Exploring factors associated with bleeding events after open heart surgery in patients on dialysis - effects of the presence or absence of warfarin therapy.

BACKGROUND: Perioperative management of patients on dialysis is critical for controlling bleeding and thrombotic risk, in addition to infection control. Postoperative anticoagulation is often difficult to control, and different institutions have different policies. Therefore, in this study, we aimed to investigate factors associated with postoperative bleeding events and whether warfarin (WF) therapy affects the incidence of postoperative bleeding events, total mortality, and stroke. METHODS: Patients who were admitted to the cardiovascular surgery department and underwent valve replacement or plasty were included, and those who underwent mechanical valve introduction were excluded. Thirty-nine patients were included in the study. The primary endpoint was to identify factors associated with the composite endpoint of postoperative bleeding events, and the secondary endpoint was to determine the effect size of WF therapy on postoperative bleeding events, all-cause mortality, and stroke and the strength of association between the crossed endpoints. The strength of the association between the crossed items was examined. RESULTS: Low body weight (p = 0.038) was identified as a factor associated with the primary endpoint of postoperative bleeding events. The secondary endpoint of whether or not patients received WF therapy was largely unrelated to bleeding events, all-cause mortality, and postoperative stroke up to 90 days after surgery. CONCLUSIONS: Preliminary studies suggest that low body weight is a risk factor for postoperative bleeding events in patients on dialysis, although further exploration of other factors will be necessary with the accumulation of similar cases.

Improved electrochemical properties of graphite electrodes incubated with iron powders in rice-paddy fields boost power outputs from microbial fuel cells.

Studies have shown that the supplementation of anode-surrounding soil with zero-valent iron (ZVI) boosts power outputs from rice paddy-field microbial fuel cells (RP-MFCs). In order to understand mechanisms by which ZVI boosts outputs from RP-MFCs, the present study operated RP-MFCs with and without ZVI, and compositions of anode-associated bacteria and electrochemical properties of graphite anodes were analyzed after 3-month operation. Metabarcoding using 16S rRNA gene fragments showed that bacterial compositions did not largely differ among these RP-MFCs. Cyclic voltammetry showed improved electrochemical properties of anodes recovered from ZVI-supplemented RP-MFCs, and this was attributed to the adhesion of iron-oxide films onto graphite surfaces. Bioelectrochemical devices equipped with graphite anodes recovered from ZVI-supplemented RP-MFCs generated higher currents than those with fresh graphite anodes. These results suggest that ZVI is oxidized to iron oxides in paddy-field soil and adheres onto graphite anodes, resulting in the boost of power outputs from RP-MFCs.

Intraoperative intact parathyroid hormone monitoring and frozen section diagnosis are essential for successful parathyroidectomy in secondary hyperparathyroidism.

Background: Total parathyroidectomy (PTx) is often performed to treat secondary hyperparathyroidism (SHPT). Successful PTx is essential to prevent recurrent and persistent SHPT because remnant parathyroid glands (PTGs) in the neck can be stimulated and may secrete excessive parathyroid hormone (PTH) in end-stage renal disease. However, to date, few studies have investigated factors contributing to successful PTx before the completion of surgery. Materials and methods: Between August 2010 and February 2020, 344 patients underwent total PTx, transcervical thymectomy, and forearm autograft for SHPT at our institute. Factors contributing to successful PTx before the completion of surgery were investigated. Preoperative imaging diagnoses, including computed tomography, ultrasonography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy, intraoperative intact PTH (IOIPTH) monitoring, and frozen section histologic diagnosis, were performed. Successful PTx was defined as intact PTH level < 60 pg/mL on postoperative day 1. A sufficient decrease in IOIPTH level was defined as > 70% decrease in intact PTH levels measured 10 min after total PTx and transcervical thymectomy compared to intact PTH levels measured before skin incision. Logistic regression analysis was conducted to investigate factors contributing to PTx success. Results: Univariate analysis showed that the number of all PTGs identified preoperatively by imaging modalities and the specimens submitted for frozen section diagnosis, which surgeon presumed to be PTGs, were not significant factors contributing to successful PTx. However, multivariate analysis revealed that the number of PTGs identified by frozen section diagnosis (P < 0.001, odds ratio [OR] 4.356, 95% confidence interval [CI] 2.499-7.592) and sufficient decrease in IOIPTH levels (P = 0.001, OR 7.847, 95% CI 2.443-25.204) significantly contributed to successful PTx. Conclusion: Sufficient intact PTH level decrease observed on IOIPTH monitoring and the number of PTGs identified by frozen section diagnosis contributed to successful PTx for SHPT. IOIPTH monitoring and frozen section diagnosis are essential for achieving successful PTx for SHPT.

