Real-world status of treatment for lymphoid neoplasms developed during the course of myeloproliferative neoplasms in Japan.

OBJECTIVES: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study. METHODS: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma. RESULTS: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n = 8; essential thrombocythemia, n = 14; and primary myelofibrosis, n = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed (n = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy. CONCLUSION: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma.

Riboflavin compounds show NAD(P)H dependent quinone oxidoreductase-like quinone reducing activity.

NAD(P)H-dependent quinone oxidoreductase (NQO) is an essential enzyme in living organisms and cells protecting them from oxidative stress. NQO reduces coenzyme Q (CoQ) using NAD(P)H as an electron donor. In the present study, we searched for coenzyme Q10 reducing activity from fractions of gel filtration-fractionated rat liver homogenate. In addition to the large-molecular-weight fraction containing NQO, CoQ10 reducing activity was also detected in a low-molecular-weight fraction. Furthermore, dicumarol, a conventional inhibitor of NQO1 (DT diaphorase), did not inhibit the reduction but quercetin did, suggesting that the activity was not due to NQO1. After further purification, the NADH-dependent CoQ10-reducing compound was identified as riboflavin. Riboflavin is an active substituent of other flavin compounds such as FAD and FMN. These flavin compounds also reduced not only CoQ homologues but also vitamin K homologues in the presence of NADH. The mechanism was speculated to work as follows: NADH reduces flavin compounds to the corresponding reduced forms, and subsequently, the reduced flavin compounds immediately reduce bio-quinones. Furthermore, the flavin-NADH system reduces CoQ10 bound with saposin B, which is believed to function as a CoQ transfer protein in vivo. This flavin-dependent CoQ10 reduction, therefore, may function in aqueous phases such as the cell cytosol and bodily fluids.

Preoperative Computed Tomography of the Right Gastroepiploic Artery for Coronary Artery Bypass Grafting.

BACKGROUND: Grafting the right gastroepiploic artery (GEA) to the right coronary artery (RCA) is effective, but preoperative evaluation of arterial conduit availability has not been established. By comparing the midterm graft results, we aimed to assess the efficacy of preoperative evaluation of the GEA using computed tomography (CT).Methods and Results: We retrospectively examined patients who underwent isolated coronary artery bypass grafting surgery between April 2010 and December 2020, and those whose GEA was grafted to the RCA were selected: 55 patients were included in the study analysis. Postoperative evaluations were performed during the early phase, 1 year postoperatively, and at follow-up evaluations. The outer diameter of the proximal GEA was compared with the midterm graft patency grade on CT and patients were classified as Functional (Grade A) or Dysfunctional (Grades O or B). The proximal GEA outer diameters were significantly different between the Functional and Dysfunctional groups (P<0.001). Furthermore, multivariate Cox regression analysis revealed that this diameter was an independent predictor of graft functionality (P<0.001). Patients with outer proximal diameters larger than the cutoff value had superior graft results at 3 years postoperatively. The rate of freedom from a dysfunctional graft at 3 years postoperatively was 95.5% and 45.5% for the Larger and Smaller diameter subgroups, respectively (P<0.001). CONCLUSIONS: Preoperative evaluation of the outer diameter of the proximal GEA, excluding calcified GEA, using CT is a minimally invasive and useful method, and may improve midterm results of in-situ GEA grafting, even in severe stenotic lesions.

Between-day reliability and minimum detectable change of the Conventional Gait Model 2 and Plug-in Gait Model during running.

