Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.

Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.

Percentage of CD19+ Cells in Peripheral Blood Lymphocytes After Rituximab-Based Desensitization as a Predictor of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

BACKGROUND: Rituximab (RIT) is effective as a part of the desensitization therapy before ABO-incompatible kidney transplantation (ABOi-KTx), and a single dose of RIT at 375 mg/m2 or less is recommended. However, adequate RIT dose recommendations have not yet been established for individual recipients. Therefore, we evaluated the relationship between the proportion of B cells in peripheral blood and acute antibody-mediated rejection (AAMR). METHODS: Forty-four consecutive ABOi-KTx recipients were enrolled in this retrospective study. Before transplantation, subjects were treated with RIT at various doses, ranging from 65 to 400 mg/body (46-263 mg/m2), followed by plasmapheresis and intravenous immunoglobulin as a desensitization therapy. The percentage of CD19+ cells in the total peripheral blood lymphocytes population (%CD19) was determined the day before transplantation. Transplant recipients were divided into 2 groups according to pretransplant %CD19, as follows: low %CD19 group, ≤ 1.2% (n = 35) and high %CD19 group, > 1.2% (n = 9). The relationship between %CD19 and incidence of AAMR was evaluated, and the predicting factors for AAMR incidence were determined by univariate and multivariate analyses. RESULTS: The incidence of AAMR was significantly higher in the high %CD19 group than in the low %CD19 group (44.4% vs 5.7%, P = .006). Furthermore, multivariate analysis showed that %CD19 > 1.2% was the only independent factor to predict AAMR, with an odds ratio of 14.31 (P = .038). CONCLUSION: High %CD19 values after rituximab administration in ABOi-KTx recipients implies insufficient depletion of B cells, which can lead to AAMR.

Optimal Settings for Double Filtration Plasmapheresis With Targeted Removal Rate of Preexisting Antibody in Antibody-Incompatible Kidney Transplant.

BACKGROUND: Elimination of preexisting donor-reactive antibodies is essential for antibody-incompatible kidney transplantation. Double filtration plasmapheresis (DFPP) using albumin (Alb) replacement fluid (Rf) removes immunoglobulin more selectively than plasma exchange; however, fixed-dose treatment can result in insufficient removal of antibody or excess loss of osmotic pressure and subsequent hypotension. The aim of this study was to determine the optimal setting (volume and concentration of Rf) of DFPP to remove donor-reactive antibodies. MATERIALS AND METHODS: One hundred seventeen DFPPs were performed in 41 patients for kidney transplant in an ABO-incompatible or crossmatch-positive setting. A formula for Rf volume was determined based on volume-removal rate (RR) curve of IgG. Another formula for Alb concentration of Rf was also established to keep plasma volume within pre-DFPP plasma volume ± 10% calculated by post- to pre-DFPP hematocrit ratio to avoid hypotensive events. RESULTS: RR-IgG was obtained based on patient data: Rf (mL) = BW (kg) × eX, [X = (RR-IgG + 10.757)/25.603] (R2 = 0.401, P < .001). Rf Alb concentration was determined by AlbRf ≥ (2.982 - 2.36 × RR-IgG) × Albpre + (2.36 × RR-IgG - 0.236) × pre-DFPP total protein. CONCLUSIONS: Optimal volume and concentration of Alb Rf can be calculated using our formulae with targeted RR-IgG.

Non-traumatic hemorrhage is controlled with REBOA in acute phase then mortality increases gradually by non-hemorrhagic causes: DIRECT-IABO registry in Japan.

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA. METHODS: Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan-Meier survival analysis was then conducted. RESULTS: Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P < 0.001). No non-trauma patients required resuscitative thoracotomy compared with 28% of the trauma patients (P < 0.001). Non-trauma patients presented a lower 24-h mortality than trauma patients (19 vs. 51%, P = 0.001). The non-trauma cases demonstrated a gradual but prolonged increased mortality, whereas survival in trauma cases rapidly declined (P = 0.009) with similar hospital mortality (68 vs. 64%). Non-trauma patients who survived for 24 h had 0 ventilator-free days and 0 ICU-free days vs. a median of 19 and 12, respectively, for trauma patients (P = 0.33 and 0.39, respectively). Non-hemorrhagic death was more common in non-trauma vs. trauma patients (83 vs. 33%, P < 0.001). CONCLUSIONS: Non-traumatic hemorrhagic shock often resulted from a single bleeding site, and resulted in better 24-h survival than traumatic hemorrhage among Japanese patients who underwent REBOA. However, hospital mortality increased steadily in non-trauma patients affected by non-hemorrhagic causes after a longer period of critical care.

