Immediate sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft at the time of sarcoma resection.

BACKGROUND: Concomitant resection of the sciatic nerve along with a malignant tumor is no longer a contraindication for limb-sparing surgery, as most of these patients remain ambulatory. However, sciatic nerve reconstruction after sarcoma resection is not commonly performed. Restoration of nerve function can improve patient quality of life. We describe our experience with four patients who underwent sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft at the time of sarcoma resection. METHODS: Because of the low chance of peroneal nerve recovery, the ipsilateral peroneal trunk was used as a graft to reconstruct the tibial trunk of the sciatic nerve. Two patients were men and two were women. Mean age was 45.3 years (range, 15-62). Mean sciatic nerve defect length was 9.4 cm (range, 8.5-12.0). Proximal thigh defects (three patients) were reconstructed with a double cable; the one patient with a distal thigh defect underwent single cable reconstruction. Mean operation time was 492 min (range, 428-682). RESULTS: Mean length of the harvested peroneal trunks was 21 cm (range, 11-26). Mean graft length was 11.9 cm (range, 11-13). Postoperative course was uneventful in all four patients. One patient died of sarcoma lung metastasis and could not be evaluated. Three patients were followed for more than 2 years. Two patients achieved British Medical Research Council grade 4 plantar flexion; the remaining patient achieved grade 5 plantar flexion and grade 4 toe flexion. Semmes-Weinstein monofilament sensory testing showed loss of protective sensation on the plantar surface in all three. Musculoskeletal Tumor Society scores at last follow-up were 60.0%, 70.0%, and 43.3%, respectively. CONCLUSIONS: Immediate sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft avoids reconstruction delay and scar tissue formation, which is advantageous for nerve recovery. This technique may be considered when sciatic nerve resection is anticipated during sarcoma resection.

Geriatric nutritional risk index as the prognostic factor in older patients with fragility hip fractures.

This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. BACKGROUND: Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. OBJECTIVE: This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. METHODS: This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients' conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. RESULTS: The mean observation period was 4.0 years (range 0-7 years). The average age at the time of admission was 82 years (range 60-101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82-91), low risk (92-98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [p = 0.004]). CONCLUSIONS: We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

Ku-band multichannel frequency comb Doppler reflectometer on the GAMMA 10/potential control and divertor simulating experiment (PDX) tandem mirror.

A Ku-band (12-18 GHz) multichannel Doppler reflectometer (DR) has been developed in the GAMMA 10/potential control and divertor simulating experiment (PDX) tandem mirror device to improve the applicability of DR measurement for simultaneous monitoring of velocity of electron density turbulence at different locations. Our previous single-channel DR circuit has been replaced by the multichannel microwave system using a nonlinear transmission line based comb generator with heterodyne technique. The multichannel DR system has been installed in the central cell of GAMMA 10/PDX. Initial results of application to GAMMA 10/PDX plasma are presented, showing Doppler frequency shifts during an additional ion cyclotron resonance frequency heating and gas-puffing experiment.

Effects of an elemental diet to reduce adverse events in patients with esophageal cancer receiving docetaxel/cisplatin/5-fluorouracil: a phase III randomized controlled trial-EPOC 2 (JFMC49-1601-C5).

BACKGROUND: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy. PATIENTS AND METHODS: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1 : 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance. RESULTS: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046). CONCLUSIONS: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.

TGFß1 signaling protects chondrocytes against oxidative stress via FOXO1-autophagy axis.

