Rapid genotyping of inversion variants in Mucopolysaccharidosis type II using long-range PCR: A case report.

Mucopolysaccharidosis II (MPS II) is a lysosomal storage disease caused by a deficiency in iduronate-2-sulfatase (IDS), leading to the accumulation of dermatan sulfate and heparan sulfate in lysosomes. Traditionally, genotyping of the IDS gene has been conducted through exome sequencing, which fails to detect inversion variants. Consequently, when no pathogenic variants are detected in exons, additional PCR-based analysis is required. Herein, we introduce a rapid genotyping technique method using long-range PCR for MPS II patients. We successfully identified an inversion variant and confirmed the sequences of the inversion regions. We also confirmed that the pathogenic variant in the patient originated de novo. These findings suggest that long-range PCR genotyping can identify inversion variants more rapidly compared to the previous PCR-based methods, making it a valuable tool for newborn screening (NBS) and genetic diagnosis.

Tensile Strength of Nerve Bridging Models Using Collagen Nerve Conduits.

BACKGROUND: In the treatment of peripheral nerve injuries with nerve defects, second-generation collagen-based conduits, such as Renerve® (Nipro, Osaka, Japan), have shown the potential for promoting nerve regeneration. However, there is concern related to the weak material properties. No previous studies have addressed the strength of the bridging model using collagen conduits. This study aimed to investigate the tensile strength and failure patterns in nerve defect models bridged with Renerve® conduits through biomechanical research. METHODS: Using fresh chicken sciatic nerves, we examined the maximum failure load of four groups: bridging models using Renerve® with one suture (group A), with two sutures (group B), with three sutures (group C), and end-to-end neurorrhaphy models with two sutures (group N). Each group had eight specimens. We also evaluated failure patterns of the specimens. RESULTS: Group N showed a significantly higher maximum failure load (0.96 ± 0.13 N) compared to groups A (0.23 ± 0.06 N, p < 0.0001), B (0.29 ± 0.05 N, p < 0.0001), and C (0.40 ± 0.10 N, p < 0.0001). Regarding failure patterns, all specimens in group A showed nerve-end dislocation from the conduit. Two specimens in group B and three specimens in group C failed due to circumferential cracks in the conduit. Six specimens in group B and five specimens in group C exhibited cutting out of sutures from the conduit. CONCLUSION: This study suggests that the number of sutures in synthetic collagen nerve conduits has little effect on the maximum failure load. To take advantage of its biomaterial benefits, a period of postoperative range of motion restriction may be required.

Sulfur-Bridged Cationic Diazulenomethenes: Formation of Charge-Segregated Assembly with High Charge-Carrier Mobility.

Sulfur-bridged cationic diazulenomethenes were synthesized and exhibited high stability even under basic conditions due to the delocalization of positive charge over the whole π-conjugated skeleton. As a result of the effective delocalization and the absence of orthogonally oriented bulky substituents, the cationic π-conjugated skeletons formed a π-stacked array with short interfacial distances. A derivative with SbF6- as a counter anion formed a charge-segregated assembly in the crystalline state, rather than the generally favored charge-by-charge arrangement of oppositely charged species based on electrostatic interactions. Theoretical calculations suggested that the destabilization caused by electrostatic repulsion between two positively charged π-conjugated skeletons is compensated by the dispersion forces. In addition, the counter anion SbF6- played a role in regulating the molecular alignment through F⋯H-C and F-S interactions, which resulted in the charge-segregated alignment of the cationic π-skeletons. This characteristic assembled structure gave rise to a high charge-carrier mobility of 1.7 cm2 V-1 s-1 as determined using flash-photolysis time-resolved microwave conductivity.

Internal rotational patellar resection and patella alta induced patellar maltracking in total knee arthroplasty: intraoperative measurement of the patellofemoral pressure.

