Association of non-steroidal anti-inflammatory drug use with encephalopathy development: An analysis using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

POST-COVID-19 INFLAMMATORY RHEUMATOID ARTHRITIS REMISSION.

People infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are at a higher risk of developing autoimmune inflammatory rheumatic disease. However, clinical studies have shown that, unlike bacterial infections, inflammatory rheumatoid arthritis is rarely triggered by viral infections. Generally, adult females have a higher incidence of rheumatoid arthritis compared to males (a female/male ratio of approximately 3:1). The secretion of female hormones is presumed to be deeply involved in the onset of rheumatoid arthritis. Furthermore, there is a definitive role of genetic factors in rheumatoid arthritis. Typically, rheumatoid arthritis is treated with steroids and antibody drugs, such as anti-tumor necrosis factor-α (TNF-α) antibodies and anti-interleukin-6 (IL-6) antibodies; however, although the symptoms of autoimmune diseases are alleviated by these drugs, the underlying pathology cannot be completely cured. Meanwhile, immunosuppressive treatment with steroids is effective against inflammatory rheumatoid arthritis associated with coronavirus disease (COVID-19). Therefore, the pathogenesis, symptoms, and pathological findings of inflammatory rheumatoid arthritis associated with COVID-19 are presumably different from those of autoimmune rheumatoid arthritis. Since COVID-19-related autoimmune-like diseases, such as COVID-19-related inflammatory rheumatoid arthritis, have pathological conditions that are different from inherited autoimmune diseases, it is possible to establish treatments that aim at remission. Further pathological analyses of patients with post-COVID-19 inflammatory rheumatoid arthritis are essential to the development of treatments for this type of arthritis.

EFFECT OF RBD MUTATIONS IN SPIKE GLYCOPROTEIN OF SARS-COV-2 ON NEUTRALIZING IGG AFFINITY.

Certain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subvariants (B.1.1.7, B.1.351, and B.1.1.248) and omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants. We investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F, N501Y or the mutants of RBD of omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants on neutralizing antibodies in serum derived from individuals including children (aged 5-11 years) inoculated with mRNA based COVID-19 vaccine (BNT162b2: Pfizer/BioNTech) or COVID-19-positive patients or children (aged 5-11 years) after vaccination with BNT162b2. Our results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients. The significantly low antibody titer of children against Omicron type SARS-CoV-2 BQ.1.1 subvariant and XBB.1.16 subvariant in Japan. Infection with SARS-CoV-2 subspecies that causes serious symptoms in humans may spread globally. In particular, since the antibody titer against the omicron type is low in children (aged 5-11 years) who have been vaccinated with conventional vaccines, therefore it is important for children to receive vaccines specific for the omicron type.

POTENTIAL LIFE PROGNOSTIC MARKER FOR MESENCHYMAL TUMOR RESEMBLING UTERINE LEIOMYOSARCOMA.

Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), both uterine mesenchymal tumors, are distinguished by the number of cells exhibiting mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiating between benign and malignant tumors, is difficult. For example, cotyledonoid dissecting leiomyoma (CDL) or uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which a differential diagnosis is challenging. To date, a standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of CDL or STUMP in the differential diagnosis have not been defined. Several clinical studies have reported that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The immunohistochemical biomarkers reported so far cannot effectively help determine the malignant potential of CDL or STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by using next-generation molecular techniques can facilitate disease prediction, diagnosis, treatment, and prognosis. We examined the oncological properties of STUMP in adults using molecular pathological techniques on tissue excised from patients with uterine mesenchymal tumor. In a clinical study conducted by our medical team, the results of gene expression profiling indicated factors that may be associated with malignancy of uterine mesenchymal tumors. We herein describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies. It is expected that the establishment of a diagnostic method targeting the characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Measurements of Strong-Interaction Effects in Kaonic-Helium Isotopes at Sub-eV Precision with X-Ray Microcalorimeters.

We have measured the 3d→2p transition x rays of kaonic ^{3}He and ^{4}He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic ^{3}He and ^{4}He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.

