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RpoS is a key stress-inducible sigma factor that regulates stress resistance genes in Escherichia coli , such as the katE gene encoding catalase HPII and the glg genes encoding glycogen synthesis proteins. Monitoring RpoS activity can provide information on the stress sensitivity of E. coli isolates in clinical settings because the RpoS in these isolates is often mutated. In the present study, we found a novel, missense point mutation at RpoS residue 128 in a clinical Shiga toxin-producing E. coli (STEC) isolate. This mutation caused RpoS dysfunction and increased stress sensitivity. A mutant rpoS was cloned from a clinical STEC that is vulnerable to cold temperature and oxidative stresses. Mutant RpoS protein expression was detected in the clinical isolate, and this RpoS was non-functional according to HPII activity and glycogen levels, which are positively regulated by RpoS and thus are used as indicators for RpoS function. A reporter assay with β-galactosidase indicated that the dysfunction occurred at the transcriptional level of genes regulated by RpoS. Furthermore, substitution analysis indicated that the hydrophobicity of the amino acid at residue 128 was critical for RpoS activity; the simulation analysis indicated that the amino acids of RNA polymerase (RNAP) that interact with RpoS residue 128 are hydrophobic, suggesting that this hydrophobic interaction is critical for RpoS activity. In addition, substitution of Ile128 to Pro128 abolished RpoS activity, possibly as a result of disruption of the secondsary structure around residue 128, indicating that the structure is also a crucial factor for RpoS activity. These results indicate that only one point mutation at a hydrophobic residue of the complex formed during transcription leads to a critical change in RpoS regulation. Moreover, we found that Ile128 is widely conserved among various bacteria: several bacterial strains have Met128 or Leu128, which are hydrophobic residues, and these strains had similar or higher RpoS activity than that observed with Ile128 in this study. These data indicate that the hydrophobicity of the amino acid at residue 128 is critical for RpoS activity and is consequently important for bacterial survival. Taken together, these findings may contribute to a deeper understanding of protein functional mechanisms and bacterial stress responses.

Purpose: To investigate ocular blood flow and correlations between ocular blood flow and variables in patients with severe non-proliferative diabetic retinopathy (S-NPDR) following panretinal photocoagulation (PRP)., Methods: In this retrospective, cross-sectional study, the blood flow on the optic nerve head (ONH) and choroid was assessed with laser speckle flowgraphy (LSFG) using the mean blur rate (MBR) in 76 eyes of 76 patients with S-NPDR who underwent PRP, 39 eyes of 39 patients with S-NPDR who did not undergo PRP, and 71 eyes of 71 normal subjects. The correlation between MBR and variables, including visual acuity (VA) and choroidal area determined by binarization method, was analyzed., Results: The mean age was 62.9 ± 11.9 years in the S-NPDR with PRP eyes, 55.6 ± 11.4 years in the S-NPDR without PRP eyes, and 60.3 ± 11.1 years in the normal subject eyes. The ONH MBR in vessel and tissue areas and the choroidal MBR were significantly lower in the S-NDR with PRP group than in the other groups (p < 0.001, p < 0.001, and p < 0.001, respectively). The luminal and the stromal areas were significantly smaller in the S-NDR with PRP group than in the other groups (p < 0.001 and p < 0.001, respectively). LogMAR best corrected visual acuity (BCVA) exhibited significant negative correlation with the ONH MBR in vessel (r = -0.386, p < 0.001), tissue (r = -0.348, p < 0.001), and the choroid MBR (r = -0.339, p = 0.002) in the S-NDR with PRP group. Stepwise multiple regression analysis demonstrated that BCVA was a common independent factor associated with the ONH MBR in vessel, tissue, and the choroidal MBR in the S-NDR with PRP group., Conclusions: ONH and choroid MBR in addition to choroidal component, including the luminal area, were significantly lower in eyes of patients with S-NPDR after PRP compared with no PRP and normal subjects group. This could suggest that the significantly reduced ocular blood flow in PRP-treated S-NPDR eyes correlated with long-term decreased post-PRP luminal area and visual acuity.

Aldehyde dehydrogenase 1 (ALDH1) is a cancer stem cell (CSC) marker that is easily evaluable. The expression and clinical significance of ALDH1 in ipsilateral breast tumor recurrence (IBTR) has yet to be investigated. In the present study, the expression profile of ALDH1 and its correlation with prognosis in IBTR tissues was examined. Patients with IBTR from eight institutions were retrospectively enrolled in the study. Immunohistochemistry was used to examine ALDH1 expression patterns in the tissue specimens of primary cancers and IBTRs. ALDH1 expression levels were investigated in 182 IBTR tumors, which included cases of invasive carcinoma selected from 271 consecutive patients with IBTR. ALDH1 was expressed in 23% of the IBTR tissue samples. The rate of concordant expression between primary cancer and IBTR tissues was 68%. There was no significant association between disease-free survival (DFS) and ALDH1 expression levels in IBTR. IBTRs that expressed ALDH1 and Ki-67 had a poorer prognosis and this expression pattern was significantly associated with DFS (P=0.0073). The percentages of ALDH1 positive expression in each tissue subtype were as follows: Luminal A, 20%; luminal B, 24%; human epidermal growth factor 2 (HER2), 35%; triple-negative, 21%. There was a significant correlation between DFS and ALDH1 expression levels in HER2-type IBTR tissue specimens (P=0.034). In conclusion, it is possible that ALDH1 and Ki-67 expression levels may be useful for predicting prognosis in patients with HER2-type tumors.

A ready-made dry medium method for Escherichia coli and coliform count, the Medi·Ca EC method, was compared with the most probable number (MPN) method using Brilliant Green Lactose Bile broth and E. coli broth (AOAC INTERNATIONAL Official MethodSM 966.24) for seven food matrixes: raw beef, raw pork, raw frozen pork, raw lamb, raw salmon, frankfurter sausage, and cooked ham. The mean difference between the two methods at each contamination level for each matrix was <0.5 log10, and the 95% confidence intervals for the mean differences fell within the range of -0.5 to 0.5, with the exception of a few cases in the independent laboratory study. sr and RSDr values of the Medi·Ca EC method were generally lower than those of the MPN method, and r2 ranged from 0.91 to 0.99. Product consistency and stability studies showed little variability between production lots and the shelf-life of 20 months. An incubation time within the range of 22-26 h did not adversely affect the results; however, variations in sample volume did affect final counts. These results showed that the Medi·Ca EC method is a reasonable alternative to the reference method for the selected food matrixes and makes it possible to simultaneously detect and enumerate E. coli and coliform in only 24 h.

Purpose: To evaluate the effects of an intravitreal ranibizumab (IVR) injection on the retinal microcirculation of eyes with macular edema secondary to a branch retinal vein occlusion (BRVO)., Methods: Twenty-six eyes of 26 patients with macular edema due to a BRVO that had received a single IVR injection (0.5 mg/0.05 mL) were studied. The retinal microcirculation was assessed by laser speckle flowgraphy (LSFG) using the mean blur rate (MBR) and relative flow volume (RFV). The size of the retinal arteries and veins surrounding the optic nerve head were measured separately. All of the examinations were made before, and at 1 week, and 1 and 2 months after the IVR., Results: The visual acuity improved significantly, and the mean central macular thickness decreased significantly during the follow-up period (both P < 0.001). The mean MBRall and MBRtissue decreased significantly at 1 week and 1 month after the IVR (both P < 0.001). The total RFV of the arteries and veins decreased significantly at 1 week and 1 month after the IVR injection in the occluded and nonoccluded quadrants (all P < 0.001). The width of the arteries and veins in the LSFG images decreased significantly at 1 week and 1 month after the IVR injection (P < 0.001)., Conclusions: An IVR injection leads to a transient vasoconstriction of the retinal arteries and veins and a reduction of the retinal blood flow and velocity in both the occluded and nonoccluded quadrants. The changes in retinal microcirculation might be related to the improvement of the macular edema and vision.

