Exposure to aerosol extract from heated tobacco products causes a drastic decrease of glutathione and protein carbonylation in human lung epithelial cells.

Heated tobacco products (HTPs) are an emerging class of tobacco goods that claim to have lower health risks than those of smoking combustible tobacco products. In this study, we exposed human lung epithelial cell lines to extracts prepared from HTP aerosols and combustible cigarette smoke to compare cytotoxicity. We focused on the effects of aldehydes present in the aerosols of HTPs at levels close to those in combustible cigarette smoke. Significant toxicity was confirmed for the HTP extract, albeit to a lesser extent than that with the combustible cigarette extract. When redox balance was evaluated by the oxidative loss of low-molecular-weight thiols in the cells, we found that total glutathione (GSH) contents and low-molecular-weight thiol levels were significantly decreased after exposure to the aerosol extract of HTPs. These results indicated that GSH is rapidly consumed during the detoxification of xenobiotics, such as aldehydes from tobacco extracts. Accordingly, exposure to the aerosol extract of HTPs resulted in the enhanced carbonylation of many proteins. In a simple comparison, the results for HTPs were significantly different from those obtained with combustible cigarette smoke, suggesting reduced toxicity of HTPs. However, we found significant and harmful effects after exposing lung epithelial cells to the aerosol extract of HTPs. Thus, a further comprehensive study is needed to clarify the lung damage induced via the long-term inhalation of aerosols from HTPs.

Outcome of autologous bone grafting with preservation of articular cartilage to treat osteochondral lesions of the talus with large associated subchondral cysts.

Aims: The aim of this study was to evaluate antegrade autologous bone grafting with the preservation of articular cartilage in the treatment of symptomatic osteochondral lesions of the talus with subchondral cysts. Patients and Methods: The study involved seven men and five women; their mean age was 35.9 years (14 to 70). All lesions included full-thickness articular cartilage extending through subchondral bone and were associated with subchondral cysts. Medial lesions were exposed through an oblique medial malleolar osteotomy, and one lateral lesion was exposed by expanding an anterolateral arthroscopic portal. After refreshing the subchondral cyst, it was grafted with autologous cancellous bone from the distal tibial metaphysis. The fragments of cartilage were fixed with 5-0 nylon sutures to the surrounding cartilage. Function was assessed at a mean follow-up of 25.3 months (15 to 50), using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot outcome score. The radiological outcome was assessed using MRI and CT scans. Results: The mean AOFAS score improved from 65.7 (47 to 81) preoperatively to 92 (90 to 100) at final follow-up, with 100% patient satisfaction. The radiolucent area of the cysts almost disappeared on plain radiographs in all patients immediately after surgery, and there were no recurrences at the most recent follow-up. The medial malleolar screws were removed in seven patients, although none had symptoms. At this time, further arthroscopy was undertaken, when it was found that the mean International Cartilage Repair Society (ICRS) arthroscopic score represented near-normal cartilage. Conclusion: Autologous bone grafting with fixation of chondral fragments preserves the original cartilage in the short term, and could be considered in the treatment for adult patients with symptomatic osteochondral defect and subchondral cysts. Cite this article: Bone Joint J 2018;100-B:590-5.

Factors affecting the potential for posterior bony impingement after total hip arthroplasty.

AIMS: Our aim was to evaluate the radiographic characteristics of patients undergoing total hip arthroplasty (THA) for the potential of posterior bony impingement using CT simulations. PATIENTS AND METHODS: Virtual CT data from 112 patients who underwent THA were analysed. There were 40 men and 72 women. Their mean age was 59.1 years (41 to 76). Associations between radiographic characteristics and posterior bony impingement and the range of external rotation of the hip were evaluated. In addition, we investigated the effects of pelvic tilt and the neck/shaft angle and femoral offset on posterior bony impingement. RESULTS: The range of external rotation and the ischiofemoral length were significantly lower, while femoral anteversion, the ischial ratio, and ischial angle were significantly higher in patients with posterior bony impingement compared with those who had implant impingement (p < 0.05). The range of external rotation positively correlated with ischiofemoral length (r = 0.49, p < 0.05), and negatively correlated with ischial length (r = -0.49, p < 0.05), ischial ratio (r =- 0.49, p < 0.05) and ischial angle (r = -0.55, p < 0.05). The range of external rotation was lower in patients with posterior pelvic tilt (p < 0.05) and in those with a high offset femoral component (p < 0.05) due to posterior bony impingement. CONCLUSION: Posterior bony impingement after THA is more likely in patients with a wider ischium and a narrow ischiofemoral space. A high femoral offset and posterior pelvic tilt are also risk factors for this type of impingement. Cite this article: Bone Joint J 2017;99-B:1140-6.

Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for younger patients with acute myeloid leukemia: a registry-based study.

Clinical efficacy of allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) for younger patients remains unclear. We therefore performed a retrospective registry-based study to evaluate outcomes for patients with AML aged between 16 and 49 years who underwent RIC allogeneic HCT. Patients receiving RIC (N=125) showed significantly worse survival than those receiving myeloablative conditioning (MAC; N=1,554) (47.7% for RIC and 54.2% for MAC at 4 years, P=0.047). However, the difference became marginal after adjustment for patient characteristics (P=0.080), and inclusion in the multivariate analysis of the HCT comorbidity index or the propensity score for estimating the likelihood of choosing RIC or MAC further reduced statistical significance (P=0.371 and 0.206, respectively), indicating the existence of a selection bias against RIC. Nevertheless, outcomes for our patients receiving RIC were still acceptable, so that RIC constitutes a potential therapeutic option for younger AML patients who are deemed unsuitable for MAC. Subgroup analyses showed that patients aged between 40 and 49 years as well as those in first or second CR at the time of transplantation exhibited similar outcomes regardless of whether they were treated with RIC or MAC.

Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling.

Reproductive management is necessary to prevent deleterious genetic disorders in purebred dogs, but comprehensive studies aimed at prevention of multiple underlying genetic disorders in a single breed have not been performed. The aims of this study were to examine mutant allele frequencies associated with multiple genetic disorders, using Border collies as a representative breed, and to make recommendations for prevention of the disorders. Genotyping of known mutations associated with seven recessive genetic disorders was performed using PCR assays. More than half (56%) of the Border collies had no mutant alleles associated with any of the seven disorders, suggesting that these disorders can be removed from the population over several generations. Since frequencies of each mutant allele differed among disorders, reproductive management should be performed after the establishment of prevention schemes that are appropriate for each disorder, the type and specificity of genetic test available, and the effective population size in each breeding colony.

Ki-67 is a strong predictor of central nervous system relapse in patients with mantle cell lymphoma (MCL).

BACKGROUND: Central nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach. PATIENTS AND METHODS: A total of 608 patients (median age, 67 years; range 22-92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis. RESULTS: None of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2-141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 ≥ 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9-19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 ≥ 30 was 25.4% (95% CI 13.5-39.1), while that in the patients with Ki-67 < 30 was 1.6% (95% CI 0.4-4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.

A Practical Technique for Electron Microscopy of Buffy Coats in Dogs and Cats.

Plastic hematocrit tubes (PHTs) are convenient tools for electron microscopy (EM) of peripheral blood buffy coats, and the PHT-EM technique is expected to be a practical method for veterinary clinical medicine. In this study, fixatives composed of various concentrations of sucrose, glutaraldehyde, and phosphate buffer (PB) were tested for preparing canine and feline buffy coats. The highest quality images were obtained using a fixative consisting of 2.5% glutaraldehyde in 0.1 m PB, and it was concluded that this method allows clinicians who are inexperienced in histological techniques can conveniently transport buffy coat samples to diagnostic laboratories for analysis by EM.

The factors associated with pain severity in patients with knee osteoarthritis vary according to the radiographic disease severity: a cross-sectional study.

OBJECTIVES: Knee osteoarthritis (OA) pain is suggested to be associated with inflammation and detrimental mechanical loading across the joint. In this cross-sectional study, we simultaneously examined the inflammation and alignment of the lower limb and examined how the pain components varied depending on the disease progression. DESIGN: One-hundred sixty female medial type of early- [n = 74 in Kellgren-Lawrence (K/L) 2] to advanced-stage (n = 96 in K/L >2) knee OA subjects (70.5 years on average) were enrolled. Knee pain was evaluated using a pain visual analog scale (VAS) and the pain-related subcategory of the Japanese Knee Osteoarthritis Measure (JKOM-pain). The serum interleukin (sIL)-6 level reflecting synovitis, and the high sensitivity C-reactive protein (hs-CRP) level were measured to evaluate the severity of inflammation. The anatomical axis angle (AAA) was measured as an alignment index. The ß-coefficient was estimated after adjusting for age and the body mass index (BMI) using a multiple linear regression analysis. RESULTS: Multiple linear regression analyses showed that the sIL-6 levels, but not AAA, associated with the pain VAS [ß = 10.77 (95% confidence interval (CI): 4.14-17.40), P < 0.01] and JKOM-pain scores [ß = 3.19 (95% CI: 1.93-4.44), P < 0.001] in the early stage. Conversely, AAA, but not the sIL-6 levels, was found to be associated with the pain VAS [ß = -1.29 (95% CI: -2.51 to -0.08), P < 0.05] and JKOM-pain scores [ß = -0.49 (95% CI: -0.82 to -0.16), P < 0.01] in the advanced stage. CONCLUSIONS: The presence of a higher level of sIL-6 and the varus alignment of the joint is associated with pain in early- and advanced-stage knee OA patients, respectively.

