Descemet Membrane Endothelial Keratoplasty in Aphakic, Aniridic, and Vitrectomized Eyes: A Review.

PURPOSE: The aim of this review is to examine the techniques, complications, and outcomes of Descemet membrane endothelial keratoplasty (DMEK) in aphakic, aniridic, and vitrectomized eyes. METHODS: A literature search was conducted in the MEDLINE database (via PubMed), using as keywords "(DMEK) AND (aphakia OR aniridia OR vitrectomy OR vitrectomized)." The research was limited to 10 years (January 2014-March 2024), in view of lack of literature before 2014. Articles, including case reports and case series, were included. RESULTS: Twenty articles were included. No randomized controlled trials were found nor comparative studies with more than 1 technique used. Mean rebubbling rate in complex eyes was 29%, whereas mean endothelial cell loss at 6 months was 37%. The mean postoperative visual acuity improved from 1.47 logarithm of the minimal angle of resolution to 0.7 logarithm of the minimal angle of resolution. CONCLUSIONS: Despite being more challenging, compared with the techniques reported in literature, DMEK can be considered a valid option for the management of endothelial decompensation in complex eyes, with rebubbling rate and endothelial cell loss at 6 months, which are similar to non-complex eyes.

Importance of Higher-Order Aberrations on Both Anterior and Posterior Surfaces After Pterygium Surgery.

PURPOSE: The purpose of this study was to investigate the changes in higher-order aberrations (HOAs), coma, and spherical aberrations (SAs) on the anterior, posterior, and total corneal surfaces after pterygium excision. METHODS: In this single-center study, we examined 19 eyes of 15 patients who underwent pterygium excision at Yokohama Minami Kyosai Hospital between January 2017 and December 2017. We also evaluated 25 eyes of 25 age-matched patients with no history of ocular disease as the control group. Corneal topography, total HOAs, coma, and SAs in all regions at 4 and 6 mm diameters were evaluated using anterior segment optical coherence tomography (CASIA SS-1000, Tomey, Japan). The pterygium area and extent were also assessed. RESULTS: Significant improvements in the HOAs, coma, and SAs at both diameters were observed in the total and anterior corneas from the first postoperative month. Notably, the posterior cornea showed significant improvements in HOAs (4 mm: P < 0.001 [log HOAs]; 6 mm: P = 0.001 [log HOAs]) and coma (4 mm: P = 0.003 [log coma], 6 mm: P = 0.002 [log coma]) within both diameters at 1 month postoperatively. A strong correlation was identified among the pterygium area, posterior HOAs, and coma (Spearman correlation = 0.651). Pterygium induced 2 D of astigmatism when extension exceeded 2.1 mm. CONCLUSIONS: HOAs in both the anterior and posterior corneas improved after pterygium excision. This finding underscores the importance of considering corneal aberrations on both anterior and posterior surfaces in pterygium management.

Application of Hilbert-Differential Phase Contrast to Scanning Transmission Electron Microscopy.

We report a novel class of scanning transmission electron microscopy with Hilbert-differential phase contrast (HDP-STEM) that displays nanostructures of thin samples in a topographical manner. A semicircular π phase plate (PP) was used as an optical device for manipulating electron waves in HDP-STEM. This is the different design from the Zernike PP used in our previous phase plate STEM (P-STEM), but both must be placed in the front focal plane of the condenser lens. HDP-STEM images of multi-walled carbon nanotubes showed higher contrast than those obtained by conventional bright-field STEM. Since the PP of the HDP-STEM is nonsymmetrical, several different images were obtained by changing the detection conditions. A two-dimensional electron detector was also used to remove the scattering contrast component in the same way as with the Zernike PP and obtain an image containing only (differential) phase contrast.

Double-Bubble Technique Assisted by Holding Forceps: A Modified Technique in Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes With Scleral Fixated Intraocular Lens.

