Published papers

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves exercise tolerance and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension. However, it is still unclear which patient characteristics contribute to the improvement in exercise tolerance after BPA in chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: We retrospectively analyzed 126 patients with chronic thromboembolic pulmonary hypertension (aged 63±14 years; female, 65%) who underwent BPA without concomitant programmed exercise rehabilitation at Keio University between November 2012 and April 2018. Hemodynamic data and 6-minute walk distance (6MWD), as a measure of exercise tolerance, were evaluated before and 1 year after BPA. The clinical characteristics that contributed to improvement in exercise tolerance were elucidated. The 6MWD significantly increased from 372.0 m (256.5–431.3) to 462.0 m (378.8–537.0) 1 year after BPA (P<0.001). The improvement rate in the 6MWD after BPA exhibited a good correlation with age, height, mean pulmonary artery pressure, and 6MWD at baseline (Spearman rank correlation coefficients=−0.28, 0.24, −0.40, and 0.44, respectively). Additional multivariable linear regression analysis revealed that young age, tall height, high mean pulmonary artery pressure, short 6MWD at baseline, and high lung capacity at baseline were significant predictors of the improvement in 6MWD by BPA (standardized partial regression coefficient −0.39, 0.22, 0.19, −0.62, and 0.25, P<0.001, 0.007, 0.011, <0.001, and <0.001, respectively). CONCLUSIONS: BPA without concomitant programmed exercise rehabilitation significantly improves exercise tolerance. This was particularly true in young patients with high stature, high mean pulmonary artery pressure, short 6MWD, and lung capacity at the time of diagnosis.

Background: Exercise therapy for cardiovascular disease (CVD) is mainly evaluated based on the heart rate (HR) or Borg scale. However, these indices can be unreliable depending on the patient's medication or their subjective decisions; thus, alternative methods are required for easier and safer implementation of aerobic exercise. Here, we examined whether real-time analysis of HR variability (HRV) can help maintain exercise intensity at the ventilatory threshold (VT) during exercise. Methods: Twenty-eight patients with CVD treated at Keio University Hospital between August 2018 and March 2020 were enrolled. Initially, oxygen uptake (VO2) and HR at the VT were determined using the cardiopulmonary exercise test. Patients then performed aerobic exercise on a stationary bicycle for 30 min while a parameter of HRV, the high-frequency (HF) component, was monitored in real time using an electrocardiograph. The work rate during exercise was adjusted every 2 min to maintain the HF range between 5 and 10. The VO2 and HR values, recorded every 2 min during exercise, were compared with those at VT. The Bland–Altman method was used to confirm similarity. Results: VO2 and HR during exercise were closely correlated with those at VT (e.g., 19 min after exercise initiation; VO2: r = 0.647, HR: r = 0.534). The Bland–Altman plot revealed no bias between the mean values (e.g., 19 min; VO2: −0.22 mL/kg/min; HR: −0.07/min). Conclusion: Real-time HRV analysis with electrocardiograph alone during exercise can provide continuous and non-invasive exercise intensity measurements at VT, promoting safer and effective exercise strategies.

Exercise therapy at the aerobic level is highly recommended to improve clinical outcomes in patients with heart failure, in which cardiopulmonary exercise testing (CPX) is required to determine anaerobic thresholds (ATs) but is not available everywhere. This study aimed to validate a method to estimate the AT using heart rate variability (HRV) analysis from electrocardiography data in patients with heart failure. Between 2014 and 2019, 67 patients with symptomatic heart failure underwent CPXs in a single university hospital. During the CPX, RR intervals was measured continuously and the HRV threshold (HRVT), defined as the inflection point of <5 ms2 of a high-frequency component (HFC) using the power spectrum analysis, was determined. Patients were divided into two groups according to the mean HFC at rest (high-HFC group, n = 34 and low-HFC group, n = 33). The high-HFC group showed good correlation between the VO2 at AT and HRVT (r = 0.63, p < 0.001) and strong agreement (mean difference, −0.38 mL/kg, p = 0.571). The low-HFC group also showed modest correlation (r = 0.41, p = 0.017) but poor agreement (mean differences, 3.75 mL/kg, p < 0.001). In conclusion, the HRVT obtained from electrocardiography may be a useful indicator for estimating AT in patients with heart failure.