Intratumoral heterogeneity of c-KIT mutations in a feline splenic mast cell tumor and their functional effects on cell proliferation.

A cat was presented with mast cell tumors (MCTs) of the skin and spleen. During the initial diagnosis, the exon 8 mutation of c-KIT was detected in the masses from skin and spleen by a commercial laboratory test. Consequently, treatment with toceranib was started. After complete remission, because of recurrence on day 117, the spleen and skin tumors were removed, but the cat eventually died on day 191. The analysis of ten cDNA clones of the c-KIT gene cloned from the surgically removed spleen revealed that seven different cDNA patterns were included, indicating the heterogeneity of this gene in the splenic MCT. The seven cDNA nucleotide patterns can be classified into four protein sequence patterns. In addition to the previously known mutations in exon 8, we identified novel mutations in exons 9, 10, and 18; four amino acids deletion in exon 9, and a point mutation in exons 10 and 18. Mouse IL-3-dependent cell line, Ba/F3, was transduced with these mutant clones, and c-KIT phosphorylation and proliferation assays were performed. We found that certain mutations affected the c-KIT phosphorylation status and cell proliferation. This suggests that heterogeneity among the population of tumor cells exists in MCTs, and that the dominant clones of this heterogeneity may contribute to the subsequent tumor cell growth.

One-Piece Frontoorbital Osteotomy With a Small Supraorbital Burr-Hole to Protect Against Intraoperative Dural Lacerations.

ABSTRACT: This paper aims to describe a new technique of 1-piece frontoorbital osteotomy with a small supraorbital burr hole, which resulted in improved safety during osteotomy of the anterior skull base. An 11 × 4 mm burr hole was created at the center of the orbit above the superior orbital rim using an "eyebrow key-window approach." Extradural dissection from the nasion to the medial side of the sphenoid ridge was performed through this hole, and dissection of the lateral side of the sphenoid ridge was completed from the edge of the coronal osteotomy. Osteotomy along the zygomaticofrontal and sphenofrontal sutures were performed using an oscillating saw with secure protection of the dura. Between December 2019 and June 2020, 3 patients with unilateral coronal craniosynostosis underwent 1-piece frontoorbital advancement with the eyebrow key-window approach. The median age was 11 months (8-15 months), median operation time was 249 minutes (244-255 minutes), and the average blood transfusion was 10.8 ml/kg (0-18 ml/kg). No complications were observed, and the technique was associated with improved safety of osteotomy around the anterior skull base for 1-piece frontoorbital advancement.

The frequencies of very long-chain acyl-CoA dehydrogenase deficiency genetic variants in Japan have changed since the implementation of expanded newborn screening.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency has been a target of expanded newborn screening (ENBS) using tandem mass spectrometry in Japan. Since the implementation of ENBS, a number of novel ACADVL variants responsible for VLCAD deficiency have been identified. In this study, genotypic differences in Japanese patients with VLCAD deficiency were investigated before and after ENBS. The ACADVL variants in 61 subjects identified through ENBS (ENBS group) and in 40 patients who subsequently developed clinical symptoms without undergoing ENBS (pre-ENBS group) were compared. Subjects in the ENBS group underwent genetic testing and/or VLCAD enzyme activity measurements. Patients in the pre-ENBS group were stratified into three clinical phenotypes and underwent genetic testing. This study revealed that the variants p.K264E, p.K382Q and c.996dupT were found in both groups, but their frequencies were lower in the ENBS group (5.2%, 3.1% and 4.2%, respectively) than in the pre-ENBS group (16.5%, 12.7% and 10.1%, respectively). In addition, p.C607S, p.T409M, p.M478I, p.G289R, p.C237R, p.T260M, and p.R229* were exclusively identified in the ENBS group. Among these variants, p.C607S exhibited the highest frequency (18.8%). The patients who were heterozygous for p.C607S demonstrated 7-42% of control enzyme activity. p.C607S is suspected to be unique to Japanese individuals. According to a comparison of enzyme activity, patients with the p.C607S variant may exhibit higher enzyme activity than those with the p.A416T, p.A180T, p.R450H, and p.K264E variants, which are responsible for the myopathic form of the disease. The VLCAD deficiency genotypes have changed since the initiation of ENBS in Japan.

