Risk factors for glioblastoma in adults in Japan: an exploratory cohort study based on the Shizuoka Kokuho Database, the Shizuoka study.

PURPOSE: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan. METHODS: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. RESULTS: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research. CONCLUSION: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research.

Risk factors, treatment and survival rates of late-onset acquired haemophilia A: A cohort study from the Shizuoka Kokuho Database.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare disease. The risk factors have yet to be studied. AIM: We aimed to identify risk factors for late-onset AHA in Japan. METHODS: A population-based cohort study was conducted using data from the Shizuoka Kokuho Database. The study population was defined as individuals aged ≥60 years. Cause-specific Cox regression analysis was performed to calculate hazard ratios. RESULTS: Of 1,160,934 registrants, there were 34 patients with newly diagnosed AHA. The mean follow-up period was 5.6 years, and the incidence of AHA was 5.21 per million person-years. Myocardial infarction, diabetes mellitus, solid tumors, antimicrobial agents, phenytoin and anti-dementia drugs, which showed significant differences in the univariate analysis, were excluded from the multivariable analysis because of the small number of cases. Multivariable regression analysis showed that the presence of Alzheimer's disease (hazard ratio [HR]:4.28, 95% confidence interval [CI]:1.67-10.97) and rheumatic disease (HR:4.65, 95% CI:1.79-12.12) increased the risk of AHA development. CONCLUSION: We found that comorbid Alzheimer's disease is a risk factor of AHA incidence in the general population. Our findings provide insight into the etiology of AHA, and the proof of the coexistence of Alzheimer's disease may support the recent notion that Alzheimer disease is an autoimmune disease.

Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for uterine cervical cancer with lymph node metastasis.

The purpose of this phase II trial was to assess the efficacy and toxicity of paclitaxel and nedaplatin (TN) as the initial postoperative adjuvant chemotherapy for uterine cervical cancer with lymph node metastases (LNM). Patients with FIGO stage IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histological confirmation of LNM was mandatory. Intravenous paclitaxel at 175 mg/m2 and nedaplatin at 80 mg/m2 were administered every 28-day cycle, of which there were 5 cycles after radical hysterectomy. Sixty-two patients were enrolled in the study from November 2011 to July 2015. Their median age was 48.5 years (range 28-64). The median tumor diameter was 37 mm (5-64). Overall, 30 patients (48.4%) had 1 metastatic lymph node, 11 (17.7%) had 2, 3 (4.8%) had 3, 5 (8.1%) had 4, and 13 (21.0%) had 5 or more. With a median follow-up of 45.7 months (range 23.4-69.5), the 2-year relapse-free survival and 2-year overall survival rates were 79.0% (90% CI, 69.0%-86.2%) and 93.5% (95% CI, 83.7%-97.5%), respectively. Almost all adverse events were relatively mild. Grade 3-4 adverse events (NCI-CTC ver. 4.0) that occurred in 5% or more of patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Postoperative adjuvant chemotherapy with TN for cervical cancer with LNM was demonstrated to be an effective and feasible treatment. A phase III trial is warranted to compare this with concurrent chemoradiotherapy.

METAMORPHOPSIA AND TANGENTIAL RETINAL DISPLACEMENT AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To determine whether the degree of metamorphopsia significantly correlated with the distance of the tangenital retinal displacement after epiretinal membrane surgery. METHODS: The M-CHARTS were used to measure the vertical metamorphopsia score and the horizontal score. The distances between the intersections of two sets of retinal vessels situated vertically or horizontally were measured in the near-infrared Spectralis images. RESULTS: Fifty eyes of 50 patients (22 men; age, 69.5 ± 7.8 years) were retrospectively studied. The vertical and horizontal metamorphopsia scores significantly improved at 1 month after the surgery, and the vertical and horizontal retinal distances increased. The baseline horizontal and vertical metamorphopsia scores significantly correlated with the ratio of the pre- and postoperative vertical and horizontal retinal displacements, respectively (P = 0.038 and P = 0.015 at 1 week; P = 0.036 and P = 0.036 at 1 month). The postoperative horizontal metamorphopsia score at 1 month and the vertical metamorphopsia score at 3 months significantly correlated with the vertical displacement at 1 month (P = 0.034) and the horizontal displacement at 3 months (P = 0.001), respectively. CONCLUSION: The degree of metamorphopsia significantly correlated with the tangential retinal displacement. Dislocated Müller cells may stimulate the photoreceptors located away from original positions, which consequently results in the sensation of metamorphopsia in patients with an epiretinal membrane.

Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial.

PURPOSE: Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC. METHODS: This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy. RESULTS: Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events. CONCLUSIONS: Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

Surgical Success Rate of Scleral Buckling Surgery and Postoperative Incidence of Cystoid Macular Edema: 10 Years of Experience at a Single Academic Hospital.

The purposes of this study were to report the surgical success rate of scleral buckling surgery (SB) for rhegmatogenous retinal detachment (RRD) in a single academic hospital, analyze the incidence of cystoid macular edema (CME) after SB using optical coherence tomography (OCT), and reveal the factors associated with the development of CME. This was a retrospective observational study of patients with RRD who underwent SB from 2010 to 2020 in a single academic hospital. The anatomical success was initially achieved in 267 of 288 eyes (92.7%), and finally achieved in 288 eyes (100%). After excluding 17 eyes that underwent vitrectomy for reoperations, a total of 271 eyes of 267 patients (173 men; age, 43.5 ± 16.9 years) were retrospectively analyzed to evaluate the incidence of postoperative CME. CME occurred in 6 of 271 eyes (2.2%) within 3 months after initial surgery. Pseudophakic and aphakic eyes appeared more likely to develop CME (chi-squared test: p = 0.0078). Five of the six cases with postoperative CME were able to be medically treated. Scleral buckling surgery showed a high success rate even in the era of small-gauge vitreous surgery, and the postoperative frequency of CME after SB was low (2.2%). Previous cataract surgery may be associated with the development of postoperative CME, which is mostly medically manageable.

[A case of left posterior inferior temporal infarction with right homonymous upper quadrantanopsia and alexia with agraphia for Kanji].

BACKGROUND: Alexia with agraphia usually represents damage in angular gyrus. We report an unusual case of alexia with agraphia caused by a posterior inferior temporal lesion. CASE REPORT: A 82-year-old, right-handed man was admitted because of reading disorder. Visual acuity was 0.7 OD and 0.7 OS. Goldmann perimetry revealed right homonymous upper quadrantanopsia. Standard Language Test of Aphasia revealed mild anomia and severe alexia with agraphia for kanji. Magnetic resonance imaging demonstrated left temporal and posterior infarction in the posterior cerebral artery region. Single photon emission computed tomography revealed decreased blood flow in the left inferior temporal, parahippocampal, fusiform, lingual and inferior occipital gyri. There were no significant lesions nor any decreased of blood flow in the angular gyrus. CONCLUSION: It is suggested that reading and writing of ideograms such as Kanji is related not only to the angular gyrus but also to the posterior inferior temporal lobe and medial posterior lobe of the visual cortex.

Inner Nuclear Layer Thickness, a Biomarker of Metamorphopsia in Epiretinal Membrane, Correlates With Tangential Retinal Displacement.