PRR11 immunoreactivity is a weak prognostic factor in non-mucinous invasive adenocarcinoma of the lung.

INTRODUCTION: Proline-rich protein 11 (PRR11) functions in the progression of cell cycle, and silencing the PRR11 gene in lung cancer cells results in the inhibition of cellular proliferation, cell cycle progression, cell migration, invasion and colony formation. PRR11 may therefore be a therapeutic target in lung cancer. MATERIALS AND METHODS: Microarrays of surgical specimens of non-mucinous invasive adenocarcinoma of the lung, from 346 subjects that were not given preoperative therapy, were autoimmunostained with PRR11 and, except for trace and pseudo-positivity, assessed as "positive" at any proportion and intensity. RESULTS: PRR11 immunoreactivity demonstrated a tendency to associate with an aggressive phenotype (tumor size, vascular invasion, and adjuvant therapy) and some effect on overall survival (Hazard ratio 1.51). CONCLUSIONS: PRR11 may be a weak prognostic indicator of overall survival of patients with non-mucinous invasive adenocarcinoma of the lung.

Increased metabolite production by deletion of an HDA1-type histone deacetylase in the phytopathogenic fungi, Magnaporthe oryzae (Pyricularia oryzae) and Fusarium asiaticum.

Histone deacetylases (HDACs) play an important role in the regulation of chromatin structure and gene expression. We found that dark pigmentation of Magnaporthe oryzae (anamorph Pyricularia oryzae) ΔMohda1, a mutant strain in which an orthologue of the yeast HDA1 was disrupted by double cross-over homologous recombination, was significantly stimulated in liquid culture. Analysis of metabolites in a ΔMohda1 mutant culture revealed that the accumulation of shunt products of the 1,8-dihydroxynaphthalene melanin and ergosterol pathways were significantly enhanced compared to the wild-type strain. Northern blot analysis of the ΔMohda1 mutant revealed transcriptional activation of three melanin genes that are dispersed throughout the genome of M. oryzae. The effect of deletion of the yeast HDA1 orthologue was also observed in Fusarium asiaticum from the Fusarium graminearum species complex; the HDF2 deletion mutant produced increased levels of nivalenol-type trichothecenes. These results suggest that histone modification via HDA1-type HDAC regulates the production of natural products in filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural products of fungi have significant impacts on human welfare, in both detrimental and beneficial ways. Although HDA1-type histone deacetylase is not essential for vegetative growth, deletion of the gene affects the expression of clustered secondary metabolite genes in some fungi. Here, we report that such phenomena are also observed in physically unlinked genes required for melanin biosynthesis in the rice blast fungus. In addition, production of Fusarium trichothecenes, previously reported to be unaffected by HDA1 deletion, was significantly upregulated in another Fusarium species. Thus, the HDA1-inactivation strategy may be regarded as a general approach for overproduction and/or discovery of fungal metabolites.

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension).

AIMS: To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months. METHODS: EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed. RESULTS: The 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤3.9mmol/L [≤70mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00-05:59h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments. CONCLUSION: Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results.

Patching retinal breaks with Seprafilm for treating retinal detachments in humans: 9 years of follow-up.

