The Impact of Corrective Surgery on Health-Related Quality of Life Subclasses in Adult Scoliosis: Will Degree of Correction Prognosticate Degree of Improvement?

PURPOSE: Objectives in scoliosis corrective surgery include restoration of normal sagittal and coronal parameters to achieve patient satisfaction. HRQLs improvements remain limited after corrective surgery. The aim of this study was to evaluate the HRQL subclass variability specific to the sagittal and coronal correction in adult scoliosis surgery. METHODS: This multi-centre prospective analysis of consecutive adult spinal deformity (ASD) patients, from five European centres, only included multilevel instrumentation for scoliosis. d-(delta) values for each parameter represented pre to post-operative changes. Parameters included demographics, baseline, 1- and 2-year. HRQL outcomes (Oswestry disability index (ODI), Scoliosis Research Society (SRS)-22 and Short Form (SF36)), sagittal correction including relative spinopelvic alignment (dRSA) and coronal correction including major Cobb (dCobb) angles. RESULTS: A total of 353 patients reached 1-year and 2-year follow up. All HRQL total scores significantly improved postoperatively, including ODI, SRS-22 and SF36. HRQL subclasses which displayed persistent improvements correlated to dRSA included sex-life, self-image, fatigue, vitality, social functioning. The only HRQL subclass improvement that correlated with dCobb was self-image. CONCLUSION: Adult scoliosis surgery improves overall HRQL, having a minimal effect on each variable. Importantly, greater coronal deformity correction affects only greater self-image scores, whereas with greater sagittal correction there are many greater HRQL sub-class impacts. Correction and restoration of coronal balance is one of the surgical goals in adult scoliosis but the degree to which Cobb angle is corrected, apart from self-image, does not correlate with gains in sub-classes of HRQL. These results need to be taken into account when planning surgery.

Growth activation of influenza virus by trypsin and effect of T-705 (favipiravir) on trypsin-optimized growth condition.

Influenza virus is activated by proteolytic cleavage of hemagglutinin by trypsin. After determining the optimal trypsin concentration, intracellular and extracellular influenza A/PR/8/34 (H1N1) and A/Victoria/361/2011 (H3N2) virus productions were compared in cultures treated with T-705 (favipiravir) and GS 4071 (an active form of oseltamivir). Although both drugs efficiently inhibited extracellular viral RNA release in a dose-dependent manner, T-705 inhibited it to the level of the inoculum without trypsin treatment, while GS 4071 inhibited it to a final level 10 times higher than that without trypsin. T-705 inhibited intracellular viral RNA production to the level of input virus in both trypsin-treated and untreated cells. In contrast, GS 4071 dose-dependently inhibited intracellular viral RNA production in cells treated with trypsin but allowed viral RNA synthesis. The level of maximum inhibition by GS 4071was 10 times higher than that of cells without trypsin and 1,000 times greater than the inoculum titer in cells without trypsin. T-705 inhibited both intracellular and extracellular virus production 1,000 and 10 times more strongly, respectively, than GS 4071. T-705 has powerful anti-influenza activity in the absence of trypsin and even in the trypsin-optimized growth condition, suggesting the therapeutic advantage in treatment of influenza complicated with bacterial pneumonia. Keywords: influenza; T-705; Tamiflu; trypsin; bacterial trypsin-like protease.

Validation of a Simplified SRS-Schwab Classification Using a Sagittal Modifier.