Purpose: To identify the risk factors associated with early implant fracture of silicone metacarpophalangeal (MCP) joint arthroplasty using the volar hinge silicone implant for patients with rheumatoid arthritis. Methods: We retrospectively reviewed 113 fingers of 31 hands that underwent MCP joint arthroplasty between 2008 and 2014, with a minimum follow-up of 3 years,. An implant fracture within 3 years after surgery was regarded as an early implant fracture. Patient records were reviewed for potential risk factors of age, affected fingers, ulnar drift angle, and range of motion of the MCP joint before surgery and 1 year after surgery. Candidate risk factors were compared at the level of the digit and at the patient level. Results: With fracture of the implants as the end point, Kaplan–Meier estimated survival rate was 74.3% at 3 years and 67.9% at 5 years. Early implant fracture was detected in 29 fingers. Bivariate analyses showed significant associations between early implant fracture and MCP joint arc of motion before surgery, MCP joint flexion range 1 year after surgery, and MCP joint arc of motion 1 year after surgery. Multiple logistic regression analysis showed that increased MCP joint flexion range 1 year after surgery was an independent risk factor for early implant fracture. Conclusions: Increasing MCP joint flexion range was associated with increased fractures of the implants. We propose that the MCP joint flexion range should be restricted to less than 60° in postoperative rehabilitation; it is necessary to educate the patient to permanently avoid excessive flexion of the MCP joint. Type of study/level of evidence: Therapeutic IV.

Chitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN−), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN− and silicone+ groups. Meanwhile, the CCN− and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects.

Background: Precision placement of implants in total elbow arthroplasty (TEA) using conventional surgical techniques can be difficult and riddled with errors. Modern technologies such as augmented reality (AR) and 3-dimensional (3D) printing have already found useful applications in many fields of medicine. We proposed a cutting-edge surgical technique, augmented reality total elbow arthroplasty (ARTEA), that uses AR and 3D printing to provide 3D information for intuitive preoperative planning. The purpose of this study was to evaluate the accuracy of humeral and ulnar component placement using ARTEA. Methods: Twelve upper extremities from human frozen cadavers were used for experiments performed in this study. We scanned the extremities via computed tomography prior to performing TEA to plan placement sites using computer simulations. The ARTEA technique was used to perform TEA surgery on 6 of the extremities, whereas conventional (non-ARTEA) techniques were used on the other 6 extremities. Computed tomography scanning was repeated after TEA completion, and the error between the planned and actual placements of humeral and ulnar components was calculated and compared. Results: For humeral component placement, the mean positional error ± standard deviation of ARTEA vs. non-ARTEA was 1.4° ± 0.6° vs. 4.4° ± 0.9° in total rotation (P = .002) and 1.5 ± 0.6 mm vs. 8.6 ± 1.3 mm in total translation (P = .002). For ulnar component placement, the mean positional error ± standard deviation of ARTEA vs. non-ARTEA was 5.5° ± 3.1° vs. 19.5° ± 9.8° in total rotation (P = .004) and 1.5 ± 0.4 mm vs. 6.9 ± 1.6 mm in total translation (P = .002). Both rotational accuracy and translational accuracy were greater for joint components replaced using the ARTEA technique compared with the non-ARTEA technique (P < .05). Conclusion: Compared with conventional surgical techniques, ARTEA had greater accuracy in prosthetic implant placement when used to perform TEA.