BACKGROUND: Anterior knee pain due to patellar maltracking following total knee arthroplasty (TKA) reduces patients' satisfaction. This study aimed to determine the patellofemoral pressure (PFP) in patients with favorable patellar tracking (FT) and impaired patellar tracking (IT) following TKA, the factors causing patellar maltracking, and the effect of lateral retinacular release (LRR) on patients with IT. METHODS: Forty-four patients with varus knee osteoarthritis undergoing cruciate-retaining TKA were enrolled. After component implantation, patients with a separation of ≥ 2 mm of the patellar medial facet from the medial femoral trochlea throughout knee range of motion were classified into the IT group; meanwhile, the others were classified into the FT group. PFP was measured intraoperatively in three phases: (1) with the resurfaced patella (RP); (2) with the resurfaced patella and knee (RPK); and (3) when LRR was performed in IT (post-LRR). The PFPs at 0°, 90°, 120°, and 135° knee flexion were compared between FT and IT using the Mann-Whitney U test. Pairwise comparison of the PFP in IT between RPK and post-LRR was performed using the Wilcoxon signed-rank test. Correlations between PFP and pre- and postoperative radiographic parameters, such as hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, anterior femoral offset, Insall-Salvati ratio (ISR), patellar tilt, and patellar resection angle (PRA), were evaluated using Spearman's rank correlation coefficients. RESULTS: High lateral PFP in the knee flexion position led to patellar maltracking. Patients with IT (n = 24) had higher lateral and lower medial PFP than did patients with FT (n = 20) at 90°, 120°, and 135° knee flexion in RP and RPK. LRR in IT reduced the lateral PFP in the knee flexion position. PRA and ISR were correlated with the lateral PFP at no less than 90° in RP and RPK. CONCLUSIONS: This study demonstrated that internal rotational patellar resection, which resulted in a thick medial patellar remnant and a thin lateral counterpart, and patella alta were the causative factors of high lateral PFP, which induced patellar maltracking after TKA. Surgeons should avoid internal rotational patellar resection to achieve FT and perform LRR in patients with patellar maltracking.

Decrease in the Internal Cerebral Vein Pulsation With Improvement of Patent Ductus Arteriosus in Premature Infants at the Risk of Intraventricular Hemorrhage: Two Interesting Case Reports.

Recently, augmenting the pulsation of the internal cerebral vein (ICV) has been reported to be a predictor of premature intraventricular hemorrhage (IVH); however, prophylaxis for IVH has not yet been established. Venous pulsation is a marker of central venous pressure elevation and may be improved after heart failure treatment. Herein, we report two cases of low-birth-weight infants (29 weeks and 31 weeks of gestational age), who exhibited improvements in ICV pulsation with relief of hemodynamically significant patent ductus arteriosus (hs-PDA) following indomethacin administration. ICV flow patterns were continuously flat early after birth. Thereafter, both patients demonstrated ICV pulsation augmentation with PDA progression and brain natriuretic peptide (BNP) elevation at 52 h and 39 h after birth (in infants born at 29 and 31 weeks of gestational age, respectively). After relieving PDA with indomethacin administration, both infants exhibited an improvement in ICV pulsation with decreased BNP levels. In both cases, ICV pulsation increased when PDA became hemodynamically significant with BNP elevation, and the pulsation improved by reduction in ductal flow with decreasing BNP when PDA was relieved by indomethacin administration. The association between hs-PDA and elevated ICV pulsation indicates that hs-PDA likely leads to heightened central venous pressure. Additionally, indomethacin treatment was effective in reducing the exacerbated ICV pulsation caused by heart failure due to hs-PDA. These cases suggest that treatment for heart failure might improve the augmented ICV pulsation, which is related to the development of premature IVH. However, further studies are needed to confirm this association.

The ICHI-FIXATOR® system, a novel wire-connected external fixator, demonstrates efficacy in managing intra-articular fractures involving the proximal phalanx of the big toe.

Proximal phalanx fractures of the big toe involving angulation or dislocation of the articular surface require repositioning and fixation. We treated a patient with such a fracture using a novel wire-connected external fixator, the ICHI-FIXATOR® system. A 45-year-old male sustained an injury when slipping down the stairs and impacting his left big toe. Plain radiography and computed tomography revealed a proximal phalangeal fracture of the left big toe with dislocation of the articular surface and comminution. The surgical intervention was performed using 1.1-mm diameter C-wires and an external fixator. The patient regained ambulation and resumed work immediately after surgery. Four weeks postoperatively, all wires were removed on an outpatient basis. Eight months postoperatively, the patient experienced no pain during strenuous activities or exercises. This novel wire-connected external fixator provides reliable and secure fixation, facilitating a prompt return to normal daily activities. This technique may be an effective option for managing toe fractures.

A Lateral Fracture Line Affects Femoral Trochanteric Fracture Instability and Swing Motion of the Intramedullary Nail: A Biomechanical Study.

