019., (© 2022. The Author(s).)

Background: There are cases of heel pressure ulcer with peripheral arterial disease (PAD). The influence of ischemia on wound healing was investigated., Methods: We retrospectively studied 253 patients with heel ulcers treated between January 2003 and March 2018. The patients were classified into PAD and non-PAD groups. The wound healing rate, wound healing time and the factors that influenced wound healing were examined., Results: There were 186 patients with PAD (73.5%). There were 41 (22.0%) and 35 (52.2%) wound healing cases with PAD and non-PAD, respectively (P < 0.001). In the non-PAD group, the deeper the ulcer, the lower the wound healing rate. However, in the PAD group, the increase in blood flow owing to revascularization affected the wound healing rate. The wound healing rate in the endovascular therapy (EVT) and bypass groups were 26.7% and 65.0%, respectively (P = 0.003). The wound healing time was 128 (interquartile range [IQR] 88－196) and 79 (IQR 35.5－187) days, with PAD and non-PAD, respectively (P = 0.0268). The wound healing time in the PAD group was 128 (IQR 93－174.5) days with bypass and 155.5 (IQR 86－237.5) days with EVT (P = 0.459)., Conclusions: Heel pressure ulcers with PAD are difficult to treat. The wound healing rate was lower in the PAD than in the non-PAD group and the wound healing time also tended to be long. Successful revascularization is important for wound healing and bypass surgery had a shorter wound healing time and a higher wound healing rate than EVT.

This study investigated the perioperative and long-term fates of patients with chronic limb-threatening ischemia (CLTI) who underwent secondary major amputations. From April 2010 to December 2018, 1653 CLTI patients primarily underwent endovascular therapy (EVT). Of these patients, 138 who underwent secondary major amputations were included in this study. The primary outcome measure was the mortality. Prognostic factors associated with perioperative (30-day) and late mortality (after 30 days) were assessed. The 30-day mortality was 9.6%. Patients who died during the perioperative period had lower ejection fractions on echocardiography than those in the perioperative survivors (49.5 ± 14.9% vs 58.6 ± 12.4%, P = .018). None of the other clinical characteristics were significantly associated with perioperative death. Two-years postoperatively, 49.6%, 12.2%, and 4.3% of the patients had died, had contralateral amputations, and had additional above-knee amputations, respectively. In the alive patients who had not undergone additional amputation at 2 years, only 25.9% were ambulatory, whereas 51.7% and 22.4% were in wheelchairs and bedridden, respectively. An age ≥80 years and serum albumin <3.0 g/dL were significantly associated with late mortality (P = .032 and P = .042, respectively). In conclusion, the perioperative and long-term fates after secondary major amputation in CLTI patients who underwent EVT were considerably poor., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Introduction: The aim of this study was to characterize the associations between sagittal spinopelvic alignment and motor symptoms in patients with Parkinson's disease (PD)., Methods: The study included patients with idiopathic PD (aged <80 years and with abnormal posture). All patients underwent whole-spine lateral and coronal radiography. Sagittal spinopelvic alignment was evaluated using nine parameters. Motor symptoms were evaluated using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score-with bradykinesia and axial motor sub-scores. Multivariate analysis was used to analyze associations between motor symptoms and sagittal spinopelvic alignment in PD patients according to sex., Results: The study subjects were 79 PD patients (39 men, 40 women; median age, 70 years). Clear sex-related differences were noted. In male patients, the MDS-UPDRS part III score correlated significantly with cervical sagittal vertical axis (SVA), and bradykinesia and axial motor scores correlated significantly with SVA, cervical SVA, and T1 slope. In female patients, the MDS-UPDRS part III score correlated significantly with thoracic kyphosis, bradykinesia score correlated significantly with cervical SVA and thoracic kyphosis, and the axial motor score correlated significantly with SVA, cervical SVA, T1 slope, sacral slope, and pelvic tilt., Conclusion: Our results showed clear correlations among various motor symptoms and sagittal global alignment in PD patients and that these correlations are different in female PD patients and their male counterparts., (© 2021 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background: The current study aimed to reveal clinical features and prognosis of asymptomatic contralateral limbs in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI)., Methods: We analyzed a database of 520 CLTI patients registered in a prospective, multicenter registry in Japan. Severe ischemia in asymptomatic contralateral limbs was determined as the Wound, Ischemia, and foot Infection (WIfI) classification system Ischemia (I) grade 2/3., Results: The prevalence of diabetes mellitus and dialysis-dependent renal failure was 74.2% and 53.5%, respectively. Asymptomatic limbs accounted for 65.0% [95% confidence interval (CI), 60.9-69.1%] of the overall population, and 55.0% (95% CI, 49.6-60.4%) of the asymptomatic contralateral limbs had WIfI I-2/3. The multivariate analysis identified age ≥65 years, dialysis-dependent renal failure, WIfI I-3 in the index limb, and loss of pressure sensation in the contralateral limb as independent risk factors for WIfI I-2/3 in asymptomatic contralateral limbs (all p < 0.05). The 3-year cumulative incidence rate of major adverse limb events (MALE) in asymptomatic contralateral limbs was 19.3% (95% CI, 15.1-23.7%), whereas that of all-cause mortality was 46.9% (95% CI, 41.0-52.5%). The corresponding rate including a composite of mortality and MALE was 58.8% (95% CI, 52.9-64.6%). In asymptomatic contralateral limbs, the adjusted hazard ratio of WIfI I-2/3 versus I-0/1 was 1.53 (95% CI, 1.11-2.10) for a composite of mortality and MALE, 1.96 (95% CI, 1.14-3.36) for MALE, and 1.37 (95% CI, 0.95-1.96) for mortality (p = 0.009, 0.015, and 0.091, respectively)., Conclusions: Two-thirds of CLTI patients had an asymptomatic contralateral limb, and approximately half of the asymptomatic contralateral limbs were exposed to severe ischemia. Older age, dialysis-dependent renal failure, WIfI I-3 in the index limb, and loss of pressure sensation in the contralateral limb were independently associated with severe ischemia in asymptomatic contralateral limbs. In addition to mortality, MALE commonly occurred in asymptomatic contralateral limbs, especially with WIfI I-2/3., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