PURPOSE: Several techniques have been developed for graft unfolding approaches in Descemet membrane endothelial keratoplasty (DMEK). However, despite these techniques, graft deployment and configuration in eyes with deep anterior chambers remain challenging in some cases. Therefore, in this study, we described a modified technique for DMEK, known as the "double-bubble technique assisted by holding forceps." METHODS: This was a retrospective interventional case series. Patients who underwent DMEK between August 2022 and July 2023, including cases with a history of vitrectomy and scleral fixation of intraocular lens, were enrolled in this study. Two experienced surgeons performed DMEK. In brief, after graft insertion into the anterior chamber, the first bubble with a small volume of air was injected above the graft to open the tight roll, and the graft edge was held using a 25-gauge graft manipulator. The second bubble was injected underneath the graft for fixation, while the graft edge was grasped using forceps during gas injection. The graft was released from the forceps. Best spectacle corrected visual acuity, central corneal thickness, endothelial cell density, and incidence of postoperative complications were measured before and after DMEK. RESULTS: Eleven eyes of 11 patients were included in this study (mean follow-up period, 4.5 ± 4.4 months). Best spectacle corrected visual acuity and central corneal thickness significantly improved postoperatively ( P < 0.001). Rebubbling was required in 2 eyes; no other postoperative complications or primary graft failure were observed. CONCLUSIONS: The present technique enables safe and feasible DMEK surgery in vitrectomized eyes with scleral fixated IOLs and in those with a deep anterior chamber.

Descemet Membrane Endothelial Keratoplasty in Corneal Endothelial Decompensation After a Forceps-Induced Corneal Birth Injury: Case Series and Technique.

PURPOSE: The aim of this study was to describe the efficacy of Descemet membrane endothelial keratoplasty (DMEK) in patients with corneal endothelial decompensation secondary to a forceps-induced corneal birth injury. METHODS: This was a retrospective, noncomparative, interventional case series. Four eyes of 4 patients (1 female and 3 males; mean age, 64.0 ± 4.7 years) with corneal endothelial decompensation due to forceps-induced corneal birth injury were included. DMEK was performed in all cases, using a combined technique, including the use of intraoperative optical coherence tomography, vital staining of Descemet membrane of both host and donor, removal of scarred Descemet membrane with side-port forceps and vitreous cutter to smoothen the posterior corneal surface, epithelial peeling, and illumination for visualization. The examination included preoperative and postoperative ophthalmologic examinations: best-corrected visual acuity (converted to logarithm of the minimum angle of resolution [logMAR]), intraocular pressure, endothelial cell density (ECD), and central corneal thickness. RESULTS: No postoperative complications were noted, and corneal transparency was maintained during follow-up (mean follow-up period, 32.0 ± 27.0 months; range, 3-71 months). The mean best-corrected visual acuity was 0.52 ± 0.35 logMAR preoperatively and 0.15 ± 0.09 logMAR at the last visit. The mean postoperative ECD was 1632 ± 631 cells/mm2 (mean ECD at baseline, 3167 cells/mm2). Central corneal thickness decreased from 640 ± 67 µm preoperatively to 576 ± 58 µm postoperatively. CONCLUSIONS: This study suggests that DMEK can be performed uneventfully in eyes with a forceps-induced corneal birth injury. The combination of surgical techniques may be an effective approach for DMEK.

Efficacy of Gefapixant, a P2X3 Antagonist, for Refractory Atopic Cough.

Cough, a frequent symptom encountered in clinical practice, often has a considerable impact on patients' lives. There is an urgent need to investigate more potent antitussive treatments for chronic refractory cough, particularly atopic cough, which is a major cause of chronic refractory cough in Japan. Previous studies have shown that eosinophilic tracheobronchitis with hypersensitivity to sensory nerve C-fibers is the pathophysiology of atopic cough. Gefapixant is a first-in-class P2X3 antagonist that has recently become available for clinical use in patients with refractory coughs. A 64-year-old female non-smoker presented to our hospital with a complaint of chronic intractable cough due to atopic cough. Addition of gefapixant (90 mg/day) to her previous treatment improved her distressing cough, despite the partial efficacy of many other drugs. The findings of this case demonstrate that P2X3 inhibition is a viable therapeutic option for patients with chronic refractory cough caused by atopic cough. This case report offers valuable information regarding currently available treatment options for refractory chronic refractory cough caused by atopic cough. There remains an urgent need to clarify the disease entities presenting with chronic cough that can be effectively treated by inhibiting P2X3.

Association of High Mobility Group Box-Protein 1 and Platelet Microparticles in Patients After Hematopoietic Stem Cell Transplantation.