OBJECTIVE: The forkhead box O1 (FOXO1) transcription factor is a key regulator of autophagy. In chondrocytes, reduced FOXO1 expression with aging causes osteoarthritis due to dysfunction of autophagy, but the mechanisms underlying regulation of FOXO1 expression and the reduction in expression with aging remain unclear. We investigated the mechanism by which transforming growth factor ß1 (TGFß1) signaling regulates the FOXO1-autophagy axis. METHODS: Expression of FOXO1 was measured in chondrocytes after TGFß1 treatment. Immunohistochemistry was performed to estimate the levels of activin receptor-like kinase 5 (ALK5) and FOXO1 in the knee joints of young, middle-aged and old mice. The effects of the ALK5 inhibitor and SMAD3 or SMAD2 knockdown on FOXO1 expression were evaluated. The role of TGFß1 in autophagy after hydrogen peroxide (H2O2) treatment was analyzed. The protective effect of TGFß1 against H2O2 treatment was assessed by cell viability assay and TUNEL assay. RESULTS: TGFß1 promoted the expression of FOXO1 mRNA and protein. Both ALK5 and FOXO1 expression decreased with aging. ALK5 inhibition and SMAD3 knockdown suppressed induction of FOXO1 expression by TGFß1, whereas SMAD2 knockdown increased it. TGFß1 promoted the expression of microtubule-associated proteins 1A/1B light chain 3B (LC3)-I protein via the SMAD3-FOXO1 pathway. Furthermore, under H2O2 treatment, TGFß1 promoted expression of LC3-II. TGFß1 pretreatment suppressed cell death of chondrocytes following H2O2 treatment, but this protective effect was abolished by FOXO1 knockdown. CONCLUSIONS: TGFß1 protects chondrocytes against oxidative stress via the FOXO1-autophagy axis, and a reduction in ALK5 expression might cause reduced FOXO1 expression with aging.

Measurement of axial phase difference of density fluctuations owing to spontaneously excited waves by using microwave reflectometer on GAMMA 10/PDX.

In the GAMMA 10/PDX tandem mirror, plasma with strong ion-temperature anisotropy is produced by using the ion cyclotron range of frequency waves. This anisotropy of ion temperature causes several Alfvén-Ion-Cyclotron (AIC) waves to spontaneously excite in the frequency range just below the ion cyclotron frequency. In addition, difference-frequency (DF) waves are excited in the radial inner region of the plasma by wave-wave coupling among the AIC waves. The radial density profiles were measured at multi-axial positions using a frequency-modulation reflectometer with an axial array of microwave antennas, and an axial variation of the density was found to be significant. In addition, a relative phase difference of the DF wave between axially separated two points was first obtained by finely choosing the probing frequency of the reflectometers with a maximum coherence used as a measure, indicating that the DF wave is a propagating wave, while the pump AIC waves are standing waves in the axial region of measurement.

Improvement in multipass Thomson scattering system comprising laser amplification system developed in GAMMA 10/PDX.

The multipass Thomson scattering (MPTS) technique is one of the most useful methods for measuring low-electron-density plasmas. The MPTS system increases Thomson scattering (TS) signal intensities by integrating all multipass (MP) signals and improving the TS time resolution by analyzing each pass signal. The fully coaxial MPTS system developed in GAMMA 10/potential-control and diverter-simulator experiments has a polarization-based configuration with image-relaying optics. The MPTS system can enhance Thomson scattered signals for improving the measurement accuracy and megahertz-order time resolution. In this study, we develop a new MPTS system comprising a laser amplification system to obtain continuous MP signals. The laser amplification system can improve degraded laser power and return an amplified laser to the MP system. We obtain continuous MP signals from the laser amplification system by improving the laser beam profile adjuster in gas scattering experiments. Moreover, we demonstrate that more MP signals and stronger amplified MP signals can be achieved via multiple laser injections to the laser amplification system in the developed MP system comprising a laser amplification system.

Continuous cell culture monitoring using a compact microplate reader with a silicone optical technology-based spatial filter.