A Three-dimensionally Printed Acrylonitrile Butadiene Styrene Model for the Reduction of Nasomaxillary Fracture.

The successful reduction of a nasomaxillary fracture was performed using a three-dimensional printed model. A 16-year-old boy was struck in the left orbit by a baseball; subsequently, he was diagnosed with the nasal bone fracture at a hospital, and was referred to the authors' department. A left nasomaxillary fracture and nasal bone fracture were diagnosed by computed tomography. Standard triangulated language data for the mirror image of the frontal process of the right maxilla were obtained from digital imaging and communications in medicine data for preparing a three-dimensional printed acrylonitrile butadiene styrene model. On postinjury day 13, the frontal process fracture was reduced via transconjunctival and intraoral approaches. After the reduction of the fracture, an absorbable plate fitting to the shape of three-dimensional printed acrylonitrile butadiene styrene model was molded, and the maxillary frontal process and infraorbital rim were reduced and fixed with an absorbable plate and screws. Postoperative computed tomography demonstrated a favorable reduction. The intraoperative use of the 3D printed acrylonitrile butadiene styrene model was helpful in the nasomaxillary fracture reduction and fixation.

Lacrimal Duct Obstruction Caused by Nasomaxillary Fracture: A Retrospective Analysis of Consecutive 12 Patients by Computed Tomographic Dacryocystography.

ABSTRACT: Nasomaxillary fracture is a characteristic mid-facial fracture, and there are no reports showing the fracture damaging the nasolacrimal system (NLS). This report described nasomaxillary fracture cases with NLS damages, which were assessed by computed tomographic dacryocystography (CT-DCG). A retrospective cohort study of nasomaxillary fractures diagnosed by CT was conducted from 2007 to 2015. Twelve patients (mean age: 27.5 years) were found, and their clinical symptoms were as follows: nasal deformity in 10 patients, infra-orbital hypoesthesia in 7, epiphora in 5, and diplopia in one. CT-DCG was performed for 2 patients who complained epiphora, and obstruction was found in 1 patient. All patients underwent open reduction and internal fixation (ORIF), and epiphora in 5 patients was improved. One patient, however, complained epiphora postoperatively, which was supposed to be due to the unsuitable screw insertion. Since nasomaxillary fracture could give NLS obstruction, CT-DCG is useful for diagnosis. Although ORIF is an optimal treatment, attention is needed to avoid the lacrimal canal in screwing on the nasomaxillary buttress.

Life-threatening ventricular arrhythmia and left ventricular dysfunction associated with anti-mitochondrial antibody-positive myositis: a case report.