Thrombotic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly impact transplant outcomes. We focused on high mobility group box-protein (HMGB)1, one causative agent of thrombotic lesions in allo-HSCT, and investigated its association with platelets. We statistically analyzed available data from 172 patients with hematopoietic malignancies receiving allo-HSCT. A significant enhancement of monocyte-chemotactant protein-1, HMGB1, and platelet-derived microparticle (PDMP) levels was observed at day 0 after transplantation as compared to pre-transplantation. Multivariate analysis of the association among HMGB1 and 16 factors on day 0 revealed a significant correlation of HMGB1 levels with thrombin-antithrombin complex, interleukin-6, and PDMPs. High mobility group box-protein 1-induced procoagulant platelet induction and PDMP generation were performed in vitro using healthy platelets. High mobility group box-protein 1-induced PDMP generation was suppressed by toll-like receptor inhibitors and recombinant thrombomodulin. These results suggest that HMGB1 contributes to platelet activation in patients after allo-HSCT and is associated with PDMP-related thrombotic complications.

Efficacy of gefapixant, a P2X3 antagonist, for lung cancer-related cough: a case report.

Cough is a frequent symptom accompanied by lung cancer. More potent antitussive treatment for this complex and distressing symptom is required, but anti-cancer chemotherapy cannot fully manage the cough. Inhibition of vagal nerves might control coughing in patients with troublesome lung cancer-related cough and P2X3 inhibitory therapy may be useful for targeting neuronal function. We report the case of a woman in her late 70s who never smoked and had advanced lung cancer. She visited our hospital complaining of serious deterioration of a non-productive cough. She was diagnosed with relapse of lung cancer, but she requested 2-week anti-tussive therapy before second-line chemotherapy. Gefapixant (P2X3 antagonist) add-on at a dose of 90 mg/day (45 mg twice daily as the usual dosage in Japan) improved her cough as indicated by an improvement in the visual analog scale for cough from 70 to 20 mm and in the Japanese version of the Leicester Cough Questionnaire from 8.2 to 16.3, despite a deterioration in lung cancer after 2 weeks. There are no current guidelines for cough accompanied by lung cancer; however, our findings suggest that P2X3 inhibition is a potent therapeutic option for lung cancer-related cough.

Incidence of Graft Rejection in Descemet Membrane Endothelial Keratoplasty After COVID-19 mRNA Vaccination.

PURPOSE: The aim of this study was to investigate the Descemet membrane endothelial keratoplasty (DMEK) rejection rate after COVID-19 vaccination with an mRNA vaccine. METHODS: This was a multicenter, retrospective cohort study. A total of 198 patients who underwent DMEK between January 2006 and December 2020 were divided into 2 cohorts: consecutive patients who received at least 1 COVID-19 vaccination in 2021 (vaccination started from February 2021 in Japan) and nonvaccinated patients (control cohort). Patients who had a postoperative observation period of less than 90 days were excluded. The main outcome measurement was the incidence of graft rejection. A Cox proportional hazards regression model was used for comparisons with the nonvaccinated group. RESULTS: Six rejection episodes were observed in 198 patients (124 nonvaccinated and 74 vaccinated patients), with 1 occurring in the nonvaccinated group and 5 in the vaccinated group. In the univariate model, vaccination had a significant effect on rejection episodes ( P = 0.003). The effect of vaccination was also significant ( P = 0.004) after adjusting for covariates. CONCLUSIONS: This study suggests that there may be a higher rejection rate after COVID-19 vaccination in patients who underwent DMEK. Patients should be warned of the rejection risk and its typical symptoms before receiving an mRNA COVID-19 vaccine, although further larger studies are needed to confirm the involvement of vaccination.

A Comparison of the Corneal Thickness Following Descemet's Stripping Automated Endothelial Keratoplasty and Descemet's Membrane Endothelial Keratoplasty.

PURPOSE: To compare the central corneal thickness before and after Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK), and to evaluate the recipient corneal thickness following DSAEK. METHODS: The corneal thickness was compared between two groups of eyes following DMEK and DSAEK, performed by a single surgeon between 2015 and 2017. We evaluated the recipient corneal thickness and central corneal thickness pre- and postoperatively at 1, 3, and 6 months using anterior segment optical coherence tomography. Recipient corneal thickness was defined as the corneal thickness without graft thickness. RESULTS: We included DMEK and DSAEK eyes (n = 26 each), which were similar in terms of their etiologies. Preoperatively, there was no significant difference in the central corneal thickness between the groups (DSAEK, median [interquartile range]: 721 [606.5 to 847.8] µm; and DMEK: 690 [618 to 722.3] µm; p = 0.30). Despite the tendency of the central corneal thickness to be significantly greater (p < .01) at 6 months following DSAEK (619.5 [607.8 to 661.3] µm) compared with that following DMEK (497.5 [475.8 to 525.3] µm), there was no significant difference at 6 months between the recipient corneal thickness following DSAEK (488.5 [443.8 to 515] µm) and central corneal thickness following DMEK (p = 0.54). CONCLUSIONS: DSAEK eyes display a similar tendency of stromal thinning as DMEK eyes.

