Study on enteral nutrient components causing decreased gastric phenytoin absorption.

BACKGROUND: Previously, we revealed that coadministration of particular enteral nutrients (ENs) decreases plasma concentrations and gastric absorption of phenytoin (PHT), an antiepileptic drug, in rats; however, the mechanism has not been clarified. METHODS: We measured the permeability rate of PHT using a Caco-2 cell monolayer as a human intestinal absorption model with casein, soy protein, simulated gastrointestinal digested casein protein (G-casein or P-casein) or simulated gastrointestinal digested soy protein (G-soy or P-soy), dextrin, sucrose, degraded guar gum, indigestible dextrin, calcium, and magnesium, which are abundant in the ENs, and measured the solution's properties. RESULTS: We demonstrated that casein (40 mg/ml), G-soy or P-soy (10 mg/ml), and dextrin (100 mg/ml) significantly decreased the permeability rate of PHT compared with the control. By contrast, G-casein or P-casein significantly increased the permeability rate of PHT. We also found that the PHT binding rate to casein 40 mg/ml was 90%. Furthermore, casein 40 mg/ml and dextrin 100 mg/ml have high viscosity. Moreover, G-casein and P-casein significantly decreased the transepithelial electrical resistance of Caco-2 cell monolayers compared with casein and the control. CONCLUSION: Casein, digested soy protein, and dextrin decreased the gastric absorption of PHT. However, digested casein decreased PHT absorption by reducing the strength of tight junctions. The composition of ENs may affect the absorption of PHT differently, and these findings would aid in the selection of ENs for orally administered PHT.

The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: allergen exposure, epidemiology, and diagnosis of anaphylaxis during general anaesthesia.

BACKGROUND: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan. METHODS: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis. RESULTS: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%). CONCLUSIONS: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases. CLINICAL TRIAL REGISTRATION: UMIN000035350.

Liquid Enteral Nutrients Alter the Pharmacokinetics of Orally Administered Carbamazepine in Rats.

The interaction between enteral nutrients (ENs) and drugs co-administered through a nasogastric (NG) tube reportedly affects the absorption and resultant plasma concentrations of the respective drugs. However, the gastrointestinal absorption of carbamazepine (CBZ), an antiepileptic drug, co-administered with liquid ENs through an NG tube has not been clarified. In this study, we measured the recovery rate (%) of CBZ (Tegretol® powder) passed through an NG tube when co-administered with distilled water or ENs (F2α®, Racol® NF, Ensure Liquid®, and Renalen® LP) of different compositions, frequently used in Japan. We also measured the plasma CBZ level in 26 rats after oral co-administration of CBZ with liquid ENs. The CBZ recovery rate was close to 100% in rats of all EN groups after passage through the NG tube. Furthermore, CBZ area under the plasma concentration-time curve from time zero to 9 h (AUC0→9h) of the Ensure liquid® group decreased compared with that of control group (P < 0.05) and Renalen® LP group (P < 0.01). However, the AUC0→9h of CBZ remained unchanged when co-administered with Ensure liquid® 2 h after initial CBZ administration. In conclusion, the co-administration of CBZ with Ensure Liquid® caused a reduction in the absorption of CBZ from the gastrointestinal tract, without adsorption on the NG tube. The administration of Ensure Liquid® 2 h after CBZ is a way to prevent a decrease in plasma CBZ concentration. Our findings suggest that carefully monitoring the plasma levels of CBZ is necessary in co-administation with Ensure liquid® to prevent the unintended effects of the interaction between CBZ and liquid EN.

Analysis of the frequency of ceftriaxone-induced encephalopathy using the Japanese Adverse Drug Event Report database.

BACKGROUND: The profile of ceftriaxone-induced encephalopathy is not well understood. AIM: To identify risk factors associated with ceftriaxone-induced encephalopathy. METHOD: In this observational study, anonymised patient data were retrieved from the open-access Japanese Adverse Drug Event Report database for ceftriaxone users aged 20 years or higher. RESULTS: Data of 256,788 individuals and 12,160 cases of encephalopathy were extracted, and 2,939 ceftriaxone users, of whom 193 had encephalopathy, were identified. A disproportionate prevalence of encephalopathy was observed among the ceftriaxone users (reported odds ratio = 1.42; 95% confidence interval [CI] = 1.23-1.65; p < 0.001). Multivariate logistic regression analysis of 2,057 ceftriaxone users showed encephalopathy was associated with female sex (odds ratio [OR] = 1.52; 95% CI, 1.05-2.19; p = 0.027), chronic kidney disease (OR = 2.32; 95% CI, 1.47-3.67; p < 0.001), a ceftriaxone dosage of > 2 g/day (OR = 2.66; 95% CI, 1.66-4.26; p < 0.001), and a treatment duration of > 14 days (OR = 1.94; 95% CI, 1.21-3.11; p = 0.006). CONCLUSION: Patients with chronic kidney disease, receiving ceftriaxone at a dosage of > 2 g/day, being treated for over 14 days, and/or females may be at an increased risk of ceftriaxone-induced encephalopathy.

