Utility of RAND/UCLA appropriateness method in validating multiple-choice questions on ECG.

OBJECTIVES: This study aimed to investigate the utility of the RAND/UCLA appropriateness method (RAM) in validating expert consensus-based multiple-choice questions (MCQs) on electrocardiogram (ECG). METHODS: According to the RAM user's manual, nine panelists comprising various experts who routinely handle ECGs were asked to reach a consensus in three phases: a preparatory phase (round 0), an online test phase (round 1), and a face-to-face expert panel meeting (round 2). In round 0, the objectives and future timeline of the study were elucidated to the nine expert panelists with a summary of relevant literature. In round 1, 100 ECG questions prepared by two skilled cardiologists were answered, and the success rate was calculated by dividing the number of correct answers by 9. Furthermore, the questions were stratified into "Appropriate," "Discussion," or "Inappropriate" according to the median score and interquartile range (IQR) of appropriateness rating by nine panelists. In round 2, the validity of the 100 ECG questions was discussed in an expert panel meeting according to the results of round 1 and finally reassessed as "Appropriate," "Candidate," "Revision," and "Defer." RESULTS: In round 1 results, the average success rate of the nine experts was 0.89. Using the median score and IQR, 54 questions were classified as " Discussion." In the expert panel meeting in round 2, 23% of the original 100 questions was ultimately deemed inappropriate, although they had been prepared by two skilled cardiologists. Most of the 46 questions categorized as "Appropriate" using the median score and IQR in round 1 were considered "Appropriate" even after round 2 (44/46, 95.7%). CONCLUSIONS: The use of the median score and IQR allowed for a more objective determination of question validity. The RAM may help select appropriate questions, contributing to the preparation of higher-quality tests.

Green-light wavelength-selective organic solar cells for agrivoltaics: dependence of wavelength on photosynthetic rate.

There is a growing demand for the development of novel solar power systems that can simultaneously solve the problems associated with both energy generation and food supply in agriculture. Green-light wavelength-selective organic solar cells (OSCs), whose transmitted blue and red light can be utilized to promote plant growth were recently reported by our group. However, the influence of wavelength variation on the photosynthetic rate in green-light wavelength-selective OSCs remains unclear. In this study, we report on the design and synthesis of new electron-accepting π-conjugated molecules containing cyclopentene-annelated thiophene with a spiro-substituted 2,7-bis(2-ethylhexyl)fluorene (FT) unit (TT-FT-ID) as a green-light wavelength-selective nonfullerene acceptor along with a reference compound TT-T-ID. Photophysical measurements indicate that the introduction of the FT unit leads to an absorption band with a small full width at half maximum in films, leading to the ability to fine-tune the absorption length. Concerning the optimization of the conditions for the fabrication of the active layers, which are composed of a green-light wavelength-selective donor polymer of poly(3-hexylthiophene) (P3HT) and the new acceptors, Bayesian optimization based on Gaussian process regression was applied to minimize the experimental batches. The green-light wavelength-selective factor (SG) and the PCEs in the green-light region (PCE-GR) of the P3HT:TT-FT-ID-based device were determined to be 0.52 and 8.6%, respectively, which are higher values than those of the P3HT:TT-T-ID blend film. The P3HT:TT-FT-ID blend film increased the photosynthetic rate of green pepper compared to that of the P3HT:TT-T-ID blend film. These results indicate that the fine-tuning of the absorbance required for crop growth is an important issue in developing green-light wavelength-selective OSCs for agrivoltaics.

Acute Megakaryoblastic Leukemia Harboring a Subclone Expressing BCR-ABL1 Fusion Gene Product.

Acute myeloid leukemia (AML) with BCR-ABL1, also termed Philadelphia chromosome-positive AML (Ph+ AML), is a rare leukemia subtype classified by the World Health Organization in 2016. The characteristics of Ph+ AML have not been fully identified yet. We herein report a patient with Ph+ AML who phenotypically exhibited megakaryoblastic characteristics, FAB:M7 and harbored a subclone expressing BCR-ABL1 gene fusion products. This case suggests that BCR-ABL1 was acquired as a subclone due to a secondary event that might have occurred late during leukemia evolution. Our findings may aid in deciphering the mechanism underlying Ph+ AML development in future studies.

Single center experience of cell-free and concentrated ascites reinfusion therapy in malignancy related ascites.