BACKGROUND: The Plug-in Gait model (PiG) is commonly used in 3D motion analysis but has limited reliability. Although an improved version of PiG has been developed, called the Conventional Gait Model 2 (CGM2), there is limited evidence on its between-day reliability for running. RESEARCH QUESTION: What is the between-day intraclass correlation coefficient (ICC3,k) and minimum detectable change (MDC) of lower limb kinematics and kinetics for CGM2 during running and does reliability differ between CGM2 and PiG. METHODS: Twenty-three healthy participants performed running at a comfortable speed in two identical test sessions at least 5 days apart. Lower limb kinematic and kinetic data in the three planes of motion were calculated using CGM2 and PiG. The ICC and MDC were calculated for the kinematic and kinetic parameters at initial contact and peak during the stance phase of running. RESULTS: CGM2 kinematics showed good-to-excellent reliability (ICC: 0.75-0.93), except for hip extension and ankle internal rotation, and less than 5° MDC (1.8°-4.9°) of the coronal and sagittal planes, except for hip extension. PiG showed poor-to-moderate reliability (ICC: -0.15 to 0.72) in the coronal and transverse planes and greater than 5° MDC (5.0°-21.8°), except for knee extension, adduction, and ankle dorsiflexion. CGM2 showed good-to-excellent reliability for peak kinetics (ICC: 0.75-0.97), except for hip internal rotation and knee extension. The ICC and MDC were higher for CGM2 than PiG, with significant differences in the coronal plane of the hip and knee joints and transverse plane of the hip joint in kinematics and in the sagittal and coronal plane of the hip and knee joints in kinetics. SIGNIFICANCE: The between-day reliability of CGM2 was mostly good to excellent for lower limb kinematics and kinetics during running. We believe that CGM2 can more accurately assess kinematic differences between the coronal and transverse planes than the PiG.

COVID-19 and Thrombosis: Clinical Aspects.

In coronavirus disease 2019 (COVID-19), thrombus formation is related to the pathogenesis of acute respiratory distress syndrome (ARDS) and the progression of clinical symptoms. Severe damage to vascular endothelial cells and the associated cytokine storm after SARS-CoV-2 infection cause thrombogenesis and contribute to the development of more severe and unique thromboses compared to other infectious diseases. Thromboses occur more often in critically ill patients. In addition to pulmonary thromboembolism (PE) and deep vein thrombosis, acute myocardial infarction, peripheral arterial thrombosis, and aortic thrombosis have also been reported. In PE, thrombi develop in both pulmonary arteries and alveolar capillaries. These, together with intraalveolar fibrin deposition, interfere with effective gaseous exchange in the lungs and exacerbate the clinical symptoms of ARDS in patients with COVID-19. Pharmacological thromboprophylaxis is recommended for all hospitalized patients to prevent both thrombosis and aggravation of ARDS, and other organ failures. Although the pediatric population is mostly asymptomatic or develops mild disease after SARS-CoV-2 infection, a new inflammatory disorder affecting the cardiovascular system, multisystem inflammatory syndrome in children (MIS-C), has been reported. Similar to Kawasaki disease, acute myocarditis, coronary vasculitis, and aneurysms are typically seen in MISC, although these two are now considered distinct entities. A similar acute myocarditis is also observed in young male adults, in which a hyperinflammatory state after SARS-CoV-2 infection seems to be involved. Several side effects following vaccination against COVID-19 have been reported, including vaccine-induced immune thrombotic thrombocytopenia and acute myocarditis. Although these could be serious and life-threatening, the cases are very rare, thus, the benefits of immunization still outweigh the risks.

Transformed Mycosis Fungoides with a Cytotoxic T-Cell Phenotype.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma and occasionally undergo large cell transformation (transformed MF, TMF), resulting in a poorer clinical outcome. We describe a case of TMF with an immunophenotypic shift. MF showed the CD4 + CD8- T-cell phenotype, while TMF exhibited the CD4-CD8 + T-cell phenotype. Moreover, TMF expressed cytotoxic markers of TIA1 and Granzyme B. A PCR analysis of T-cell receptor genes revealed peak sizes that were the same in both biopsies, indicating that these two lymphomas were derived from the same clone.

Therapeutic-Dose Warfarin (International Normalized Ratio >1.6) Plus Aspirin Improved Long-Term Patency of Saphenous Vein Graft without Bleeding Complication.

