Construction and Quality Evaluation of the Japanese Sarcopenic Dysphagia Database.

OBJECTIVES: To describe the activity and evaluate the quality of the Japanese sarcopenic dysphagia database. DESIGN: Cohort registry study. SETTING: 19 hospitals including 9 acute care hospitals, 8 rehabilitation hospitals, 2 long-term care hospitals, and 1 home visit rehabilitation team. PARTICIPANTS: 467 dysphagic patients, aged 20 years and older. MEASUREMENTS: The following indices were assessed at baseline: age, sex, main disease, sarcopenic dysphagia, whole body sarcopenia, Food Intake Level Scale (FILS), malnutrition diagnosed by the Global Leadership Initiative on Malnutrition criteria, oral status assessed by the Revised Oral Assessment Guide or the Oral Health Assessment Tool, activities of daily living assessed by the Functional Independence Measure (FIM) or the Barthel Index (BI), Charlson comorbidity index, C-reactive protein and serum albumin levels, dysarthria, hoarseness, aphasia, pressure ulcers, bladder, bowel, and kidney function, respiratory status, polypharmacy, number of drugs, and involvement of health care professionals and rehabilitation nutrition team. FILS, FIM or BI, and outcome including discharge destination were assessed at follow-up. A simple comparison of cases and evaluation of the quality of data were performed. RESULTS: The mean age was 80.4 ± 11.4 yr. The variable input error was 0. The number of patients with missing data was high for estimated glomerular filtration rate, C-reactive protein, serum albumin, skeletal mass index, and tongue pressure. The prevalence of either probable, possible, or no sarcopenic dysphagia was 105 (23%), 182 (39%), or 179 (38%), respectively. Doctors including physiatrists, nurses, physical therapists, and registered dietitians were involved with most patients, while the rehabilitation nutrition team was involved in only 16% of patients. CONCLUSIONS: The quality of the database was relatively high. Sarcopenic dysphagia is common in patients with dysphagia.

Concurrent and predictive validity of the Mini Nutritional Assessment Short-Form and the Geriatric Nutritional Risk Index in older stroke rehabilitation patients.

BACKGROUND: Malnutrition may worsen clinical outcomes in stroke patients. Few malnutrition screening tools have been validated in the rehabilitation setting. The present study aimed to assess the concurrent and predictive validity of two malnutrition screening tools. METHODS: We retrospectively collected scores for the Mini Nutritional Assessment Short-Form (MNA-SF) and the Geriatric Nutritional Risk Index (GNRI) in consecutive stroke patients aged ≥65 years in a rehabilitation hospital. Concurrent validity was confirmed against the European Society for Clinical Nutrition and Metabolism diagnostic criteria for malnutrition (ESPEN-DCM). Malnutrition risk within the ESPEN-DCM process was assessed using the Malnutrition Universal Screening Tool. Cut-off values with maximum Youden index, and with sensitivity (Se) >90% and specificity (Sp) >50%, were defined as appropriate for identification and screening of malnutrition, respectively. The Functional Independence Measure and discharge destination were used to explore predictive validity. RESULTS: Overall, 420 patients were analysed. Of these, we included 125 patients in the malnutrition group and 295 in the non-malnutrition group based on the ESPEN-DCM. Cut-off values for the identification and screening of malnutrition were 5 (Se: 0.78; Sp: 0.85) and 7 (Se: 0.96; Sp: 0.57) for the MNA-SF; 92 (Se: 0.74; Sp: 0.84) and 98 (Se: 0.93; Sp: 0.50) for the GNRI, respectively. The GNRI predicted discharge to acute care hospital, whereas the MNA-SF did not predict all outcome measures. CONCLUSIONS: The MNA-SF and the GNRI have a fair concurrent validity in stroke patients, although lower cut-off values than currently used were required for the MNA-SF. The GNRI exhibits good predictive validity for discharge destination.

Association of salivary lactate dehydrogenase level with systemic inflammation in a Japanese population.