STUDY DESIGN: Multicenter, prospective study of consecutive adult spinal deformity (ASD) patients. OBJECTIVE: To Validate Schwab's classification accuracy for surgical indication, and to evaluate a simplified sagittal modifier. SUMMARY OF BACKGROUND DATA: The SRS-Schwab Radiologic Classification based on clinical impact parameters, offers 27 different sagittal classification possibilities regarding sagittal vertical alignment (SVA), pelvic tilt (PT), and pelvic incidence-lumbar lordosis (PI-LL). The high number of classification possibilities makes it complex to use. METHODS: Inclusion criteria were ASD patients, presenting at least 1 criteria: Cobb ≥ 20°, SVA ≥ 5 cm, thoracic kyphosis ≥ 60°, or PT ≥ 25°. A total of 1,004 patients (410 nonoperative and 594 operative) were classified regarding SVA, PT, and PI-LL (0, +, ++), and 27 possibilities were identified. Categories were formed by adding the number of + signs, considering PT, SVA, and PI-LL. Three specific categories were identified: Aligned: 0 +; Moderate deformity: 1 to 3+; and Severe deformity: 4 to 6+. A χ-square test was performed for surgical indication (operated or not) and an analysis of variance was performed to evaluate the relationship between categories and Oswestry Disability Index (ODI). Probability <.05 was considered significant. RESULTS: Significant differences for HRQoL scores and surgical indication were found in the 27 sagittal parameter possibilities. For nonoperative patients, 230 (56.1%) were classified as aligned, 145 (35.4%) as moderate, and 35 (8.5%) as severe. For operative patients, there were 200 (33.7%), 215 (36.2%), and 179 (30.1%) in each respective subgroup. For HRQoL scores and surgical indication, no significant differences were found within each category, but significant differences were found when comparing the subgroups. CONCLUSIONS: Despite the correlation between SRS-Schwab classification and surgical indication, it is complex to use, with a total of 27 possibilities regarding sagittal modifiers. This simplification into three categories offers more readability, without losing any significant information, and could replace Schwab sagittal modifiers. In association with other parameters, they could be used for decision-making. LEVEL OF EVIDENCE: Level II.

High-throughput powder diffraction measurement system consisting of multiple MYTHEN detectors at beamline BL02B2 of SPring-8.

In this study, we developed a user-friendly automatic powder diffraction measurement system for Debye-Scherrer geometry using a capillary sample at beamline BL02B2 of SPring-8. The measurement system consists of six one-dimensional solid-state (MYTHEN) detectors, a compact auto-sampler, wide-range temperature control systems, and a gas handling system. This system enables to do the automatic measurement of temperature dependence of the diffraction patterns for multiple samples. We introduced two measurement modes in the MYTHEN system and developed new attachments for the sample environment such as a gas handling system. The measurement modes and the attachments can offer in situ and/or time-resolved measurements in an extended temperature range between 25 K and 1473 K and various gas atmospheres and pressures. The results of the commissioning and performance measurements using reference materials (NIST CeO2 674b and Si 640c), V2O3 and Ti2O3, and a nanoporous coordination polymer are presented.

Factors related to continuous and discontinuous attendance at memory clinics.

BACKGROUND AND PURPOSE: Few studies have examined why some patients with dementia stop attending medical consultations. We conducted a retrospective study to investigate factors associated with discontinuous clinic attendance. METHODS: Participants were 988 patients with dementia from university hospital (UH) clinics and affiliated local hospital (LH) clinics. We compared continuous and discontinuous attenders on cognitive and affective functions and activities of daily living (ADL), and also compared UH and LH patients (UH: continuous, n = 176; discontinuous, n = 207; LH: continuous, n = 418; discontinuous, n = 187). RESULTS: The total annual rate of discontinuation was 8.0%, and the mean period of attendance before discontinuation was 2.2 ± 2.4 years (UH, 2.8 ± 3.0; LH, 1.5 ± 1.3, P < 0.01). Scores for the Mini-Mental State Examination, Hasegawa Dementia Scale - Revised, Geriatric Depression Scale, apathy scale, Abe's behavioral and psychological symptoms of dementia (BPSD) score, and ADL were significantly worse in the discontinuous group than the continuous group for both UH and LH patients (P < 0.01). The best predictor of discontinuation was ADL decline (UH and LH) and Abe's BPSD score (UH). The most common reason for discontinuation was returning to the family doctor (39.1% for UH), and cessation of hospital attendance at their own discretion (35.3% for LH). CONCLUSIONS: We identified the main reasons for discontinuation of attendance as returning to the family doctor and cessation of hospital attendance at their own discretion. The best predictors of discontinuation were ADL decline and worsening BPSD. There were significant differences in discontinuation between UH and LH patients with dementia.

Urinary podocalyxin levels were associated with urinary albumin levels among patients with diabetes.

Diabetic nephropathy has dramatically increased worldwide. In this study, we measured urinary podocalyxin in 240 patients with diabetes. The relationship between urinary podocalyxin and clinical parameters and the effects of dipeptidyl peptidase-4 inhibitors (DPP4i) and alpha-glucosidase inhibitor (a-GI) on urinary podocalyxin levels were examined. Urinary podocalyxin levels were significantly higher in patients with microalbuminuria than in those with normoalbuminuria. Urinary podocalyxin levels were also significantly related to albumin-to-creatinine ratio. Neither DPP4i nor α-GI ameliorated the increase in urinary podocalyxin levels. Our results indicated that urinary podocalyxin will be not only an early marker but also a treatment target for DN.