Background: An unstable trochanteric femoral fracture is a serious injury, with a 1-year mortality rate of 5.4% to 24.9%, for which there is currently no standard treatment method. The lag screw insertion site is one of the primary contact areas between the cortical bone and an intramedullary nail. We hypothesized that a posterolateral fracture causes intramedullary nail instability when the posterolateral fracture line interferes with lag screw insertion. The purpose of the present study was to investigate the effect of posterolateral fracture line morphology on intramedullary nail stability by simulating unstable trochanteric femoral fractures with a posterolateral fracture fragment. Methods: Eighteen custom-made synthetic osteoporotic bone samples were used in the present study. Nine samples had a posterolateral fracture line interfering with the lag screw insertion hole (Fracture A), and the other 9 had a fracture line 10 mm away from the hole (Fracture B). Cyclic loading (750 N) was applied to the femoral head 1,500 times. Movement of the end cap attached to the intramedullary nail was recorded. The amplitudes of motion in the coronal plane (coronal swing motion), sagittal plane (sagittal swing motion), and axial plane (total swing motion) were evaluated. The change in the neck-shaft angle was evaluated on photographs that were made before and after the test. Medial cortical displacement was measured before and after the test. Results: Two Fracture-A samples were excluded because the amplitude of sagittal swing motion was too large. The mean values for coronal, sagittal, and total swing motion were 1.13 ± 0.28 mm and 0.51 ± 0.09 mm (p < 0.001), 0.50 ± 0.12 mm and 0.46 ± 0.09 mm (p = 0.46), and 1.24 ± 0.24 mm and 0.69 ± 0.11 mm (p < 0.001) for Fractures A and B, respectively. The mean neck-shaft angle change was -8.29° ± 2.69° and -3.56° ± 2.35° for Fractures A and B, respectively (p = 0.002). The mean displacement of the medial cortex was 0.38 ± 1.12 mm and 0.12 ± 0.37 mm for Fractures A and B, respectively (p = 0.57). Conclusions: This study showed that an unstable trochanteric femoral fracture with a posterolateral fracture line that interferes with the lag screw insertion holes is a risk factor for increased intramedullary nail instability.

Reverse Posterior Interosseous Artery Flap for Human Bite Injury to the Hand.

Bite injuries frequently occur on human hands. Human bite injuries to the hand may lead to an infection because of limited soft tissue protection and wound contamination. However, no studies have reported severe bite injuries on hands treated by flaps. We report a case of an 80-year-old woman diagnosed with a major neurocognitive disorder. The patient accidentally had a self-bite injury accompanied with an open metacarpal fracture. Debridement and fixation of the first metacarpal fracture were performed. Afterward, skin necrosis occurred gradually on the dorsum of the hand. Therefore, a reverse posterior interosseous artery (PIA) flap was used, and the postoperative course was uneventful. Given the high risk of infection, human bite injuries, particularly hand bites, should be treated immediately. Delayed treatment for such injuries may lead to extensive soft tissue defects requiring reconstruction with flaps.

Frequency of iduronate-2-sulfatase gene variants detected in newborn screening for mucopolysaccharidosis type II in Japan.

Mucopolysaccharidosis II (MPS II) is an X-linked, recessive, inborn metabolic disorder caused by defects in iduronate-2-sulfatase (IDS). The age at onset, disease severity, and rate of progression vary significantly among patients. This disease is classified into severe or mild forms depending on neurological symptom involvement. The severe form is associated with progressive cognitive decline while the mild form is predominantly associated with somatic features. Newborn screening (NBS) for MPS II has been performed since December 2016, mainly in Kyushu, Japan, where 197,700 newborns were screened using a fluorescence enzyme activity assay of dried blood spots. We diagnosed one newborn with MPS II with lower IDS activity, elevated urinary glycosaminoglycans, and a novel variant of the IDS gene. In the future, NBS for MPS II is expected to be performed in many regions of Japan and will contribute to the detection of more patients with MPS II, which is crucial to the early treatment of the disorder.

Evaluation of the effect of granule size of raw tableting materials on critical quality attributes of tablets during the continuous tablet manufacturing process using near-infrared spectroscopy.