Cell-Free and Concentrated Ascites Reinfusion Therapy (CART) is expected to improve patients' symptoms related to ascites. Use of a patient's own proteins in ascites might reduce the risk of infection. However, several reports have described that reinfusion of concentrated ascites might elevate body temperature. The aim of this study is to examine the safety and efficacy of the CART system performed exclusively on patients with malignancies. In this retrospective cohort observational study, we examined 81 CART processes performed on 24 patients with malignancies. Data were collected from medical records and records during processing of ascites. We investigated the effectiveness and adverse events during the procedures. The amount of ascites processed was 2.6 ± 1.4 L on average. The concentration ratio was 9.31 ± 5.45 on average. We found an increase in the urine volume after the procedure, which was significantly related to the amount of reinfused protein. The body temperature increased by 0.44°C. Systolic blood pressure decreased by 4 mm Hg after paracentesis, but no significant difference was found between the pressure before paracentesis and after reinfusion. In platelet counts, no significant change was observed. After all, no clinically significant adverse event was confirmed during CART procedures. Results show that CART can be performed safely even on patients with malignancy-related ascites and that the procedure might improve diuresis.

A study of the postoperative course in cases of GIST of the stomach. The efficacy of imatinib in cases of recurrence.

BACKGROUND: The postoperative course of cases of gastrointestinal stromal tumor (GIST) of the stomach was studied in patients who underwent surgery in this Department. In addition, treatment with the molecular-targeted drug imatinib was studied in cases of recurrence. PATIENTS AND METHODS: We studied 40 cases with a diagnosis of GIST of the stomach where the patient subsequently underwent surgery in this Department between July 1985 (when this facility opened) and December 2007. Six of these cases involved patients with carcinoma or carcinoid tumors, which could have affected the procedure and prognosis, and 2 cases involved patients who developed cancer during the postoperative course of the GIST. Therefore these 8 patients were excluded, thus resulting in the study of a total of 32 patients. RESULTS: The male:female ratio for the 32 patients was 17:15, the average tumor size was 4.7+/-3.4 cm (with a range of 1.3-16.0 cm), and the median follow-up was 92.2+/-73.7 months (with a range of 2-238 months). Recurrence occurred in 6 out of the 32 patients (18.8%) and was observed in the liver of 5 patients, in the lungs of 2 patients, in the peritoneum of 2 patients, locally in 1 patient, and in the bone of 1 patient (including patients with multiple sites). With respect to the tumor size, the incidence of recurrence of tumors smaller than 2 cm was 0%, 16.7% for patients with tumors 2 to 5 cm in size, and 27.3% for these with tumors larger than 5 cm. The incidence of recurrence was particularly marked in patients with tumors larger than 10 cm (66.7%). The treatment for recurrence was transcatheter arterial embolization for 1 patient and imatinib for 5 patients. In cases where imatinib was administered, 1 patient exhibited partial response, 1 patient exhibited stable disease, and 3 patients exhibited progressive disease, indicating a response rate of 20%. Postoperative recurrence of GIST of the stomach in this study occurred in 6 of 32 patients (18.8%). The incidence of recurrence of tumors larger than 10 cm was 2 out of 3 patients. CONCLUSION: In cases of recurrence, the response rate to imatinib was 20%. Imatinib was effective against GIST that were positive for KIT protein, but future study is needed to clarify the risk factors for recurrence and indications for adjuvant therapy in cases of GIST.

Comparison of the effects of omeprazole and famotidine in treatment of upper abdominal symptoms in patients with reflux esophagitis.

PURPOSE: The purpose of this study was to compare the efficacy of proton pump inhibitor (PPI) with H(2) receptor antagonist (H(2)RA) in treatment of upper abdominal symptoms. METHODS: This was a multi-center, open study conducted at 102 hospitals in Japan. Patients with reflux esophagitis received famotidine 10 mg twice daily for 2 weeks, then omeprazole 10 mg once daily for 2 weeks. Thereafter, patients were switched to famotidine 10 mg twice daily for a third 2-weekperiod, provided those with a medical condition agreed to continue the study. Patients evaluated the treatment response to each gastrointestinal symptom using a predefined patient questionnaire and gastrointestinal symptom rating scale (GSRS). RESULTS: 161 patients entered the study, of whom 8 were excluded from all analyses due to lack of participation following entry. Overall symptom improvement rate (n = 130) at week 4, after the 2-week omeprazole treatment, was 75.4% and this was significantly higher than that after the first 2-week famotidine treatment (41.5%) at week 2. In patients (n = 36) who completed 6 weeks of treatment, 2-week omeprazole treatment at week 4 showed a significantly higher overall symptom improvement rate compared with both the first 2-week and third 2-week famotidine treatments. CONCLUSIONS: Omeprazole was superior to famotidine for treatment of upper abdominal symptoms in patients with reflux esophagitis, which suggested that gastric acid might be a cause not only of reflux symptoms, but also of ulcer symptoms and dysmotility symptoms such as epigastric pain and feeling of fullness in reflux esophagitis.