BACKGROUND: Anti-mitochondrial antibody (AMA)-positive myositis is an atypical inflammatory myopathy characterized by chronic progression of muscle atrophy and cardiac involvement. Few detailed reports have shown the clinical course of the cardiac complications of AMA-positive myositis. CASE SUMMARY: A 47-year-old man presented with shortness of breath on exertion. Cardiac dilatation was visible on chest X-ray, and echocardiography demonstrated diffuse hypokinesis with a reduced left ventricular (LV) ejection fraction of 30%. He had mild muscle weakness in the bilateral iliopsoas muscles, and his creatine kinase (CK) and anti-mitochondrial M2 antibody levels were elevated. A liver biopsy showed no findings of primary biliary cholangitis. Coronary angiography revealed normal coronary arteries. An endomyocardial biopsy showed interstitial fibrosis and marked degeneration of the mitochondria. Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed circumferential abnormal accumulation in the LV myocardium, and he was diagnosed with cardiomyopathy associated with AMA-positive myositis. Optimal drug therapy for heart failure was started, and a cardiac resynchronization therapy-defibrillator was implanted. However, his cardiac function did not improve, and he was hospitalized due to ventricular tachycardia storm 5 years after the diagnosis. Ventricular tachycardia was terminated by radiofrequency catheter ablation on the LV-anterior papillary muscle. Steroid therapy was initiated and resulted in a decreased uptake of FDG and a normalized CK level at 3 months after his second discharge; however, LV systolic dysfunction remained 1 year later. DISCUSSION: Anti-mitochondrial antibody-positive myositis can affect the myocardium and cause severe LV dysfunction and life-threatening ventricular arrhythmia over time. KEYWORDS: Anti-mitochondrial antibody-positive myositis • Endomyocardial biopsy • Ventricular tachycardia • Left ventricular dysfunction • Case report • Magnetic resonance imaging • Near-infrared spectroscopy-intravascular ultrasound.

Application of the Caprini Risk Assessment Model for Evaluating Postoperative Deep Vein Thrombosis in Patients Undergoing Plastic and Reconstructive Surgery.

BACKGROUND: The optimal approach for assessing the risk of venous thromboembolism (VTE) in patients undergoing plastic surgery is yet to be established. This study aimed to determine the validity of the Caprini Risk Assessment Scale in identifying patients undergoing plastic surgery who are at a high risk of developing VTE. METHODS: Between December 2014 and November 2015, we enrolled 90 patients. Risk factors for VTE were assessed at baseline. The Caprini Risk Assessment Model was used to stratify patients into Caprini <4, Caprini 5-6, Caprini 7-8, and Caprini >8 groups before examination. We preoperatively screened for deep vein thrombosis (DVT) using duplex ultrasound. During operation, surgical duration and blood loss were recorded. Duplex ultrasound was repeated 2 and 7 days postoperatively to evaluate for DVT. We used a univariate analysis to determine risk factors for postoperative VTE. Confounding predictors were finally tested using a multivariate logistic regression analysis. RESULTS: One patient had preoperative DVT and was excluded from the study. Eighty-nine patients were included in the final analyses. Of the 89 patients, 7 (8%) developed postoperative DVT. Mean age, body mass index, Caprini score, and surgical duration were significantly higher in patients who developed postoperative DVT. Variables associated with increased risk of postoperative DVT using univariate analysis were Caprini scores of 7-8 and >8. Multivariate logistic regression analysis finally identified Caprini scores 7-8 [odds ratio (OR) 13, 95% confidence interval (CI) 1.67-101.98, P = 0.014] and >8 (OR 19.5, 95% CI 1.02-371.96, P = 0.048) to be independently associated with postoperative DVT. CONCLUSIONS: Although the incidence of postoperative DVT is relatively low among patients undergoing plastic surgery, Caprini scores can be used to predict postoperative VTE complications.

Inhibition of Interleukin 10 Transcription through the SMAD2/3 Signaling Pathway by Ca2+-Activated K+ Channel KCa3.1 Activation in Human T-Cell Lymphoma HuT-78 Cells.

The hyperpolarization induced by intermediate-conductance Ca2+-activated K+ channel (KCa3.1) activation increases the driving force for Ca2+ influx, which generally promotes cell proliferation, migration, and cytokine production in immunocompetent cells. Interleukin-10 (IL-10) from tumor-infiltrating lymphocytes and macrophages, lymphoma, and carcinoma cells facilitates escape from cancer immune surveillance; however, the role of KCa3.1 in IL-10 production remains unclear. The objective of the present study was to elucidate the involvement of KCa3.1 in IL-10 expression and production using the human T-cell lymphoma HuT-78 cells. In HuT-78 cells, IL-10 gene expression and production were reduced by treatment with the KCa3.1 activator, as 6-hour Western blotting showed that the protein expression ratio of phosphorylated Smad2 (P-Smad2)/Smad2, but not P-Smad3/Smad3, was decreased by the treatment with KCa3.1 activator in HuT-78 cells. Concomitant with this, the nuclear translocation of P-Smad2 was inhibited by KCa3.1 activator. Furthermore, the KCa3.1 activator-induced transcriptional repression of IL-10 disappeared with pretreatment with the calmodulin kinase II (CaMKII) inhibitor KN-62 for 1 hour, and KCa3.1 activator-induced decreases in the nuclear translocation of P-Smad2 were also prevented by pretreatment with KN-62. Taken together, the KCa3.1 activator-induced transcriptional repression of IL-10 is due to the inhibition of the nuclear translocation of P-Smad2 in HuT-78 cells, resulting in the prevention of P-Smad2/3 complex formation in nuclei, and the activation of CaMKII induced by KCa3.1 activators suppresses the constitutive activation of P-Smad2/3 in HuT-78 cells. Therefore, KCa3.1 activators have potential as a therapeutic option to suppress the tumor-promoting activities of IL-10.