Changes in bone metabolism occur in mothers during pregnancy or lactation that may decrease bone mass and result in fragility fractures after partum. However, use of drugs during pregnancy or lactation to counteract these effects is often prohibited or strongly discouraged. Therefore, approaches to protect mothers from fragility fractures have not been established. Here we show that bone mineral density was significantly lower in female mice after partum than in age-matched female mice without partum. We also show that temporary administration of the bisphosphonate alendronate, either just before or just after pregnancy, to female mice was protective against bone loss due to pregnancy or lactation and had no adverse effects on offspring, such as growth retardation. Furthermore, we show that alendronate administration to female mice during lactation was effective in increasing bone mass in mothers without promoting bone abnormalities or growth retardation in offspring. Calcium levels in milk from female mice administered alendronate during lactation were equivalent to those in milk from mothers not treated with alendronate. Overall, we propose that alendronate administration to mothers could prevent bone loss and fragility fractures during pregnancy and lactation.

Estrogen deficiency can be caused by ovarian dysfunction in females. Mechanisms underlying osteoporosis in this condition have been characterized in animal models, such as ovariectomized mice and rats, although it remains unclear how hypothalamic dysfunction promotes osteoporosis. Here, we show that administration of a gonadotropin-releasing hormone antagonist (GnRHa) significantly decreases uterine weight, a manifestation of hypothalamic dysfunction, and promotes both cortical and trabecular bone loss in female mice in vivo. We also report that osteoclast number significantly increased in mice administered GnRHa, and that the transcription factor hypoxia inducible factor 1 alpha (HIF1α) accumulated in those osteoclasts. We previously reported that treatment of mice with the active vitamin D analogue ED71, also known as eldecalcitol, inhibited HIF1α accumulation in osteoclasts. We show here that in mice, co-administration of ED71 with GnRHa significantly rescued the reduced cortical and trabecular bone mass promoted by GnRHa administration alone. GnRHa-dependent HIF1α accumulation in osteoclasts was also blocked by co-administration of ED71. We conclude that hypothalamic dysfunction promotes HIF1α accumulation in osteoclasts and likely results in reduced bone mass. We conclude that treatment with ED71 could serve as a therapeutic option to counter osteoporotic conditions in humans.

Background: This retrospective study was designed to evaluate a surgical treatment for swan neck deformity of the fingers involving the volar transfer of the lateral band using the transverse retinacular ligament. Methods: Ten patients who underwent this surgical procedure for swan neck deformity treatment and were followed up for a mean of 26 months (range: 12-65 months) were included in the study. The dorsally located lateral bands were transferred toward the volar aspect of the finger, and their position was maintained using the transverse retinacular ligament. Improvement of the snapping and swan neck deformity was confirmed by intraoperative active motion of the finger. The active range of motion of the affected finger was evaluated pre- and postoperatively. Results: Extension of the proximal interphalangeal (PIP) joint averaged 30° (range: 20°-40°) preoperatively and improved to -2° (range: -5°-0°) postoperatively. Extension of the distal interphalangeal (DIP) joint averaged -30° (range: -15° to -70°) preoperatively and improved to -15° (range: 0° to -55°) postoperatively. The mean improvement in range of motion of the DIP joint was 15° (range: 10°-25°). The flexion of both the PIP and DIP joint did not significantly change in any of the patients postoperatively. Conclusions: Surgical transfer of the lateral band using the transverse retinacular ligament is effective in correcting mild swan neck deformity. Hyperextension of the PIP joint is corrected well, but the severe extension lag of the DIP joint remains uncorrected postoperatively.

Intra-articular metacarpal head fracture is relatively rare. We report a case of coronal intra-articular and epiphyseal fractures of Salter-Harris type IV injury in the metacarpal head of the index finger. Surgery was performed by a dorsal approach. The volar fragment that was displaced proximally was gently reduced while bending the metacarpophalangeal (MP) joint, and it was fixed with cortical screws inserted proximal to the articular cartilage facilitating early rehabilitation. We consider the mechanism of injury to be a force applied from the distal phalanx that was transmitted unevenly to the volar side when the MP joint was slightly flexed. A three-dimensional computed tomography scan was useful in making the precise diagnosis, confirming the fracture pattern and planning fixation of the fracture.