Alectinib in a patient with ALK-positive non-small lung cancer unable to swallow capsules.

INTRODUCTION: The treatment landscape of metastatic non-small-cell lung cancer (NSCLC) has changed dramatically in the last decade. Anaplastic lymphoma kinase (ALK) rearrangement has been a focus of interest since ALK inhibitors produced outstanding clinical results compared with chemotherapy with cytotoxic agents in patients with ALK-positive NSCLC. CASE REPORT: We present the case of a 56-year-old woman with metastatic ALK-positive NSCLC and an inability to swallow capsules or tablets. Unfortunately, all ALK inhibitors are capsule or tablet formulations. MANAGEMENT AND OUTCOME: We, therefore, decided to administer alectinib orally by opening the capsules and suspending the contents in water. Clinical imaging performed 12 months after initiating alectinib therapy indicated a complete response (CR). After 54 months of follow-up, CR has been maintained, and oral alectinib therapy has continued with no recurrence of the swallowing disturbance. DISCUSSION: There are no current guidelines for oral targeted therapy in patients with swallowing disturbance, but alectinib administered orally by opening the capsules and suspending the contents in water can be a treatment option in patients with ALK-positive NSCLC and swallowing difficulty.

Risk factors for intraocular pressure elevation following Descemet membrane endothelial keratoplasty in Asian patients.

PURPOSE: To investigate risk factors for increased intraocular pressure (IOP) after Descemet membrane endothelial keratoplasty (DMEK) in Asian patients. METHODS: Data from January 2015 to February 2021 were obtained from our prospective database. IOP elevation after DMEK was defined as IOP ≥ 22 mmHg or an increase in IOP of ≥ 10 mmHg from baseline. In addition, we examined maximum IOP. Using iCare, we measured IOP 1, 2, 3, and 6 months after DMEK, and every 6 months thereafter. Logistic regression and linear regression were performed to find factors predictive of IOP elevation and maximum IOP, respectively, based on the results of univariate analysis. RESULTS: We enrolled 90 eyes (mean patient age, 74.9 ± 7.5 years; mean follow-up duration, 25.6 ± 9.9 months) that underwent DMEK. IOP elevation was present in 19 eyes (21%). IOP increased from 12.6 ± 3.9 mmHg preoperatively to a postoperative maximum of 17.0 ± 5.5 mmHg up to 36 months after DMEK (p < 0.0001). In univariate logistic regression analysis for IOP elevation, only one variable, pseudoexfoliation syndrome (PEX) and preexisting glaucoma, was significant (p < 0.05). Preexisting glaucoma without PEX (OR, 19.33; 95% CI, 4.75-93.46), PEX without glaucoma (OR, 7.25; 95% CI, 1.20-41.63), and PEX glaucoma (OR, 58.00; 95% CI, 6.78-1298.29) were associated with higher risk of IOP elevation. CONCLUSIONS: In this cohort, the eyes of patients with PEX and preexisting glaucoma were found to be prone to IOP elevation after DMEK.

Atomically Precise Incorporation of BN-Doped Rubicene into Graphene Nanoribbons.

Substituting heteroatoms and non-benzenoid carbons into nanographene structure offers a unique opportunity for atomic engineering of electronic properties. Here we show the bottom-up synthesis of graphene nanoribbons (GNRs) with embedded fused BN-doped rubicene components on a Au(111) surface using on-surface chemistry. Structural and electronic properties of the BN-GNRs are characterized by scanning tunneling microscopy (STM) and atomic force microscopy (AFM) with CO-terminated tips supported by numerical calculations. The periodic incorporation of BN heteroatoms in the GNR leads to an increase of the electronic band gap as compared to its undoped counterpart. This opens avenues for the rational design of semiconducting GNRs with optoelectronic properties.

Tiotropium Add-On and Treatable Traits in Asthma-COPD Overlap: A Real-World Pilot Study.