The aim of the present study was to evaluate the association between changes in the neutrophil-to-lymphocyte ratio and the survival rate, as well as tumor subtype, in recurrent breast cancer. Patients with recurrent breast cancer following surgery were included in this study. NLR was calculated and compared between two time points: Pre-treatment and recurrence. The associations between the longitudinal NLR change, the NLR at the time of recurrence and overall survival following recurrence (OSrec) were evaluated. A total of 89 patients were evaluated. NLR increased by 0.59 at recurrence, as compared with the initial treatment (P<0.05). The triple negative (TN) type demonstrated 4.59 in NLR, which was the highest among the four subtypes at the time of recurrence (P<0.05). The highest change (an increase of 2.0) was observed in TN type cancer (P<0.05). Patients with high NLR upon recurrence demonstrated significantly shorter OSrec rates (P<0.05). On the other hand, patients with an NLR increased by more than a third quartile demonstrated a shorter OSrec rate (P=0.06). When adjusted by covariates, the NLR and tumor subtype were determined to be associated with OSrec (P<0.05). Therefore, an increased NLR predicts survival, even in patients with recurrent breast cancer, and the NLR is potentially useful as an inflammation marker for TN breast cancer.

Ocular trauma is one of the leading causes of visual impairment worldwide. Because of the popularity of cataract surgeries, aged individuals with ocular trauma commonly have a surgical wound in their eyes. The purpose of this study was to evaluate the visual outcome of cases that were coincident with intraocular lens (IOL) ejection in the eyes with ruptured open-globe ocular injuries. Consecutive patients with open-globe ocular injuries were first reviewed. Patients' characteristics, corrected distance visual acuities (CDVAs) over 3 years after the trauma, causes of injuries, traumatic wound patterns, and coexistence of retinal detachment were examined. The relationships between poor CDVA and the other factors, including the complications of crystalline lens and IOL ejection, were examined. A total of 105 eyes/patients [43 eyes with rupture, 33 with penetrating, 28 with intraocular foreign body (IOFB), and 1 with perforating injuries] were included. Rupture injuries were common in aged patients and were mostly caused by falls, whereas penetrating and IOFB injuries were common in young male patients. CDVAs of the eyes with rupture injuries were significantly worse than those of the eyes with penetrating or IOFB injuries. CDVA from more than 50% of the ruptured eyes resulted in no light perception or light perception to 20/500. CDVA of the ruptured eyes complicated by crystalline lens ejection was significantly worse than that of those complicated by IOL ejection. The wounds of the ruptured eyes complicated by IOL ejection were mainly located at the superior corneoscleral limbus, whereas those of the eyes complicated by crystalline lens ejection were located at the posterior sclera. There were significant correlations between poor CDVA and retinal detachment and crystalline lens ejection. These results proposed a new trend in the ocular injuries that commonly occur in aged patients; history of cataract surgery might affect the final visual outcome after open-globe ocular injuries., Competing Interests: The authors have declared that no competing interests exist.

Objective: Social capital, the collective resources of groups including perceptions of trust and reciprocity, is recognized as an important contributor to suicide. We examined the association of individual- and community-level social capital with suicidal ideation after adjusting for social support among older adults living in the community., Methods: In August 2010 we sent questionnaires to all residents aged 65 years and older living in 3 rural municipalities (N = 21,232) in Okayama Prefecture, Japan; 13,919 questionnaires were returned (response rate: 65.6%). The final analysis included 10,094 participants. The outcome variable was suicidal ideation. Exposure variables were individual-level mistrust and lack of reciprocity (level 1), and the aggregated responses of these variables from 35 communities in the municipalities (level 2). Covariates included age, sex, educational attainment, marital status, the number of cohabitants, years of residence, self-rated socioeconomic status, disability, social support, and psychological distress. Multilevel logistic regression analysis was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs)., Results: After adjusting for social support and psychological distress, we found that mistrust and lack of reciprocity were only associated with suicidal ideation at the individual level. Stratified analysis showed that among subjects with psychological distress, mistrust was associated with suicidal ideation at individual (OR: 1.88; 95% CI: 1.42-2.51) and community levels (OR: 1.98; 95% CI: 1.02-3.81)., Conclusions: Our findings show that individual- and community-level social capital is a possible protective factor for suicidal ideation, particularly for people with psychological distress., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: Proliferative vitreoretinopathy (PVR) is one of the most severe ocular diseases. Fibrotic changes in retinal cells are considered to be involved in the pathogenesis of PVR. Epithelial-mesenchymal transition (EMT) of RPE cells is one of the main concepts in the pathogenesis of fibrovascular membranes (FVMs) in PVR. In this study, we examined the expression of Caveolin-1 in human FVMs from patients with PVR. We also examined the role of Caveolin-1 in the pathogenesis of PVR., Methods: Western blotting, real-time PCR, and immunohistochemistry were performed with human FVMs and mouse eyes with PVR. Cell migration assays were performed to evaluate the involvement of Caveolin-1 in EMT using primary human and mouse RPE cells., Results: Caveolin-1 was expressed in human FVMs and upregulated in the mouse eyes with PVR. The alpha-smooth muscle actin (αSMA) expression and migration ability were increased in RPE cells with knockout or knockdown of Caveolin-1, whereas zonula occludens-1 (ZO-1) immunohistochemistry showed reduced morphology and expression of ZO-1. In addition, migration assays showed that Caveolin-1 reduction increased RPE cell migration abilities., Conclusions: These results indicated that Caveolin-1 in RPE cells prevents PVR by blocking EMT.

Background: The aim of this study was to examine the change in retinal thickness after vitrectomy with internal limiting membrane (ILM) peeling and/or silicone oil (SO) endotamponade in proliferative diabetic retinopathy (PDR)., Methods: The actual amount and ratio of changes in the retinal thickness were calculated., Results: Compared to control eyes in the ILM peeling (-)/SO (-) group, the central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, inferior inner, temporal inner, and nasal inner retina in the ILM peeling (+)/SO (+) group showed a significant reduction of the retinal thickness. The central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, superior inner, inferior inner, and temporal inner retina in the ILM peeling (+)/SO (+) group showed a significantly increased reduction rate of the retinal thickness compared to the control group., Conclusions: Macular retinal thinning in PDR was observed after ILM peeling and SO endotamponade, and it was increased by the combination of these 2 factors., (© 2017 S. Karger AG, Basel.)