Surgical Treatment of Growing Skull Fracture: Technical Aspects of Cranial Bone Reconstruction.

BACKGROUND: Growing skull fracture (GSF) is a rare, posttraumatic complication observed mainly in young infants. In GSF, the skull fracture associated with an underlying dural tear gradually expands due to herniation of the intracranial tissue into the fracture site. Many reports have discussed GSF from various points of view. However, only a few studies have focused on the details of cranial reconstruction. The present study aims to redress this omission by shedding some light on bone work in GSF surgery. METHODS: Patients registered in the institutional database who underwent surgical repair of GSF were retrospectively reviewed. RESULTS: Four patients underwent surgical repair for GSF. The site of injury was parietal in 3 patients and occipital in 1 patient . Age at the time of injury ranged from 3 months to 1 year 5 months (mean: 7 months). The duration from injury to surgery ranged from 5 to 7 months (mean: 5 months). In all patients, dural reconstruction was performed with autologous periosteum and cranial reconstruction was performed with an autologous calvarial bone graft. Regardless of the age distribution, split bone grafting was possible for all patients. CONCLUSION: To diagnose GSF promptly and thereby reduce the risk of neurologic sequelae, careful observation of the course, and education of the patients' parents are desirable. Although most children with GSF are under 3 years old, the age before the formation of the diploic layer, split bone grafts should be considered for the treatment of GSF to reduce the risk of residual cranial bone defects.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

Percutaneous ultrasound-guided sclerotherapy with polidocanol microfoam for lymphatic malformations.

BACKGROUND: Lymphatic malformations (LMs) are low-flow congenital lesions that consist of cysts of varying size. Sclerotherapy with intralesional bleomycin and OK-432 has been reported to yield dramatically beneficial results for this disorder. However, inflammation-related symptoms are often seen after treatment with these sclerosing agents. On the other hand, polidocanol (POL) is reportedly associated with fewer allergic and inflammatory reactions. Up to now, however, very few reports have documented the use of POL microfoam for treatment of LMs. This study was performed to assess the efficacy and safety of POL microfoam sclerotherapy for LMs. METHODS: Between 2003 and 2016, cases were identified from a prospectively compiled database on low-flow congenital vascular malformations before undertaking a retrospective electronic chart review. Patients were included if they had LMs that had been treated by POL microfoam sclerotherapy. The location, size, and type of LMs were assessed using ultrasound and magnetic resonance imaging. Twenty-gauge venous catheters were inserted into the lymphatic space under ultrasound visualization. The LMs were then fully aspirated if they were macrocystic in form. Microfoam composed of 3% POL was then injected under ultrasound guidance. Microcystic LMs were treated by direct injection with POL microfoam under ultrasound guidance. The outcome was assessed by clinical examination combined with findings of postsclerotherapy imaging using ultrasound and magnetic resonance imaging. RESULTS: During a 13-year period, 32 patients met the inclusion criteria. These were 11 (34%) male patients and 21 (66%) female patients with a mean age of 18 years. The LMs were localized to the head and neck (47%), the trunk (38%), and the extremities (15%). The lesions were subdivided into macrocystic (56%), mixed macrocystic and microcystic (31%), and microcystic (13%) LMs. The average lesion size was 6.6 × 4.6 × 3.0 cm. The mean number of treatment sessions was 2.8 (range, 1-15), with a mean foam volume of 4.6 (range, 1-10) mL. Excellent (47%) and moderate (41%) responses were seen in 88% of the patients. Notably, half of the patients achieved excellent or moderate resolution with a single treatment session. Intralesional hemorrhage occurred in four patients (13%) but resolved spontaneously. Only one patient with mixed macrocystic and microcystic LMs developed post-therapy infection. However, the other patients did not develop any post-therapy inflammation-related symptoms, including fever, pain, and marked swelling. CONCLUSIONS: Percutaneous sclerotherapy using POL microfoam appears to be safe and effective for treatment of LMs. Ultrasound-guided POL microfoam sclerotherapy should be considered for such lesions, particularly those that are exclusively macrocystic.