Influence of using history of immune checkpoint inhibitor therapy for neutropenia caused by combination therapy of ramucirumab and docetaxel.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

Genetic characterization of Shigatoxigenic and enteropathogenic Escherichia coli O80:H2 from diarrhoeic and septicaemic calves and relatedness to human Shigatoxigenic E. coli O80:H2.

AIM: The purpose of this work was to identify and genetically characterize enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) O80:H2 from diarrhoeic and septicaemic calves in Belgium and to comparing them with human EHEC after whole genome sequencing. METHODS AND RESULTS: Ten EHEC and 21 EPEC O80 identified by PCR between 2009 and 2018 from faeces, intestinal content and a kidney of diarrhoeic or septicaemic calves were genome sequenced and compared to 19 human EHEC identified between 2008 and 2019. They all belonged to the O80:H2 serotype and ST301, harboured the eaeξ gene, and 23 of the 29 EHEC contained the stx2d gene. Phylogenetically, they were distributed in two major sub-lineages: one comprised a majority of bovine EPEC whereas the second one comprised a majority of stx2d bovine and human EHEC. CONCLUSIONS: Not only EPEC but also EHEC O80:H2 are present in diarrhoeic and septicaemic calves in Belgium and are genetically related to human EHEC. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings support the need to assess cattle as potential source of contamination of humans by EHEC O80:H2 and to understand the evolution of bovine and human EHEC and EPEC O80:H2.

Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.

BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients.

BACKGROUND: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. PATIENTS AND METHODS: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. RESULTS: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). CONCLUSIONS: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

Quantum Criticality inside the Anomalous Metallic State of a Disordered Superconducting Thin Film.

The field-induced superconductor-insulator transition (SIT) in two-dimensional (2D) systems is a famous example of a quantum phase transition. However, an emergence of an anomalous metallic state induced by field has been a long-standing problem in 2D superconductors. While theories predicted that the emergence is attributed to strong phase fluctuations of the superconducting order parameter due to quantum fluctuations, usual resistance measurements have not probed them directly. Here, using Nernst effect measurements, we uncover superconducting fluctuations in the vicinity of the field-induced metallic state in an amorphous Mo_{x}Ge_{1-x} thin film. The field range where the vortex Nernst signals are detectable remains nonzero toward zero temperature, and it locates inside the metallic state defined by the magnetoresistance, indicating that the metallic state results from quantum vortex liquid (QVL) with phase fluctuations due to quantum fluctuations. Slow decay of transport entropy of vortices in the QVL with decreasing temperature suggests that the metallic state originates from broadening of a quantum critical point in SIT.

Energy of the

The low-lying isomeric state of ^{229}Th provides unique opportunities for high-resolution laser spectroscopy of the atomic nucleus. We determine the energy of this isomeric state by taking the absolute energy difference between the excitation energy required to populate the 29.2-keV state from the ground state and the energy emitted in its decay to the isomeric excited state. A transition-edge sensor microcalorimeter was used to measure the absolute energy of the 29.2-keV γ ray. Together with the cross-band transition energy (29.2 keV→ground) and the branching ratio of the 29.2-keV state measured in a recent study, the isomer energy was determined to be 8.30±0.92 eV. Our result is in agreement with the latest measurements based on different experimental techniques, which further confirms that the isomeric state of ^{229}Th is in the laser-accessible vacuum ultraviolet range.

Non-invasive three-dimensional bone-vessel image fusion using black bone MRI based on FIESTA-C.

AIM: To evaluate the image quality of bone-vessel fused volume-rendering (VR) images reconstructed by three-dimensional "black bone" magnetic resonance imaging (MRI) based on the fast imaging employing steady-state acquisition cycled phases (FIESTA-C) sequence and time-of-flight magnetic resonance angiography (TOF-MRA). MATERIALS AND METHODS: Seventeen patients were analysed in this retrospective study. All patients underwent both MRI techniques including FIESTA-C and TOF-MRA and computed tomography angiography (CTA). MRI- and CT-based bone-vessel VR images were reconstructed. Visual depictions of frontal and parietal branches from the superficial temporal artery (STA) were independently scored by three experienced radiological technologists using a four-grade system. RESULTS: In the visual evaluation, the scores of the both right and left frontal branches in MRI-based VR image were significantly larger those at CT (p<0.01, respectively). The scores of both the right and left parietal branches tended to be larger in MRI-based than that in CT-based VR imaging, but were not significantly so (p=0.06, 0.13 respectively). In the interobserver agreement analysis, κ values were all good (range: 0.6-0.76) for STA branch evaluation in MRI-based VR images. CONCLUSION: MRI bone-vessel fused VR imaging can non-invasively depict STA frontal branches with better visibility compared to the CT-based VR imaging. This technique may be useful for the preoperative evaluation of donor branches for STA-middle cerebral artery bypass surgery.

