Closure of the Entire Fistula With Highly Effective Chemocauterization Using the Distal Hood Endoscope: A Novel Procedure for the Treatment of Pyriform Sinus Fistula.

BACKGROUND: Pyriform sinus fistula (PSF) causes a recurrent abscess in the neck. Endoscopic chemocauterization with trichloroacetic acid (TCA) for PSF is a simple, reproducible, and reliable procedure for treating PSF; however, there is concern about complications caused by TCA overflowing into the larynx. To prevent these complications, we devised a highly effective chemocauterization using a distal hooded endoscope (HuDHE). Our aim is to determine the efficacy and safety of HuDHE in children with PSF. METHODS: The main features of HuDHE are as follows (1) an endoscope with a translucent silicon hood at the tip was made; (2) TCA was endoscopically injected into the PSF; and (3) the color change of the mucosa into PSF was endoscopically evaluated. Data on children receiving HuDHE for PSF in the past seven years were collected from medical records. RESULTS: Data were obtained for eight children receiving HuDHE. The success rate of treatment for PSF after the first TCA chemocauterization was 87.5% (7/8) and the cumulative success rate after the second treatment was 100% (8/8). None of the children had recurrent PSF or serious complications such as vocal cord paralysis after HuDHE. CONCLUSION: HuDHE appears to be a less invasive, safe, and effective treatment for PSF.

Genome-wide association study identifies a new susceptibility locus in PLA2G4C for Multiple System Atrophy.

To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European and North American samples. In the GWAS stage rs2303744 on chromosome 19 showed a suggestive association ( P = 6.5 × 10 -7 ) that was replicated in additional Japanese samples ( P = 2.9 × 10 -6 . OR = 1.58; 95% confidence interval, 1.30 to 1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data ( P = 5.0 × 10 -15 . Odds ratio= 1.49; 95% CI 1.35 to 1.72). The association of rs2303744 with MSA remained significant in combined European/North American samples ( P =0.023. Odds ratio=1.14; 95% CI 1.02 to 1.28) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution in PLA2G4C that encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform that may perturb membrane phospholipids and α-synuclein biology.

[Global Testicular Infarction during Treatment for Epididymitis].

We report a case of global testicular infarction associated with epididymitis. A 26-year-old man with a history of clean intermittent self-catheterization since he was 1 year old presented to our hospital with left scrotal pain and swelling. He was diagnosed with epididymitis and was prescribed levofloxacin. On the next day, he returned with worsened symptoms of left scrotal pain, swelling, and fever. He was admitted because of his severe symptoms and high C-reactive protein level in the blood test. Antimicrobial therapy with intravenous flomoxef and analgesic treatment with pentazocine and loxoprofen were started but the symptoms did not improve. The color-Doppler ultrasound repeated on the 1st, 4th, and 5th day of admission showed left epididymal hypervascularity but it did not indicate testicular hypovascularity in any examinations. On the 6th day of admission, a contrast-magnetic resonance imaging (MRI) scan revealed no contrast enhancement in the left testis and high orchiectomy was performed. On pathological examination, abscess of the entire epididymis and generalized necrosis of the testes were observed. Inflammatory cell infiltration and thrombus formation were observed in almost all veins of the testis and spermatic cord, and the diagnosis of global testicular infarction associated with epididymitis was made. Global testicular infarction has been reported as a rare complication of epididymitis and should be considered in the case of atypical course of epididymitis.

Fibrodysplasia ossificans progressiva: Review and research activities in Japan.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic skeletal disorder manifesting progressive heterotopic ossification (HO) and congenital malformation of the great toes. Since 2007, we have conducted research on FOP. Here, we review the findings on FOP published to date, including the results of our research. Epidemiological studies in Japan have indicated that FOP has nearly the same prevalence in Japan as in the rest of the world. Basic research on its pathoetiology has progressed rapidly since the identification of the causal gene in 2006. Clinical and radiological findings have been thoroughly researched, including early radiological signs, and diagnostic criteria were established, designating FOP as an intractable disease in Japan. In patients with FOP, the progression of HO is associated with numerous disabilities, often manifesting in vicious cycles that can lead to early mortality. Through cross-sectional and short-term longitudinal studies, we have explored patient education, quality of life, and activities of daily living among Japanese patients. The management of FOP requires education of patients and caregivers, the use of medications to settle inflammation and flare-ups, instructions to ensure proper oral care, and other compensatory approaches that aid in rehabilitation. An avoidance of medical intervention, which may cause HO to progress, is also important. The advent of new drugs to prevent HO could have clinical benefit.