Right and left inverted lobar lung transplantation.

Adult recipients frequently withdraw from living-donor lobar lung transplantation because of the small size of donor grafts. The right lower lobe is 120% larger than the left lower lobe. We developed a novel surgical technique in which an inverted right lower lobe graft can be transplanted into the left thorax. The first patient was a 43-year-old woman with end-stage idiopathic interstitial pneumonia. Her husband was the only eligible donor for living-donor lobar lung transplantation. His right lower lobe was estimated to provide 45% of the recipient's predicted forced vital capacity, which would provide the borderline function required for living-donor lobar lung transplantation. Since lung perfusion scintigraphy of the recipient showed a right-to-left ratio of 64:36, transplanting the right lower lobe graft into the left thorax and sparing the native right lung was considered the only treatment option. We simulated this procedure using three-dimensional models produced by a three-dimensional printer. In living-donor lobar lung transplantation, all anastomoses were performed smoothly as planned preoperatively. Because of the initial success, this procedure was performed successfully in two additional patients. This procedure enables larger grafts to be transplanted, potentially solving critical size matching problems in living-donor lobar lung transplantation.

Analysis of radiotherapy in 1054 patients with primary central nervous system lymphoma treated from 1985 to 2009.

AIMS: Data on primary central nervous system lymphoma that had been collected through surveys for four consecutive periods between 1985 and 2009 were analysed to evaluate outcomes according to treatment. MATERIALS AND METHODS: All had histologically proven disease and had received radiotherapy. No patients had AIDS. Among 1054 patients, 696 died and 358 were alive or lost to follow-up. The median follow-up period for surviving patients was 37 months. RESULTS: For all patients, the median survival time was 24 months; the 5 year survival rate was 25.8%. Patients treated with methotrexate-based chemotherapy and radiation had a higher 5 year survival rate (43%) than those treated with radiation alone (14%) and those treated with non-methotrexate chemotherapy plus radiation (20%), but differences in relapse-free survival were smaller among the three groups. The 5 year survival rate was 25% for patients treated with whole-brain irradiation and 29% for patients treated with partial-brain irradiation (P = 0.80). Patients receiving a total dose of 40-49.9 Gy had a higher 5 year survival rate (32%) than those receiving other doses (21-25%, P = 0.0004) and patients receiving a whole-brain dose of 30-39.9 Gy had a higher 5 year survival rate (32%) than those receiving ≥40 Gy (13-22%, P < 0.0005). Patients receiving methotrexate-based chemotherapy and partial-brain radiotherapy (≥30 Gy) had a 5 year survival rate of 49%. CONCLUSIONS: The optimal total and whole-brain doses may be in the range of 40-49.9 and <40 Gy, respectively, especially in combination with chemotherapy. Patients receiving partial-brain irradiation had a prognosis similar to that of those receiving whole-brain irradiation. With methotrexate-based chemotherapy, partial-brain radiotherapy may be worth considering for non-elderly patients with a single tumour.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with α-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on sulfonylurea alone (SUCCESS-2): a multicenter, randomized, open-label, non-inferiority trial.

We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2 mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24 weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p < 0.001) relative to αGI. At 24 weeks, the reduction was almost identical between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia.

Osteoinduction of porous Ti implants with a channel structure fabricated by selective laser melting.

Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 µm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5mm from the end of the implants. A distance of 5mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes.

Bioactive Ti metal analogous to human cancellous bone: Fabrication by selective laser melting and chemical treatments.

Selective laser melting (SLM) is a useful technique for preparing three-dimensional porous bodies with complicated internal structures directly from titanium (Ti) powders without any intermediate processing steps, with the products being expected to be useful as a bone substitute. In this study the necessary SLM processing conditions to obtain a dense product, such as the laser power, scanning speed, and hatching pattern, were investigated using a Ti powder of less than 45 µm particle size. The results show that a fully dense plate thinner than 1.8 mm was obtained when the laser power to scanning speed ratio was greater than 0.5 and the hatch spacing was less than the laser diameter, with a 30 µm thick powder layer. Porous Ti metals with structures analogous to human cancellous bone were fabricated and the compressive strength measured. The compressive strength was in the range 35-120 MPa when the porosity was in the range 75-55%. Porous Ti metals fabricated by SLM were heat-treated at 1300 °C for 1h in an argon gas atmosphere to smooth the surface. Such prepared specimens were subjected to NaOH, HCl, and heat treatment to provide bioactivity. Field emission scanning electron micrographs showed that fine networks of titanium oxide were formed over the whole surface of the porous body. These treated porous bodies formed bone-like apatite on their surfaces in a simulated body fluid within 3 days. In vivo studies showed that new bone penetrated into the pores and directly bonded to the walls within 12 weeks after implantation into the femur of Japanese white rabbits. The percentage bone affinity indices of the chemical- and heat-treated porous bodies were significantly higher than that of untreated implants.