Correction to: Development of micro mechanical device having two-dimensional array of micro chambers for cell stretching.

The original article has been corrected. Instances of the character "µ" should be replaced by the term "micro".

Development of micro mechanical device having two-dimensional array of micro chambers for cell stretching.

This paper presents a novel cell stretching micro device having two-dimensional array of micro chambers. It enables an in situ time-lapse observation of stretched cell by using an optical microscope with high measurement efficiency. The presented device consists of a cell culture dish and the array of micro chambers made of silicone elastomer and extension structures made of photocurable resin, and is fabricated with MEMS technology. The fabrication process of the thin micro chamber array combines photoresist mold and lift-off process based on conventional photolithography. The fabricated device has 134micro chambers in 5µm or less thickness. It was demonstrated that the fabricated micro device could be used to make in-situ time-lapse observation of cell responses to stretching under optical microscopy. In addition, the influence of the chamber thickness to the quality of the microscope image observed was evaluated. It is confirmed that the proposed device having two-dimensional array of the thin micro chambers makes it possible to observe cell response for stretch stimuli with high quality and efficiency.

Clinical pattern of primary systemic therapy and outcomes of estrogen receptor-positive, HER2-negative metastatic breast cancer: a review of a single institution.

PURPOSE: In the management of estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (ER+HER2-MBC) patients, endocrine therapy (ET) is preferred to chemotherapy (CT) as a primary systemic therapy (PST) when tumor burden is not high. However, there are no definite criteria for choosing a PST, transitioning from ET to CT or using maintenance ET subsequent to CT. METHODS: We reviewed the medical records of 311 ER+HER2-MBC patients who underwent CT from September 2002 to December 2016 and assessed their outcomes. RESULTS: Of the 311 patients, 178 (57%) received ET as a PST (ET-first group), and 133 (43%) received CT prior to ET (CT-first group). The ET-first group showed a median overall survival (OS) from the diagnosis of MBC (OSMBC) of 1593 days, and the median OS from the initiation of CT (OSCT) was 938 days. Patients with visceral involvement, liver metastasis, soft tissue metastasis, ≥3 organ involvement, or primary advanced BC at the MBC diagnosis showed a significantly higher tendency to be assigned to the CT-first group (P < 0.01 for any visceral involvement, P < 0.05 for all others). Maintenance ET was available in 74 (55.6%) patients in the CT-first group, who showed a significantly better OSMBC and OSCT than patients without maintenance ET (median OSMBC 1423 and 867 days, respectively, P < 0.0001; median OSCT 1350 and 637 days, respectively, P < 0.0001). CONCLUSION: Our findings suggest the possibility for changing the treatment paradigm of patients with ER+HER2-MBC, so a randomized prospective study is warranted to determine the optimum sequence of systemic therapies.

Influence of ABCB1 and ABCG2 polymorphisms on the antiemetic efficacy in patients with cancer receiving cisplatin-based chemotherapy: a TRIPLE pharmacogenomics study.

Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.

Der f 35: An MD-2-like house dust mite allergen that cross-reacts with Der f 2 and Pso o 2.