Probability of target attainment of oral antimicrobials for Escherichia coli and Klebsiella pneumoniae based on Monte Carlo simulations.

Although early transition from intravenous to oral antimicrobials can reduce hospitalization duration, susceptibility breakpoints have not been established for many oral antimicrobials against Escherichia coli and Klebsiella pneumoniae bacteremia. Thus, we used population pharmacokinetic models, pharmacokinetic/pharmacodynamic indices, and Monte Carlo simulations to evaluate the probability of target attainment (PTA) for common oral antimicrobial dosages against E. coli and K. pneumoniae. The oral antimicrobial agents evaluated included cephalexin, cefaclor, cefditoren, amoxicillin/clavulanic acid, faropenem, and levofloxacin. For E. coli, the percentage of isolates with minimum inhibitory concentrations for which a PTA >90% was achieved was 53% and less than 20% for levofloxacin and the ß-lactams, respectively. For K. pneumoniae, the percentages of isolates for which a PTA >90% was achieved were comparatively higher (cephalexin, 73%; amoxicillin/clavulanic acid, 83%; levofloxacin, 96%). Our results suggest clinicians should check if pharmacokinetic/pharmacodynamic indices are achieved in individual patients before transitioning to oral antimicrobial therapy.

Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. METHODS: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. RESULTS: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). CONCLUSIONS: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.

Risk of Pregabalin-Induced Hypoglycemia: Analysis of the Japanese Adverse Drug Event Report Database.

Pregabalin is a first-line treatment option for neuropathic pain. Recently, some cases of pregabalin-induced hypoglycemia have been reported, which can complicate the treatment of neuropathic pain and worsen patient outcomes. Therefore, a better understanding of the clinical condition of patients with pregabalin-induced hypoglycemia is desirable. In this study, we evaluated the risk of hypoglycemia in patients administered pregabalin, using the Japanese Adverse Drug Event Report database. All patients on pregabalin not taking any antidiabetic agents were screened from April 2004 to July 2020, and data on adverse events related to hypoglycemia, sex, age, weight, and the presence of chronic kidney disease were collected. Gabapentin and duloxetine, which are usually indicated for neuropathic pain, were used for comparison. Among 242 275 patients, 4287 were administered pregabalin, which included 37 patients who reported hypoglycemic incidents. Disproportionality of hypoglycemia was observed in patients administered pregabalin (reporting odds ratio, 2.25; 95%CI, 1.16-3.13; P < .01), whereas this was not the case in patients taking gabapentin and duloxetine. Multivariate logistic regression showed that hypoglycemia in patients on pregabalin was associated with age ≥70 years (odds ratio, 2.76; 95%CI, 1.29-5.91; P < 0.01) and weight <40 kg (odds ratio, 2.97; 95%CI, 1.32-6.71; P < 0.01). These findings suggest that pregabalin may be associated with a higher risk of hypoglycemia, especially in elderly individuals with low body weight. Health care providers may need to be aware of pregabalin-induced hypoglycemia in patients with these risk factors during therapy.

Transcriptome analysis of Pará rubber tree (H. brasiliensis) seedlings under ethylene stimulation.