PurposeTo describe the long-term surgical outcomes of four patients treated for retinal detachment using Seprafilm as a novel technique.MethodsRetinal breaks in four eyes were covered with Seprafilm using a transvitreal approach after cataract surgery, pars plana vitrectomy, fluid-air exchange, and laser photocoagulation. Neither long-standing gas nor silicone oil was used. The patients were not instructed to maintain a specific head positioning postoperatively.ResultsSuccessful retinal reattachment was achieved with a single surgery in all four eyes, and none developed proliferative vitreoretinopathy. The mean best-corrected visual acuity preoperatively and 9 years postoperatively were 20/97 and 20/33, respectively. The intraocular pressure increased several days postoperatively that lasted no longer than 2 weeks. Visual field defects either in the inferonasal or inferotemporal quadrant were detected postoperatively. The mean electroretinogram a- and b-wave amplitude ratios of the operated eyes to the fellow eyes were 0.68 and 0.64 preoperatively and 0.87 and 0.92 postoperatively, respectively. The mean corneal endothelial cell density was 2365 cells/mm2 preoperatively and 2592 cells/mm2 postoperatively.ConclusionCovering retinal breaks with Seprafilm may promote retinal reattachment without gas tamponade and postoperative head positioning. The visual outcomes 9 years postoperatively showed no apparent adverse effects of intraocular application of Seprafilm.

Highly Immunogenic DQB1 Mismatch Eplets Are Associated With Development of Chronic Active Antibody-Mediated Rejection: A First Report From Japan.

BACKGROUND: De novo donor-specific antibody (dnDSA), especially against class II HLA, correlates with chronic active antibody-mediated rejection (CAAMR), which eventually leads to graft loss. It would be helpful if we could identify the patients at high risk of dnDSA development in terms of histocompatibility. Structure-based matching strategy assessing mismatched epitopes/eplets by comparing polymorphic amino acid sequences can predict the risk of development of dnDSA and CAAMR. However, it has not been evaluated in Japanese patients whose diversity in HLA is limited. PATIENTS AND METHODS: We retrospectively studied 55 living related kidney transplant patients and ascertained donor and recipient HLA-A, -B, -DRB1, and -DQB1. The number of mismatched eplets was determined using an algorithm, HLAMatchmaker version 3. The relationship between characteristics of mismatched eplets and development of CAAMR was evaluated. RESULTS: There were 8 patients in the CAAMR group and 47 in the control group. The numbers of mismatched HLAs (3.6 ± 1.2 in CAAMR and 3.7 ± 2.0 in control groups), mismatched eplets (32.2 ± 10.4 in CAAMR and 34.4 ± 19.8 in control groups), mismatched DRB1 eplets (11.2 ± 4.3 in CAAMR and 11.5 ± 7.9 in control groups), and mismatched DQB1 eplets (9.2 ± 4.3 in CAAMR and 10.5 ± 7.3 in control groups) were not significantly different. Significantly more patients had at least one highly immunogenic mismatched eplet (62.5% in CAAMR and 25.5% in control groups; P = .024 by χ2 test). CONCLUSIONS: The presence of highly immunogenic mismatched eplets is associated with development of CAAMR.

Clinical use of the co-formulation of insulin degludec and insulin aspart.

AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. METHODS: Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. RESULTS: In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. CONCLUSIONS: IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins.

New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 2).

AIMS: To compare the efficacy and safety of insulin glargine 300 U/ml (Gla-300) with glargine 100 U/ml (Gla-100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)]. METHODS: The EDITION JP 2 study (NCT01689142) was a 6-month, multicentre, open-label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m(2), mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla-300 or Gla-100, while continuing OAD(s). Basal insulin was titrated to target fasting self-monitored plasma glucose 4.4-5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change. RESULTS: Gla-300 was non-inferior to Gla-100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] -0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla-300 and Gla-100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla-300 versus Gla-100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between-treatment difference in weight change favoured Gla-300 [LS mean difference -1.0 (95% CI -1.5, -0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups. CONCLUSIONS: Japanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla-300 than with Gla-100, while glycaemic control did not differ.

New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese adults with type 1 diabetes using basal and mealtime insulin: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 1).