Incidence of deep vein thrombosis in patients undergoing breast reconstruction with autologous tissue transfer.

Background Breast reconstruction is associated with multiple risk factors for venous thromboembolism. However, the incidence of deep vein thrombosis in patients undergoing breast reconstruction is uncertain. Objective The aim of this study was to prospectively evaluate the incidence of deep vein thrombosis in patients undergoing breast reconstruction using autologous tissue transfer and to identify potential risk factors for deep vein thrombosis. Methods Thirty-five patients undergoing breast reconstruction were enrolled. We measured patients' preoperative characteristics including age, body mass index (kg/m2), and risk factors for deep vein thrombosis. The preoperative diameter of each venous segment in the deep veins was measured using duplex ultrasound. All patients received intermittent pneumatic pump and elastic compression stockings for postoperative thromboprophylaxis. Results Among the 35 patients evaluated, 11 (31.4%) were found to have deep vein thrombosis postoperatively, and one patient was found to have pulmonary embolism postoperatively. All instances of deep vein thrombosis developed in the calf and were asymptomatic. Ten of 11 patients underwent free flap transfer, and the remaining one patient received a latissimus dorsi pedicled flap. Deep vein thrombosis incidence did not significantly differ between patients with a free flap or pedicled flap (P = 0.13). Documented risk factors for deep vein thrombosis demonstrated no significant differences between patients with and without deep vein thrombosis. The diameter of the common femoral vein was significantly larger in patients who developed postoperative deep vein thrombosis than in those who did not ( P < 0.05). Conclusions The morbidity of deep vein thrombosis in patients who underwent breast reconstruction using autologous tissue transfer was relatively high. Since only the diameter of the common femoral vein was predictive of developing postoperative deep vein thrombosis, postoperative pharmacological thromboprophylaxis should be considered for all patients undergoing breast reconstruction regardless of operative procedure.

Time taken to the maximum increase in the oxygenated hemoglobin level in calf muscle as a predictor of mild and moderate post-thrombotic syndrome.

BACKGROUND: Near-infrared spectroscopy (NIRS) allows continuous noninvasive monitoring of changes in the tissue levels of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) and can identify the severity of chronic venous diseases. Here we investigated the predictors of post-thrombotic syndrome (PTS) using NIRS in patients with a first episode of deep venous thrombosis (DVT). METHODS: The study enrolled 129 patients with DVT. Risk factors in each patient were assessed at presentation. Venous abnormalities confirmed by ultrasound and parameters derived from NIRS were evaluated at 6 months after DVT. On standing, increases in O2Hb and HHb (ΔO2Hbst and ΔHHbst) and the times taken for each concentration to become maximal (TO2Hbst, and THHbst) were measured. During 10 tiptoe movements, O2Hb showed a continuous decrease (ΔO2Hbex), whereas venous expulsion (ΔHHbEex) and subsequent retention (ΔHHbRex) were observed. The oxygenation index (HbD; HbD = O2Hb - HHb) was also calculated at the end of standing and at the end of 10 tiptoe movements (ΔHbDst and ΔHbDex). Final clinical manifestations were evaluated at 6 years, and PTS was considered to be present if the Villalta score was ≥5. RESULTS: Thirteen patients were excluded and 116 patients were finally included. Of these, 19 (16%) developed PTS. Among various NIRS-derived parameters, TO2Hbst had the highest area under the curve (0.88; 95% confidence interval [CI], 0.80-0.93; P < .01) with the best cutoff value (TO2Hbst ≤48 seconds). On univariate analysis, variables associated with greater risk for development of PTS were stroke (odds ratio [OR], 5.59; 95% CI, 0.74-42.41; P = .06), idiopathic DVT (OR, 4.13; 95% CI, 1.36-12.55; P < .01) and iliofemoral DVT (OR, 4.31; 95% CI, 1.48-12.60; P < .01) at initial presentation, venous occlusion combined with reflux (OR, 4.24; 95% CI, 1.50-12.00; P < .01), and NIRS-derived TO2Hbst ≤48 seconds (OR, 43.03; 95% CI, 9.04-204.81; P < .01) at 6 months. Multivariate logistic regression analysis finally revealed venous occlusion combined with reflux (OR, 4.80; 95% CI, 1.03-22.36; P < .05) and NIRS-derived TO2Hbst ≤48 seconds (OR, 53.73; 95% CI, 8.43-342.41; P < .01) to be independently associated with PTS progression. CONCLUSIONS: NIRS-derived TO2Hbst ≤48 seconds is a promising time-course predictor of PTS progression.