OBJECTIVE: The effects of granule size of raw materials on tablet hardness (TH) and weight (TW) in the continuous tablet manufacturing process (CTMP) were investigated using near-infrared spectroscopy (NIRS). METHODS: Granule materials of different sizes were prepared by extrusion granulation from a standard granule formula powder containing lactose/starch and 4.5% acetaminophen. Large-, small-, and medium-sized granules were sequentially filled in a hopper, and tablets were produced continuously using a single-shot tableting machine. After arranging approximately 500 tablets in order, the tablets were subjected to NIRS. A total of 450 NIRS datasets were divided into three groups of 150 each (calibration, validation 1, and validation 2 datasets). RESULTS: The best fitted calibration models for predicting TH and TW were obtained, with sufficient accuracy, based on NIRS using the partial least squares regression, and comprised both physical and chemical information. The regression and loading vectors of the calibration models suggested that the models used to predict TH and TW involve physical information based on geometrical factors of the tablet and chemical information related to binder-related intermolecular interactions. CONCLUSIONS: The changes in the predicted value profiles of TH and TW using NIRS reflected the changes in the measured values depending on the raw granule size during CTMP.

Nontuberculous mycobacteriosis oligoarthritis of the right hand misdiagnosed as rheumatoid arthritis: A case report.

Infection with Mycobacterium marinum has several different clinical presentations. Most commonly, it appears as a solitary papulonodular lesion on an extremity. A rare presentation of osteoarticular M. marinum involving multiple small joints and tenosynovitis of the hand, which was misdiagnosed as rheumatoid arthritis, is reported. The patient was initially treated for seronegative rheumatoid arthritis but failed to respond to methotrexate. Magnetic resonance imaging showed arthritis and tenosynovitis. Subsequently, synovial biopsy led to histological and microbiological diagnosis. Antimycobacterial treatment should be started promptly in such cases. The combined use of rifampicin, ethambutol, and clarithromycin appears to be effective, and debridement is indicated in patients with deep-seated infections.

A biomechanical analysis of the effect of hydroxyapatite augmentation for trochanteric femoral fractures.

Hydroxyapatite (HA) augments are used to treat trochanteric femoral fractures. However, the efficacy of HA augmentation has not been fully described in trochanteric femoral fracture surgery. In total, 85 patients were enrolled in the present study; all had trochanteric femoral fractures between January 2016 and October 2020, 45 with HA (HA group) and 40 without HA (N group). The intraoperative lag screw insertion torque was directly measured and the amount of lag screw telescoping with and without HA augmentation after surgery was analyzed. Maximum lag screw insertion torque (max-torque), bone mineral density in the opposite femoral neck (n-BMD), tip apex distance (TAD) of the lag screw, radiographic findings including fracture union, the amounts of lag screw telescoping and occurrence of complications were evaluated. A total of 12 patients were excluded if they were aged under 60 years old, had ipsilateral surgery and disorders in the hip joint, TAD of the lag screw ≥26 mm on postoperative radiographs and had measurement errors. A total of 73 fractures could be analyzed: HA group (n=36) and N group (n=37). Max-torque/n-BMD ratios were higher in the HA group compared with in the N group (7.23±2.71 vs. 5.93±1.91 g/cm2·N·m; P=0.04). The amounts of lag screw telescoping in the HA group were smaller compared with the N group (1.41±2.00 vs. 2.58±2.34; P=0.05). Evaluation of screw insertion torque showed maximum screw insertion torque correlated well with n-BMD in both groups, HA (R=0.57; P<0.01) and N group (R=0.64; P<0.01). No correlation was found between maximum screw insertion torque and TAD in both groups, HA (R=-0.10; P=0.62) and N group (R=0.02; P=0.93). All fractures were radiographically united without any complications. These results support the effectiveness of HA augmentation, indicating higher resistance against rotational instability and reduced lag screw telescoping in trochanteric femoral fracture treatment.

Median Nerve Recovery and Morphological Change on MRI at 24 Months after Open Carpal Tunnel Release.