Primary histiocytic sarcoma of the spleen associated with hemophagocytosis.

We report a patient with primary histiocytic sarcoma of the spleen associated with prominent hemophagocytosis. Although thrombocytopenia, probably due to hemophagocytosis, was refractory to corticosteroid therapy, the transfusion of platelets, and splenic irradiation, partial splenic embolization was effective and facilitated splenectomy for a diagnosis. The majority of the spleen showed necrosis, but viable neoplastic cells with pleomorphic nuclei and abundant cytoplasm, showing occasional erythrocytes or leukocytes, were still discernible. The neoplastic cells expressed CD68, lysozyme, and S-100 protein, and were negative for lymphoid, myeloid, and epithelial cell markers. CD163, a monocyte/macrophage-specific molecule, was positive in only some of them. Despite multiagent chemotherapy, the patient died of the disease, showing a rapidly progressive clinical course. Although the preoperative diagnosis of primary splenic histiocytic sarcoma is difficult, it has been confirmed in patients with splenomegaly of unknown etiology that clinicolaboratory features suggestive of hemophagocytosis may be important clues suggestive to the disease. CD163 expression by neoplastic cells could be confirmed only after careful observation, because the molecule may only be seen in some of the neoplastic cells.

A case of acute myeloblastic leukemia with a novel variant of t(8;21)(q22;q22).

We encountered a case of acute myeloblastic leukemia (AML), with extramedullary leukemia (EML) and a masked type of the variant translocation t(8;21)(q22;q22). Morphologically, the AML M2 subtype according to the French-American-British (FAB) classification was present. Phenotypically, leukemic cells were negative for CD19 and positive for CD56. Clinically, the case showed chemo-refractoriness and a poor outcome. The initial karyotypic interpretation was t(8;9)(q22;q34) on G-banding. Multiplex-fluorescence in situ hybridization (multiplex-FISH) analysis revealed a three-way translocation involving chromosomes 8, 9, and 21, and identified a masked type of variant t(8;21)q22;q22) translocation. The karyotype was finally determined as 45,X,-Y,der(8)t(8;21)(q22;q22), der(9)(8;9)(q22;q34), and der(21)t(9;21)(q34;q22). Results of FISH using the AML1/ETO probe and detection of the AML1/ETO fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) support the karyotype as well as the sequence of the PCR product. Additionally, C-KIT mutation was detected.

Detection of the CBFB/MYH11 fusion gene in de novo acute myeloid leukemia (AML): a single-institution study of 224 Japanese AML patients.

The cytogenetic findings in acute myeloid leukemia (AML) are a powerful prognostic indicator. Among these abnormalities, the World Health Organization has classified inv(16)(p13q22), which is closely associated with the M4E classification in the French-American-British system, as indicating a good-risk AML. However, this chromosomal abnormality can often be difficult to detect. In this study, we used RT-PCR and FISH analysis to examine 224 Japanese adult de novo AML patients for the presence of the CBFB/MYH11 fusion transcript at the time of diagnosis. The CBFB/MYH11 fusion gene was detected in 17 patients (7.6%): eight patients had the inv(16) chromosome and in all of them it was M4E; nine patients did not have abnormalities in chromosome 16. AML with the CBFB/MYH11 fusion gene but without inv(16) was found in M2, M4, and M5, but not in M4E patients. There were no statistically significant differences in the clinical features of patients with the inv(16) and those with the cryptic inv(16) chromosome. These results indicate that even if eosinophilia is not found, molecular screening for CBFB/MYH11 fusion gene should be performed in all AML patients at the time of diagnosis to help guide disease management.

Enhanced photoluminescence from very thin double-wall carbon nanotubes synthesized by the zeolite-CCVD method.

Photoluminescence (PL) from purified (>90%) double-wall carbon nanotubes (DWNTs), which have been synthesized by zeolite catalyst-supported chemical vapor deposition (zeolite-CCVD), of very small diameters (0.8-nm average inner tube) is reported. The PL contour mappings for various ratios (1-90%) of double- versus single-wall carbon nanotubes by thermal oxidation have enabled us to unambiguously identify the chirality of inner tubes for the DWNTs synthesized. After the extensive high-temperature oxidation at 700 degrees C, high-purity (>90%) DWNTs of approximately 0.8 nm inner diameter are obtained, and most of these correspond to the DWNTs having inner tubes with chiralities of (7,5), (7,6), and (9,4).