Continuous cell monitoring is very important for the maintenance and control of cell multiplication and differentiation. This paper presents a compact microplate reader that is able to continuously measure a 24-well microplate (6 × 4 wells) using the optical absorption measurement method. The 24-channel plate reader consisted of a spatial filter, light emitting diode light source, and color sensors and was similarly sized with the cell culture microwell plates. A spatial filter was previously fabricated by our group using silicone optical technology (SOT). This SOT-based spatial filter has an excellent noise reduction effect. Light reflection at the optical path interface can be absorbed and only forward light can be transmitted; accordingly, a larger S/N ratio than that of conventional optical systems is expected. The fabricated 24-channel plate reader permits real-time cell monitoring during cultivation on the clean bench and in cell culture conditions by incorporating the SOT spatial filter. Using the device, it was possible to continuously evaluate the concentration and pH of reagents in the 24 wells in real time. Moreover, cell activity and protein production were detectable using the device. These results suggest that the newly fabricated device is a promising tool for the evaluation of cell behaviors for cell management.

Prospective multinational serosurveillance study of Bordetella pertussis infection among 10- to 18-year-old Asian children and adolescents.

OBJECTIVES: Bordetella pertussis continues to cause outbreaks worldwide. To assess the role of children and adolescent in transmission of pertussis in Asia, we performed a multinational serosurveillance study. METHODS: From July 2013 to June 2016, individuals aged 10 to 18 years who had not received any pertussis-containing vaccine within the prior year were recruited in 10 centres in Asia. Serum anti-pertussis toxin (PT) IgG was measured by ELISA. Demographic data and medical histories were obtained. In the absence of pertussis immunization, anti-PT IgG ≥62.5 IU/mL was interpreted as B. pertussis infection within 12 months prior, among them levels ≥125 IU/mL were further identified as infection within 6 months. RESULTS: A total of 1802 individuals were enrolled. Anti-PT IgG geometric mean concentration was 4.5, and 87 (4.8%) individuals had levels ≥62.5 IU/mL; among them, 73 (83.9%) had received three or more doses of pertussis vaccine before age 6 years. Of 30 participants with persistent cough during the past 6 months, one (3.3%) had level ≥125 IU/mL. There was no significant difference in proportions with anti-PT IgG ≥62.5 IU/mL among age groups (13-15 vs. 10-12 years, 16-18 vs. 10-12 years), between types of diphtheria, pertussis and tetanus (DTP; whole cell vs. acellular), number of doses before age 6 years within the DTP whole-cell pertussis vaccine (five vs. four doses) or acellular pertussis vaccine (five vs. four doses) and history of persistent cough during the past 6 months (yes vs. no). CONCLUSIONS: There is significant circulation of B. pertussis amongst Asian children and adolescents, with one in 20 having serologic evidence of recent infection regardless of vaccination background.

Activation of Toll-like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients.

The aim of this study was to determine the expressions of Toll-like receptors (TLRs) 7-9 and type I interferon (IFN) signal in labial salivary glands (LSGs) and cultured salivary gland epithelial cells (SGECs) from primary Sjögren's syndrome (pSS) patients. We performed an immunohistochemistry analysis of LSGs from 11 patients with pSS as defined by American-European Consensus Group classification criteria and five healthy subjects. The pSS patients' SGECs were analyzed by immunofluorescence and western blotting. IFN-α expression was examined by immunosorbent assay and flow cytometry. Mononuclear cells (MNCs) from pSS patients' LSGs showed TLR-7-dominant expression. B cells, plasma cells and plasmacytoid dendritic cells (pDCs) co-expressed with TLR-7. Myeloid differentiation primary response gene 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6) and interferon regulatory factor 7 (IRF7) co-expressed with the pDC marker CD303 in LSGs. Ducts from pSS patients dominantly expressed TLR-7, and TLR-7 in the ducts co-expressed with MyD88, TRAF6 and IRF7. Type I IFNs including IFN-α and IFN-ß were detected in MNCs and ducts in pSS patients' LSGs. Increased TRAF6 expression and the nuclear translocation of IRF7 in SGECs were detected by immunofluorescence following loxoribine (a TLR-7 ligand) stimulation despite IFN-ß pretreatment. Western blotting showed increased TRAF6 expression in SGECs following IFN-ß and loxoribine stimulation. Although no increase in IFN-α was detected in supernatant from stimulated SGECs, the IFN-α in supernatant from stimulated peripheral blood pDCs from pSS patients was significantly increased. Our findings suggest that TLR-7 is dominantly expressed in both MNCs and ducts with downstream signals for type I IFNs, indicating that TLR7-dominant innate immunity is related to the development of sialadenitis in pSS.