PURPOSE: To examine correlations of inner nuclear layer (INL) thickness with metamorphopsia and tangential retinal displacement in epiretinal membrane (ERM). DESIGN: Retrospective, consecutive, interventional case series. METHODS: Setting: Institutional study. PATIENT POPULATION: Fifty eyes of 50 patients undergoing epiretinal membrane surgery. OBSERVATION PROCEDURES: M-CHARTS were used to measure metamorphopsia. Inner nuclear layer (INL) thickness and outer retinal layer (ORL) thickness in the macula and distances between the intersections of 2 sets of retinal vessels situated vertically or horizontally were measured in Spectralis optical coherence tomography and infrared images. MAIN OUTCOME MEASURES: Correlations of INL and ORL thicknesses with M-CHARTS scores and distances of retinal displacement. RESULTS: Preoperative INL thickness significantly correlated with preoperative and postoperative metamorphopsia scores at 3 months (Spearman correlation coefficient: P = .036 and P = .003, respectively). The baseline INL thickness and its change at 3 months significantly correlated with the postoperative vertical retinal displacements at 3 months (P < .001 for both). Preoperative and postoperative ORL thicknesses were not correlated with preoperative and postoperative metamorphopsia scores at any periods. CONCLUSIONS: INL thickness is a useful biomarker to evaluate metamorphopsia and appears to be determined by tangential retinal displacement in ERM. Structural changes of the inner retinal layer, which cause Müller cells to be distorted, play a more important role for generation of metamorphopsia than outer retina. Our results provide evidence for the theory that Müller cell functions as an optic fiber in humans.

Evaluation of microvascular changes in the macular area of eyes with rhegmatogenous retinal detachment without macular involvement using swept-source optical coherence tomography angiography.

PURPOSE: To evaluate microvascular changes in the macular area of eyes with rhegmatogenous retinal detachment (RRD) without macular involvement (macula-on RRD) using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: Five patients with macula-on RRD were eligible for analysis. All patients underwent SS-OCTA examination (Triton) for the macular area. The healthy fellow eyes were included as controls. The vessel density (VD) was calculated using binarization, and the foveal avascular zone (FAZ) was measured. The VD and FAZ area were compared between the eyes with RRD and the fellow eyes using the Wilcoxon signed rank test. RESULTS: The patients' clinical characteristics were as follows: age, 49.0 years (21.0, 54.0) (median [25, 75th percentile]); preoperative best-corrected visual acuity, -0.08 (-0.08, 0.11) for RRD and -0.08 (-0.08, -0.03) for the fellow eye (P=0.50); and axial length, 27.0 (25.1, 28.7) mm for RRD and 27.4 (25.6, 28.5) mm for the fellow eye (P=0.31). The parafoveal VD was not significantly different between the eyes with RRD and the fellow eyes (P=1.00 for the superficial retina and P=0.44 for the whole retina). The FAZ area was also similar for the eyes with RRD and the fellow eyes (P=0.31 for the superficial retina and P=0.13 for the whole retina). CONCLUSION: The findings of this study suggest that the macular microvasculature remains intact in eyes with macula-on RRD.

Analysis of clinical characteristics and prognostic factors for angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct peripheral T-cell lymphoma entity exhibiting peculiar clinical features and poor prognosis. Its clinical characteristics and prognostic factors are not well established. To clarify the clinical characteristics and prognostic features of AITL, we conducted a multicenter, retrospective study. Fifty-six patients were enrolled. The median patient age was 68 years. Immunohistochemical examinations of tumor cells showed positivity for CD10 and T-cell markers, and chromosomal examination detected several types of abnormalities. More than 80 % of patients show advanced disease at diagnosis and poor prognostic scores. A high proportion of patients showed accompanying B symptoms, splenomegaly, and hepatomegaly at diagnosis. The 5-year overall survival (OS) rate was 48 % and progression-free survival was 25 %. Univariate analysis revealed higher age, fever, poor performance status, anemia, and low albumin level to be poor prognostic factors for OS. In addition to these factors, both IPI and PIT were also predictive of OS. Multivariate analysis indicated only a low level of serum albumin to be a significant prognostic factor for OS. Serum albumin may be one of the important prognostic factors for AITL. Further investigation is needed to confirm these results.

Monitoring the expression profiles of doxorubicin-resistant K562 human leukemia cells by serial analysis of gene expression.