Loop-mediated isothermal amplification (LAMP) rapidly amplifies DNA under isothermal conditions. The aim of this study was to detect Candida albicans and compare the positivity rate in the LAMP reaction with that of conventional methods for oral exfoliative cytology (EC) samples. Sixty-eight EC samples from 53 patients were subjected to LAMP analysis. These patients had been clinically diagnosed with leukoplakia, squamous cell carcinoma, oral lichen planus (OLP), stomatitis, oral candidiasis, and other malignancies. LAMP reactions were defined as positive when the sample turbidity exceeded 0.1 (arbitrary unit). Periodic acid-Schiff (PAS) staining and microbial culture were also performed to detect Candida species in EC samples. The LAMP reaction detected C. albicans in 42.6% of EC samples. Candida species were detected in 32.4% of the same samples by culturing and in 29.4% of samples by PAS staining. C. albicans DNA was detected most frequently in samples from OLP patients. We conclude that, in comparison to conventional methods for detection of C. albicans, the LAMP method is highly sensitive and time-saving, and does not require expensive equipment or diagnostic technology. It may therefore be useful for on-site screening of C. albicans at dental clinics.

Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor whose expression level is positively correlated with tumor aggressiveness and metastatic potential. However, the mechanism underlying SLPI-induced enhancement of malignant phenotype is not completely understood. The malignancy of cancer cells is highly dependent on cell migration activity. Our previous study revealed that gingival carcinoma Ca9-22 cells, but not colorectal adenocarcinoma HT-29 cells, expressed SLPI. Therefore, we investigated the migration activity of these two cell types to understand the nature of SLPI-mediated tumor aggressiveness and metastatic potential. In vitro wound healing assay indicated that HT-29 cells and SLPI-deleted Ca9-22 cells showed lower migration activity than wild-type Ca9-22 cells, suggesting that SLPI-induced cell migration plays an important role in tumor aggressiveness and metastatic potential. In addition, our gene expression profiling study based on microarray data for the three cell types identified a number of candidates, including LCP1 and GLI, that could be key molecules in the mechanism of SLPI-induced cell migration.

Purpose: The thoracic spine is considered a rigid region because it is restricted by the rib cage. Previously, we reported functional alignments and range of motion (ROM) at all segmental levels. The purpose of this study was to investigate dynamic changes of the dural sac and spinal cord in the thoracic spine using a multidetector-row computed tomography (MDCT)., Methods: Fifty patients with cervical or lumbar spinal disease were prospectively enrolled. After preoperative myelography, MDCT was performed at maximum passive flexion and extension. The anteroposterior diameter and cross-sectional area of the dural sac and spinal cord in the axial plane were measured using Scion imaging software. We also evaluated the correlation between the change ratio of the cross-sectional area and segmental kyphotic angle and ROM., Results: In flexion, the anteroposterior diameter of the dural sac was larger than in extension. The cross-sectional area in the upper and middle regions was smaller, but was larger in the lower region. The anteroposterior diameter and cross-sectional area of the spinal cord in the upper and middle regions were smaller than in extension, but these values were nearly the same in both flexion and extension in the lower region. Change ratios of the cross-sectional area were correlated with segmental kyphotic angle rather than ROM., Conclusions: The thoracic spine showed some dynamic changes of the dural sac and spinal cord in the axial plane within functional motion. Segmental kyphotic angle, rather than segmental ROM, was the more important factor affecting dimensions of the dural sac and spinal cord.

Purpose. We had earlier reported positive hsa-miR-148a-3p expression in eyes with rhegmatogenous retinal detachment (RRD) and its involvement in the epithelial-mesenchymal transition of retinal pigment epithelium in vitro. Here we investigated the association of hsa-miR-148a-3p expression levels in the vitreous fluid of patients with RRD with severity of RRD. Methods. The hsa-miR-148a-3p expression levels in the vitreous fluid, range (degree) of retinal detachment (RD), and pixels of retinal break were measured in 27 eyes with RRD. The association of hsa-miR-148a-3p expression levels with other factors was evaluated by multiple regression analysis. Results. The hsa-miR-148a-3p expression levels, time from onset of RRD to vitrectomy, range of RD, and pixels of retinal breaks were 23.68 ± 43.00, 12.07 ± 15.36 days, 155.85 ± 86.67 degrees, and 37000 ± 67100 pixels, respectively. Five eyes with RRD had vitreous hemorrhage preoperatively. The hsa-miR-148a-3p expression levels were significantly associated with pixels of retinal breaks ( β = 0.699) and the time from onset of RRD to vitrectomy ( β = 0.358) but not with the range of RD or presence of vitreous hemorrhage. Conclusion. The hsa-miR-148a-3p expression levels in the vitreous fluid were significantly associated with the size of retinal break and disease duration., Competing Interests: The authors declare that they have no competing interests.

Nipro-Toyobo-paracorporeal pulsatile flow VAD (Nipro VAD; Nipro, Osaka, Japan) has been used most commonly as a paracorporeal VAD (p-VAD) in Japan. There are few reports describing clinical course of post LVAD explantation and its complication. We herein present two cases of apical abscess after the explantation of the device. SSI is a main risk factor of formation of the apical abscess at the time of LVAD explantation. It is mandatory to perform sufficient debridement and closure of the layers including abdominal muscle and anterior abdominal fascia at exit sites in the explantation surgery. Omentopexy is also helpful for prevention from infection. Routine removal of apical cuff and outflow graft could be considered as one of the options when LVAD is explanted as bridge to recovery.

Purpose: To determine the long-term changes in the intraocular pressure (IOP) following vitrectomy for rhegmatogenous retinal detachment (RRD), epiretinal membrane (ERM), and macular hole (MH), and to investigate the relationship between the retinal disease and the incidence of late-onset IOP elevation., Methods: This was a retrospective, observational, comparative study. We reviewed the medical records of 54 eyes of 54 RRD patients, 117 eyes of 117 ERM patients, and 75 eyes of 75 MH patients who underwent 20-, 23- or 25-gauge vitrectomy. The IOPs before surgery and 1, 3, 6, and 12 months following vitrectomy, and also at the final visit (average, 23.95 months) were evaluated. We defined a significant increase in the IOP as an increase of ≥4 mmHg from the preoperative IOP, and this increase was taken to be a 'death' event for the Kaplan-Meier survival analyses., Results: The mean follow-up period was not significantly different among the groups. The mean IOP at 3 (P = 0.001) and 12 (P = 0.011) months following the vitrectomy and at the final visit (P = 0.002) were significantly higher than that before the vitrectomy in the RRD group. The mean IOP in the RRD group was significant higher than that in the ERM group at 1 (P = 0.005), 3 (P = 0.009), and 12 (P = 0.013) months following vitrectomy, and at the final visit (P = 0.032). Kaplan-Meier survival analyses showed that the RRD group had a significantly higher risk of an IOP increase following vitrectomy than the other groups (P<0.001 by log-rank test). Multivariate logistic regression analyses showed that a preoperative diagnosis of RRD was the only risk factor that was significantly associated with a postoperative IOP elevation after excluding eyes with a low preoperative IOP (odds ratio, 3.208; P = 0.003)., Conclusions: A late-onset IOP elevation following vitrectomy was observed only in eyes that underwent RRD surgery. The elevation was probably caused by the specific characteristics and surgical procedures of RRD. Clinicians should pay more attention to the IOP elevation for long times after vitrectomy especially in eyes with RRD., Competing Interests: The authors have declared that no competing interests exist.

Klebsiella oxytoca can be either pathogenic or beneficial, depending on conditions. These opposing characteristics have not been fully elucidated. Here, we report the complete sequence of the K. oxytoca JKo3 genome, consisting of a single circular chromosome of 5,943,791 bp and four plasmids., (Copyright © 2016 Iwase et al.)