BACKGROUND: Natural rubber (cis-1,4-polyioprene, NR) is an indispensable industrial raw material obtained from the Pará rubber tree (H. brasiliensis). Natural rubber cannot be replaced by synthetic rubber compounds because of the superior resilience, elasticity, abrasion resistance, efficient heat dispersion, and impact resistance of NR. In NR production, latex is harvested by periodical tapping of the trunk bark. Ethylene enhances and prolongs latex flow and latex regeneration. Ethephon, which is an ethylene-releasing compound, applied to the trunk before tapping usually results in a 1.5- to 2-fold increase in latex yield. However, intense mechanical damage to bark tissues by excessive tapping and/or over-stimulation with ethephon induces severe oxidative stress in laticifer cells, which often causes tapping panel dryness (TPD) syndrome. To enhance NR production without causing TPD, an improved understanding of the molecular mechanism of the ethylene response in the Pará rubber tree is required. Therefore, we investigated gene expression in response to ethephon treatment using Pará rubber tree seedlings as a model system. RESULTS: After ethephon treatment, 3270 genes showed significant differences in expression compared with the mock treatment. Genes associated with carotenoids, flavonoids, and abscisic acid biosynthesis were significantly upregulated by ethephon treatment, which might contribute to an increase in latex flow. Genes associated with secondary cell wall formation were downregulated, which might be because of the reduced sugar supply. Given that sucrose is an important molecule for NR production, a trade-off may arise between NR production and cell wall formation for plant growth and for wound healing at the tapping panel. CONCLUSIONS: Dynamic changes in gene expression occur specifically in response to ethephon treatment. Certain genes identified may potentially contribute to latex production or TPD suppression. These data provide valuable information to understand the mechanism of ethylene stimulation, and will contribute to improved management practices and/or molecular breeding to attain higher yields of latex from Pará rubber trees.

ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease.

Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak neurofibrillary tangles stage, Aß accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.

African pygmy hedgehog adenovirus: Virus replication, virus-induced cytopathogenesis and activation of mitogen-activated protein kinase signaling pathways in infected MDCK cells.

We examined several aspects of African hedgehog adenovirus (AhAdv-1) that was isolated from an African pygmy hedgehog, including: replication kinetics of, virus-induced cytopathic effect (CPE), activation status of mitogen-activated protein kinase (MAPK) signaling pathways, and possible roles of these signaling pathways in virus replication and virus-induced CPE in MDCK cells. AhAdv-1 efficiently replicated and induced CPE in infected cells and caused accumulation of cleaved caspase-3 at 24 h post-infection (p.i.), suggesting apoptosis induction. Analysis of several intracellular signal transduction pathways, which are involved in apoptosis, showed activation of p38 MAPK, Akt and ERK1/2 pathways at 3 h p.i., and upregulation of phosphorylated SAPK/JNK at 24 h p.i. Although p38 MAPK inhibitor and SAPK/JNK inhibitor suppressed activation of the respective pathways in infected cells, they did not inhibit virus-induced CPE. Treatment of infected cells with inhibitor of the Akt pathway, the p38 pathway, the SAPK/JNK pathway or the ERK pathway revealed that inhibitors of p38 pathway inhibited viral replication by real-time PCR and TCID50 assay in infected MDCK cells, suggesting that AhAdv-1 uses p38 pathway for multiplication in infected cells.

Interaction Between APOE Genotype and Diabetes in Longevity.

BACKGROUND: While both apolipoprotein E (APOE) genotype and diabetes affect longevity as well as Alzheimer's disease, their relationship remains to be elucidated. OBJECTIVE: The current study investigated the potential interaction between diabetes and APOE for lifespan and their relationship with cognitive status. METHODS: We reviewed the National Alzheimer's Coordinating Center (NACC) dataset, which documents longitudinally clinical records of 24,967 individuals with APOE genotype and diabetic status. RESULTS: Diabetes was associated with shorter lifespan in APOE3 carriers (n = 12,415, HR = 1.29, 95%CI = 1.17-1.42, p < 0.001) and APOE2 carriers (n = 2,390, HR = 1.37, 95%CI = 1.10-1.69, p = 0.016), while such associations were weaker and not significant in APOE4 carriers (n = 9,490, HR = 1.11, 95%CI = 0.99-1.24, p = 0.162). As there is a significant interactive effect of cognitive status and diabetes on lifespan (p < 0.001), we stratified subjects by cognitive status and observed persistent APOE-dependent harmful effects of diabetes in nondemented individuals but not demented individuals. Notably, questionnaire-based activity status, with which we previously observed an association between APOE genotype and longevity, was also significantly affected by diabetes only in non-APOE4 carriers. CONCLUSION: The effects of diabetes on longevity vary among APOE genotype. These effects are observed in nondemented individuals and are potentially associated with activity status during their lifespan.

Evaluation of the effect of apixaban using a viscoelastic coagulation assay with Russell's viper venom reagent.