AIM: To compare efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of insulin glargine 100 U/ml (Gla-100) in Japanese adults with type 1 diabetes. METHODS: The EDITION JP 1 study (NCT01689129) was a 6-month, multicentre, open-label, phase III study. Participants (n = 243) were randomized to Gla-300 or Gla-100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self-monitored plasma glucose target of 4.4-7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight. RESULTS: Gla-300 was non-inferior to Gla-100 for the primary endpoint of HbA1c change over the 6-month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) -0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla-300 than with Gla-100 at night [rate ratio 0.66 (95 % CI 0.48-0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65-0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla-300 0.35 U/kg/day, Gla-100 0.29 U/kg/day). A between-treatment difference in body weight change over 6 months favouring Gla-300 was observed [LS mean difference -0.6 kg (95 % CI -1.1 to -0.0); p = 0.035]. Adverse event rates were comparable between the groups. CONCLUSIONS: In Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycaemic control did not differ.

Living situations associated with poor dietary intake among healthy Japanese elderly: the Ohasama Study.

BACKGROUND: Rapid increases in life expectancy have led to concurrent increases in the number of elderly people living alone or those forced to change living situations. Previous studies have found that poor dietary intake was common in elderly people living alone. However, there have been few studies about the dietary intake in elderly people living in other situations, particularly those living with family other than a spouse (nonspouse family), which is common in Japan. OBJECTIVE: To examine the differences in dietary intake by different living situations in elderly Japanese people. We analyzed the data of 1542 healthy residents in the town of Ohasama aged 60 years and over who had completed self-administered questionnaires. METHODS: The dietary intake was measured using a validated 141-item food frequency questionnaire. Multiple regression models with robust (White-corrected) standard errors were individually fitted for nutrients and foods by living situation. RESULTS: In men, although the presence of other family was correlated with significantly lower intake of protein-related foods, e.g., legumes, fish and shellfish, and dairy products, these declines were more serious in men living with nonspouse family. Conversely, in men living alone the intake of fruits and vegetables was significantly lower. In women, lower intakes of fruit and protein-related foods were significantly more common in participants living with nonspouse family than those living with only a spouse. CONCLUSION: These findings revealed that elderly people living alone as well as those living with family other than a spouse had poor dietary intake, suggesting that strategies to improve food choices and skills for food preparation could promote of healthy eating in elderly Japanese people.

Factors associated with deterioration of mini nutritional assessment-short form status of nursing home residents during a 2-year period.

OBJECTIVE: A number of other studies have been conducted to verify the Mini Nutritional Assessment (MNA) or the MNA short form (MNA-SF) as a nutritional assessment/screening tool in various clinical settings or communities. However, there are few longitudinal studies using these tools to analyze which factors affect the incidence of deteriorating nutritional status. We tried to identify the factors associated with deterioration of MNA-SF status of nursing home residents during a 2-year period. METHODS: Participants were 392 people with a mean age of 84.3 in 12 nursing homes in Japan. The factors associated with deterioration in MNA-SF categories during the study period compared to stable/improved MNA-SF categories were identified. RESULTS: At baseline, 19.9% of the participants were malnourished and 60.2% were at risk of malnutrition, according to the MNA-SF classification. After 2 years, 66.3% participants maintained and 6.1% participants improved their nutritional status according to the MNA-SF classification, while 27.6% showed deterioration in MNA-SF status. Stepwise logistic-regression procedure indicated that basic ADL impairment and hospitalization during the follow-up period were associated with declining MNA-SF status. CONCLUSIONS: Poor basic ADL status and hospitalization during the follow-up period were associated with malnutrition and risk of malnutrition as assessed by MNA-SF of nursing homes residents during a 2-year period.

Randomized clinical trial comparing lightweight or heavyweight mesh for mesh plug repair of primary inguinal hernia.

BACKGROUND: The aim of this study was to assess whether the application of a lightweight mesh for mesh plug repair (MPR) for primary inguinal hernia could reduce chronic pain or other symptoms associated with the insertion of the prosthesis. METHODS: Patients over 20 years of age with a unilateral primary inguinal hernia were eligible to participate in the study. The patients were randomly assigned to a lightweight mesh (LWM) or a heavyweight mesh (HWM) group. All the operations were performed under local anesthesia. The operative details, including the hernia type and the nerves that were identified, and the postoperative complications were recorded. All follow-up and outcome measures were obtained based on a physical examination and a questionnaire regarding pain and other symptoms at 1 week, 1, 3, 6, and 12 months after the surgery in a double-blinded manner. RESULTS: The use of LWM significantly reduced foreign body sensation after 12 months to one-third of the incidence reported for the use of HWM (5.8 vs. 17.9%; P = 0.013), while no significant differences were found in pain parameters, including the use of pain relief medications, between the groups throughout the study period. CONCLUSION: This study indicated that the use of LWM in the MPR decreases the incidence of foreign body sensation at 1 year after surgery for primary inguinal hernia. LWM may be preferable to MPR, similar to results described previously for Lichtenstein repair.