BACKGROUND AND OBJECTIVE: Salivary lactate dehydrogenase (LDH) was reported to be a useful parameter for the screening of periodontal disease. We performed a cross-sectional study to verify the usefulness of salivary LDH as a biomarker of periodontitis and to investigate the association of severity of periodontitis with systemic inflammation by measuring salivary LDH and serum high sensitive C-reactive protein (hs-CRP) levels in a community-based middle-aged and elderly population in Japan. MATERIAL AND METHODS: We recruited 644 men and 1171 women, aged 30-79 years, who participated in the Toon Health Study during 2011-15. Periodontal condition was assessed by full-mouth examination including mean value of probing depth, percentage of probing depth of ≥4 mm and ≥6 mm, and bleeding on probing. Saliva and blood serum samples were collected for measurement of salivary LDH level and hs-CRP, respectively. A linear trend across quartiles of salivary LDH was calculated using linear regression. Interaction of salivary LDH and overweight status (body mass index of ≥25 kg/m2 ) was tested using the cross-product term of log-transformed continuous salivary LDH and overweight status. RESULTS: Analysis of covariance adjusted for potential confounders revealed strong associations between salivary LDH level and the indicators of periodontal condition (P < .01) in both men and women. Sex- and age-adjusted mean values of hs-CRP according to salivary LDH quartiles were 0.40, 0.45, 0.45 and 0.50 mg/L (P for trend <.01). Although the association was attenuated after further adjustment for body mass index, hypertension, diabetes mellitus, dyslipidemia, alcohol intake, smoking status and physical activity. When stratified by overweight status, the association remained significant in overweight individuals (P = .03). The multivariable adjusted odds ratio of hs-CRP level of ≥1 mg/L for the highest vs lowest quartile of salivary LDH was 1.93 (95% CI, 1.01-3.69) in overweight individuals, but not significant in non-overweight individuals. CONCLUSION: Salivary LDH appears to be a promising biomarker for the mass screening of periodontitis in local community health settings. High salivary LDH levels, particularly in overweight individuals might contribute to prevention of cardiovascular disease, through measuring systemic inflammatory burdens as well as traditional cardiovascular risk factors.

SU-E-J-31: Direct Point Dose Verification Using IGRT for Actual Beam Delivery.

PURPOSE: In radiation therapy, treatment planning for patients is performed using pre-acquired CT images. However, many patients with head-and-neck (H&N) cancer have tumor shrinkage and/or weight loss during their treatment course. Daily positional error of patients also causes unexpected deviations from the planning. Thus, it is essential to evaluate actual delivered dose for accurate clinical dosimetric consequence. In this study, actual delivered dose for an H&N site was determined by direct point dose measurement with metal-oxide-semiconductor field-effect transistor (MOSFET) detectors using IGRT procedure. We experimentally evaluated usefulness of the IGRT procedure for accurate irradiations. METHODS: Treatment processes from planning to beam delivery were performed for an H&N site of an anthropomorphic phantom. The MOSFET detectors were fixed inside the phantom in advance. Then, the anthropomorphic phantom was immobilized with a mould and mask and scanned by simulation-CT. Beam irradiation condition was field size of 12 cm × 12 cm, gantry angle of 0°, 90° and 330°, and 6 MV X-ray. Dose distribution was calculated with superposition algorithm with 2 mm calculation grid. Before the dose measurement, the anthropomorphic phantom was positioned using a localization system of mega-voltage cone-beam CT (MVCBCT). The MOSFET detectors were exposed five times according to a treatment plan. Measured doses with the MOSFET detectors were compared with calculated doses. RESULTS: Using the MVCBCT, the set-up of the anthropomorphic phantom was achieved within 1 mm in all directions of anterior/posterior, left/right, and superior/inferior. The calculated doses agreed well to the measured doses within ±3% even in evaluated region with high dose gradient. CONCLUSIONS: The actual delivered dose for an H&N site of an anthropomorphic phantom was evaluated experimentally with the MOSFET detectors. The IGRT procedure was useful for accurate irradiations.

Clinical implementation of a GPU-based simplified Monte Carlo method for a treatment planning system of proton beam therapy.

We implemented the simplified Monte Carlo (SMC) method on graphics processing unit (GPU) architecture under the computer-unified device architecture platform developed by NVIDIA. The GPU-based SMC was clinically applied for four patients with head and neck, lung, or prostate cancer. The results were compared to those obtained by a traditional CPU-based SMC with respect to the computation time and discrepancy. In the CPU- and GPU-based SMC calculations, the estimated mean statistical errors of the calculated doses in the planning target volume region were within 0.5% rms. The dose distributions calculated by the GPU- and CPU-based SMCs were similar, within statistical errors. The GPU-based SMC showed 12.30-16.00 times faster performance than the CPU-based SMC. The computation time per beam arrangement using the GPU-based SMC for the clinical cases ranged 9-67 s. The results demonstrate the successful application of the GPU-based SMC to a clinical proton treatment planning.