BACKGROUND: Conventional coagulation tests, such as prothrombin time and activated partial thromboplastin time, are not sensitive to anticoagulation by apixaban. We evaluated the antithrombotic effect of apixaban using a Russell viper venom (RVV) test for a patient who underwent posterior spine fusion surgery. CASE PRESENTATION: An 84-year-old man was scheduled for percutaneous posterior spine fusion. He continued apixaban until the night before surgery and resumed it on the first day after surgery. We performed an RVV test as point-of-care coagulation monitoring in combination with chromogenic anti-activated factor X (anti-Xa) activity, prothrombin time, and activated partial thromboplastin time. Clotting time with the RVV test was prolonged according to the anti-Xa activity of apixaban, which was in the therapeutic range during surgery. CONCLUSIONS: An RVV test might be useful as a point-of-care assay for estimation of the anti-Xa level induced by apixaban during the perioperative period.

Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes-linked obesity and Alzheimer's disease.

Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at molecular levels, we performed gene expression analysis of APP;ob/ob mice, which were generated by crossing transgenic AD model mice (APP23 mice) with ob/ob mice, which are obese and mildly diabetic. The Aß level in these mice was reduced compared with that in pure APP mice. However, we identified a cluster of genes (cluster 10) upregulated in APP;ob/ob mice but not in either APP or ob/ob mice. Interestingly, genes upregulated in the human AD brain were enriched in cluster 10. Moreover, genes in cluster 10 formed a network and shared upregulated genes with a cell model of neurodegeneration and other models of neurological disorders such as ischemia and epilepsy. In silico analyses showed that serum response factor (SRF), recently identified in a single-cell analysis of human brains as a transcription factor that can control the conversion from healthy cells to AD cells, might be a common transcriptional regulator for a subset of cluster 10 genes. These data suggest that upregulation of genes uniquely associated with APP;ob/ob mice is an evidence of the interaction between obesity/diabetes and AD.

Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion.

BACKGROUND: Subcortical ischemic vascular dementia, one of the major subtypes of vascular dementia, is characterized by lacunar infarcts and white matter lesions caused by chronic cerebral hypoperfusion. In this study, we used a mouse model of bilateral common carotid artery stenosis (BCAS) to investigate the role of B-cell translocation gene 2 (BTG2), an antiproliferation gene, in the white matter glial response to chronic cerebral hypoperfusion. METHODS: Btg2-/- mice and littermate wild-type control mice underwent BCAS or sham operation. Behavior phenotypes were assessed by open-field test and Morris water maze test. Brain tissues were analyzed for the degree of white matter lesions and glial changes. To further confirm the effects of Btg2 deletion on proliferation of glial cells in vitro, BrdU incorporation was investigated in mixed glial cells derived from wild-type and Btg2-/- mice. RESULTS: Relative to wild-type mice with or without BCAS, BCAS-treated Btg2-/- mice exhibited elevated spontaneous locomotor activity and poorer spatial learning ability. Although the severities of white matter lesions did not significantly differ between wild-type and Btg2-/- mice after BCAS, the immunoreactivities of GFAP, a marker of astrocytes, and Mac2, a marker of activated microglia and macrophages, in the white matter of the optic tract were higher in BCAS-treated Btg2-/- mice than in BCAS-treated wild-type mice. The expression level of Gfap was also significantly elevated in BCAS-treated Btg2-/- mice. In vitro analysis showed that BrdU incorporation in mixed glial cells in response to inflammatory stimulation associated with cerebral hypoperfusion was higher in Btg2-/- mice than in wild-type mice. CONCLUSION: BTG2 negatively regulates glial cell proliferation in response to cerebral hypoperfusion, resulting in behavioral changes.

Localized intestinal AL amyloidosis detected as bright green using autofluorescence endoscopy.

Amyloidosis is classifiable as systemic, with amyloid deposition in organs throughout the body, or localized, involving only one organ. Amyloidosis localized in the intestinal tract is rare. This report describes three cases of localized AL amyloidosis in the intestinal tract and presents their clinical characteristics, endoscopic findings, and prognoses. All three cases were asymptomatic, and were found accidentally during endoscopy for closer examination after a positive fecal occult blood test. Endoscopic findings included patchy redness and meandering dilated vessels of the lesion. Using autofluorescence (AFI) endoscopy, the lesion of amyloid deposition was enhanced as bright green. We used fluorescence microscopy to observe unstained specimens obtained from an amyloid deposition site with excitation light. Autofluorescence was detected with the broad excitation wavelength at amyloid deposition lesion sites of the specimen. Results revealed that AL amyloid has autofluorescence that engenders its detection by AFI endoscopy as bright green. In none of the three cases was systemic amyloidosis or organ failure observed. The long-term course of all the cases was favorable.

Intravenous infusion of rocuronium bromide prolongs emergence from propofol anesthesia in rats.