PURPOSE: Saphenous vein graft (SVG) is the most commonly used conduits in coronary artery bypass grafting (CABG), but the disadvantage of SVG is its tendency for progressive failure. We hypothesized that therapeutic-dose warfarin (international normalized ratio [INR] >1.6) plus aspirin improve SVG patency. This study aimed to evaluate the factors contributing to SVG patency. METHODS: Since 2010-2020, 199 patients who underwent isolated CABG using SVG were divided into two groups according to their INR values in the first year: group T (INR >1.6) and group L (INR <1.6). RESULTS: Group T had 162 SVGs (105 patients) and group L had 151 SVGs (94 patients). The 1-, 4-, and 7-year SVG patency rates were higher in group T than in group L (99%, 96%, and 92% vs. 93%, 86%, and 79%, respectively; p = 0.00378). The 1-, 4-, and 7-year freedom from repeat-revascularization was higher in group T than in group L (100%, 100%, and 99% vs. 98%, 95%, and 87%, respectively; p = 0.0264). Multivariate analysis showed that therapeutic-dose warfarin (p = 0.00204) and target vessel diameter (p <0.0001) were independent risk factors of SVG occlusion. CONCLUSION: Therapeutic-dose warfarin (INR >1.6) plus aspirin after CABG improved the long-term patency of SVG and decreased repeat-revascularization rate.

[Treatment of ITP].

Helicobacter eradication therapy is the first-line therapy for patients with Helicobacter positive idiopathic thrombocytopenic purpura (ITP) in Japan. Indications for treatement in patients with Helicobacter negative, or post-Helicobacter eradicated ITP are platelet counts less than 20×106/l or severe bleeding. The first-line treatment for these patients is corticosteroids. Thrombopoietin receptor agonists (TPO-RAs), rituximab, and splenectomy are second-line treatments for patients with corticosteroid refractory ITP. The choice of a second-line treatment should be determined in consideration of the advantages and disadvantages of each treatment. TPO-RAs are effective in over 80% of patients; however, long-term administration is usually needed. Rituximab treatment ends in four weeks, but its durable response rate is relatively low. The durable response rate of splenectomy is relatively high; however, it causes long-term complications. Effective treatments for patients with ITP who are refractory to second-line treatments have not been established. Some novel drugs are under clinical trials, and a treatment strategy for these patients is expected to be established.

Limiting the Pitch Count in Youth Baseball Pitchers Decreases Elbow Pain.

BACKGROUND: Reducing the number of pitches thrown is regarded as the most effective way to prevent throwing injuries in youth baseball pitchers. However, few studies have compared the effectiveness of limiting the pitch count versus the limiting the number of innings pitched in terms of elbow injuries. HYPOTHESIS: We hypothesized that, compared with inning limits, pitch count limits would lead to greater decreases in elbow pain, range of motion deficits, positive moving valgus stress test results, and the risk of capitellar osteochondritis dissecans (OCD). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study retrospectively reviewed baseball pitchers aged 8 to 12 years in 2017 and 2018. Inning and pitch count limits in games were set to a daily maximum of 7 innings in 2017 and 70 pitches in 2018. Elbow pain, range of motion, and moving valgus stress test results were evaluated. The presence of capitellar OCD was assessed on ultrasonographic and radiographic images. RESULTS: A total of 352 pitchers in 2017 and 367 pitchers in 2018 participated. The mean pitch count per game was lower in the pitch count limit (CL) group (52.5 ± 16.0) than in the inning limit (IL) group (98.2 ± 19.5) (P < .001). Compared with the IL group, the CL group had significantly lower rates of elbow pain (40.9% vs 31.9%, respectively; P = .01) and reduced flexion (19.0% vs 10.6%, respectively; P = .001). Multivariate analysis revealed a significant association between elbow pain and age in both the IL and the CL groups (P < .0001 and P = .02, respectively) and between OCD and elbow pain in the CL group (P = .04). CONCLUSION: A pitch count limit of ≤70 pitches per day for baseball pitchers ≤12 years could be more protective against elbow pain and reduced flexion than a limit of ≤7 innings per day, but it may not be effective for reducing the risk of capitellar OCD.

Repair Tension During Arthroscopic Rotator Cuff Repair is Correlated With Preoperative Tendon Retraction and Postoperative Rotator Cuff Integrity.