Electron reemission processes following photoelectron recapture due to post-collision interaction in inner-shell photoionization of water molecules.

Electron reemission following photoelectron recapture due to post-collision interaction has been studied at 0.7 eV the inner-shell photoionization threshold of water molecules, using a multi-electron coincidence method. Electron reemissions after single Auger decay occur from O and OH fragments which are produced by the dissociations of high-n Rydberg H2O(+) states populated through photoelectron recapture. In addition, electron reemissions after double Auger decay are identified in triple coincidence events, where autoionization lines from O and O(+) fragments are observed.

Arabic version of the Global Mental Health Assessment Tool-Primary Care version (GMHAT/PC): a validity and feasibility study.

Mental health services are far from satisfactory in the Eastern Mediterranean Region. The Global Mental Health Assessment Tool-Primary Care version (GMHAT/PC) is a semi-structured, computerized clinical assessment tool that was developed to assist health workers in making quick, convenient and comprehensive standardized mental health assessments. A study was carried out in the United Arab Emirates to evaluate the validity and feasibility of the Arabic version of the GMHAT/PC. Mental health nurses administered the GMHAT/PC Arabic version to 50 patients in mental health and rehabilitation settings and their GMHAT/PC diagnosis was compared with the psychiatrist's independent ICD-10 based clinical diagnosis on the same patients. The nurses found GMHAT/PC easy to administer in an average of 16 minutes. The GMHAT/PC-based diagnosis had a good agreement with the psychiatrist's diagnosis (kappa = 0.91) and a high sensitivity (97%) and specificity (94%).

Arabic version of the Global Mental Health Assessment Tool-Primary Care version [GMHAT/PC]: a validity and feasibility study

Mental health services are far from satisfactory in the Eastern Mediterranean Region. The Global Mental Health Assessment Tool-Primary Care version [GMHAT/PC] is a semi-structured, computerized clinical assessment tool that was developed to assist health workers in making quick, convenient and comprehensive standardized mental health assessments. A study was carried out in the United Arab Emirates to evaluate the validity and feasibility of the Arabic version of the GMHAT/PC. Mental health nurses administered the GMHAT/PC Arabic version to 50 patients in mental health and rehabilitation settings and their GMHAT/PC diagnosis was compared with the psychiatrist's independent ICD-10 based clinical diagnosis on the same patients. The nurses found GMHAT/PC easy to administer in an average of 16 minutes. The GMHAT/PC-based diagnosis had a good agreement with the psychiatrist's diagnosis [kappa = 0.91] and a high sensitivity [97%] and specificity [94%]

A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies.

BACKGROUND: Because of the less graft-facilitating effect by bone marrow (BM), we need to assess a dosage of conditioning more accurately particularly in combination with reduced-intensity conditioning. Thus we examined that modified continual reassessment method (mCRM) is applicable for deciding appropriate conditioning of allogeneic BM transplantation. PATIENTS AND METHODS: The conditioning regimen consisted of i.v. fludarabine (125 mg/m2) plus an examination dose of i.v. melphalan. The primary endpoint was a donor-type T-cell chimerism at day 28 with successful engraftment defined as >90% donor cells. Five patients per dose level were planned to be accrued and chimerism data were used to determine the next dose. RESULTS: Seventeen patients were enrolled at doses between 130 and 160 mg/m2. The dose was changed from 160 to 130 mg/m(2) (second level) after five full-donor chimerisms. With one patient of 0% chimera in the second level, the dose was increased to 135 mg/m2 (third level). Following five full-donor chimerisms in the third level, the study was complete as projected. CONCLUSIONS: mCRM was shown to be a relevant method for dose-finding of conditioning regimen. The melphalan dose of 135 mg/m2 was determined as the recommended phase II dose to induce initial full-donor chimerism.