BACKGROUND: Neuromuscular blocking agents induce muscle paralysis via the prevention of synaptic transmission at the neuromuscular junction and may have additional effects at other sites of action. With regard to potential effects of neuromuscular blocking agents on the central nervous system, a definitive view has not been established. We investigated whether intravenous infusion of rocuronium bromide affects the emergence from propofol anesthesia. METHODS: Using an in vivo rat model, we performed propofol infusion for 60 minutes, along with rocuronium bromide at various infusion rates or normal saline. Sugammadex or normal saline was injected at the end of the infusion period, and we evaluated the time to emergence from propofol anesthesia. We also examined the neuromuscular blocking, circulatory, and respiratory properties of propofol infusion along with rocuronium bromide infusion to ascertain possible factors affecting emergence. RESULTS: Intravenous infusion of rocuronium bromide dose-dependently increased the time to emergence from propofol anesthesia. Sugammadex administered after propofol infusion not containing rocuronium bromide did not affect the time to emergence. Mean arterial pressure, heart rate, partial pressures of oxygen and carbon dioxide, and pH were not affected by rocuronium bromide infusion. Neuromuscular blockade induced by rocuronium bromide, even at the greatest infusion rate in the emergence experiment, was rapidly antagonized by sugammadex. CONCLUSIONS: These results suggest that intravenous infusion of rocuronium bromide dose-dependently delays the emergence from propofol anesthesia in rats. Future studies, such as detection of rocuronium in the cerebrospinal fluid or central nervous system, electrophysiologic studies, microinjection of sugammadex into the brain, etc., are necessary to determine the mechanism of this effect.

Prognosis of Incomplete Avulsion of the Proximal Hamstring Tendon Is Determined by the Avulsion Location of the Proximal Hamstring Tendon Footprint.

OBJECTIVE: To test the hypothesis that prognosis of incomplete avulsion of the proximal hamstring tendon would be worse whether avulsion location reached the proximal part of the conjoined tendon (CJ) footprint or not. DESIGN: Retrospective chart review. SETTING: Outpatient specialty clinic. PATIENTS: We reviewed 345 consecutive athletes with hamstring injury. INTERVENTIONS: Based on magnetic resonance imaging, incomplete avulsion of the proximal hamstring tendon was divided into 2 cases according to avulsion location without (cases A) or with (cases B) avulsion of the proximal part of the CJ footprint. OUTCOME MEASURES: We compared the time until return to play, subjective outcomes, and success rate of avoiding surgery between cases. RESULTS: Incomplete avulsion of the proximal hamstring tendon was detected in 47 athletes (13.6%). Thirty-four athletes were classified as cases A, and 13 as cases B. Forty-two athletes (89.4%) were followed up until return to play. The median time from pain onset to return to play was significantly longer in cases B than in cases A (B, 39.3 weeks; A, 8.0 weeks; P = 0.00015). Subjective outcomes at return to play were significantly poorer in cases B than in cases A (P = 0.00054). Success rate of avoiding surgery were significantly poorer in cases B (55%) than in cases A (100%) (P = 0.00062). CONCLUSIONS: Incomplete avulsion of the proximal hamstring tendon was observed in 13.6% of hamstring injuries. Return to play, subjective outcomes, and success rate of avoiding surgery were significantly poorer with avulsion of the proximal part of the CJ footprint.

Saline Solution Irrigation of the Bile Duct after Stone Removal Reduces the Recurrence of Common Bile Duct Stones.

Common bile duct (CBD) stone is a relatively common but potentially life-threatening disease. Endoscopic sphincterotomy (EST) has been performed as standard therapy for CBD stones, but the rate of recurrence of CBD stones is high. Risk factors have been poorly defined, and no effective means for the prevention of the recurrence of CBD stones have been established so far. We aimed to identify significant risk factors for the recurrence of bile duct stones. This study included 477 patients (231 women; mean age, 80.5 years) who underwent EST and cleared CBD stones on cholangiography. A retrospective analysis was performed for the consecutively collected data. During the follow-up period of 6-75 months, the recurrence of CBD stones was observed in 99 patients (20.8%). The median time to the recurrence was 19.0 months (range 4-72 months). Multivariate analysis identified the need for mechanical lithotripsy, which was used for stone fragmentation, as a risk factor. Mechanical lithotripsy caused cholangiography-negative small residua. Notably, saline solution irrigation of the bile duct reduced the recurrence of CBD stones. These results demonstrate that subsequent biliary irrigation after stone removal may prevent the recurrence of CBD stones by clearing small residual fragments.