PURPOSE: This study aimed to examine the correlation of repair tension during arthroscopic rotator cuff repair (ARCR) with preoperative factors and to evaluate whether measuring tension during ARCR is effective for predicting rotator cuff integrity after ARCR. METHODS: Patients who underwent ARCR from May 2014 to June 2017 were enrolled in this study. Inclusion criteria were patients with medium or larger-sized tears and with a minimum of 6 months' follow-up. Patients with a partial repair were excluded. Intraoperative repair tension was measured according to Davidson's method. Correlation of repair tension with preoperative factors was evaluated with Pearson and Spearman correlation coefficient tests. Logistic regression analysis was performed on intraoperative factors, including repair tension, to identify independent predictors of retear after ARCR. Receiver operating characteristic (ROC) curve was used to determine the cutoff value of repair tension for retear. RESULTS: One-hundred twenty patients met the inclusion criteria. Mean repair tension was 26.6 ± 12.6 N, and retear was found in 29 shoulders (24.2%). Among the preoperative factors, tear size in the mediolateral (P < .001) and anteroposterior (P < .001) directions, DeOrio and Cofield's classification (P <0.001), geometric classification (P <.001), and fatty infiltration of supraspinatus (P = .006) and infraspinatus (P = .003) were significantly correlated with repair tension. However, multivariable logistic regression analysis identified only tear size in the mediolateral direction as an independent predictor of repair tension (P = .036). Logistic regression analysis showed that repair tension (P = .02) and geometric classification (P < .001) are significant factors affecting rotator cuff integrity after ARCR. ROC curve analysis showed the cutoff value of repair tension of large to massive tears for retear to be 35.6 N. CONCLUSION: This study demonstrated that intraoperative repair tension is strongly correlated with tear size in the mediolateral direction based on preoperative magnetic resonance imaging and that measuring tension during ARCR is effective for predicting rotator cuff integrity after ARCR. LEVEL OF EVIDENCE: Level IV, prognostic study.

Comparison of the Humphrey Field Analyzer and Photopic Negative Response of Focal Macular Electroretinograms in the Evaluation of the Relationship Between Macula Structure and Function.

Purpose: To investigate the association between macular inner retinal layer thickness and macula visual field (VF) mean deviation as measured by the Humphrey Field Analyzer (HFA) or macular function as measured by focal macular electroretinograms (ERGs) in patients with glaucoma. Methods: The participants in this cross-sectional study were 71 patients with glaucoma and 10 healthy controls. Macular inner retinal layer thickness and function were measured in all participants using optical coherence tomography (OCT) and HFA or focal macular ERGs, respectively. Macular OCT images were segmented into the macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer/inner plexiform layer (GCL/IPL), and ganglion cell complex (GCC). Spearman correlation analysis was used to assess the relationship between macular inner retinal layer thickness and function. Results: Focal macular ERGs were composed of a negative wave (N1), a positive wave (P1), and a slow negative wave (N2). The N2 response density was significantly reduced in eyes with glaucoma, and was significantly associated with the thickness of the mRNFL (R = 0.317), GCL/IPL (R = 0.372), or GCC (R = 0.367). The observed structure-function relationship was also significantly correlated with the HFA VF mean deviation for each thickness [mRNFL (R = 0.728), GCL/IPL (R = 0.603), or GCC (R = 0.754)]. Conclusions: Although a significant correlation was found between the N2 response density and the thickness of the macular inner layer, the observed structure-function relationship with the mean deviation of the HFA VF was higher than that of the N2 response density.

Left atrial schwannoma in schwannomatosis: a case report.

BACKGROUND: Primary cardiac schwannoma in the left atrium and schwannomatosis are rare diseases. CASE PRESENTATION: We report the case of a 46-year-old asymptomatic man who had tumor resection for parapharyngeal schwannoma at another institute 1 year ago. He was presented to our hospital for further evaluation of an abnormal cardiac shadow that was found incidentally. Computed tomography and transesophageal echocardiography revealed a cardiac tumor originating from the posterior wall of the left atrium, an atrial septal defect, and two other mediastinal tumors. The cardiac mass was completely excised with normal margins of the surrounding atrial wall. The post-resection defect and atrial septal defect were repaired using bovine pericardium. Pathological findings were compatible with benign schwannoma, and a diagnosis of schwannomatosis was made based on his medical history. CONCLUSION: Primary cardiac schwannoma is an exceedingly rare tumor, and the incidence in schwannomatosis has not been reported in the literature.

COVID-19-Related Thrombosis in Japan: Final Report of a Questionnaire-Based Survey in 2020.