Purpose: The 'treatable traits' strategy for patients with chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD), is a focus of interest, because it implements precision and personalized medicine. Asthma-COPD overlap (ACO), a phenotype involving both asthma and COPD, is an important disease entity because patients with ACO have significantly worse outcomes, conferring greater economical and social burdens. Some guidelines for ACO recommend add-on therapy of long-acting muscarinic antagonists to inhaled corticosteroids and long-acting ß2 agonists. However, this approach is based on extrapolation from patients with asthma or COPD alone. Consequently, a 'treatable traits' approach suitable for ACO remains obscure. Methods: A 12-week open-label cross-over pilot study was conducted in patients with ACO to investigate the effect of tiotropium bromide (TIO) 5 µg/day add-on therapy to fluticasone propionate/formoterol fumarate (FP/FM) 500/20 µg/day compared with FP/FM 500/20 µg/day alone. A 4-week run-in period and two 4-week treatment periods were included. Results: A total of 18 male patients with stable ACO participated in this pilot study. All patients were ex-smokers. Mean values ± standard deviation (SD) for forced expiratory volume in 1 second (FEV1) were 1.21 ± 0.49 L after the run-in period, 1.20 ± 0.51 L after the FP/FM combination therapy period, and 1.30 ± 0.48 L after the TIO add-on therapy to FP/FM period. FEV1 values after the TIO add-on therapy FP/FM period were significantly higher than those after the run-in period (p < 0.01). Conclusion: TIO add-on therapy to FP/FM in patients with ACO, considered difficult to treat because of the presence of both asthma and COPD, resulted in improvements in lung function parameters in this real-world pilot study, indicating the potential value of TIO add-on therapy as a "treatable traits" option for standard treatment for ACO.

Time-Resolved Imaging of Stochastic Cascade Reactions over a Submillisecond to Second Time Range at the Angstrom Level.

Many chemical reactions, such as multistep catalytic cycles, are cascade reactions in which a series of transient intermediates appear and disappear stochastically over an extended period. The mechanisms of such reactions are challenging to study, even in ultrafast pump-probe experiments. The dimerization of a van der Waals dimer of [60]fullerene producing a short carbon nanotube is a typical cascade reaction and is probably the most frequently studied in carbon materials chemistry. As many as 23 intermediates were predicted by theory, but only the first stable one has been verified experimentally. With the aid of fast electron microscopy, we obtained cinematographic recordings of individual molecules at a maximum frame rate of 1600 frames per second. Using Chambolle total variation algorithm processing and automated cross-correlation image matching analysis, we report on the identification of several metastable intermediates by their shape and size. Although the reaction events occurred stochastically, varying the lifetime of each intermediate accordingly, the average lifetime for each intermediate structure could be obtained from statistical analysis of many cinematographic images for the cascade reaction. Among the shortest-living intermediates, we detected one that lasted less than 3 ms in three independent cascade reactions. We anticipate that the rapid technological development of microscopy and image processing will soon initiate an era of cinematographic studies of chemical reactions and cinematic chemistry.

Evaluation of corneal nerves and dendritic cells by in vivo confocal microscopy after Descemet's membrane keratoplasty for bullous keratopathy.

This study evaluated changes in corneal nerves and the number of dendritic cells (DCs) in corneal basal epithelium following Descemet membrane endothelial keratoplasty (DMEK) surgery for bullous keratopathy (BK). Twenty-three eyes from 16 consecutive patients that underwent DMEK for BK were included. Eyes of age-matched patients that underwent pre-cataract surgery (12 eyes) were used as controls. In vivo confocal microscopy was performed pre- and postoperatively at 6, 12, and 24 months. Corneal nerve length, corneal nerve trunks, number of branches, and the number of DCs were determined. The total corneal nerve length of 1634.7 ± 1389.1 µm/mm2 before surgery was significantly increased in a time-dependent manner to 4485.8 ± 1403.7 µm/mm2, 6949.5 ± 1477.1 µm/mm2, and 9389.2 ± 2302.2 µm/mm2 at 6, 12, and 24 months after DMEK surgery, respectively. The DC density in BK cornea pre- and postoperatively at 6 months was significantly higher than in the controls, and decreased postoperatively at 12 and 24 months and was significantly lower than that at 6 months postoperatively. Thus, our results suggest that DMEK can repair and normalize the corneal environment.

Expression profiles and functional characterization of common carp (Cyprinus carpio) T2Rs.