Serum interleukin-6 response after spinal surgery: estimation of surgical magnitude.

BACKGROUND: Serum interleukin-6 (IL-6) has been used for quantitative estimation of the surgical magnitude of major cardiac and thoracoabdominal surgery, but there have been few studies assessing IL-6 as a marker of surgical magnitude of spinal surgery. METHODS: We investigated the changes in IL-6 response in comparison to other parameters of surgical magnitude and spinal surgery procedures. The study included 40 patients electively undergoing spinal surgery. The patients were divided into four groups: lumbar laminectomy with posterolateral fusion (PLF), lumbar laminotomy, lumbar open discectomy, and cervical laminoplasty. Serum IL-6, C-reactive protein (CRP), creatine kinase (CK), and the white blood cell (WBC) count were determined in venous blood before surgery, at the end of surgery, and 6 h and the first, third, and seventh days after surgery. RESULTS: Serum IL-6 peaked on the first day and returned to a normal value by the seventh day. The peak IL-6 concentrations on the first day after surgery significantly correlated with CRP, CK, duration of surgery, and estimated blood loss. Regarding lumbar surgeries, the peak IL-6 for laminectomy/PLF was significantly higher than that for laminotomy/open discectomy or for cervical laminoplasty. CONCLUSIONS: Serum IL-6 on the first day varied depending on the surgical procedure used. Therefore, it might be a quantitative marker of surgical magnitude following spinal surgery.

Molecular analysis of PDGFRalpha/beta genes in core binding factor leukemia with eosinophilia.

Eosinophilia sometimes occurs in acute myeloid leukemia (AML), especially in core binding factor (CBF) leukemia. However, the pathogenesis of the differentiation from leukemic progenitors to eosinophils is not well understood in this type of leukemia. Recent reports showed that a novel fusion tyrosine kinase, Fip1-like1 (FIP1L1) platelet-derived growth factor receptor alpha (PDGFRalpha), is found in idiopathic hypereosinophilic syndrome. The involvement of another chimeric gene, PDGFRbeta, was also reported in myeloproliferative disorder with eosinophilia. These chimeric genes cause constitutive activation of PDGFR tyrosine kinases. On the other hand, a two-hit model for the pathogenesis of AML, which seems to be caused by inactivating mutations in transcription factors and genetic lesions in tyrosine kinase resulting in constitutive activation, has been proposed. On the basis of these findings, we screened for the expression of the FIP1L1-PDGFRalpha fusion gene and for mutations in the juxtamembrane and tyrosine kinase domains of PDGFRalpha/beta genes in 22 cases of CBF leukemia with eosinophilia. Among these cases, no FIP1L1-PDGFRalpha fusion gene was found. Although cDNA sequencing also detected three types of single-nucleotide alterations at kinase domains in PDGFRalpha/beta genes, all of them were silent changes and polymorphisms. Therefore, PDGFRalpha/beta genes do not appear to play a significant pathogenetic role in eosinophilia or leukemogenesis of CBF leukemia.

Successful treatment by double filtrate plasmapheresis in a pregnant woman with the rare P blood group and a history of multiple early miscarriages.

Individuals of P type, a rare blood group, have anti-PP(1)P(k) antibody in their serum, which causes spontaneous abortion in the early stages. We report a patient of p type suffering from multiple spontaneous abortions. We also review previously reported cases from published work. A 36-year-old woman (gravida 2, para 0) was referred to our hospital because of habitual abortion. At the third pregnancy, we started double filtration plasmapheresis (DFPP) from 7 weeks 3 days to remove the antibody. We attained rapid decline in the titer and normal fetal growth. Gradual tapering of the DFPP frequency caused neither a rebound of the titer nor growth retardation. During the course, she experienced only one episode of catheter infection as an adverse effect. At 37 weeks 3 days, after 57 DFPP repetitions, a 2496 g girl was delivered by cesarean section. The infant suffered neither from anemia nor from severe jaundice. A review of previous reports indicates that the titer of the pathogenic antibody should be kept as low as possible from the early gestational stage in P-incompatible habitual abortion cases, otherwise the case typically comes to an unfavorable outcome. Plasma exchanges with fresh plasma potentially induce contamination by either known or unknown pathogens. Such risks are reduced using DFPP because the volume of albumin solution that replaces fresh plasma is less than that by plasma exchange. The present case, along with previous reports, shows that DFPP is an effective therapy for treating P-incompatible pregnancy.