BACKGROUND: Dermatophagoides farinae is a source of airborne house dust mite (HDM) allergens. We elucidated IgE-reactive allergens from D. farinae by two-dimensional immunoblotting-based allergenome analysis, and identified one new allergen, named Der f 35, that possesses IgE-binding capacity comparable to that of Der f 2. The aim of this study was to clarify the allergenic capacity of new HDM allergen Der f 35. METHODS: We cloned der f 35 from D. farinae mRNA and produced recombinant Der f 35 in Escherichia coli. The IgE-binding capacity of Der f 35 and its cross-reactivity with group 2 allergens from D. farinae and Psoroptes ovis were determined by enzyme-linked immunosorbent assay (ELISA) and ELISA inhibition assays, respectively. RESULTS: The deduced amino acid sequence for der f 35, which possesses the MD-2-related lipid-recognition domain, showed higher identity with group 2 allergens from P. ovis (61.5%) and Blomia tropicalis (50.7%) than with Der f 2 (40.8%). Der f 35 showed IgE-binding frequencies of 77.5% (31/40) for the native form upon allergenome analysis and 51.4% (18/35) for recombinant structure by ELISA. Der f 35 showed cross-reactivity with Der f 2 and Pso o 2 in reaction with HDM-allergic patients' IgE by ELISA inhibition assay. CONCLUSION: Der f 35 is a candidate major allergen from D. farinae, which is more similar to group 2 allergens from sheep scab mite and storage mites. Der f 35 could be responsible for the cross-reactivity among group 2 mite allergens.

Risk factors for severe dysphagia in acute cervical spinal cord injury.

STUDY DESIGN: A retrospective, consecutive case series. OBJECTIVES: The relationship between dysphagia and acute cervical spinal cord injury (CSCI) has been recently reported; however, the cause and mechanism of dysphagia are still not well understood. No definitive factors have yet been established according to multivariate analysis. The objective is to elucidate the incidence and risk factors of dysphagia in patients with acute CSCI. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: A total of 298 patients with acute CSCI, who were evaluated for neurological impairment within 3 days after injury, were reviewed. CSCI patients with tube dependence due to obvious aspiration after injury were defined as having dysphagia. The factors postulated to increase the risk for dysphagia, including the patient's age, sex, American Spinal Injury Association (ASIA) impairment scale at 3 days after injury, level of injury, tracheostomy and operative treatment, were analyzed using a multiple logistic regression model. RESULTS: Of 298 patients, 21 were suffering from severe dysphagia after acute CSCI (7.0%). Of these 21 patients, 12 (57%) had CSCI at the C3-C4 level. Multivariable logistic regression analysis revealed that old age (>72 years), severe ASIA impairment scale (A or B) and presence of tracheostomy were significant risk factors of dysphagia. Level of injury ⩾C3-C4 was not a significant risk factor after adjustment for several potential confounders. CONCLUSION: The incidence of severe dysphagia associated with aspiration was 7%. Old age, severe paralysis and presence of tracheostomy may be the risk factors for dysphagia. The risk for dysphagia should be evaluated to prevent aspiration pneumonia.

Effects of orthotic therapeutic electrical stimulation in the treatment of patients with paresis associated with acute cervical spinal cord injury: a randomized control trial.

STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To determine the effects of orthotic therapeutic electrical stimulation (TES) on the hand in patients with paresis associated with acute cervical spinal cord injury. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: The study included patients treated for spinal cord injuries (Frankel classification, grades B and C) at our institution within 1 week post injury between May 2011 and December 2014. The patients were allocated randomly to TES and control groups at the time of admission and underwent TES+conventional training or conventional training alone, respectively. Both hands of each patient were treated in the same way. The primary outcome was total passive motion (TPM) of the fingers (degrees). The secondary outcomes were edema (cm) and the upper-extremity motor scores of the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI). After randomization, outcomes were assessed at 1 week, 1 month and 3 months post injury in both groups. RESULTS: Twenty-nine individuals were assessed at 3 months (15, TES; 14, control). There were no significant between-group differences for TPM of the fingers, edema and upper-extremity motor scores at 1 week, 1 month and 3 months after injury, although TPM of the fingers tended to be lower in the control group. CONCLUSIONS: It is unclear from the results of this study whether TES has a therapeutic effect on TPM, edema or the upper-extremity motor score of the ISNCSCI. The results of this study provide useful data for future meta-analyses.

Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study.

BACKGROUND: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). RESULTS: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). CONCLUSION: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. CLINICAL TRIAL REGISTRY IDENTIFIER: UMIN000004863.