Development of a laser amplification system for the multi-pass Thomson scattering system for GAMMA 10/PDX.

The multi-pass Thomson scattering (MPTS) system is a useful technique for increasing the Thomson scattering (TS) signal intensities and improving the TS diagnostic time resolution. The MPTS system developed in GAMMA 10/PDX has a polarization-based configuration with an image relaying system. The MPTS system has been constructed for enhancing the Thomson scattered signals for the improvement of measurement accuracy and the megahertz sampling time resolution. However, in the normal MPTS system, the MPTS signal intensities decrease with the pass number because of the damping due to the optical components. Subsequently, we have developed a new MPTS system with the laser amplification system. The laser amplification system can improve the degraded laser power after six passes in the multi-pass system to the initial laser power. For the first time worldwide, we successfully obtained the continued multi-pass signals after the laser amplification system in the gas scattering experiments.

Differences in pain thresholds elicited by intraoral electrical stimuli between individuals with and without diabetes mellitus.

There is little evidence of sensation in individuals with diabetes mellitus (DM) in the dental research field. We investigated whether pain thresholds (PTs) differ between individuals with and without DM (non-DM; NDM). To this end, we assessed whether PTs obtained from the oral cavity, hands, and feet differed from each other and across groups, and whether PTs differed for the three current frequencies used for testing (2000 Hz, 250 Hz, and 5 Hz). Pain threshold measurements were obtained from the oral mucosa and the tips of the fingers and toes of 56 volunteers, including 21 individuals with DM (12 men and 9 women, average age: 72.1 ± 4.7 years) and 35 NDM individuals (17 males and 18 females, average age: 51.2 ± 23.9 years) using the Neurometer CPT/C® device to deliver electrical stimulation. A single operator obtained PT measurements from around the left greater palatine foramen and from the tip of the left first finger and of the left great toe. Individuals with DM had significantly lower PT values than those without DM. The PT values for the oral cavity, hands, and feet differed significantly from each other (foot > hand, foot > oral cavity, hand > oral cavity). Moreover, there was a significant difference in the PT values for 5 Hz and 2000 Hz, as well as for 250 Hz and 2000 Hz. This study concluded that PT values derived from DM participants are lower than those from NDM participants, although PT measurements varied across regions and with current frequency.

Variable tibiofemoral articular contact stress in fixed-bearing total knee arthroplasties.

BACKGROUND: Rotational allowance at the tibiofemoral joint would be required during deep flexion. However, the amount of flexion and rotation has not been investigated in modern total knee arthroplasty (TKA) designs. The present study aimed to determine the contact stress in five posterior-stabilized fixed-bearing TKA designs. HYPOTHESIS: We hypothesized that the contact area and stresses at the tibiofemoral articular surfaces vary according to the type of implant design and tested condition. MATERIALS AND METHODS: The contact area and mean and peak contact stresses at the tibiofemoral articular surfaces were determined when a compressive load of 1200N was applied to a NexGen LPS Flex, Scorpio NRG, Genesis II, PFC Sigma, and Foundation implant. Measurements were performed at 0° and 45° flexion with 0°, 5°, 10°, and 15° rotation, and at 90° and 135° flexion with 0, 5°, 10°, 15°, and 20° rotation. RESULTS: The LPS Flex showed that the femoral component could not achieve 20° rotation at 135° flexion. The Scorpio NRG showed less than 20MPa of contact stress at all conditions. The Genesis II showed higher contact stress than 20MPa at 135° flexion with 20° rotation. The PFC Sigma showed that the femoral component could not achieve >10° rotation at any flexion angle. The Foundation showed more than 20MPa of contact stress at 90° flexion with 20° rotation and at 135° flexion with 10°, 15°, and 20° rotation. DISCUSSION: Surgeons should be more aware of the variable contact conditions of the tibiofemoral articular surfaces in individual TKA designs. LEVEL OF EVIDENCE: Level IV, basic science study.

Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study.

BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others. KEY RESULTS: The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea. CONCLUSIONS & INFERENCES: This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS-C.

Effects of intertrochanteric osteotomy plane and preoperative femoral anteversion on the postoperative morphology of the proximal femur in transtrochanteric anterior rotational osteotomy: 3D CT-based simulation study.

BACKGROUND: Transtrochanteric anterior rotational osteotomy (ARO) is joint-preserving surgery for patients with osteonecrosis of the femoral head (ONFH). During ARO, femoral neck-shaft varus angulation by changing intertrochanteric osteotomy plane is often designed to obtain a sufficient postoperative intact ratio. However, the effect of intertrochanteric osteotomy plane on postoperative femoral anteversion has not been well examined. Therefore, we performed a simulation study of ARO to determine how intertrochanteric osteotomy plane and preoperative femoral anteversion affect both femoral neck-shaft varus angle and postoperative femoral anteversion. HYPOTHESIS: Both femoral neck-shaft varus angle and postoperative femoral anteversion are predicted by intertrochanteric osteotomy plane and preoperative femoral anteversion in ARO. MATERIALS AND METHODS: Using CT-data obtained from 10 hips in 10 patients with ONFH, ARO was simulated. On anteroposterior view, basic intertrochanteric osteotomy line (AP-view line) was defined as the perpendicular line to the femoral neck axis. On lateral view, basic intertrochanteric osteotomy line (lateral-view line) made through the cut surface of greater trochanter was defined as the perpendicular line to the lateral axis of the femur. By changing either AP-view or lateral-view line, 49 ARO models/hip were produced, in which femoral neck-shaft varus angle and postoperative femoral anteversion were assessed. RESULTS: With increase in the vertically-inclined degree of AP-view line, both neck-shaft varus angle and postoperative femoral anteversion increased. With increase in the posteriorly-tilted degree of lateral-view line, neck-shaft varus angle increased, whereas postoperative femoral anteversion decreased. The approximation equations based on the multiple regression analyses were as follows: neck-shaft varus angle≈vertically-inclined degree of AP-view line×0.9+posteriorly-tilted degree of lateral-view line×0.8+preoperative femoral anteversion×0.7; postoperative femoral anteversion≈vertically-inclined degree of AP-view line×1.1-posteriorly-tilted degree of lateral-view line×0.8. DISCUSSION: The postoperative morphology of proximal femur was nearly defined by intertrochanteric osteotomy plane with preoperative femoral anteversion, which is useful for preoperative planning in terms of both achieving a sufficient postoperative intact ratio and maintaining femoral anteversion. LEVEL OF EVIDENCE: Level IV case series without control group.

Multi-point measurement using two-channel reflectometer with antenna switching for study of high-frequency fluctuations in GAMMA 10.