Bone bonding bioactivity of Ti metal and Ti-Zr-Nb-Ta alloys with Ca ions incorporated on their surfaces by simple chemical and heat treatments.

Ti15Zr4Nb4Ta and Ti29Nb13Ta4.6Zr, which do not contain the potentially cytotoxic elements V and Al, represent a new generation of alloys with improved corrosion resistance, mechanical properties, and cytocompatibility. Recently it has become possible for the apatite forming ability of these alloys to be ascertained by treatment with alkali, CaCl2, heat, and water (ACaHW). In order to confirm the actual in vivo bioactivity of commercially pure titanium (cp-Ti) and these alloys after subjecting them to ACaHW treatment at different temperatures, the bone bonding strength of implants made from these materials was evaluated. The failure load between implant and bone was measured for treated and untreated plates at 4, 8, 16, and 26 weeks after implantation in rabbit tibia. The untreated implants showed almost no bonding, whereas all treated implants showed successful bonding by 4 weeks, and the failure load subsequently increased with time. This suggests that a simple and economical ACaHW treatment could successfully be used to impart bone bonding bioactivity to Ti metal and Ti-Zr-Nb-Ta alloys in vivo. In particular, implants heat treated at 700 °C exhibited significantly greater bone bonding strength, as well as augmented in vitro apatite formation, in comparison with those treated at 600 °C. Thus, with this improved bioactive treatment process these advantageous Ti-Zr-Nb-Ta alloys can serve as useful candidates for orthopedic devices.

Phase I study of chemoradiation with nedaplatin and ifosfamide in patients with advanced squamous cell carcinoma of the uterine cervix.

Cisplatin and ifosfamide are considered among the most active drugs in both neoadjuvant and salvage treatments for patients with cervical cancer. Nedaplatin is an analog of cisplatin and it exhibits lesser nephrotoxicity, neurotoxicity, and gastrointestinal toxicity than cisplatin. This study aimed to determine the recommended dosage of nedaplatin plus ifosfamide chemoradiotherapy for advanced squamous cell carcinoma (SCC) of the uterine cervix. Beginning with a dose of 65 mg/m(2), nedaplatin (day 1) combined with ifosfamide 1 g/m(2) (days 1-5) was designed to be administered for three cycles (minimum: two cycles); its dose was gradually escalated up to 80 mg/m(2). Dose-limiting toxicity (DLT) was defined as a more than 7-day delay in the planned radiation therapy and/or planned chemotherapy (prior to the completion of two cycles) due to toxicity. Chemotherapy was not interrupted prior to the completion of two cycles in any patients. Of the 12 patients, 11 received three cycles of chemotherapy. DLT did not occur in any patient. We confirmed a clinical complete response (CR) in ten and partial response (PR) in two patients. The median follow-up period was 39 months (range: 18-57 months). Ten patients (83%) were alive and disease free, one patient was alive with disease, and only one patient died due to the disease. Nedaplatin and ifosfamide combination chemotherapy is a feasible and active chemoradiation strategy for patients with advanced SCC of the uterine cervix. With the ifosfamide dose fixed to 1 g/m(2), the recommended nedaplatin dosage was determined to be 80 mg/m(2) to be administered for three cycles.

Nephrin is involved in podocyte maturation but not survival during glomerular development.