Attempted suicide with liraglutide overdose did not induce hypoglycemia.

We document the first reported case of attempted suicide with the GLP-1 receptor agonist, liraglutide: a 33-year-old Japanese woman with type 2 diabetes reported subcutaneously injected 72 mg of liraglutide. She experienced gastrointestinal symptoms but no hypoglycemia.

SU-E-J-117: Computer-Assisted Verification of Accumulated Dose Distribution during the Treatment Time Based on Estimation of Four-Dimensional Dose Distribution Using an Electronic Portal Imaging Device.

PURPOSE: The accumulated dose distributions during the course of radiation treatment are substantially important for verifying whether treatment dose distributions are produced according to planned dose distributions. The purpose of this study was to develop a computer-assisted verification method of accumulated dose distribution during the irradiation of a tumor based on estimation of four-dimensional (4D) dose distribution using an electronic portal imaging device (EPID). METHODS: The 4D 'treatment' computed tomography (CT) images during the irradiation were estimated based on affine transformations including respiratory motions, which were derived by registration between a planning portal dose image and treatment portal dose dynamic image. Planning portal dose images were calculated from planning CT images and an algorithm for calculation of dose spatial distribution. Treatment portal dose images were estimated from EPID dynamic images obtained during a treatment time. The planning portal dose images were registered to the treatment portal dose images to obtain the affine transformation, which could include respiratory motion in a patient body. The CT images at a treatment time were determined by deforming the planning CT images using the affine transformation matrix. 4D dose distributions during a treatment delivery were obtained by applying a dose calculation algorithm to the 4D treatment CT images. Finally, accumulated dose distributions during the course of radiation treatment were verified with planned dose distributions. RESULTS: We applied the proposed method to EPID dynamic images of 2 lung cancer patients, and evaluated the difference in accumulated dose distribution between the plan and treatment using a gamma evaluation (3mm/3%). The average pass rate for 2 cases was 78.2%. CONCLUSIONS: The proposed method can be used for adaptively modifying the plan based on the dose discrepancy between the plan and treatment. This work was partially supported by Grant-in-Aid for Scientific Research (C) (22611011) and Okawa Foundation for Information and Telecommunications.

Evaluation of the efficacy and safety of the combination of gemcitabine and nedaplatin for elderly patients with advanced non-small-cell lung cancer.

OBJECTIVE: The aim of the present study was to retrospectively assess the safety and efficacy of the combination of gemcitabine and nedaplatin in elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Patients ≥75 years with previously untreated NSCLC who underwent chemotherapy consisting of gemcitabine (800 mg/m(2) on days 1 and 8) and nedaplatin (80 mg/m(2) on day 1) every 3 weeks were retrospectively analyzed. RESULTS: Of the 35 patients, 28 were men and 7 were women, with a mean age of 78 years (range 75-87); 10 patients had stage IIIB disease and 25 patients had stage IV disease. The overall response rate was 45.7% (95% confidence interval 28.8-63.4). The median survival time was 14 months (range 3-44). Grade 3-4 toxicities included neutropenia in 74.3%, thrombocytopenia in 48.6%, anemia in 34.3%, hepatic dysfunction in 11.4%, and infection in 2.9%. There were no treatment-related deaths. There were no differences in response rate and survival between patients aged 75-79 years and patients ≥80 years, although grade 3-4 thrombocytopenia and anemia were significantly more frequent in patients ≥80 years. CONCLUSION: Our results suggest that the combination of gemcitabine and nedaplatin is effective and well tolerated for selected elderly patients with advanced NSCLC.