Clinical, biochemical and molecular investigation of adult-onset glutaric acidemia type II: Characteristics in comparison with pediatric cases.

INTRODUCTION: An increasing number of adult patients have been diagnosed with fatty acid ß-oxidation disorders with the rising use of diagnostic technologies. In this study, clinical, biochemical, and molecular characteristics of 2 Japanese patients with adult-onset glutaric acidemia type II (GA2) were investigated and compared with those of pediatric cases. METHODS: The patients were a 58-year-old male and a 31-year-old male. In both cases, episodes of myopathic symptoms, including myalgia, muscle weakness, and liver dysfunction of unknown cause, had been noted for the past several years. Muscle biopsy, urinary organic acid analysis (OA), acylcarnitine (AC) analysis in dried blood spots (DBS) and serum, immunoblotting, genetic analysis, and an in vitro probe acylcarnitine (IVP) assay were used for diagnosis and investigation. RESULTS: In both cases, there was no obvious abnormality of AC in DBS or urinary OA, although there was a increase in medium- and long-chain ACs in serum; also, fat deposits were observed in the muscle biopsy. Immunoblotting and gene analysis revealed that both patients had GA2 due to a defect in electron transfer flavoprotein dehydrogenase (ETFDH). The IVP assay indicated no special abnormalities in either case. CONCLUSION: Late-onset GA2 is separated into the intermediate and myopathic forms. In the myopathic form, episodic muscular symptoms or liver dysfunction are primarily exhibited after later childhood. Muscle biopsy and serum (or plasma) AC analysis allow accurate diagnosis in contrast with other biochemical tests, such as analysis of AC in DBS, urinary OA, or the IVP assay, which show fewer abnormalities in the myopathic form compared to intermediate form.

Elevation of pivaloylcarnitine by sivelestat sodium in two children.

BACKGROUND: Sivelestat sodium (sivelestat), a neutrophil elastase inhibitor, is used to treat acute respiratory distress syndrome (ARDS). We report two cases that developed elevated C5-acylcarnitine (C5-AC) levels following treatment with sivelestat. Case 1 was a 14-day-old female infant born at 25 weeks and 1 day of gestation who was treated with sivelestat for the prophylaxis of Wilson-Mikity syndrome soon after birth. Isovaleric acidemia (IVA) was suspected based on a newborn screening using tandem mass spectrometry (MS/MS). Her C5-AC level was elevated to 4.49 µM (cut-off, <1.0) after treatment with sivelestat. Case 2 was a 4-year-old female with pneumocystis pneumonia that developed during chemotherapy for disseminated medulloblastoma. Sivelestat was given for the complication of ARDS. Her C5-AC level increased (1.09 µM) after eight days of treatment with sivelestat. RESULTS: In both cases, IVA was ruled out because isovalerylglycine was not observed in the urinary organic acid analysis. Case 1 was associated with carnitine deficiency (C0 9.16 µM; reference value, 10-60). Liquid chromatography-MS/MS confirmed elevated pivaloylcarnitine (PVC) in both cases. DISCUSSION: Similar to antibiotics containing pivalic acid (PVA), sivelestat contains PVA, which has the potential to cause secondary carnitine deficiency. In addition, elevated PVC can lead to false positive findings of IVA in newborns screened using MS/MS.