Longitudinal study of the activities of daily living and quality of life in Japanese patients with fibrodysplasia ossificans progressiva.

PURPOSE: Fibrodysplasia ossificans progressiva is a rare congenital disorder that causes systemic heterotopic ossification, leading to systemic ankyloses and mobility losses. This study aimed to ascertain the natural history of fibrodysplasia ossificans progressiva. METHODS: In addition to the medical history questionnaire, patients aged 16 years and older were asked to complete activities of daily living and quality of life surveys using the Barthel Index, MOS 36-Item Short-Form Health Survey, and Health Assessment Questionnaire. The surveys were conducted over a 4-years period. RESULTS: Of the 15 participating patients, 13 reported swelling during the study period. The Barthel Index and Health Assessment Questionnaire surveys indicated a tendency for questionnaire items related to arm function to reflect early decreases in the activities of daily living. Decreases in activities of daily living functioning were closely related to decreases in the quality of life in physical function domains. Activities of daily living and quality of life were maintained at a similar level to baseline values over the study period (Barthel Index: p = 0.42, MOS 36-Item Short-Form Health Survey: p = 0.43, Health Assessment Questionnaire: p = 0.87). CONCLUSIONS: We obtained longitudinal information relating to natural history on fibrodysplasia ossificans progressiva patients. Implications for rehabilitation Fibrodysplasia ossificans progressiva is a rare congenital disease that causes heterotopic ossification of muscle tissue throughout the body, leading to systemic ankyloses and mobility losses. When the Barthel Index was high and the activities of daily living were relatively stable, the items on the Health Assessment Questionnaire that are related to arm function began to show impairment. Early focus on upper extremity function that includes the use of assistive devices during the period when a patient is still able to perform many activities of daily living is important. Although decreases in activities of daily living functioning were closely related to decreases in the quality of life in the physical function domains, the scores of the domains other than physical function were similar to the national standard score.

Early Rehabilitation and In-Hospital Mortality in Intensive Care Patients With Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia is one of the most common infectious diseases and can be fatal. The benefits of early rehabilitation in intensive care units are known, but the association between early rehabilitation and in-hospital mortality of patients with community-acquired pneumonia admitted to intensive care units has not been studied. OBJECTIVES: To study the association between early rehabilitation and the in-hospital mortality of patients with community- acquired pneumonia admitted to intensive care units, effects of early rehabilitation on unit and hospital lengths of stay, and total costs of hospitalization. METHODS: A retrospective observational cohort study using a national inpatient database of patients with community-acquired pneumonia admitted to intensive care units in acute care hospitals in Japan from July 2011 through March 2014. Propensity score-matching analysis was used to compare outcomes between patients with and without early rehabilitation (within 2 days of admission). RESULTS: Among 8732 eligible patients, propensity score matching created 972 pairs of patients with and without early rehabilitation. The early rehabilitation group had significantly lower in-hospital mortality than did the group without early rehabilitation (17.9% vs 21.9%, respectively; P = .03). The groups did not differ significantly in intensive care unit or hospital lengths of stay or in total costs of hospitalization. CONCLUSIONS: Early rehabilitation within 2 days of admission was associated with reduced in-hospital mortality of patients with community-acquired pneumonia admitted to intensive care units.

Maternal smoking as a risk factor for childhood intussusception.