The lactate threshold (LT1), which is defined as the first rise in lactate concentration during incremental exercise, has not been non-invasively and conveniently determined in a clinical setting. We aimed to visualize changes in lactate concentration in sweat during exercise using our wearable lactate sensor and investigate the relationship between the lactate threshold (LT1) and ventilatory threshold (VT1). Twenty-three healthy subjects and 42 patients with cardiovascular diseases (CVDs) were enrolled. During exercise, the dynamic changes in lactate values in sweat were visualized in real-time with a sharp continuous increase up to volitional exhaustion and a gradual decrease during the recovery period. The LT1 in sweat was well correlated with the LT1 in blood and the VT1 (r = 0.92 and 0.71, respectively). In addition, the Bland–Altman plot described no bias between the mean values (mean differences: − 4.5 and 2.5 W, respectively). Continuous monitoring of lactate concentrations during exercise can provide additional information for detecting the VT1.

This retrospective study evaluated procedural failures of closed reductions using an extension-block Kirschner wire (K-wire) for bony mallet finger. A total of 132 patients who underwent a closed reduction for bony mallet finger in a procedure using an extension-block K-wire were radiographically assessed. Radiographs were used to evaluate (1) postoperative displacement of the reduction before or after K-wire removal and (2) inaccurate reduction of the fragment immediately after surgery. The causes of procedural failure and bone union were evaluated using radiographs and medical records of the intraoperative findings. Out of 132 patients, 17 with procedural failure were enrolled. Displacement of the reduction before and after K-wire removal occurred in seven and six cases, respectively. Inaccurate reduction immediately after surgery occurred in four cases. The most common cause of procedural failure was inaccurate insertion of the K-wire to fix the distal interphalangeal joint (eight cases) followed by inaccurate insertion of the extension-block pin (five cases). All patients had bone union regardless of the displacement of the reduction or inaccurate reduction of the fragment. Caution should be exercised during the reduction and fixation when an extension-block K-wire is used in a closed reduction procedure.

Objective: Diminished physical capacity is common and progressive in patients undergoing dialysis, who are also prone to deficiency in carnitine, which plays a pivotal role in maintaining skeletal muscle and cardiac function. The present study aimed to evaluate the association of carnitine profile with exercise parameters in patients with incident dialysis. Design and Methods: This was a single-center cross-sectional study including 87 consecutive patients aged 20–90 years who were initiated on dialysis in Keio University Hospital between December 2019 and December 2022 and fulfilled the eligibility criteria. Exercise parameters were evaluated via cardiopulmonary testing (CPX) using the electronically braked STRENGTH ERGO 8 ergometer, whereas the carnitine profile was assessed by determining serum free carnitine (FC), acylcarnitine (AC) levels and AC/FC ratio. Results: The mean cohort age was 62.1 ± 15.2 years, with male and hemodialysis predominance (70% and 73%, respectively). AC/FC was 0.46 ± 0.15, and CPX revealed peak oxygen consumption (VO2) of 13.9 ± 3.7 (mL/kg/min) with percent-predicted peak VO2 of 53.6% ± 14.7% and minute ventilation (VE)/carbon dioxide output (VCO2) slope of 35.1 ± 8.0. Fully-adjusted multivariate linear regression analysis showed that AC/FC was significantly associated with decreased peak VO2 (β, −5.43 [95% confidence interval (CI), −10.15 to −0.70]) and percent-predicted peak VO2 (β, −19.98 [95% CI, −38.43 to −1.52]) and with increased VE/VCO2 slope (β, 13.76 [95% CI, 3.78–23.75]); FC and AC did not exhibit similar associations with these parameters. Moreover, only AC/FC was associated with a decreased peak work rate (WR), percent-predicted WR, anaerobic threshold, delta VO2/delta WR, and chronotropic index. Conclusion: In patients on incident dialysis, exercise parameters, including those related to both skeletal muscle and cardiac function, were strongly associated with AC/FC, a marker of carnitine deficiency indicating altered fatty acid metabolism. Further studies are warranted to determine whether carnitine supplementation can improve exercise capacity in patients on incident dialysis.