Bitter taste perception is mediated by a family of G protein-coupled receptors (T2Rs) in vertebrates. Common carp (Cyprinus carpio), which has experienced an additional round of whole genome duplication during the course of evolution, has a small number of T2R genes similar to zebrafish, a closely related cyprinid fish species, and their expression pattern at the cellular level or their cognate ligands have not been elucidated yet. Here, we showed through in situ hybridization experiments, that three common carp T2R (ccT2R) genes encoding ccT2R200-1, ccT2R202-1, and ccT2R202-2, were specifically expressed in the subsets of taste receptor cells in the lips and gill rakers. ccT2R200-1 was co-expressed with genes encoding downstream signal transduction molecules, such as PLC-ß2 and Gαia. Heterologous expression system revealed that each ccT2R showed narrowly, intermediately, or broadly tuned ligand specificity, as in the case of zebrafish T2Rs. However, ccT2Rs showed different ligand profiles from their orthologous zebrafish T2Rs previously reported. Finally, we identified three ccT2Rs, namely ccT2R200-1, ccT2R200-2, and ccT2R203-1, to be activated by natural bitter compounds, andrographolide and/or picrotoxinin, which elicited no response to zebrafish T2Rs, in a dose-dependent manner. These results suggest that some ccT2Rs may have evolved to function in the oral cavity as taste receptors for natural bitter compounds found in the habitats in a species-specific manner.

Aqueous humour cytokine profiles after Descemet's membrane endothelial keratoplasty.

The aim of this study was to compare aqueous humour (AqH) cytokine profiles before and after Descemet's membrane endothelial keratoplasty (DMEK) in eyes with bullous keratopathy (BK) and age-matched normal eyes. A total of 49 participants (mean age 75.0 ± 13.5 years) were divided into three groups: (1) BK patients scheduled for DMEK (BK group); (2) patients after DMEK (DMEK group; average postoperative time 1,018 ± 460 days); and (3) control participants without corneal endothelial disease scheduled for cataract surgery (control group). AqH (0.2 mL) was collected from all participants, and the levels of various AqH cytokines were simultaneously measured using a multiplex bead immunoassay. The DMEK group exhibited significantly lower concentrations of several pro-inflammatory cytokines, such as IL-1ß, IL-5, IL-6, IL-10, and IL-8, and granulocyte colony stimulating factor than the BK group. In addition, the levels of IL-1ß and IL-5 were significantly lower in the DMEK group than in the control group. The AqH levels of several pro-inflammatory cytokines were significantly reduced after DMEK, indicating that regeneration of the endothelial pump owing to the transplantation of a healthy endothelium might have a positive effect on anterior chamber inflammation.

A Single-Center Retrospective Observational Study Evaluating the Favorable Predictive Factors for the Disease Control Time of Treatment with Tocilizumab in Patients of Rheumatoid Arthritis.

BACKGROUND: Tocilizumab (TCZ) is humanized monoclonal antibody against the interleukin-6 (IL-6) and receptor that has prominent efficacy for the treatment of rheumatoid arthritis (RA). We conducted a retrospective observational study to determine how long TCZ controls RA. PATIENTS AND METHODS: We retrospectively reviewed the medical records of RA patients treated with TCZ. The aim of this study was to evaluate the contribution of clinical parameters to disease control time (DCT) in RA patients. RESULTS: Overall, 144 patients were enrolled in the study. The median age of patients was 66 years (range: 34-85 years). In univariate analysis, DCT was significantly increased in patients who had never received previous biologic disease-modifying anti-rheumatic drugs treatment (P = 0.0064). We also analyzed the contribution of the base line value of C-reactive protein (CRP) to DCT. We divided the patients with RA into two groups according to a cutoff value of 1.000 mg/dl. The median control times were 77.5 months (95% confidence interval [CI]: 44.8-not reached to median) and 34.5 months (95% CI: 17.0-79.3) for patients with high and low CRP value, respectively. In univariate analysis, DCT was significantly increased in patients with a high CRP value (P = 0.0283). Multivariate analysis clearly revealed that a high baseline CRP value was an independent favorable predictive factor for longer DCT (hazard ratio, 0.608, 95% CI: 0.378-0.981, P = 0.0416). CONCLUSION: These data clearly demonstrate that the baseline value of CRP was closely associated with long time DCT in patients of RA treated with TCZ.