Purpose: To determine the preoperative characteristics and the changes in retinal blood flow following vitrectomy in eyes with a rhegmatogenous retinal detachment (RRD)., Methods: Twenty-five-gauge vitrectomy without scleral bucking was performed on 31 eyes of 31 patients with macula-on RRD. The retinal blood flow on the optic nerve head (ONH) was assessed by laser speckle flowgraphy (LSFG), and the mean blur rate (MBR) and pulse waveform parameters before and at 10 days, 1, 2, 3, and 6 months after the surgery were examined. Eyes treated by scleral buckling, and eyes with an epiretinal membrane and cataract that underwent surgery were used as controls., Results: The mean preoperative MBR-vessel on the ONH was significantly lower in eyes with RRD than in the fellow unaffected eyes (P < 0.001), but it was not significantly different from the operated eye and the fellow eye in the control group. A significant increase in the mean MBR-vessel on the ONH was observed following vitrectomy in eyes affected by RRD (P < 0.001), whereas no significant difference was observed in the fellow eye, the scleral buckling-treated eyes, and the control eyes. Of the eight pulse waveform parameters, only the flow acceleration index was significantly lower in eyes with a RRD than in the fellow eyes preoperatively, but then it significantly increased with time following vitrectomy. The changes in the MBR-vessel were not correlated with that of other parameters (e.g., the ocular perfusion pressure)., Conclusions: These results indicate that the retinal blood flow is reduced in eyes affected by RRD preoperatively, and can recover following successful RRD repair by vitrectomy.

We report a case of breast-conserving surgeryusing real-time virtual sonography(RVS)in a breast cancer patient who received neoadjuvant chemotherapy(NAC). The patient was a 63-year-old woman. Ultrasound(US)showed a lobulated 45 ×40×40mm diameter mass in the C area of the right breast. Histological examination found invasive ductal carcinoma that was negative for estrogen and progesterone receptors and for human epidermal growth factor receptor type 2/neu protein expression, and the Ki-67 index was 50%. The patient was diagnosed with breast cancer clinical stage II A(T2N0M0). The basal-like subtype is more sensitive to anthracycline-based NAC than luminal breast cancers. The patient wanted breastconserving surgery. Therefore, we treated the patient with NAC. First, we obtained US volume data of the tumor as a Digital Imaging and Communication in Medicine(DICOM)file, simplyscanning the skin over the lesion gentlywith the probe. We administered tri-weeklynanoparticle albumin-bound paclitaxel(nab PTX)followed bya fluorouracil, epirubicin, and cyclophosphamide( FEC)regimen. Follow-up computed tomography(CT)and US showed good tumor concentric shrinkage without anysurrounding lesion after NAC. Finally, right breast-conserving surgerywas performed, using RVS to detect the area where the tumor was before NAC in the US image after NAC. Histopathologically, the effect of the chemotherapy was Grade 2a and the surgical margins were negative.

The aim of the study was to investigate the relationship between choroidal blood flow and systemic and ocular variables in patients with healthy eyes.In this prospective cross-sectional study, we examined 241 eyes of 241 healthy Japanese subjects (92 males and 149 females; mean age, 37.8 ± 17.0 years). The mean blur rate, a measure of the relative blood flow of the choroid, was determined using laser speckle flowgraphy. The total cross-sectional choroidal, luminal, and stromal areas of the choroid were determined by the binarization method. We investigated the correlation between choroidal MBR and systemic and ocular variables.Choroidal mean blur rate correlated with age (r = -0.385, P < 0.001) and choroidal thickness (r = 0.264, P < 0.001). The choroidal area correlated with choroidal mean blur rate (r = 0.374, P < 0.001), age (r = -0.184, P = 0.004), axial length (r = -0.251, P < 0.001), and choroidal thickness (r = 0.468, P < 0.001). The luminal area correlated with choroidal mean blur rate (r = 0.403, P < 0.001), age (r = -0.244, P < 0.001), axial length (r = -0.218, P = 0.001), and choroidal thickness (r = 0.435, P < 0.001). On multiple stepwise regression analyses, age (β = -0.321, P < 0.001) and luminal area (β = 0.320, P < 0.001), heart rate (β = 0.136, P = 0.018), and mean ocular perfusion pressure (β = 0.126, P = 0.045) were independent factors indicating the choroidal mean blur rate. Furthermore, axial length (β = -0.352, P < 0.001), choroidal mean blur rate (β = 0.273, P < 0.001), age (β = -0.247, P < 0.001), gender (β = -0.226, P < 0.001), and mean ocular perfusion pressure (β = 0.193, P = 0.002) were independent factors indicating the luminal area.The choroidal blood flow positively correlated with the luminal area and negatively correlating with age. In addition, the luminal area was negative correlated with age. It is suggested that aging causes a reduction in choroidal blood flow and luminal area, and as a result of aging effect, decreased choroidal blood flow would correlate with decreased luminal area., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The aim of the present study was to assess midterm results after acetabular impaction bone grafting (IBG) in primary total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH) with large acetabular segmental defect., Methods: Primary THA with IBG for DDH with large acetabular segmental defect was performed in 40 hips of 38 patients. The average age was 61.6 years (range: 33-82 years), and the average follow-up period was 7.5 years (range: 3-10.3 years). The Merle d'Aubigné and Postel hip score and complications were assessed. For radiological assessment, postoperative location of the hip rotation center, the socket inclination angle, and the socket center-edge angle were assessed. Kaplan-Meier survival analysis was performed with the end points of any type of reoperation and aseptic acetabular loosening., Results: The mean Merle d'Aubigné and Postel hip score improved from 10.4 points to 16.2 points at the final follow-up. Reoperation was performed in 1 case for acute infection without loosening. In 39 out of 40 hips (97.5%), the center of hip rotation was located beneath the "high hip center." The average socket inclination angle was 39.3° (range: 30°-54°), and the average socket center-edge angle was -11.8° (range: -23° to 9°). Survival rate of acetabular component at 8 years with the end point of any reoperation and of aseptic loosening was 96.6% (95% confidence interval: 89.9%-100%) and 100%, respectively., Conclusion: Acetabular IBG represents one of the useful options for restoring a normal hip center and acetabular bone stock in primary THA for DDH with large acetabular defect., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: We report a newly developed device to fragment thrombi in retinal vein occlusion., Methods: The new instrument consists of a 23-gauge (G) pipe and a 37-G needle with an internal wire. A total of 40 porcine eyes were used; 20 eyes for experiments in the branch retinal vein (BRV group) and 20 eyes for experiments in the central retinal vein (CRV group). We placed 25-G 3-port trocars, and core vitrectomy was performed. Another 23-G scleral incision was performed for insertion of the needle. The needle pierced the retinal vein at a distance of three- to four- or one-disc diameters from the optic disc (BRV or CRV group, respectively), and the internal wire was advanced toward the disc. The success rates of needle piercing and cannulation of the internal wire were recorded in each group. In the CRV group, the cannulation was deemed successful when the tip reached inside the optic disc. Real-time optical coherence tomography imaging also was performed using the Zeiss Rescan 700 device in porcine eyes. Histologic examination of the retinal vessel inserted with the internal wire was performed., Results: The success rates of needle piercing into the BRV and CRV were 85% and 95%, respectively. The success rates of cannulation of the internal wire into the BRV and CRV were 85% and 0%, respectively. The process of cannulation was recorded successfully with the Rescan 700. Histologic examination showed no damages to the endothelial cell layer., Conclusions: The needle and internal wire intended to be used for recanalization of BRV occlusion were successfully pierced and cannulated into the BRV., Translational Relevance: This newly developed device could become a treatment modality for retinal vein occlusion to fragment thrombi that present treatment methods cannot reach and remove directly.