Inference of hysteretic respiratory tumor motion from external surrogates: a state augmentation approach.

It is important to monitor tumor movement during radiotherapy. Respiration-induced motion affects tumors in the thorax and abdomen (in particular, those located in the lung region). For image-guided radiotherapy (IGRT) systems, it is desirable to minimize imaging dose, so external surrogates are used to infer the internal tumor motion between image acquisitions. This process relies on consistent correspondence between the external surrogate signal and the internal tumor motion. Respiratory hysteresis complicates the external/internal correspondence because two distinct tumor positions during different breathing phases can yield the same external observation. Previous attempts to resolve this ambiguity often subdivided the data into inhale/exhale stages and restricted the estimation to only one of these directions. In this study, we propose a new approach to infer the internal tumor motion from external surrogate signal using state augmentation. This method resolves the hysteresis ambiguity by incorporating higher-order system dynamics. It circumvents the segmentation of the internal/external trajectory into different phases, and estimates the inference map based on all the available external/internal correspondence pairs. Optimization of the state augmentation is investigated. This method generalizes naturally to adaptive on-line algorithms.

Derivation of the tumor position from external respiratory surrogates with periodical updating of the internal/external correlation.

In this work we develop techniques that can derive the tumor position from external respiratory surrogates (abdominal surface motion) through periodically updated internal/external correlation. A simple linear function is used to express the correlation between the tumor and surrogate motion. The function parameters are established during a patient setup session with the tumor and surrogate positions simultaneously measured at a 30 Hz rate. During treatment, the surrogate position, constantly acquired at 30 Hz, is used to derive the tumor position. Occasionally, a pair of radiographic images is acquired to enable the updating of the linear correlation function. Four update methods, two aggressive and two conservative, are investigated: (A1) shift line through the update point; (A2) re-fit line through the update point; (C1) re-fit line with extra weight to the update point; (C2) minimize the distances to the update point and previous line fit point. In the present study of eight lung cancer patients, tumor and external surrogate motion demonstrate a high degree of linear correlation which changes dynamically over time. It was found that occasionally updating the correlation function leads to more accurate predictions than using external surrogates alone. In the case of high imaging rates during treatment (greater than 2 Hz) the aggressive update methods (A1 and A2) are more accurate than the conservative ones (C1 and C2). The opposite is observed in the case of low imaging rates.

Duodenal erosions after eradication of Helicobacter pylori infection.

BACKGROUND: There is interest in the development of GERD after Helicobacter pylori eradication. In contrast, the development of duodenal erosions after therapy has received scant attention. Patients were examined after eradication of H pylori infection to determine the frequency of post-therapy duodenal erosions (primary outcome) and whether there was a relation between development of duodenal and esophageal erosions. Additionally, factors were searched for that would identify patients at increased risk for duodenal erosions. METHODS: A single-center, endoscopist-blinded, observational study was conducted of 196 patients in whom H pylori was eradicated. The presence of esophageal or duodenal erosions was evaluated 4 weeks and 6 months after eradication. Serum gastrin and pepsinogen I (PG I) and II (PG II) levels were also determined for 83 patients entering the study during its final year. RESULTS: Multiple small duodenal erosions developed in 8.6% of patients after H pylori eradication and were more common in patients with pre-eradication duodenal ulcer (27.8%) compared with those with gastric ulcer (6.7%) or atrophic gastritis (1.4%) (p < 0.05). Duodenal erosions were associated with high levels of PG I before and after eradication. The frequency of duodenal erosions decreased over time (3.1% by 6 months). CONCLUSION: Duodenal erosions occur after H pylori eradication and appear to be related to duodenal ulcer and increased PG I levels, both of which are associated with increased acid secretion. Measurement of PG I may help to identify patients who have duodenal erosions develop after H pylori therapy for studies of the pathogenesis of these lesions.

Tattoos as risk factors for transfusion-transmitted diseases.