Risk factors for intussusception have only rarely been reported. We examined the association between the risk of hospital admission for intussusception and maternal smoking, using a nationwide population-based longitudinal survey begun in Japan in 2010. Maternal smoking status was queried at 6 months of age, and responses to questions at 18 months of age about history of hospitalization for intussusception during the previous year were used as an outcome of interest. We conducted logistic regression analyses controlling for potential confounding factors. Maternal smoking increased the risk of hospitalization for intussusception (adjusted OR = 2.75, 95% CI [1.09, 6.96]) compared with not smoking, and a dose-response relationship was observed for the association. Maternal smoking is associated with an increased risk of intussusception development in children between the ages of 6 and 18 months.

Risk Factors for In-hospital Mortality and Reamputation Following Lower Limb Amputation.

OBJECTIVE: Studies on the outcomes of lower limb amputation have been limited by the use of selected study populations and small sample sizes. Although reamputation is an important outcome following lower limb amputation, the risk factors for reamputation remain to be elucidated. The present study was performed to identify risk factors for in-hospital death and reamputation following lower limb amputation. METHODS: Using a national inpatient database in Japan, we identified 13,774 patients who underwent lower limb amputation. We examined the patients' backgrounds and employed a multivariable logistic regression analysis to identify factors associated with in-hospital death or reamputation. RESULTS: The average age of the 13,774 patients was 72.4 years, and 63.1% (n=8694) were male. The overall in-hospital mortality rate was 10.8% (1481/13,774). The reamputation rate was 10.1% (782/7779) for patients who initially underwent foot or transtibial amputation (18.2% [391/2148] for foot amputations and 6.9% [391/5631] for transtibial amputations). Multivariable logistic regression analysis revealed higher age, male sex, peripheral vascular disease, use of insulin, hemodialysis, and higher numbers of comorbidities as significant risk factors for reamputation or in-hospital death. Use of hemodialysis was the strongest risk factor (odds ratio, 2.10; 95% confidence interval, 1.87-2.35). CONCLUSIONS: The in-hospital mortality and reamputation rates following lower limb amputation were considerably high, reflecting the severely ill conditions of patients with advanced chronic diseases. Risk factors for in-hospital death and reamputation following lower limb amputation were identified. These should aid surgeons in determining a patient's risk of a poor outcome and deciding on the level of amputation.

Reversible Motor Paralysis and Early Cardiac Rehabilitation in Patients With Advanced Heart Failure Receiving Left Ventricular Assist Device Therapy.

Advanced heart failure (HF) is sometimes complicated with brain impairment because of a microthrombosis caused by decreased left ventricular contraction or reduced brain circulation. Some patients may recover after left ventricular assist device (LVAD) implantation. However, little is known about the perioperative therapeutic strategy in patients suffering from such complications, particularly from a cardiac rehabilitation viewpoint. We report on a 58-year-old male patient with a previous history of poliomyelitis and a light paralysis in the left upper extremity, who suffered left hemiplegia with no evidence of stroke after hemodynamic deterioration. The combination therapy of perioperative cardiac rehabilitation and LVAD therapy improved his left hemiplegia as well as activities of daily living, and the patient was discharged on foot on postoperative day 72 after briefing the family on LVAD home management. Early initiation of cardiac rehabilitation before LVAD implantation may be a key for the smooth discharge and resocialization of patients suffering from brain impairment complicated with advanced HF.

Mortality-Reducing Effect of Rehabilitation for COPD: Observational Propensity-Matched Cohort Study Using a Nationwide Database.