The effect of Katsura-uri (Japanese pickling melon, Cucumis melo var. conomon) and its derived ingredient methylthioacetic acid on energy metabolism during aerobic exercise.

PURPOSE: We investigated the effect of Katsura-uri (Japanese pickling melon; Cucumis melo var. conomon) on energy metabolism during exercise in human and animal studies. METHODS: Eight healthy men (mean age, 21.4 ± 0.7 years) participated in a single-blind, crossover study. Thirty minutes after ingesting the Katsura-uri drink or placebo drink, they exercised on a cycle ergometer at 40% maximal heart rate for 30 min. Respiratory gas analysis was performed during exercise to examine oxygen consumption and substrate utilization. Blood biochemical parameters were evaluated during exercise. In the animal study, the effect of methylthioacetic acid (MTA), a Katsura-uri derived component was examined in mice. Immediately after running at 25 m/min for 30 min, biochemical parameters in the hind limb muscle and blood of mice were measured. RESULTS: Oxygen consumption during exercise was higher in the Katsura-uri condition (19.8 ± 3.5 mL/kg/min) than the placebo condition (18.6 ± 3.0 mL/kg/min) (P < 0.05). The elevation of blood lactate was lower in the Katsura-uri condition (1.7 ± 0.4 mM) than the placebo condition (2.2 ± 0.6 mM) 15 min after beginning exercise (P < 0.05). There was a higher positive correlation between lactate concentration and carbohydrate oxidation during exercise in the Katsura-uri condition (R(2) = 0.86) compared to the placebo condition (R(2) = 0.47). The decrease in intermuscular pH and the increase in blood lactate following exercise were prevented by MTA supplementation (250 ppm) with significant differences in the MTA-supplemented group compared to the control group. CONCLUSIONS: These results suggest that the ingestion of Katsura-uri and/or MTA improves glucose metabolism and acidification in skeletal muscles during exercise in human and animal studies.

Possible involvement of 15-deoxy-Δ(12,14) -prostaglandin J2 in the development of leptin resistance.

Obesity is a worldwide health problem that urgently needs to be solved. Leptin is an anti-obesity hormone that activates satiety signals to the brain. Evidence to suggest that leptin resistance is involved in the development of obesity is increasing; however, the molecular mechanisms involved remain unclear. We herein demonstrated that 15-deoxy-Δ(12,14) -prostaglandin J2 (15d-PGJ2 ) was involved in the development of leptin resistance. A treatment with 15d-PGJ2 inhibited the leptin-induced activation of signal transducer and activator of transcription 3 (STAT3) in neuronal cells (SH-SY5Y-Ob-Rb cells). Furthermore, the intracerebroventricular administration of 15d-PGJ2 reversed the inhibitory effects of leptin on food intake in rats. The peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist, GW9662, slightly reversed the inhibitory effects of 15d-PGJ2 on the leptin-induced activation of STAT3 in neuronal cells. The PPAR-γ agonist, rosiglitazone, also inhibited leptin-induced STAT3 phosphorylation. Therefore, the inhibitory effects of 15d-PGJ2 may be mediated through PPAR-γ. On the other hand, 15d-PGJ2 -induced leptin resistance may not be mediated by endoplasmic reticulum stress or suppressor of cytokine signaling 3. The results of the present study suggest that 15d-PGJ2 is a novel factor for the development of leptin resistance in obesity. Leptin resistance, an insensitivity to the actions of leptin, is involved in the development of obesity. Here, we found 15-deoxy-Δ(12,14) -prostaglandin J2 (15d-PGJ2 ) may be involved in the development of leptin resistance. The present results suggest that the 15d-PGJ2 may be a novel factor for the development of leptin resistance in obesity. 15d-PGJ2 , 15-Deoxy-Δ(12,14) -prostaglandin J2; STAT3, signal tranducer and activator of transcription 3.