BACKGROUND: Several infectious diseases have been found to be associated with tattooing, including some transfusion-transmitted diseases (TTDs). Information on tattooing has been included in screening interviews of prospective blood donors and may be a reason for deferral. METHODS: Review of articles identified through Medline (and other computerized data bases) using medical subject heading (MeSH) terms and textwords for "tattooing," "transfusion", "hepatitis", "human immunodeficiency virus", "acquired immunodeficiency syndrome", "syphilis", "Chagas disease", "infection", "risk factors", and their combinations. RESULTS: There is strong evidence for the transmission of hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and syphilis by tattooing. Tattooing may also transmit the human immunodeficiency virus (HIV), although convincing evidence is still lacking. There is little or no evidence that other TTDs can be transmitted by tattooing. Epidemiologic studies to date have shown a large variation in odds ratio estimates of the association between tattooing and HBV, HCV, and HIV infections. CONCLUSION: Further studies are required to clarify the risk of tattoos in transmitting infectious diseases through blood transfusions. A reassessment of tattoos as a screening criterion among blood donors is justified.

Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas.

We characterized the genomic structure of the human ING1 gene, a candidate tumor suppressor gene, and found that the gene has three exons. We also demonstrated that four mRNA variants were transcribed from three different promoter regions. Of 34 informative cases of head and neck squamous cell carcinoma, 68% of tumors showed loss of heterozygosity at chromosome 13q33-34, where the ING1 gene is located. Here we present the first report that three missense mutations and three silent changes were detected in the ING1 gene in 6 of 23 tumors with allelic loss at the 13q33-34 region. These missense mutations were found within the PHD finger domain and nuclear localization motif in ING1 protein, probably abrogating the normal function.

Inhibitory neural pathway regulating gastric emptying in rats.

The relaxation of the pylorus is one of the most important factors for promoting gastric emptying. However, the role of inhibitory neurotransmitters in the regulation of pyloric relaxation and gastric emptying remains unclear. In this study, we investigated the effects of NO biosynthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), and calcium dependent potassium channel blocker, apamin, on vagal stimulation-induced pyloric relaxation and gastric emptying in rats. Sodium nitroprusside (SNP), adenosine 5'-triphosphate (ATP), vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) caused pyloric relaxations in a dose dependent manner in vivo. Apamin (120 microg/kg) significantly reduced ATP and PACAP-induced pyloric relaxations without affecting SNP- or VIP-induced relaxations. Vagal stimulation (10 V, 1 ms, 1-20 Hz)-induced pyloric relaxation was significantly inhibited by L-NAME (10 mg/kg). The combined administration of L-NAME and apamin almost completely abolished vagal stimulation-induced pyloric relaxation. L-NAME and apamin significantly increased spontaneous contractions in the antrum, pylorus and duodenum. Increased motility index by L-NAME and apamin was significantly higher in the pylorus and duodenum, compared to that of antrum. L-NAME and apamin significantly delayed liquid gastric emptying. These results suggest that besides NO, probably ATP and PACAP, act as inhibitory neurotransmitters in the rat pylorus and regulate gastric emptying.

Comparison of tumor markers in patients with squamous cell carcinoma of the head and neck.

The serum concentrations of three separate tumor markers, squamous cell carcinoma antigen (SCC Ag), carcinoembryonic antigen (CEA) and Cyfra 21-1 were clinically correlated in 86 randomly selected patients with squamous cell carcinoma involving the head and neck. Positive findings for each tumor marker were totalled and statistically analysed. The upper limits of normal for SCC Ag, CEA and Cyfra 21-1 were set at 1.5, 2.5 and 2.0 ng/ml, respectively. Positivity rates were 20.6% for SCC Ag, 14.0% for CEA and 41.7% for Cyfra 21-1. Elevated Cyfra 21-1 concentrations correlated somewhat with age, whereas elevated CEA levels correlated with the site of tumor involvement. Overall, Cyfra 21-1 appeared to be the most useful marker in head and neck squamous cell carcinoma.

Human papillomavirus as a risk factor for head and neck cancers--a case-control study.

A retrospective, case-control study was conducted to examine the relationship between the presence of human papillomavirus types 16 and 18 (HPV16/18) DNA and the risk of head and neck cancers. Twelve out of 74 (16.2%) head and neck cancers contained HPV16/18 DNA, while 3 out of 70 (4.2%) non-cancer controls showed HPV16/18 positivity by polymerase chain reaction. The presence of HPV16/18 DNA was associated with an increased risk of head and neck cancer formation, showing an odds ratio of 4.32, with a 95% confidence interval of 1.26-14.78. Although its epidemiological impact might be smaller than that of other factors like cigarette smoking, the presence of HPV16/18 DNA in the aerodigestive tract is suggested to be a risk factor for human head and neck cancers.