Background: Pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) has been regarded as a surrogate endpoint for disease-free survival (DFS) and overall survival (OS) of patients with breast cancer. No consensus regarding the definition of pCR has been established; there are several definitions according to a variety of classifications. Eradication of cancer cells in both breast and lymph nodes has been better associated with improved prognosis than in the breast alone. Even in patients diagnosed as having clinically node-negative cancer before NAC, postoperative pathological examination often shows axillary lymph node metastases., Patients and Methods: Of the 771 patients with breast cancer who underwent NAC in the Cancer Institute Hospital between January 2000 and May 2009, 146 patients preoperatively diagnosed as having node-negative breast cancer were retrospectively evaluated. We have made the definition of clinically lymph node-negative (N0) as follows: first, ultrasonography before NAC did not show any lymphadenopathy. Second, a cytological procedure confirmed negative study for each patient when ultrasonography suggested lymphadenopathy., Results: The median observation period was 79.7 months, and the median age of the subjects was 51 years. Pathological examination at the time of the surgery showed lymph node metastases (ypN+) in 46 patients (31.5%). Histological therapeutic effects revealed ypT0/is in 9 patients (6.2%) and ypTinv in 137 (93.8%). Multivariate analysis demonstrated that younger age (49>), large tumor size, NG3, and ypN+ were significant poor prognostic factors for DFS (p = 0.020, p = 0.008, P = 0.022 and p = 0.010, respectively). Moreover, ypN+ was the only significant poor prognostic factor for OS (p = 0.022). The predictive factors of ypN+ in clinically lymph node-negative breast cancer were ypTinv (p = 0.036) and the luminal type (HR+ and HER2-) (p = 0.029)., Conclusion: The prognosis of clinically lymph node negative breast cancer depended on ypN+, which was associated with ypTinv and luminal subtype., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Pulmonary tumor thrombotic microangiopathy (PTTM) is rare, cancer-related pulmonary complication leading to hypoxia, pulmonary hypertension, and heart failure. The standard treatment for PTTM is not established. However, imatinib, a tyrosine kinase inhibitor of the PDGF receptor, may cause regression of pulmonary hypertension and pulmonary artery remodeling in PTTM., Case Descriptions: We report two cases of PTTM who received an anti-PDGF agent of imatinib for PTTM developed during chemotherapy for metastatic breast cancer. Case 1: 61-year-old woman who underwent resection of the left breast and axillary lymph node dissection and received adjuvant chemotherapy (CAF followed by docetaxel), then endocrine therapy for 5 years. Twelve years after surgery, multiple bone and mediastinal lymph node metastases occurred. She was under treatment with eribulin for one year but admitted because of rapid progressing dyspnea. Case 2: 45-year-old woman with metastatic breast cancer in multiple bones was under treatment for 5 years. Receiving capecitabine, she suffered from dyspnea for 2 months, she was admitted to our hospital with diagnosis of severe hypoxia. In both cases, the wedged pulmonary arterial blood cell sampling revealed cytologically malignant cells which confirmed the diagnosis of PTTM. They were treated with imatinib, which alleviated pulmonary hypertension. However, they died due to progression of metastatic breast cancer., Discussion and Evaluation: Single use of imatinib did not showed sufficient efficacy. It is necessary to conduct a well-designed clinical trial using chemotherapies combined with imatinib for PTTM., Conclusions: Imatinib, which alleviated pulmonary hypertension, could be a new strategy for pulmonary tumor thrombotic microangiopathy in patient with metastatic breast cancer.

Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that diminishes tissue destruction during inflammation. A recent report revealed high levels of SLPI expression in the oral carcinoma cell. In addition, overexpression of SLPI up-regulates metastasis in lung carcinoma cells. On the other hand, matrix metalloproteinases (MMPs) are proteinases that participate in extracellular matrix degradation. SLPI and MMPs are involved as accelerators of the tumor invasion process; however, their exact roles are not fully understood. Understanding the mechanism of tumor invasion requires models that take the effect of microenvironmental factors into account. In one such in vitro model, different carcinoma cells have been shown to invade myoma tissue in highly distinct patterns. We have used this myoma model, as it provides a more natural stroma-like environment, to investigate the role of SLPI in tumor invasion. Our results indicate that the model provides a relevant matrix for tumor invasion studies, and that SLPI is important for the invasion of oral carcinoma Ca9-22 cells in conjunction with MMPs. Furthermore, using bioinformatics analysis, we have identified candidates as key molecules involved in SLPI-mediated tumor invasion., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

ATP-driven motor proteins, which function in cell motility and organelle transport, have potential applications as bio-inspired micro-devices; however, their control remains unsatisfactory. Here, we show rapid-velocity control of actin filaments interacting with myosin motors using voltage applied to Pt electrodes in an in vitro motility system, by which immediate increases and decreases in velocity were induced beside the cathode and anode, respectively. Indicator dye revealed pH changes after voltage application, and alternate voltage switching allowed actin filaments to cyclically alter their velocity in response to these changes. This principle provides a basis for on-demand control of not only motor proteins but also pH-sensitive events at a microscopic level., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Design: Retrospective., Purpose: This study aims to investigate the accuracy of the oblique fluoroscopic view, based on preoperative computed tomography (CT) images for accurate placement of lumbosacral percutaneous pedicle screws (PPS)., Overview of Literature: Although PPS misplacement has been reported as one of the main complications in minimally invasive spine surgery, there is no comparative data on the misplacement rate among different fluoroscopic techniques, or comparing such techniques with open procedures., Methods: We retrospectively selected 230 consecutive patients who underwent posterior spinal fusion with a pedicle screw construct for degenerative lumbar disease, and divided them into 3 groups, those who had undergone: minimally invasive percutaneous procedure using biplane (lateral and anterior-posterior views using a single C-arm) fluoroscope views (group M-1), minimally invasive percutaneous procedure using the oblique fluoroscopic view based on preoperative CT (group M-2), and conventional open procedure using a lateral fluoroscopic view (group O: controls). The relative position of the screw to the pedicle was graded for the pedicle breach as no breach, <2 mm, 2-4 mm, or >4 mm. Inaccuracy was calculated and assessed according to the spinal level, direction and neurological deficit. Inter-group radiation exposure was estimated using fluoroscopy time., Results: Inaccuracy involved an incline toward L5, causing medial or lateral perforation of pedicles in group M-1, but it was distributed relatively equally throughout multiple levels in groups M-2 and controls. The mean fluoroscopy time/case ranged from 1.6 to 3.9 minutes., Conclusions: Minimally invasive lumbosacral PPS placement using the conventional fluoroscopic technique carries an increased risk of inaccurate screw placement and resultant neurological deficits, compared with that of the open procedure. Inaccuracy tended to be distributed between medial and lateral perforations of the L5 pedicle, as a result of pedicle morphology and the PPS pathway. Oblique fluoroscopic views, based on CT measurement, may allow accurate PPS insertion with a shorter fluoroscopy time., Competing Interests: No potential conflict of interest relevant to this article was reported.