[Rehabilitation for the patients with low-back pain].

The first choice for the treatment of low-back pain should be physical therapy, or rehabilitation. These are mainly divided into two modalities; passive and active modality. The former includes bed rest, hot pack, massage, and brace. The latter includes therapeutic exercise. The modality used should be dependent of the stages in each patient. Bed rest is indicated in the acute stage within a week after the occurrence low-back pain. The rest longer than a week is basically contraindicated, because of disuse syndrome such as muscle weakness, osteoporosis, and soft tissue contracture. Therapeutic exercise is the mainstay in the chronic stage. It includes trunk muscles strengthening exercise and stretching. Lumbar stabilization exercise has currently drawn attention for the treatment of low-back pain. Patient education such as back-school also plays an important role to manage low-back pain.

[Effective treatment for a methotrexate-associated lymphoproliferative disorder with R-CHOP following administration of rituximab].

A 65-year-old male had a two-month history of fever and fatigue. He had been receiving low dose MTX administration for about 2 years for rheumatoid arthritis. The blood chemistry findings showed elevated liver function including lactic dehydrogenase (LDH) levels. The quantified serum EBV-DNA level was 200 copies/105 peripheral blood mononuclear cells. Computed tomographic scan demonstrated splenomegaly and intraperitoneal mass lesions. One of the masses was biopsied. Some tumor cells showed a large Hodgkin cell-like appearance. These were CD3e-, CD20 +, CD30 +, CD15-, LMP1 +, EBNA2-, EBER-ISH + without imbalance of the kappa/lambda ratio. A diagnosis of MTX-associated B-lymphoproliferative disorder was made. Although the patient's fever subsided and the serum LDH levels were normalized after withdrawal of the MTX, the masses showed almost no change. Therefore, we administered rituximab weekly for a total of four doses, resulting in normalization of the serum EBV-DNA load and serum CD4/CD8 ratio. The masses persisted, however, so we carried out eight courses of R-CHOP therapy, which induced complete response without any episode of serious infection.

[Early onset invasive pulmonary zygomycosis following allogeneic peripheral blood stem cell transplantation in a patient with therapy-related myelodysplastic syndrome].

A 39-year-old woman received an allogeneic peripheral blood stem cell transplantation from her daughter for secondary myelodysplastic syndrome. On day +12, a cough and fever developed. Chest X-ray and computed tomography demonstrated a consolidation in the left lung. A diagnosis of pulmonary zygomycosis was made on the histology from a transbronchial lung biopsy. Although amphotericin B (AMPH-B) showed efficacy, dose reduction was necessary because of renal toxicity. The patient died of pulmonary zygomycosis, confirmed by an autopsy. We strongly hope for authorization as soon as possible of the use of such a drug as liposomal AMPH-B which appears less toxic.

A case of latent primary biliary cirrhosis.

A 53-year-old housewife was the donor when living-related donor liver transplantation (LRLT) was performed in her younger sister (49-year-old) with terminal primary biliary cirrhosis (PBC). The donor's liver histology was diagnostic and compatible with PBC, although she was negative for antimitochondrial antibody (AMA: a specific marker of PBC) by immunofluorescence and had normal liver function tests as well as no symptoms of liver disease. In this patient with latent PBC, AMA was eventually detected by immunoblotting, although it was not detected by ELISA. These findings indicate that a family history of PBC is a risk factor for the development of this disease. Our patient was diagnosed before the advent of any clinical or biochemical indicators and before or at the onset of AMA positivity, so her liver histology revealed the earliest stage of PBC.

Ternary complex factor SAP-1 is required for Erk-mediated thymocyte positive selection.

Thymocyte selection and differentiation requires extracellular signal-regulated kinase (Erk) signaling, but transcription factor substrates of Erk in thymocytes are unknown. We have characterized the function of SAP-1 (Elk4), an Erk-regulated transcription factor, in thymocyte development. Early thymocyte development was normal, but single-positive thymocyte and peripheral T cell numbers were reduced, reflecting a T cell-autonomous defect. T cell receptor-induced activation of SAP-1 target genes such as Egr1 was substantially impaired in double-positive thymocytes, although Erk activation was normal. Analysis of T cell receptor transgenes showed that positive selection was reduced by 80-90% in SAP-1-deficient mice; heterozygous mice showed a moderate defect. Negative selection was unimpaired. SAP-1 thus directly links Erk signaling to the transcriptional events required for thymocyte positive selection.