Clinicopathological manifestations and treatment of intestinal transplant-associated microangiopathy.

Intestinal transplant-associated microangiopathy (i-TAM) is an important complication after allogeneic hematopoietic SCT. From 1997 to 2006, 87 of 886 patients with diarrhea after transplantation received colonoscopic biopsy. i-TAM, GVHD and CMV colitis were diagnosed histopathologically. The median duration from transplantation to the onset of diarrhea was 32 days (range: 9-130 days) and that from the onset of diarrhea to biopsy was 12 days (range: 0-74 days). The median maximal amount of diarrhea was 2 l/day (range: 130-5600 ml/day). Histopathological diagnosis included i-TAM (n=80), GVHD (n=26), CMV colitis (n=17) and nonspecific findings (n=2) with overlapping. Among 80 patients with i-TAM, abdominal pain was a major symptom, and only 11 patients fulfilled the proposed criteria for systemic TAM. Non-relapse mortality (NRM) among patients without resolution of diarrhea was 72% and i-TAM comprised 57% of NRM. NRM was 25% among patients without intensified immunosuppression, but was 52, 79 and 100% among those with intensified immunosuppression before diarrhea, after diarrhea, and before and after diarrhea, respectively. In conclusion, i-TAM is a major complication presenting massive refractory diarrhea and abdominal pain, which causes NRM. Avoiding intensified immunosuppression that damages vascular endothelium until the resolution of i-TAM may improve transplant outcome.

Abnormal fundus autofluorescence patterns in myopic choroidal neovascularisation.

BACKGROUND/AIMS: To investigate fundus autofluorescence (FAF) findings in eyes with myopic choroidal neovascularisation (CNV). METHODS: Observational case series. Twenty-seven consecutive eyes with CNV for at least 1 year were included. FAF patterns, time after the onset of CNV seen on FAF and FAF changes were evaluated. RESULTS: The following patterns were observed: pattern I (n = 2), relative hypoautofluorescence around the CNV surrounded by hyperautofluorescence a mean of 17 months after CNV onset; pattern II (n = 11), small lobular or multilobular well-defined FAF defects within a relatively hypoautofluorescent region surrounded by hyperautofluorescence a mean of 35 months after onset; pattern III (n = 4), large lobular or multilobular well-defined FAF defects surrounded by hyperautofluorescence a mean of 59 months after onset; and pattern IV (n = 10), large lobular or crescent-shaped well-defined FAF defects a mean of 107 months after onset. Well-defined FAF defects corresponded to chorioretinal atrophy on colour fundus photographs. During the follow-up period, two eyes with pattern I evolved into pattern II. Lobular or multilobular well-defined FAF defects enlarged in 11 eyes (pattern II, nine eyes; pattern III, two eyes). CONCLUSION: Autofluorescent changes progress over time through pattern grading. A pattern classification might be helpful to predict chorioretinal atrophy changes around myopic CNV.

Marked vascular changes of polypoidal choroidal vasculopathy after photodynamic therapy.

AIMS: To clarify vascular changes of polypoidal choroidal vasculopathy (PCV) after photodynamic therapy (PDT). METHODS: Thirty-one eyes underwent PDT with verteporfin and were followed every 3 months with indocyanine green angiography (ICGA) using confocal scanning ophthalmoscope and optical coherence tomography (OCT) for over 15 months and the findings recorded. RESULTS: The mean follow-up period was 19.2 months. Regression of the polypoidal lesions were confirmed once in 29 eyes (94%) on ICGA and OCT. Some lesions recurred at the initial regions (n = 5 eyes), at different regions connected to the branching vascular network (n = 4 eyes), and at both regions (n = 1 eye) (mean 11.4 (SD 1.9) months) after initial PDT. The branching vascular network remained in all eyes and enlarged in 13 eyes (42%) at the final visit. The vascular features of residual branching vascular networks changed (n = 7 eyes); fibrinous subretinal exudation developed (n = 4 eyes), and the retinal pigment epithelium was elevated similar to vascularised pigment epithelial detachment (n = 3 eyes). CONCLUSION: Polypoidal lesions of PCV are treatable with PDT; however, they often recur. The branching vascular networks do not regress and allow the recurrence of polypoidal lesions at the network termini. Alterations of the vascular features may occur; careful observation is needed after PDT.