We examined the expression profiles of doxorubicin-resistant K562 cells by serial analysis of gene expression (SAGE) to identify novel and/or partially characterized genes that might be related to drug resistance in human leukemia. SAGE complementary DNA (cDNA) libraries were constructed from K562 and doxorubicin-resistant K562 (K562/ADM) cells, and concatamer sequences were analyzed with SAGE 2000 software. We used 9792 tags in the identification of 1076 different transcripts, 296 of which were similarly expressed in K562 and K562/ADM cells. There were 343 genes more actively expressed in K562/ADM than in parental K562 cells and 437 genes expressed less often in K562/ADM cells. K562/ADM cells showed increased expression of well-known genes, including the genes for spectrin beta, eukaryotic translation initiation factor 1A (EIF1A), RAD23 homolog B, laminin receptor 1, and polyA-, RAN-, and PAI-1 messenger RNA-binding proteins. K562/ADM cells showed decreased expression of the genes for fatty acid desaturase 1 (FADS1), hemoglobin epsilon 1, N-myristoyltransferase 1, hemoglobin alpha 2, NADH dehydrogenase Fe-S protein 6, heat shock 90-kDa protein, and karyopherin beta 1. Quantitative reverse transcription-polymerase chain reaction analysis confirmed the increased expression of EIF1A and the decreased expression of FADS1 in K562/ADM cells. Prior to this investigation, such differences in the expression of these genes in doxorubicin-resistant leukemia cells were unknown. Although we do not provide any evidence in the present report for the potential roles of these genes in drug resistance, SAGE may provide a perspective into our understanding of drug resistance in human leukemia that is different from that provided by cDNA microarray analysis.

Gene expression profiling of human erythroid progenitors by micro-serial analysis of gene expression.

We compared the expression profiles of highly purified human CD34+ cells and erythroid progenitor cells by micro-serial analysis of gene expression (microSAGE). Human CD34+ cells were purified from granulocyte colony-stimulating factor-mobilized blood stem cells, and erythroid progenitors were obtained by cultivating these cells in the presence of stem cell factor, interleukin 3, and erythropoietin. Our 10,202 SAGE tags allowed us to identify 1354 different transcripts appearing more than once. Erythroid progenitor cells showed increased expression of LRBA, EEF1A1, HSPCA, PILRB, RANBP1, NACA, and SMURF. Overexpression of HSPCA was confirmed by real-time polymerase chain reaction analysis. MicroSAGE revealed an unexpected preferential expression of several genes in erythroid progenitor cells in addition to the known functional genes, including hemoglobins. Our results provide reference data for future studies of gene expression in various hematopoietic disorders, including myelodysplastic syndrome and leukemia.

Retinal displacement toward optic disc after internal limiting membrane peeling for idiopathic macular hole.

PURPOSE: To examine the retinal displacement following successful macular hole (MH) surgery with internal limiting membrane (ILM) peeling and gas tamponade, and to determine the correlation between the extent of displacement and the basal MH size. DESIGN: Retrospective, interventional, observational case series. METHODS: The medical records of consecutive patients with an idiopathic MH that had undergone vitrectomy with ILM peeling and gas tamponade were studied. The distances between the optic disc and the intersection of 2 retinal vessels located nasal or temporal to the fovea were measured manually preoperatively (A), and 2 weeks and 1, 3, 6, and 12 months postoperatively (B), on the fundus autofluorescence or near-infrared images. The basal and minimum diameters of the MHs were measured in the spectral-domain optical coherence tomographic images. The correlations between the ratio of the retinal displacement (A - B/A) and basal diameters of the MHs were determined. RESULTS: Twenty-one eyes of 21 patients (9 men, mean age: 64.6 ± 8.4 years) were studied. Ten eyes (47.6%) had stage 2 MH, 9 eyes (42.9%) had stage 3 MH, and 2 eyes (9.5%) had stage 4 MH. The temporal retinal vessels were displaced 260.8 ± 145.8 µm toward the optic disc at 2 weeks postoperatively, which was significantly greater than the 91.1 ± 89.7 µm of the nasal retinal vessels (paired t test, P < .001). The ratio of retinal displacement in the temporal field at 2 weeks was significantly correlated with the basal diameter of the MH (Spearman's rank correlation coeffieient = -0.476, P = .033. CONCLUSIONS: The greater displacement of the temporal retina than the nasal retina toward the optic disc postoperatively suggests that the temporal retina is more flexible and can be retracted toward the optic disc during the MH closure.