BACKGROUND: In the course of therapy of patients with COPD, non-pharmacologic treatment, such as rehabilitation, plays an important role. Although some studies have provided concrete evidence of the effectiveness of rehabilitation in improving functional outcomes in subjects with COPD, evidence of its mortality-reducing effect has been insufficient. In the present study, we examined whether rehabilitation had positive effects on in-hospital mortality of subjects with COPD. METHODS: We used the Japanese Diagnosis Procedure Combination nationwide administrative claims database. This was a retrospective cohort study, and there were 18,037 eligible subjects with COPD from 1,055 hospitals. The main outcome was in-hospital mortality rates. A one-to-one propensity score matching method was used to compare hospital mortality rates after admission between rehabilitation and non-rehabilitation groups. RESULTS: A total of 3,356 pairs of subjects were selected from the rehabilitation and non-rehabilitation groups (n = 6,712). Subjects in the rehabilitation program showed a reduction in the odds of mortality (odds ratio = 0.80, 95% CI 0.65-1.00, P = .045). In the subgroup analyses, the rehabilitation group had a lower in-hospital mortality in the pre-obese subgroup (body mass index 25.0-29.9) than the non-rehabilitation group (P = .02). Although not significant, the rehabilitation group showed a relatively low in-hospital mortality in the Hugh-Jones dyspnea scale class 5 subgroup (P = .066). CONCLUSIONS: This large nationwide cohort study showed that rehabilitation indeed contributed to a reduction of in-hospital mortality. These findings underscore the importance of adopting rehabilitation as part of the treatment of COPD.

Three-Dimensional Motion Analysis of Lumbopelvic Rhythm During Trunk Extension.

Hip-spine coordination, known as the lumbopelvic rhythm, can be expressed as the lumbar-hip ratio. The lumbopelvic rhythm and lumbar-hip ratio can be used to assess lower limb function. We clarified the lumbopelvic rhythm and lumbar-hip ratio during trunk extension. We established a novel set of marker positions for three-dimensional motion analysis to assess the lumbar spinal angle. The original markers were placed on both paravertebral muscle groups at the 11th thoracic spinous process level, the 10th and 12th thoracic spinous processes, and the pelvis. We measured angle data during trunk extension using three-dimensional motion analysis, and the data for eight healthy male subjects were categorized into backward and forward phases. The lumbar-hip ratio increased significantly from 1.2 to 1.9 (mean, 1.6) in the backward phase, indicating considerable movement of the lumbar spine compared with hip movement in the latter phase. In the forward phase, the ratio decreased significantly from 1.9 to 0.5 (mean, 1.5). After completion of 80% of the forward phase, the lumbar-hip ratio decreased to <1.0. The lumbopelvic rhythm for trunk extension was better expressed by a cubic or quadratic function than a linear function. According to a linear function, when the hip extends by 1°, lumbar spine extends by 1.9°. Therefore, lumbar spinal movement was greater than hip movement in the sagittal plane. The implication of the curved line would indicate lumbar extension instead of the limitation of hip extension.

Variants associated with Gaucher disease in multiple system atrophy.

OBJECTIVE: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. METHODS: We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. RESULTS: In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10(-3)). INTERPRETATION: The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

Phenotypic differences of patients with fibrodysplasia ossificans progressive due to p.Arg258Ser variants of ACVR1.

Fibrodysplasia ossificans progressiva (FOP) is a rare, congenital disorder caused by heterozygous mutation of the bone morphogenetic protein type I receptor ACVR1. Various forms of atypical FOP have recently been identified, and a recurrent mutation, ACVR1 (p.Arg258Ser) was reported. We encountered a 17-year-old Japanese female patient with sporadic occurrence of FOP. At the age of 7 years, radiological examination revealed progressive heterotopic ossification and cervical spine malformations. Although great toe malformation was not observed, we diagnosed her as having FOP. Then, ACVR1 was analyzed and a recurrent mutation of p.Arg258Ser was identified. We noticed that there may be phenotypic differences between c.774G>T and c.774G>C, which lead to the same amino-acid change, p.Arg258Ser. Genotype-phenotype correlation was discussed with the review of the previous reports.

Education and related support from medical specialists for Japanese patients with major skeletal dysplasias.