Nephrin, a major component of the glomerular slit diaphragm (SD), is both a structural protein as well as a signaling molecule influencing foot process (FP) formation and maintenance of podocyte integrity. Analyses of near-term embryonic kidneys showed normal cellular viability and no apoptosis in glomeruli from nephrin knockout mice. Moreover, expression and location of other SD or glomerular basement membrane components were similar in wild-type and mutant mice as was the location and levels of most podocyte-specific proteins. Transcriptional profiling showed that the lack of nephrin had minor impact on the expression of genes for FPs and SD proteins. Claudin 3, a tight-junction protein normally absent in glomeruli, was upregulated threefold in the knockout mice, suggesting a role of nephrin in claudin 3 gene expression within the glomeruli. Our results suggest that nephrin is expressed late in the process of podocyte differentiation and is a locus for the formation of SD and FP maintenance and physical integrity in vivo. Nephrin does not seem to have a primary role in cell survival but has a small impact on gene regulation during glomerular development.

Phase I study of weekly nedaplatin and concurrent pelvic radiotherapy as adjuvant therapy after radical surgery for cervical cancer.

Nedaplatin is an analog of cisplatin that was developed in Japan, and it exhibits less nephrotoxicity, neurotoxicity, and gastrointestinal toxicity than cisplatin. This study aimed to determine the recommended dose of weekly nedaplatin chemoradiotherapy in high-risk patients following radical surgery. Fifteen patients who required postoperative pelvic radiotherapy after radical surgery for cervical cancer were enrolled in the present study. Nedaplatin was designed to be administered for eight cycles (minimum five cycles) beginning at a weekly dose of 22.5 mg/m(2) and then escalating to 25, 27.5, and then to 30 mg/m(2). Dose-limiting toxicity was defined as a more than 7-day delay in the planned radiation therapy and/or planned chemotherapy (prior to the completion of five cycles) due to toxicity. Nedaplatin administration was interrupted prior to the completion of five cycles in one of six patients at a dose of 27.5 mg/m(2). A more than 7-day delay in the planned radiation therapy did not occur in any patient. Nedaplatin at a dose of 30 mg/m(2) was safely administered, and two of three patients could receive the planned chemotherapy consisting of eight cycles of weekly nedaplatin. Our recommended weekly nedaplatin dose was determined to be 30 mg/m(2) administered for more than five cycles and up to eight cycles if possible. Weekly administration of nedaplatin may be more tolerable and less toxic than weekly administration of cisplatin.

Glomerulus-specific mRNA transcripts and proteins identified through kidney expressed sequence tag database analysis.

The kidney glomerulus plays a crucial role in blood filtration but the molecular composition and physiology of the glomerulus is not well understood. We previously constructed and large-scale sequenced four mouse glomerular expressed sequence tag (EST) libraries from newborn and adult mouse glomeruli. Here, we compared glomerular EST profiles with whole kidney EST profiles, thereby identifying 497 transcripts corresponding to UniGene clusters that were glomerulus-enriched, that is expressed more abundantly in glomeruli than in whole kidney. These include several known protein-coding glomerulus-specific transcripts critical for glomerulus development and function, but also a large number of gene transcripts, which have not previously been shown to be expressed in the glomerulus, or implicated in glomerular functions. We used in situ hybridization to demonstrate glomerulus-specific RNA expression for six novel glomerular genes and the public Human Protein Atlas to verify glomerular protein expression for another two. The higher mRNA abundance for the eight genes in glomeruli compared with whole kidney was also verified by Taqman quantitative polymerase chain reaction. We surmise that the further characterization of these genes and proteins will increase our understanding of glomerular development and physiology.

Analysis of MxA, IL-4, and IRF-1 genes in Filipino patients with subacute sclerosing panencephalitis.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a chronic and debilitating disease of the central nervous system caused by a latent measles virus infection. Three candidate genes, MxA, IL-4, and IRF-1 genes were shown to be associated with SSPE in Japanese patients. These genes have been suggested to play a role in the establishment of persistent viral infection in the central nervous system. SUBJECTS AND METHODS: Sixty Filipino SSPE patients and 120 healthy control subjects were included in the study. Single nucleotide polymorphisms at promoter regions ( IL-4-590C/T and MXA-88G/T) were screened using PCR-RFLP method. Genotyping was done for GT repeat polymorphism within intron 7 of IRF-1. RESULTS: The TT genotype of MXA, as well as the CT genotype of IL-4, were seen a little more frequently among the SSPE patients as compared to the control subjects. The values though, did not reach statistical significance. IRF-1 analysis did not differ between the two groups. CONCLUSION: Our study failed to demonstrate a significant association between IL-4, MXA, or IRF-1, and SSPE in the Filipino population. Our results might be explained by a greater contribution of environmental factors such as the socio-economic and nutritional factors in the susceptibility of Filipinos to SSPE other than genetic factors.