The aim of this study was to compare changes in refraction following lens-sparing vitrectomy between patients with rhegmatogenous retinal detachment (RRD) and epiretinal membrane (ERM) and to investigate factors associated with the change in refraction.We reviewed medical records of 49 eyes of 49 patients with RRD (53.6 ± 7.8 years, mean ± standard deviation) and 24 eyes of 24 patients with ERM (50.9 ± 15.7 years) who underwent lens-sparing vitrectomy. Spherical equivalent refractive power was evaluated before and up to 18 months after surgery. The relationship between the change in refraction and several parameters was evaluated.A significant progressive myopic shift in refractive power was observed after vitrectomy in operated RRD and ERM eyes (P < 0.001, P = 0.016, respectively), with no significant difference in fellow eyes. The refraction values observed at ≥3 and ≥12 months following vitrectomy were significantly different as compared with those observed at baseline in the RRD group (P < 0.001) and the ERM group (P < 0.05), respectively. The change in refraction between the RRD and ERM groups was significant (P = 0.030). The multiple linear regression analysis showed that only age was significantly correlated with the change in refraction in RRD (P = 0.018) and ERM (P < 0.001) groups. The change in refraction was significantly and positively correlated with age in RRD (r = -0.461, P = 0.001) and ERM (r = -0.687, P < 0.001) groups. Following lens-sparing vitrectomy, cataract surgery was performed on 30 eyes after 0.89 ± 0.26 years in the RRD group and on 10 eyes after 1.11 ± 0.14 years in the ERM group; there was a significant difference in time to cataract surgery between the groups (P = 0.007). Kaplan-Meier survival analysis demonstrated that there was a significant difference in the rate of cataract surgeries between the RRD and ERM groups (P = 0.022).Following lens-sparing vitrectomy for RRD and ERM, a progressive myopic shift in refraction owing to nuclear sclerosis was observed. Core vitrectomy itself would cause a myopic shift of refraction. The only risk factor associated with cataract progression following lens-sparing vitrectomy is age for both types of patients.

The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response.

Background: Eribulin is a non-taxane, microtubule dynamics inhibitor that increases survival of patients with metastatic breast cancer. Although eribulin is well tolerated in patients with heavily pretreated disease, eribulin-induced liver dysfunction (EILD) can occur, resulting in treatment modification and subsequent poor disease control. We aimed to clarify the effect of EILD on patient survival., Methods: The medical records of 157 metastatic breast cancer patients treated with eribulin between July 2011 and November 2013 at Cancer Institute Hospital were retrospectively analyzed. EILD was defined as 1) an increase in alanine aminotransferase or aspartate aminotransferase levels >3 times the upper limit of normal, and/or 2) initiation of a liver-supporting oral drug therapy such as ursodeoxycholic acid or glycyron. Fatty liver was defined as a decrease in the liver-to-spleen attenuation ratio to <0.9 on a computed tomography scan., Results: EILD occurred in 42 patients, including one patient for whom eribulin treatment was discontinued due to severe EILD. The patients who developed EILD had significantly higher body mass indices (BMIs) than those who did not develop EILD (24.5 vs. 21.5, respectively; P < 0.0001), with no difference in the dose intensity of eribulin between the two groups (P = 0.76). Interestingly, the patients with EILD exhibited significantly longer progression-free survival (PFS) and overall survival (OS) than those without EILD (P = 0.010 and P = 0.032, respectively). Similarly, among 80 patients without liver metastasis, 19 with EILD exhibited significantly longer PFS and OS than the others (P = 0.0012 and P = 0.044, respectively), and EILD was an independent prognostic factor of PFS (P = 0.0079) in multivariate analysis. During eribulin treatment, 18 patients developed fatty liver, 11 of whom developed EILD, with a median BMI of 26.7., Conclusions: Although EILD and fatty liver occurred at a relatively high frequency in our study, most of the patients did not experience severe adverse effects. Surprisingly, the development of EILD was positively associated with patient survival, especially in patients without liver metastases. EILD may be a clinically useful predictive biomarker of survival, but further studies are needed to confirm these findings in another cohort of patients.

Taxane drugs play a central role in chemotherapy for breast cancer. However, previous studies have reported that taxanes are relatively ineffective in patients with operable luminal breast cancer compared with other subtypes. Between January 2000 and August 2008, 293 patients with metastatic breast cancer were treated with taxanes in The Cancer Institute Hospital of The Japanese Foundation for Cancer Research and were included in the present study. The patients were divided into 4 subtypes based on the immunohistochemically evaluated estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status. The clinicopathological features, response rate (RR) and time to progression (TTP) were analyzed retrospectively. In total, 159 patient tissues were classified as luminal type (ER + and/or PgR + and HER2 - ), 28 patient tissues were classified as luminal-HER2 type (ER + and/or PgR + and HER2 + ), 57 patient tissues were classified as HER2 type (ER - , PgR - and HER2 + ), and 49 patient tissues were classified as triple-negative type (ER - , PgR - and HER2 - ). Among the 4 subtypes, the clinical benefit rate was 51.6, 78.6, 71.9 and 40.8%, respectively. There were significant differences in TTP between subtypes (median TTP, 8.3 months in luminal, 14.1 months in luminal-HER2, 10.6 months in HER2, and 4.2 months in triple-negative; P<0.001). Patients with luminal type tumors had a significantly longer TTP than patients with triple-negative type tumors. The present data suggested that the immunohistochemical subtypes were associated with the therapeutic effect of taxanes for metastatic breast cancer and that taxanes yielded an acceptable RR and TTP in luminal metastatic breast cancer. Additional investigations are required to elucidate the predictive markers of taxane therapy for patients with metastatic breast cancer in each immunohistochemical subtype.

Purpose: Although improved long-term prognoses for patients with metastatic breast cancer (MBC) have been demonstrated, few reports address overall survival (OS) with sufficient follow-up. Furthermore, the relevance of immunohistological subtypes to OS in MBC has not been clarified., Methods: We evaluated, retrospectively, the OS of patients who had been initiated on systemic therapy for MBC between 2000 and 2008., Results: The subjects of this study were 527 patients with MBC treated by systemic therapy. The median survival time (MST) was 55.5 months. The MST for each immunohistological subtype was as follows: luminal, 59.9 months; luminal-HER2, not reached; triple-negative, 18.6 months; and HER2-enriched, 49.9 months. According to multivariate analysis, metastasis-free intervals of ≥2 years and treatment with anthracycline for MBC were predictive of better OS. The predictors of shorter OS included disease progression after first-line treatment for MBC, triple-negative, and all histological factors, except papillotubular carcinoma, with liver metastasis, and having three or more initial metastatic sites., Conclusions: The prognosis of the patients with MBC in this series was better than that reported before 2000, which is probably attributable to the use of novel, improved pharmacological agents. For example, luminal-HER2 tumors can be treated using both aromatase inhibitors and trastuzumab. Because of the lower toxicities, it is now possible to administer these agents for longer periods, resulting in better prognoses.