Screening for aetiology of thrombophilia: a high prevalence of protein S abnormality.

We systematically screened for the aetiology of thrombophilia in 115 patients with venous, arterial and small vessel thromboses. Forty-one patients (36% of those we examined) suffering from a variety of thromboses, including deep vein thrombosis, pulmonary embolism, arterial occlusion, cerebral infarction, Moyamoya disease and ulcerative colitis, were characterized either with positive lupus anticoagulants or with decreased activities of protein S, protein C, antithrombin III and/or plasminogen. Eight mutation sites were confirmed in 11 thrombotic patients using gene analysis. Decreased protein S activity was found with a high incidence (23 out of 115) in Japanese patients who suffered from not only venous thrombosis but also arterial and small vessel thrombosis. We emphasize here the important role of protein S in the pathogenesis of thrombosis in the Japanese population.

Hereditary angioedema with gastrointestinal involvement: endoscopic appearance.

We present the first reported case of hereditary angioedema (HAE) with gastric involvement to be successfully evaluated by endoscopy both during and after an attack. A 31-year-old man who had a family history of angioedema was admitted to our hospital with complaints of abdominal pain and swelling of extremities. Computed tomography scan and endoscopy carried out during this attack revealed transient gastrointestinal wall edema which, along with decreased levels of serum C4 and C1 inhibitor, confirmed the diagnosis of HAE with gastrointestinal involvement. During the attack, the gastric mucosa was erythematous and edematous, and parts of its surface bulged into the gastric lumen, resembling a submucosal tumor, as a result of massive submucosal edema. During the healing process, a number of small nodules and raised erosions developed over the entire gastric mucosal surface after healing of prominent gastric edema. Within 55 days, the gastric mucosa had returned to normal. The endoscopic findings for the stomach in HAE have not, to our knowledge, been previously described.

Fetal development of the pituitary gland in the beagle.

BACKGROUND: The pituitary gland of the dog is different from all animals and is described as "typical" for mammals. How might this complex pituitary gland of the dog be formed in fetal life? The current study examined the fetal development of the complex and unique dog pituitary and the ontogeny of specific cell types in the pars distalis. METHODS: Adenohypophysis of the beagle, from 25 to 60 days of gestation and at 2 days of age, was studied by immunocytochemical and histological staining. RESULTS: At 25 days gestation, the primordium (Rathke's pouch) of the adenohypophysis began to form by an upward evagination from the epithelium of the primary oral cavity. At 38 days, the pituitary gland showed the same morphology as in adult dogs, being merely smaller. Five walls of Rathke's pouch (anterior wall [A], lateral walls [L], posterior wall [P], and upper wall [U] were found at 25 days, and by 38 days they had specialized into specific regions of the adenohypophysis through complex and unique processes. The pars intermedia was derived from the U and the dorsal area of the A. The pars tuberalis was derived from the dorsal area of the A. The pars distalis was formed by more singular processes: the peripheral areas of the pars distalis were first formed by A and P; then the ventral lumen of the extensive Rathke's lumen surrounded by these areas was filled up by proliferation of cells, although the dorsal lumen remains as Rathke's lumen after 38 days. The blood capillaries may play an important role in the development of parencymal cells in the Rathke's pouch during canine fetal life. At 30 days gestation, the first adrenocorticotropic hormone cells were found in the anterior- and posterior-ventral regions (derived from middle and ventral areas of the A and the P) of the pars distalis anlage, and blood capillaries invaded the parenchymal cells from the mesencyme surrounding the anlage. At 38 days, portal vessels without capillary loops in the median eminence had appeared, and growth hormone and luteinizing hormone cells appeared in the ventral areas of A and P in the pars distalis. By 52 days, when capillary loops were seen in the portal vessels in the median eminence, these types of cells spread through the whole pars distalis. CONCLUSION: These areas in the epithelium of Rathke's pouch at 25 days may differentiate into specific regions of the pars distalis during subsequent fetal life, through complex processes that are characteristics to the canine species.