The current study aimed to reveal the clinical impact of plasma homocysteine levels in chronic limb-threatening ischemia (CLTI) patients undergoing revascularization. This was a sub-analysis of a prospective multicenter registry of CLTI patients, named the Surgical reconstruction versus Peripheral INtervention in pAtients with critical limb isCHemia (SPINACH) study. The current analysis included 192 non-dialysis-dependent CLTI patients who underwent revascularization for CLTI, and whose plasma homocysteine levels at baseline were available. The association of clinical characteristics with homocysteine levels was evaluated with the linear regression model. The association of homocysteine levels with the mortality risk was investigated using the Cox proportional hazards regression model. Cystatin C-based estimated glomerular filtration rate (eGFR) was independently associated with log-transformed homocysteine levels; the adjusted standardized regression coefficient (95% confidence interval) was - 0.432 (- 0.657 to - 0.253; P < 0.001). Homocysteine levels were significantly associated with the mortality risk in the univariate model (P = 0.017); the unadjusted hazard ratio was 1.71 (1.13-2.50) per twofold increase. The association was significantly attenuated when adjusted for cystatin C-based eGFR (P < 0.001); the hazard ratio adjusted for cystatin C-based eGFR was 1.28 (0.80-1.90; P = 0.29). An apparent association of homocysteine levels with an increased risk of mortality could be explained by renal dysfunction. Future studies will be needed to validate the current findings., (© 2021. The Author(s).)

We herein report an 84-year-old woman with right middle cerebral artery (MCA) stenosis who presented with persistent left hemichorea preceding cerebral infarction. She visited our hospital on day 9 after the hemichorea onset. Magnetic resonance imaging (MRI) showed no acute cerebral infarction. Magnetic resonance angiography revealed right MCA stenosis. Her hemichorea persisted for 19 days and subsequently disappeared. On day 21, she developed left hemiplegia. Repeat MRI revealed a cerebral infarction in the right putamen. MCA stenosis can present with persistent hemichorea, even in the absence of cerebral infarction. Persistent hemichorea with MCA stenosis may presage cerebral infarction.

Advanced mandibular osteoradionecrosis (ORN) sometimes requires extended resection (e.g., hemimandibulectomy). Bacterial infection contributes to ORN pathogenesis. To control infection and determine the extent of debridement required, an understanding of bacterial spread within sites of mandibular ORN is important. The current study used a histopathological approach to assess bacterial colonization in the mandibular condyle and elucidate possible paths of bacterial spread towards the mandibular condyle. Four hemimandibulectomy specimens were selected. Areas of bone destruction were macroscopically assessed and confirmed using hematoxylin and eosin staining. Bacterial presence within mandibular condyle was confirmed with Gram staining. Bone exposure was observed in the molar area in all specimens. Macroscopic bone destruction was apparent especially near the medial side of the cortical wall. Gram staining revealed bacterial colonization of the mandibular condyle in three of the four specimens. In conclusion, bacteria tended to spread posteriorly and through the medial side of the mandibular cortical wall. In patients with advanced ORN, the potential for bacterial colonization of the mandibular condyle should be considered during treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Daisuke Takeda et al.)