Background: Microsurgery requires high skills for suturing using fragile threads, often within narrow surgical fields. Precise tension is required for good healing and to avoid the risk of thread breakage. Methods: To meet the demands, we developed a novel assist robot utilizing high-precision sensorless haptic technology. The robot adopts a cable-driven mechanism to maintain a distance from the surgical area and enhances compatibility with surgical equipment such as microscopes. The robot performance was verified through in vitro and in vivo experiments using a rat model. Results: The realization of precise tension control was confirmed in both experiments. In particular, in the in vivo experiments, the developed robot succeeded to produce a knot with an accurate tension of 0.66% error. Conclusions: The developed robot can realize to control traction force precisely. This technology might open up the window for a full assist robot for microsurgery with haptic feeling.

The dual task is an important factor affecting knee biomechanics during jump-landing tasks. Athletes often have trouble in performing two tasks concurrently and a dual task can deteriorate landing performance. However, it is still unknown whether a dual task will affect the entire lower extremity. The purpose of this study was to clarify the effects of cognitive task interference on biomechanics of hip and ankle joints as well as the knee joint during the drop vertical jump (DVJ). A total of 20 female collegiate athletes participated in the study. Athletes performed a DVJ with or without a cognitive task. The DVJ was captured using a motion analysis system. Mental arithmetic of 2-digit addition was used as a cognitive task. Maximum vertical ground reaction force (vGRF), joint angles at initial contact (IC), joint moments within 40 milliseconds (ms) after IC, and joint angles and moments at peak vGRF were assessed. The data were statistically compared between with and without a cognitive task condition using a two-tailed paired t-test or the Wilcoxon singed rank test. The peak external knee abduction moment on both limbs within 40 ms after IC during the DVJ was significantly larger in the dual task than in the single task with less knee and hip flexion at initial contact. In addition, all moments of hip and ankle joints within 40 ms after IC were significantly larger in the dual task than in the single task accompanied with greater vGRF, except for the hip internal rotation moment. Cognitive tasks during a DVJ will result in biomechanical changes of the entire lower extremity in female athletes.

Background: Peripheral triangular fibrocartilage complex (TFCC) tears may induce instability of the distal radioulnar joint (DRUJ). In this biomechanical study, simulated peripheral tears of the TFCC were examined on the stability of the DRUJ. Restabilization effect of the DRUJ by ulnar shortening and direct repair of those injuries were sequentially examined. Method: The DRUJ stiffness was measured in intact, simulated two types of peripheral tears (ulnar and extended ulnodorsal) at three forearm positions: neutral, 60° pronation and 60° supination in 8 fresh frozen cadaver specimens. After the tears were sutured with stitches or after simulated ulnar shortening of 3 mm, the DRUJ stiffness was again measured. Results: The ulnar and ulnodorsal TFCC tears decreased the DRUJ stiffness significantly compared with the intact in all forearm positions. When ulnar shortening was done for the ulnar tear, the DRUJ stiffness increased significantly in the neutral and 60° pronated positions. When the ulnar TFCC tear was repaired, the DRUJ stiffness increased significantly in all forearm positions. DRUJ stiffness did not increase either with ulnar shortening or repair in ulnodorsal tear of the TFCC, however. Conclusion: The simulated TFCC tears indicated significant loss of DRUJ stiffness. Direct repair or ulnar shortening was effective only on treatment of the ulnar tear of the TFCC in this study.