A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information on 6,202 COVID-19 patients. Of these, 333 and 56 required ventilation or extracorporeal membrane oxygenation (ECMO), respectively, and 212 died (3.4%). D-dimer levels were measured in 75.0% of the patients, revealing that 9.2% and 7.6% exhibited D-dimer increases of 3-8-fold and ≥8-fold the reference value, respectively. Thrombotic events occurred in 108 patients (1.86% of the 5,807 patients with available data) including symptomatic cerebral infarction in 24, myocardial infarction in 7, deep vein thrombosis in 41, pulmonary thromboembolism in 30, and other thrombotic events in 22. Some patients developed multiple thrombotic events. Thrombosis occurred in 32 patients with mild or moderate COVID-19 severity (0.59% of those with data available) and in 52 patients on ventilation or ECMO (13.5% of severe patients for whom data were available). Thrombosis occurred in 67 patients during worsening clinical condition and in 26 during recovery. Anticoagulant therapy was provided to 893 patients (14.6% of the 6,119 patients with available data), the main reasons being provided as elevated D-dimer levels and worsening clinical condition.

Clonally Related Plasmablastic Lymphoma Simultaneously Occurring with Diffuse Large B-Cell Lymphoma.

Plasmablastic lymphoma (PBL) is a rare aggressive lymphoma. Although it was first described in HIV- (human immunodeficiency virus-) infected patients, PBL has been diagnosed in patients with other immunodeficiencies as well as in immunocompetent patients. PBL immunohistochemically expresses plasmacytic markers and lacks pan B-cell markers. The cells of origin of PBL are considered to be plasmablasts. MYC gene rearrangement and MYC overexpression are frequently found in PBL, but the pathogenesis of PBL is yet to be elucidated. Here, we report a case of composite lymphoma of PBL and diffuse large B-cell lymphoma (DLBCL); that is, PBL in the urinary bladder and DLBCL in the nasal cavity occurred simultaneously. We extracted DNA from the two lymphomas for polymerase chain reaction and sequenced the amplified immunoglobulin heavy variable genes and the complementarity-determining region- (CDR-) 3. The sequence of the CDR3 region of both tumors matched. MYC rearrangement was found in the bladder tumor but not in the nasal tumor. The patient was treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone), and durable remission had been obtained. The results of the DNA analysis indicated that both PBL and DLBCL emerged from common postgerminal B cells. This case may help to elucidate the pathogenesis of PBL.

Triboelectric charging of polytetrafluoroethylene antithrombotic catheters.

This study proposes that a polytetrafluoroethylene (PTFE) electret tube charged by frictional electricity can prevent the solidification of the indwelling catheter in blood vessels. Coagulation in intravascular indwelling catheters may discontinue the treatment because of thrombus-derived bacteria-adhesion infections or poor blood removal. Current commercially available intravascular catheters lack complete antithrombotic measures, even with heparin or urokinase antithrombotic coatings. Herein, we tested the effectiveness of an antithrombotic treatment that prevents coagulation using a static electric charge on the interior of the PTFE tube via the triboelectric effect by rubbing the tube's inner wall with a round glass rod. The anticoagulation properties were evaluated by enclosing a sample of blood in an electret tube and observing the coagulase adhering to the inner wall using a microscope. To confirm the effectiveness of this treatment, the charge-distribution on the inner surface of the electret tube was measured, surface irregularities were observed, and the elements on the surface were analyzed. The surface potential inside the electret tube was - 366.4 V, which proved effective for an antithrombotic treatment, as it discouraged coagulation, and the triboelectric charging process caused neither surface element denaturation nor significant surface irregularities. The nearly uniform negative surface charge on the inside of the tube was responsible for the antithrombotic effect because no surface irregularities or change in the surface element denaturation was observed. Triboelectrically charged PTFE electret tubes are highly useful for intravascular indwelling catheters.

Influence of blood pressure on the effects of low-dose asprin in elderly patients with multiple atherosclerotic risks.