Introduction: Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR., Patients and Methods: A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed., Results: The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p < 0.001). Multivariate analysis showed that the lymph node status of the primary tumor was a significantly independent predictive factor of local recurrence-free survival (p = 0.02)., Conclusion: The lymph node status of the primary tumor might be a predictive factor of local recurrence-free survival after salvage mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Fulvestrant 500 mg is currently approved for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer after failure of prior endocrine therapies., Methods: A total of 117 postmenopausal women with metastatic breast cancer, who experienced progression after previous endocrine therapies, were treated with fulvestrant 500 mg between January 2012 and June 2014. Clinical response, time to progression (TTP) and adverse events were investigated., Results: Ninety-nine patients had recurrent breast cancer and 18 patients had stage IV disease. Patients had received a median of two endocrine therapies and a median of two chemotherapies, prior to fulvestrant. There were 10 patients with partial response, 39 patients with long stable disease, 18 patients with stable disease, and 50 patients with progressive disease, so that the objective response rate was 8.5 %, with a clinical benefit rate of 41.9 %. The median TTP was 6.1 months. The absence of liver metastases, a small number of previous chemotherapies, and the longer duration of first-line endocrine therapy were positively correlated with TTP in univariate analysis. In multivariate analysis, a significant association was observed between TTP and duration of first-line endocrine therapy. Serious adverse events were observed in one patient with pulmonary embolism and in one patient with psychiatric symptoms., Conclusions: Fulvestrant 500 mg is an effective and well-tolerated treatment for postmenopausal women with metastatic breast cancer that had progressed after prior endocrine therapies. Patients with acquired resistance to endocrine therapies might be good candidates for fulvestrant therapy regardless of the number of prior endocrine treatments.

Background: There were several reports suggesting α-adrenoceptor antagonists are effective to treat neuropathic pain. The aims of this study were as follows: (1) to introduce drug delivery system for dorsal root ganglion (DRG) neurons; (2) to elucidate the effects of α-adrenoceptor antagonists in acute, subacute or chronic phase and (3) to determine which subtype of adrenoceptor was mainly involved., Method: We used 130 male Sprague-Dawley rats. After root constriction, rats received three local injections of α-adrenoceptor antagonists around DRG. We administered the non-selective α-adrenoceptor antagonist phentolamine for 3 consecutive days from day 0, 4 or 11 after the surgery, and the α1-adrenoceptor antagonist prazosin, the α1-adrenoceptor antagonist silodosin, the more preferred α1-adrenoceptor than prazosin and the α2-adrenoceptor antagonist yohimbine for 3 consecutive days from day 0 after the surgery., Results: Phentolamine and yohimbine continually attenuated pain behaviour. Prazosin at high dose attenuated pain behaviour, however, prazosin at low dose did not attenuate pain behaviour every experimental day. Silodosin had no analgesic effect. Phentolamine injections from day 4 after surgery attenuated pain behaviour that had been established on the 3rd experimental day until the 28th post-operative day, although effect of phentolamine wore off. Phentolamine injections from day 11 after surgery temporarily attenuated pain behaviour that had been established on the 3rd, 7th and 10th experimental days., Conclusions: This study showed α-adrenoceptor antagonists could suppress pain behaviour via α2-adrenoceptor in acute phase and temporary attenuate pain behaviour in chronic phase. These findings presented potentials sympathetic nerve blockade contributed to treat neuropathic pain., (© 2015 European Pain Federation - EFIC®)

Background: The pattern of strain distribution in the proximal femur changes following total hip arthroplasty (THA) and decreases in bone mineral density (BMD) occur around the stem following cemented and uncemented THA. We herein prospectively examined changes in BMD for 3 years after THA with a cemented Exeter universal stem., Methods: One hundred and sixty five hips from 150 patients who underwent unilateral THA were included as a cohort. Our patients included 20 men (20 hips) and 130 women (145 hips) with a mean age of 63.9 years. BMD was measured 2 weeks postoperatively (baseline) and 3, 6 12, 18, 24, 30, and 36 months (3 years) after surgery using dual-energy X-ray absorptiometry (DEXA) on the lumbar spine and proximal femur of the operated side according to the Gruen zone classification. We quantified longitudinal changes in BMD for more than 3 years after surgery and detected several factors which affected these changes., Results: In the first year, BMD in the most proximal femur showed a 5.5% reduction at the lateral side (zone 1) and 13% reduction at the medial side (zone 7), with no significant BMD reductions being observed thereafter. BMD reductions at 3 years were the most apparent at the proximal medial part of the femur (zone 7; -10.3%), while BMD ratio change in zone 1 was over the baseline (+2.9%). Especially in zone 7, the BMD ratio decreased with female, decreases in weight, decreases in height, decreases in BMI, and increases in age at the time of surgery., Conclusions: Bone restoration is expected with a cemented Exeter universal stem. Male patients, a younger age, a high body weight, being tall, and a high BMI were identified as factors associated with the restoration of BMD in proximal femur., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro., Methods: Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT)., Results: MicroRNA microarray profiling revealed that hsa-miR-148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of α-smooth muscle actin by Western blotting and increased migration ability during scratch assays., Conclusions: The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE.

We report here the complete genome sequence ofKlebsiella pneumoniaestrain YH43, isolated from sweet potato. The genome consists of a single circular chromosome of 5,520,319 bp in length. It carries 8 copies of rRNA operons, 86 tRNA genes, 5,154 protein-coding genes, and thenifgene cluster for nitrogen fixation., (Copyright © 2016 Iwase et al.)

Introduction: Mastectomy is the current standard surgical procedure for ipsilateral breast tumor recurrence (IBTR). However, there is little evidence about the prognostic impact of the surgical procedure (mastectomy versus repeat lumpectomy) for IBTR., Patients and Methods: A total of 271 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent definitive surgery for IBTR between 1989 and 2008 were included from eight institutions in Japan. The impact of the surgical procedure for IBTR on distant disease-free survival (DDFS) and overall survival (OS) was evaluated using and multivariable proportional hazards regression and propensity score matching methods., Results: Of the 271 patients, 149 patients (55%) underwent repeat lumpectomy and 122 patients (45%) underwent mastectomy after IBTR. The median follow-up period from definitive surgery for IBTR was 55 months. There was no difference in terms of DDFS and OS between repeat lumpectomy and mastectomy after IBTR, adjusted for various clinical and tumor characteristics. In addition, for the matched patient cohort, no difference in DDFS and OS was seen between the 2 groups., Conclusion: In our study, both multivariate analysis and the propensity score matching method demonstrated that there was no difference in terms of DDFS and OS between repeat lumpectomy and mastectomy after IBTR. Further studies are warranted (UMIN-CTR number UMIN000008136)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The critical issue related to breast-conserving therapy (BCT) is that cosmetic outcomes deteriorate with long-term follow-up. There is little research for breast density as a predictor of cosmetic outcomes at the late stage after BCT. To improve the long-term quality of life after BCT of breast cancer patients, the correlation of volumetric breast density (VBD) and cosmetic outcome at the late stage after BCT was evaluated., Study Design: Breast volume, fibroglandular tissue volume, adipose tissue volume, and VBD were calculated on mammography using image analysis software (Volpara(®)) in 151 patients with BCT. Furthermore, the correlation of breast density and the change of breast volume over time was analyzed on mammography in 99 patients who were followed-up long-term after BCT., Results: On multivariate analysis, VBD was a predictor of cosmetic outcome after BCT with percent breast volume excised (PBVE). Decreased adipose tissue volume and increased fibrosis were more common in patients with VBD < 15%. Furthermore, remnant breast volume continued to decrease over time in low breast density patients during long-term follow-up. 93% of patients with VBD ≥ 15% and PBVE < 10% had a better cosmetic outcome, while 60% of patients with VBD < 15% and PBVE ≥ 10% had a worse cosmetic outcome after BCT., Conclusions: While PBVE was involved in cosmetic outcome at the early stage after BCT, VBD was associated with cosmetic outcome at the late stage after BCT. Thus, a combination of VBD and PBVE could predict cosmetic outcome after BCT and contribute to the selection for the appropriate BCT., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: In order to evaluate the diagnostic and therapeutic potential of mammary ductoscopy and watchful follow-up for treating bloody nipple discharge, we investigated the incidence of cancer evolving from the location related to the affected duct and the disappearance of nipple discharge., Patients and Methods: Between April 1998 and March 2008, we assessed 709 lesions among 624 patients without a diagnosis of malignancy at the time of 6 months after mammary ductoscopy. The median follow-up time was 5.5 years. We reviewed the subjects' charts retrospectively and investigated the dates on which discharge-related cancer was diagnosed and the disappearance of discharge was noted after the initial examination with mammary ductoscopy., Results: The incidence of cancer evolving from the location related to the pathological duct was 11 % (78/709). Nipple discharge disappeared in 480 (85.1 %) of the 564 followed up lesions, with the exception of 78 breast cancers and 67 resected benign lesions. The rate of disappearance for nipple discharge in the cases of intraductal papilloma at the first examination was 82.5 %. In cases in which no obvious lesions were observed on mammary ductoscopy, there was a 90 % probability that the nipple discharge would disappear, and the rate of evolving breast cancer in the cases of atypical papillary lesions at the first examination was significantly higher than that observed in the cases of intraductal papilloma, at 50 and 8.9 %, respectively., Conclusions: Information revealed by mammary ductoscopy is useful for differentiating patients who should be subjected to intensive examinations and those who should expect disappearance of their discharge. Mammary ductoscopy and watchful follow-up can substitute microdochectomy in patients with bloody nipple discharge.