Background: This study aimed to investigate the relationship between postoperative clinical results and long-term morphological changes in patients with carpal tunnel syndrome (CTS) as observed on magnetic resonance imaging (MRI) before and after open carpal tunnel release (OCTR). Methods: We retrospectively analysed data for 28 hands that had undergone OCTR with at least 24 months of follow-up data. Two-point discrimination (2PD) test results were examined for the first three fingers, as were the distal motor latency (DML) and sensory conduction velocity (SCV) of the median nerve. We also calculated the cross-sectional area (CSA) of the carpal tunnel and the distance from the median nerve to the volar carpal bone at the hamate and the pisiform levels using MRI images. Variables were compared before and 24 months after OCTR. Results: Significant improvements in all variables were observed, including average 2PD scores (Finger I: 13.1 ± 6.2 vs. 7.7 ± 4.3, p < 0.01, Finger II: 11.9 ± 6.6 vs. 7.0 ± 3.5, p < 0.01, Finger III: 13.6 ± 6.1 vs. 7.8 ± 4.5, p < 0.01), average DML (8.3 ± 3.3 vs. 4.3 ± 0.6 m/s, p < 0.01), average SCV (30.8 ± 11.0 vs. 41.3 ± 5.3 m/s, p < 0.01), CSA of the carpal tunnel (hamate level: 194.9 ± 30.6 vs. 254.2 ± 47.6 mm2, p < 0.01, pisiform level: 244.2 ± 46.5 vs. 274.7 ± 75.1 mm2, p = 0.01) and the distance between the median nerve and volar carpal bone (hamate level: 8.7 ± 1.4 vs. 11.2 ± 1.6 mm, p < 0.01, pisiform level: 11.8 ± 1.7 vs. 13.8 ± 2.5 mm, p < 0.01). Conclusions: Our results demonstrate that OCTR is successful in achieving long-term decompression and recovery of the median nerve in patients with CTS. Level of Evidence: Level III (Therapeutic).

Elective Cesarean Section during Preterm Prevents Pulmonary Hypoplasia Development in Potter Sequence.

Potter syndrome, first reported in 1946 by Edith Potter, refers to fatal cases of bilateral renal aplasia with pulmonary hypoplasia, peculiar facial features, and limb deformities. Presently, patients with oligohydramnios showing similar pathological manifestations due to oligohydramnios caused by conditions other than bilateral renal aplasia have been reported, and are known as the Potter sequence. There are limited studies and unclear guidelines on the safest delivery time and detailed postpartum management for patients with the Potter sequence. We experienced a case of Potter sequence, in which the patient was born by elective cesarean section at gestational age (GA) of 34 weeks. Fetal ultrasound at GA of 26 weeks 4 days showed oligohydramnios, multilocular cystic lesions in the left kidney, and an absent right kidney. Prenatal fetal MRI at GA of 33 weeks and 3 days showed pulmonary hypoplasia, and the ratio of fetal lung volume (FLV) to fetal body weight (FBW) was 0.0135 ml/g. We suspected that the fetal lung could not grow because of persistent oligohydramnios, which leads to a further decline in the ratio of FLV to FBW during pregnancy. We performed a cesarean section at GA of 34 weeks to prevent the exacerbation of the imbalance between lung volume and physique. We struggled to keep her condition stabilized with strict management of her respiratory condition, dialysis, and nutrition. She was discharged from the hospital at 169 days of age. Elective caesarean section in the term of premature birth prevented the progression of pulmonary hypoplasia and made it possible to save her life. Potter sequence is still relatively unknown, and it is necessary for more studies to be conducted in the future.

Charge-Segregated Stacking Structure with Anisotropic Electric Conductivity in NIR-Absorbing and Emitting Positively Charged π-Electronic Systems.

Squarylium-based π-electronic cation with an augmented dipole was synthesized by methylation of zwitterionic squarylium. The cation formed various ion pairs in combination with anions, and the ion pairs exhibited distinct photophysical properties in the dispersed state, ascribed to the formation of J- and H-aggregates. The ion pairs provided solid-state assemblies based on cation stacking. It is noteworthy that complete segregation of cations and anions was observed in a pseudo-polymorph of the ion pair with pentacyanocyclopentadienide as a π-electronic anion. In the crystalline state, the ion pairs exhibited photophysical properties and electric conductivity derived from cation stacking. In particular, the charge-segregated ion-pairing assembly induces an electric conductive pathway along the stacking axis. The charge-segregated mode and fascinating properties were derived from the reduced electrostatic repulsion between adjacent π-electronic cations via dipole-dipole interactions.

Algorithm and hyperparameter optimizations for hetero-device classification by near-infrared spectra of falsified and substandard amoxicillin capsules.

In this work, we optimized classification algorithms and the hyperparameters for screening falsified and substandard amoxicillin capsules. The distribution of low-quality medical products is a serious problem, especially in low- and middle-income countries. Near-infrared (NIR) spectroscopy has been proposed as the first choice for a screening device. However, preparation of the reference library for the classification training is a highly difficult process. We herein propose a hetero-device classification between training and test devices. In this proposal, Fourier-transform NIR spectrometer and portable wavelength dispersive NIR spectrometer were used as training and test devices, respectively. As the classifier candidates, we examined 13 algorithms and selected 8. We then optimized the hyperparameters for these classifiers by the grid search and cross validation methods. In the final analysis, few classifiers were found to give acceptable prediction results by the hetero-device classification. When using these methods, it is crucial to examine the results by the classification probability, due to the trade-off between sensitivity and specificity. Finally, we suggest that k-nearest neighbors, extra trees, and gradient boosting classifiers are the optimal algorithms with high classification probability for the substandard and falsified amoxicillin capsules.