OBJECTIVE: We examined whether the efficacy of low-dose acetylsalicylic acid (aspirin) for primary prevention of cardiovascular events is influenced by blood pressure (BP) using data from patients aged 60-85 years with hypertension, dyslipidemia, and/or diabetes, but without cardiovascular disease of the Japanese Primary Prevention Project. METHODS: All patients had received aspirin (100 mg/day) or no aspirin. BP subgroups were defined as low (average SBP from the baseline to the year of the events <130 mmHg), moderate (≥130 and <140 mmHg), and high (≥140 mmHg). The mean duration of follow-up was 5.02 years. RESULTS: In hypertensive patients (n = 12 278) aspirin had no significant impact on the primary outcome of death from cardiovascular disease, nonfatal stroke, and nonfatal myocardial infarction. On the other hand, aspirin increased the incidence of serious extracranial hemorrhage [hazard ratio, 1.81; 95% confidence interval (CI), 1.18-2.77; P = 0.0064] and tended to increase hemorrhagic stroke (hazard ratio, 1.75; CI, 0.99-3.07; P = 0.053). Aspirin had no effect on the primary outcome in any of the BP subgroups, and was associated with increased hemorrhagic stroke in the high BP group (hazard ratio, 3.51; CI, 1.29-9.51; P = 0.014); serious extracranial hemorrhage was elevated or tended to elevate in the moderate (hazard ratio, 2.53; CI, 1.18-5.45; P = 0.017) and high (hazard ratio, 2.14; CI, 1.00-4.56; P = 0.050) BP groups. CONCLUSION: In aged Japanese hypertensive patients, these data demonstrated no overall benefit of low-dose aspirin therapy although treatment was associated with an elevated risk of hemorrhagic events.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors: Subanalysis of a Randomized Clinical Trial (JPPP-70).

INTRODUCTION: This post hoc subanalysis of the randomized Japanese Primary Prevention Project investigated whether once-daily low-dose aspirin versus no aspirin reduced the risk of cardiovascular events (CVEs) in patients aged ≥ 70 years with atherosclerotic risk factors. METHODS: Patients aged < 70 years (young-old) or ≥ 70 years (old) with hypertension, dyslipidemia, or diabetes participated between 2005 and 2007. Patients were randomized 1:1 to receive 100 mg enteric-coated aspirin once daily or no aspirin plus standard of care. The primary outcome was a composite of death from cardiovascular causes plus nonfatal stroke and nonfatal myocardial infarction. The secondary outcome was a composite of the primary outcome plus transient ischemic attack, angina pectoris, and arteriosclerotic disease requiring medical or surgical intervention. Old (n = 7971) and young-old (n = 6493) patients were followed up for a median 5.02 years. RESULTS: Aspirin did not reduce the risk of primary (hazard ratio [HR] 0.92 [95% confidence interval {CI} 0.74-1.16]; P = 0.50) or secondary (0.85 [0.70-1.04]; P = 0.11) outcomes in patients aged ≥ 70 years. In old men with high-density lipoprotein < 40 mg/dL, treatment with low-dose aspirin was associated with a reduction in the incidence of the primary endpoint compared with the group not receiving aspirin (10/260 vs 22/250; HR 0.44 [95% CI 0.20-0.93]; P = 0.03). This subgroup was also found to contain significant larger proportions of patients with elevated body mass index, patients with diabetes mellitus, and smokers (P < 0.001). Old patients also showed differences in bleeding outcomes. Serious extracranial hemorrhage requiring transfusion or hospitalization occurred significantly more frequently in the aspirin-treated group than in the non-aspirin-treated group (35 [0.88%] vs 18 [0.45%]; HR 1.96 [1.11-3.46]; P = 0.020). Gastrointestinal hemorrhage occurred significantly more frequently in the aspirin-treated group than the non-aspirin-treated group (63 [1.58%] vs 18 [0.45%]; relative risk [RR] 3.5 [2.08-5.90]; P < 0.0001). Cerebral hemorrhage (intracranial hemorrhage) tended to occur more frequently in the aspirin-treated group than the non-aspirin-treated group (22 [0.55%] vs 11 [0.28%]; RR 2.01 [0.97-4.14]; P = 0.058). Cerebral hemorrhage occurred significantly more frequently in old patients than in young-old patients (33 [0.41%] vs 10 [0.15%]; HR 2.7 [1.34-5.53]; P = 0.0055). Gastrointestinal hemorrhage occurred in a slightly higher proportion of old patients compared with young-old patients (81 [1.02%] vs 53 [0.82%]; RR 1.2 [0.88-1.76]; P = 0.21). DISCUSSION/CONCLUSIONS: Aspirin did not reduce the risk of the primary or secondary outcomes in old patients. Aspirin treatment may have reduced CVEs within a high CVE risk elderly population subgroup. Aspirin treatment in such a group requires caution, because of the increased risk of intracranial hemorrhage, severe extracranial hemorrhage requiring hospitalization or transfusion, and gastrointestinal bleeding in old patients receiving aspirin therapy. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov [NCT00225849].