BACKGROUND: Skeletal dysplasias manifest various clinical symptoms. Age at onset, severity, and progression of symptoms differ even among individuals with the same diagnosis. Though necessary support in education is presumed to differ among patients with different disorders, few articles report on education in patients with skeletal dysplasias. OBJECTIVE: To clarify what types of schools children with major skeletal dysplasias attend, what kind of support they needed at schools, and how the advice on such support was conveyed from medical specialists to schools. METHODS: Questionnaire study on patients with achondroplasia or hypochondroplasia (A/HCH), and osteogenesis imperfecta (OI). RESULTS: In A/HCH childhood locomotion ability was high and most patients had received general education, irrespective of their generation. Children with OI showed a lower level of locomotion ability; only about half of them had received general education. In selecting schools, the patients received advice from pediatricians, physiatrists, and orthopedic surgeons. The degree of necessity and content of support at the schools differed between A/HCH and OI. Remodeling of the lavatory, washbasin, and chair and support during swimming lessons were common in A/HCH patients. Support in school for OI patients was more frequent and included propelling wheelchairs, assisting in the use of the bathroom, and remodeling the lavatory. Most children were restricted from participating in physical education classes. CONCLUSIONS: Locomotion ability and the necessary support at school differed between A/HCH and OI. Support and advice from medical specialists who recognize disability of patients with skeletal dysplasias may improve patients' participation and education in schools.

[Pulmonary artery sling and single ventricle treated with a simultaneous operation of slide tracheoplasty, left pulmonary artery reimplantation, and bidirectional cavo-pulmonary shunt].

Pulmonary artery sling is frequently combined with tracheal stenosis, and occasionally combined with congenital heart defects. However, there are few reports of successfully treated cases that were combined with single ventricle. In this article, we report a successfully treated case of pulmonary artery sling combined with tracheal stenosis, single ventricle, pulmonary atresia, vascular ring, and bilateral superior vena cava. A male infant was referred to our hospital for central cyanosis, and was diagnosed with single ventricle (tricuspid stenosis, multiple ventricular septal defect, and hypoplastic right ventricle)with pulmonary atresia by echocardiogram. Tracheal stenosis was shown at cardiac catheterization. Pulmonary artery sling and tracheal diverticulum were diagnosed by computed tomography (CT) and magnetic resonance imaging(MRI)examination. Furthermore, the patient was complicated by vascular ring, which consisted of right aortic arch, an aberrant left subclavian artery, and patent ductus arteriosus, and this ductus arteriosus was connected to the left subclavian artery and pulmonary arterial trunk. After 6 months of medical treatment, including continuous infusion of prostaglandin, re-evaluation was performed by cardiac catheterization. We considered that bidirectional cavo-pulmonary shunt was appropriate for the patient since his pulmonary vasculature had matured well. An operation was performed under the use of cardio-pulmonary bypass. Release of vascular ring by division of the ductus, bilateral bidirectional cavo-pulmonary shunt, and a slide tracheoplasty for tracheal stenosis were performed simultaneously. His recovery was uneventful, and he is currently waiting to receive a Fontan-type operation.

Modified Collis-Nissen procedure for long gap pure esophageal atresia.

BACKGROUND/PURPOSE: Esophageal reconstruction in long gap esophageal atresia (EA) is technically challenging, and several procedures have been described. The purpose of this study is to review our experience with the modified Collis-Nissen procedure in the repair of long gap pure EA. METHODS: Six patients with pure EA were treated at our institution from 1985 to 2008. Patients' demographics, surgical technique, timing of repair, early and late complications, and long-term functional outcomes were retrospectively reviewed. RESULTS: Five primary cases and 1 redo case were included. The mean gap length was 5.3 vertebral bodies (range, 4-6). Modified Collis-Nissen procedure was performed at a mean age of 11.6 months (range, 9-14 months) in primary cases. There was 1 anastomotic leak in the redo case, which healed spontaneously. Two patients had anastomotic strictures requiring balloon dilatations. Patients were weaned from tube feeding at a mean duration of 4 months (range, 1-6 months) postoperatively. All patients have normal oral intake at the last follow-up visit. Two adult patients had normal growth and development and no digestive symptoms. Endoscopic examination and pH monitoring showed no signs of significant gastroesophageal reflux. CONCLUSIONS: Modified Collis-Nissen procedure is a good option to consider in patients with long gap pure EA and is associated with an acceptable complication rate and promising short- and long-term results.