A simple, non-invasive algorithm for maximal lactate steady state (MLSS) assessment has not been developed. We examined whether MLSS can be estimated from the sweat lactate threshold (sLT) using a novel sweat lactate sensor for healthy adults, with consideration of their exercise habits. Fifteen adults representing diverse fitness levels were recruited. Participants with/without exercise habits were defined as trained/untrained, respectively. Constant-load testing for 30 min at 110%, 115%, 120%, and 125% of sLT intensity was performed to determine MLSS. The tissue oxygenation index (TOI) of the thigh was also monitored. MLSS was not fully estimated from sLT, with 110%, 115%, 120%, and 125% of sLT in one, four, three, and seven participants, respectively. The MLSS based on sLT was higher in the trained group as compared to the untrained group. A total of 80% of trained participants had an MLSS of 120% or higher, while 75% of untrained participants had an MLSS of 115% or lower based on sLT. Furthermore, compared to untrained participants, trained participants continued constant-load exercise even if their TOI decreased below the resting baseline (P < 0.01). MLSS was successfully estimated using sLT, with 120% or more in trained participants and 115% or less in untrained participants. This suggests that trained individuals can continue exercising despite decreases in oxygen saturation in lower extremity skeletal muscles.

Introduction This study aimed to assess the carpal arch dynamics during active finger and wrist motion following carpal tunnel release using four-dimensional computed tomography (4D-CT). Materials and Methods Four patients who diagnosed with bilateral carpal tunnel syndrome and underwent unilateral carpal tunnel release were prospectively included. 4D-CT of the bilateral wrists during active finger and wrist motion was performed for 10 seconds at five frames per second. The distances between the tip of tuberosity of the scaphoid and the volar ridge of the pisiform (S-P distance) and volar ridge of trapezium and the tip of hook of hamate (T-H distance) were measured at each position and the values of S-P and T-H distances were compared between the postoperative and contralateral wrists. Results During finger motion, the S-P and T-H distances were not different at any position between the postoperative side and contralateral side. Conversely, S-P and T-H distances gradually increased in the postoperative wrists. The differences between the sides of S-P distance were significant, with >0 degrees of wrist extension, and differences of T-H distance were significant with >15 degrees of wrist extension. Conclusion This study demonstrated the carpal arch dynamics using 4D-CT and revealed that the carpal arch was widened with the wrist in extension after carpal tunnel release. This study suggests that the transverse carpal ligament plays an important role in maintaining carpal arch stability.

Background: Hook of the hamate fractures can be managed conservatively or fixed using a screw, but excision is recommended for prompt return to activities. Although various approaches have been described, there is no gold standard. Herein, the authors have described their clinical experiences in excising the hook of the hamate using the carpal tunnel approach, in athletes. Methods: A total of 36 athletes underwent excision of the hamate hook using the carpal tunnel approach. The mean age of the patients was 23 years, and most of them were baseball players (n = 31). Results: The mean operation time was 33 min. None of the patients presented with any complications aside from transient pillar pain in five cases. All of them returned to their sports activities within an average of 27 days. Conclusions: In our study, excision of the hook of the hamate was performed safely via the carpal tunnel. The carpal tunnel approach reportedly provides superior benefits over other approaches.

The relationship between increased volar tilt of the distal radius and distal radioulnar joint stability was examined. Distal radioulnar joint stiffness was recorded at 10° intervals from 10° dorsal angulation to 20° of volar angulation from the anatomical position of the radius. Tests were performed with the intact radioulnar ligament and repeated after partial and then complete sectioning of the radioulnar ligament at the ulnar fovea. With the intact radioulnar ligament, distal radioulnar joint stiffness increased significantly at 10° and 20° of volar angulation. Partial sectioning of the radioulnar ligament resulted in an approximate 10% decrease of distal radioulnar joint stiffness compared with the intact state, but distal radioulnar joint stiffness still increased significantly with greater volar tilt. Complete sectioning of the radioulnar ligament significantly decreased distal radioulnar joint stiffness, and increasing the volar tilt did not result in increased distal radioulnar joint stiffness. These results suggest that volar angulation deformities of the distal radius should be corrected to 10° of volar tilt when the triangular fibrocartilage complex is intact.