Purpose: To establish an optimal surveillance schedule after surgery for breast cancer, patients included in an institutional database were retrospectively investigated with respect to the first metastatic site and timing of recurrence., Patients and Methods: We investigated 11,676 pT1-4pN0-2M0 breast cancer patients treated from 1985 to 2009 and followed up until June 2014. Our surveillance protocol included physician visits and examinations with bone scans, liver echography, chest roentgenography and laboratory tests. We evaluated the liver, bones, lungs and pleura as surveillance covering sites (SCS) in addition to parameters such as time points exceeding 80 % with respect to the accumulated percentage of patients of recurrence and the number of surveillance per one recurrence (NSR), calculated by dividing the number of patients at risk of recurrence at the start of a particular time frame by the number of patients of recurrence at SCS within that period., Results: There were a total of 1,962 recurrent patients, including 601 patients with locoregional recurrence, nine patients with recurrence in the opposite breast, 1,349 patients with recurrence at distant sites and three unknown patients. The number of patients with the bones, lungs, liver and pleura as the first site of recurrence was 447, 324, 144 and 69, respectively, and 72.9 % of the distant metastatic lesions belonged to SCS. The five-year overall survival rate after recurrence among the patients with single recurrent site was longer than that observed among the patients with multiple sites of recurrence (43.3 vs 25.3 %; p < 0.0001). In addition, more than 80 % of the patients of liver metastasis were detected within 5 years after surgery, while 80 % of the patients of pleura metastasis were detected within 10 years. The NSR was below 200 for the 10-year period, as was the NSR of the patients with lymph node metastasis and a positive hormone receptor status. In contrast, the NSR of the patients with a negative hormone receptor status was above 200 after 5 years., Conclusions: In this study, the prognosis of the patients with a single site of recurrence was superior to that of the patients with multiple sites. Curable patients with distant metastases included those with single metastatic sites. The optimal surveillance schedule should be established taking into consideration that the incidence of metastasis differs among metastatic sites during follow-up.

Purpose: The purpose of this study was to evaluate foveal regeneration and the association between retinal restoration and visual acuity following reattachment surgery for rhegmatogenous retinal detachment (RRD)., Methods: Twenty-nine eyes of 29 patients with successfully reattached macula-off RRD were retrospectively analyzed. We used spectral-domain optical coherence tomography to image macular regions and measure retinal thickness and Snellen chart visual acuity (VA) to evaluate best-corrected VA (BCVA) at 1, 2, 3, 6, 9, and 12 months after vitrectomy. Best-corrected visual acuity data were converted to the logarithm of the minimum angle of resolution scale. Opposite eyes were used as controls., Results: The thicknesses of the external limiting membrane (ELM)-ellipsoid zone (EZ) and EZ-retinal pigment epithelium (RPE) were significantly thinner in involved eyes than in corresponding unaffected eyes at 1 month after surgery (P < 0.001 for both), and the thickness increased over time (P < 0.001 for both). Best-corrected visual acuity significantly improved over time (P < 0.001), and the improvement correlated with EZ-RPE thickness (r = -0.45, P = 0.021). Multiple regression analysis demonstrated the presence of a foveal bulge as the independent predictor of final BCVA (P < 0.001). Eyes with a foveal bulge had significantly better BCVA and greater EZ-RPE thickness than those without throughout the follow-up period. Significant restoration of the integrity of EZ and cone interdigitation zone (CIZ) was observed over time (P < 0.001 for both) in eyes with a foveal bulge., Conclusions: The thickness of EZ-RPE and cone density increased during foveal regeneration, as demonstrated by the continuous improvements in CIZ integrity over time, leading to the formation of foveal bulge and good vision following successful reattachment of macula-off RRD.

Background: Axillary dissection omission for sentinel lymph node-negative patients has been a practice at Cancer Institute Hospital, Japanese Foundation for Cancer Research since 2003. We examined the long-term results of omission of axillary dissection in sentinel lymph node-negative patients treated at our hospital, as well as their axillary lymph node recurrence characteristics and outcomes., Methods: Our study included 2,578 patients with cTis or T1-T3N0M0 primary breast cancer for whom dissection was omitted because they were sentinel lymph node negative. The median observation period was 75 months., Results: In sentinel lymph node-negative patients for whom dissection was omitted, the rates of axillary lymph node recurrence, distant recurrence, and breast cancer mortality were 0.9, 2, and 1 %, respectively. Eighteen patients underwent additional dissection if axillary lymph node recurrence was observed at the first recurrence. Four triple-negative (TN) patients experienced distant recurrence after additional dissection. All four patients were administered anticancer agents after axillary lymph node recurrence and experienced recurrence within 1 year of additional dissection. The axillary lymph node recurrence rate was 0.8 % for luminal and 4.5 % for TN subtypes., Conclusions: The long-term prognoses of patients for whom dissection was omitted owing to negative sentinel lymph node metastases were similar to those reported previously-low recurrence and mortality rates. The frequency of axillary lymph node recurrence and the post-recurrence outcome differed between luminal and TN cases, with recurrence being more frequent in patients with the TN subtype. TN patients also had poorer prognoses, even after receiving additional dissection and anticancer agents after recurrence.

An 86-year-old woman was scheduled to undergo aortic valve replacement and coronary artery bypass graft. On postoperative day 3, she developed sudden-onset neck pain followed by weakness in the right arm. Her symptoms worsened with time, and she developed paraplegia. At 60 h after the first complaint, spontaneous spinal epidural hematoma (SSEH) from C2 to C6 with spinal cord compression was diagnosed from a magnetic resonance image of the cervical region. We decided on conservative therapy because operative recovery was impossible. Delayed diagnosis led to grievous results in the present case. When neurological abnormalities follow neck or back pain after open heart surgery, SSEH must be considered in the differential diagnosis. Further, if it is suspected, early cervical computed tomography/magnetic resonance imaging and surgery should be considered.