Comparative study on the real-time monitoring of a fluid bed drying process of extruded granules using near-infrared spectroscopy and audible acoustic emission.

The process of fluidized bed drying of granules was comparatively evaluated by on-line real-time measurements of granule moisture content (MC) using near-infrared spectroscopy (NIR) and audible acoustic emission (AAE). The extruded granules were prepared by kneading a powder blend containing lactose, starch, crystalline cellulose, and riboflavin, with water. The MC of the granules (while they were dried at 35 °C in a fluidized bed dryer) was monitored simultaneously with NIR and AAE. The prediction accuracy of the NIR and AAE using partial least squares (PLS) was verified by measuring MC of the granules. The best calibration models following NIR and AAE evaluations consisted of five latent variables with correlation coefficients of 1.000 and 0.998 and root mean square error of 0.259 and 0.615, respectively. As a result of external verification, the accuracy of MC analysis by AAE was slightly lower than that of NIR; however, it was still applicable in practice. Furthermore, the end point of fluidized bed drying process was automatically determined using the PLS discriminant analysis. From the above results, it can be concluded that the AAE-mediated granule drying process can be monitored with sufficient accuracy (compared with NIR).

Mechanochemical Effect on Controlled Drug Release of Konjac Glucomannan Matrix Tablets during Dry Grinding.

To design a controlled drug release preparation based on a safe natural material, a Konjac glucomannan (KGM) mixture containing 16.0 w/w% calcium hydroxide (Ca(OH)2) was ground in a planetary ball mill for 0-120 min. The mechanochemical effect on the physicochemical properties of the KGM ground product was investigated by Fourier-transform infrared spectroscopy (FT-IR), powder X-ray spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and drug release testing. The FT-IR spectra of the ground KGM indicated that the deacetylation reaction of KGM was accelerated in the Ca(OH)2-containing sols by mechanochemical energy, and the degree of deacetylation of KGM was dependent on the grinding time. The time required for tablet disintegration of the KGM matrix tablets containing theophylline increased as the grinding time increased; therefore, drug release was sustained. The Higuchi plots of the matrix tablets obtained from KGM ground for 60-120 min exhibited good linearity because they maintained their gel matrix tablet shape during the release test. However, KGM tablets ground for 0-30 min exhibited nonlinear curves, which were caused by tablet disintegration. This suggests that drug release from the KGM matrix tablet can be freely controlled by the degree of mechanochemical treatment.

Sex-related differences in the prognosis of patients with cardiac sarcoidosis treated with cardiac resynchronization therapy.

BACKGROUND: Past studies have shown the sex-related difference in the efficacy of cardiac resynchronization therapy (CRT). However, the data for cardiac sarcoidosis (CS) are limited. OBJECTIVE: The purpose of this study was to assess the sex-related prognostic differences in CS patients with CRT. METHODS: This multicenter CS survey included 430 patients (295 females) who met the diagnostic criteria for CS. Patients were divided into those treated with primary CRT or upgraded CRT from the pacemaker (CRT group; n = 73) and others (control group; n = 357). Sex differences in the incidence of all-cause death, heart failure (HF) death including heart transplantation, ventricular arrhythmia events (VAEs) (sudden death, appropriate device therapy), cardiac adverse events (CAEs) (HF death, VAEs), changes in serum brain natriuretic peptide (BNP) levels, and left ventricular ejection fraction (LVEF) over the follow-up period were analyzed. RESULTS: During median follow-up of 5.2 years, males, but not females, in the CRT group had significantly worse all-cause mortality than patients in the control group (P <.001). In the CRT group, there was no significant sex-related difference in the incidence of HF death; however, females had significantly better VAE- and CAE-free survival than males (P = .033 and P = .008, respectively). Multivariate analysis of the CRT group showed that female sex (hazard ratio 0.37; 95% confidence interval 0.15-0.89; P = .02 and P = .6) independently predicted freedom from CAEs. During follow-up, BNP levels were significantly improved in all groups. LVEF was maintained in females with CRT. CONCLUSIONS: In CS patients with CRT, HF death-free survival was similar between sexes. However, females exhibited better VAE- and CAE-free survival than males.