Comparable clinical and structural outcomes after arthroscopic rotator cuff repair in diabetic and non-diabetic patients.

PURPOSE: To compare clinical outcome and rotator cuff integrity after arthroscopic rotator cuff repair (ARCR) in patients with and without diabetes mellitus. METHODS: This retrospective study involved 264 consecutive patients who underwent ARCR from 2012 to 2015. Inclusion criteria were a medium or large-sized tear and a minimum of 1-year follow-up. Clinical outcome measures included range of motion (ROM) and the Japanese Orthopaedic Association (JOA) and University of California, Los Angeles (UCLA) scores preoperatively and at final follow-up. Rotator cuff retear was evaluated with magnetic resonance imaging at 3 months post-surgery and final follow-up. Diabetic patients with poor control were pre-operatively hospitalized for intensive diabetic control. RESULTS: Our inclusion criteria were met by 30 diabetic patients and 126 non-diabetic patients. Demographic data were not significantly different between the groups, except body mass index (p = 0.021). Preoperative JOA and UCLA scores of the diabetic patients were significantly lower than those of the non-diabetic patients (p < 0.001, and p = 0.006, respectively); however, the scores at final follow-up were not different. ROM was significantly restricted in the diabetic patients before surgery (forward flexion, abduction, internal rotation: p < 0.001, external rotation: p = 0.035), but at the final follow-up, there was no significant difference except for internal rotation (p = 0.005). The retear rate in diabetic patients (23.3%) was not significantly different from that in non-diabetic patients (15.1%). CONCLUSIONS: Diabetic patients who had good perioperative glycemic control showed clinical and structural outcomes comparable to non-diabetic patients after ARCR. Intensive perioperative glycemic control and patient education are recommended for preoperative uncontrolled diabetic patients. LEVEL OF EVIDENCE: III.

Effects of daily aspirin on cancer incidence and mortality in the elderly Japanese.

BACKGROUND: Long-term follow-up of studies to investigate preventive effects of aspirin on arterial thrombosis indicate that aspirin reduces the incidence and mortality of some cancers in Western populations. OBJECTIVES: To explore the effects of aspirin on cancer incidence and mortality in the elderly Japanese. PATIENTS/METHODS: Patients aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus (n = 14 601, 7297 in the aspirin group and 7304 in the no-aspirin group) participated the Japanese Primary Prevention Project (JPPP), a multicenter, open-label, randomized, parallel-group trial. A subanalysis of JPPP was performed to analyze the incidence of newly diagnosed cancer and death related to cancer. RESULTS: The cumulative incidence of newly diagnosed cancer was 5.60% (4.65-6.64%) in the aspirin group and 4.14% (3.67-4.66%) in the no-aspirin group. The hazard ratio for newly diagnosed cancer was 1.24 (1.06-1.46), and the cancer incidence was significantly higher in the aspirin group. The cumulative cancer mortality was 1.96% (1.65-2.31%) in the aspirin group and 1.87% (1.56-2.22%) in the no-aspirin group, with no statistically significant difference. The Fine and Gray model suggested that the difference in the incidence of newly diagnosed cancer between the two groups decreased year by year. CONCLUSIONS: Low-dose aspirin use did not reduce the cancer incidence or cancer mortality during a 5-year-average study period in the elderly Japanese. The cancer incidence in the aspirin group might decrease, however, to less than that in the no-aspirin group after the study period. Aspirin use might have led to earlier cancer diagnosis in our study.