A two-channel microwave reflectometer system with fast microwave antenna switching capability was developed and applied to the GAMMA 10 tandem mirror device to study high-frequency small-amplitude fluctuations in a hot mirror plasma. The fast switching of the antennas is controlled using PIN diode switches, which offers the significant advantage of reducing the number of high-cost microwave components and digitizers with high bandwidths and large memory that are required to measure the spatiotemporal behavior of the high-frequency fluctuations. The use of two channels rather than one adds the important function of a simultaneous two-point measurement in either the radial direction or the direction of the antenna array to measure the phase profile of the fluctuations along with the normal amplitude profile. The density fluctuations measured using this system clearly showed the high-frequency coherent fluctuations that are associated with Alfvén-ion-cyclotron (AIC) waves in GAMMA 10. A correlation analysis applied to simultaneously measured density fluctuations showed that the phase component that was included in a reflected microwave provided both high coherence and a clear phase difference for the AIC waves, while the amplitude component showed neither significant coherence nor clear phase difference. The axial phase differences of the AIC waves measured inside the hot plasma confirmed the formation of a standing wave structure. The axial variation of the radial profiles was evaluated and a clear difference was found among the AIC waves for the first time, which would be a key to clarify the unknown boundary conditions of the AIC waves.

Patient perceptions of symptoms and concerns during cancer chemotherapy: 'affects my family' is the most important.

BACKGROUND: Cancer chemotherapy is associated with a variety of side effects/adverse events. It is very important that patients adhere to the planned chemotherapy regimen, which necessitates a minimum of side effects and that these side effects be kept under control. We have investigated patients' concerns and symptoms during chemotherapy with the aim to seek solutions that will improve patients' quality of life during chemotherapy. METHODS: Forty-nine patients with malignant diseases on parenteral antineoplastic agents were sequentially enrolled in this study. These patients completed a questionnaire consisting of 42 items related to non-physical concerns and 52 items of physical symptoms related to chemotherapy. Each patient was also asked to select the three items among these 94 items which affected him/her the most. RESULTS: The median age of the cancer patients was 62 years and the male-to-female ratio was 18:31. Among the non-physical concerns, the most frequently chosen concern was 'affects my family or partner,' followed by anxiety related to treatment. Regarding the physical symptoms, the most frequent complaints were fatigue, alopecia and constipation, while the most troublesome symptoms were nausea, poor taste and paresthesia. Overall, the most frequently expressed concerns were 'affects my family or partner' and anxiety related to treatment. Male patients suffered most from fever, fatigue and nausea, and female patients complained more of poor taste and gastrointestinal problems. CONCLUSION: Patient perceptions of adverse events associated with cancer chemotherapy apparently have changed from physical symptoms to non-physical concerns. In our patient cohort 'affects my family or partner' was the most important concern. One important point to note is that female patients often complained of poor taste because this meant they were unable to cook well.

Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro.

OBJECTIVES: Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. METHODS: Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays. RESULTS: After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 µm2, sd 14660 versus 9421 µm2, sd 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-ß1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. CONCLUSION: We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts.Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73-81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1.

Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study.

BACKGROUND: Previous studies showed that 5 µg of ramosetron, a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist, is only effective in male patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D). We hypothesized that either dose 1.25, 2.5, or 5 µg of ramosetron would be effective in female patients with IBS-D. METHODS: This randomized, double-blind, placebo-controlled, phase II dose-finding exploratory trial included 409 female outpatients with IBS-D treated in Japan. They were administered oral placebo (n=102), or 1.25 µg (n=104), 2.5 µg (n=104), or 5 µg (n=99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rates of global improvement of IBS symptoms in the first month. Secondary endpoints included global improvement in the other months, abdominal pain/discomfort, weekly mean changes in the Bristol Stool Form Scale (BSFS), and IBS-QOL. KEY RESULTS: Middle dose (2.5 µg) of ramosetron significantly improved abdominal pain/discomfort at second month (62.5%, P=.002), third month (60.6%, P=.005), and the last evaluation point (63.5%, P=.002) and weekly BSFS (P<.05) except at Week 8, 11, and 12 than placebo. IBS-QOL did not change. Ramosetron induced more constipation than placebo. CONCLUSIONS & INFERENCES: The trial suggested that 2.5 µg of ramosetron is the most effective and least harmful option for treating female patients with IBS-D (Clinicaltrials.gov ID: NCT01274000).