Summary Background Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ...ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. Methods Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progessive disease or unacceptable toxic effects. Rituximab 375 mg/m2 was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3–8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov , number NCT01880567 , and is still ongoing, but no longer accruing patients. Findings Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45–86), and the median number of previous regimens was three (range 1–9). At a median follow-up of 16·5 months (IQR 12·09–19·28), 44 (88%, 95% CI 75·7–95·5) patients achieved an objective response, with 22 (44%, 30·0–58·7) patients achieving a complete response, and 22 (44%, 30·0–58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one patient each. Adverse events led to discontinuation of therapy in five (10%) patients (atrial fibrillation in three 6% patients, liver infection in one 2%, and bleeding in one 2%). Two patients died while on-study from cardiac arrest and septic shock; the latter was deemed possibly related to treatment. Interpretation Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma. Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data. Funding Pharmacyclics LLC, an AbbVie Company.
To examine patient outcomes for nine cancer-specific procedures performed in teaching versus non-teaching hospitals.
Few contemporary studies have evaluated patient outcomes in teaching versus ...non-teaching hospitals across a comprehensive set of cancer-specific procedures.
Use of national Medicare data to compare 30-, 60-, and 90-day mortality rates in teaching and non-teaching hospitals for cancer-specific procedures. Risk-adjusted 30-day, all-cause, postoperative mortality overall and for each specific surgery, as well as overall 60- and 90-day mortality rates, were assessed.
The sample consisted of 159,421 total cancer surgeries at 3,151 hospitals. Overall thirty-day mortality rates, adjusted for procedure type, state, and invasiveness of procedure were 1.3% lower at major teaching hospitals (95%CI=-1.6% to -1.1%; p<0.001) relative to non-teaching hospitals. After accounting for patient characteristics, major teaching hospitals continued to demonstrate lower mortality rates compared with non-teaching hospitals (-1.0% difference 95%CI -1.2% to -0.7%; p<0.001). Further adjustment for surgical volume as a mediator reduced the difference to -0.7% (95%CI -0.9% to -0.4%, p<0.001). Cancer surgeries for four of the nine disease sites (bladder, lung, colorectal and ovarian) followed this overall trend. Sixty- and ninety-day overall mortality rates, adjusted for procedure type, state, and invasiveness of procedure showed that major teaching hospitals had a 1.7% (95%CI -2.1% to -1.4%; p<0.001) and 2.0% (95%CI -2.4 to -1.6%, p<0.001) lower mortality relative to non-teaching hospitals. These trends persisted after adjusting for patient characteristics.
Among cancer-specific procedures for Medicare beneficiaries, major teaching hospital status was associated with lower 30-, 60-, and 90-day mortality rates overall and across four of the nine cancer types.
Summary There is a significant sex disparity favoring males among hepatocellular carcinoma (HCC) patients. Although various risk factors have been identified, the exact etiology of such sexual ...dimorphism(s) in HCC is uncertain. Previous studies showed that overexpression of the Y-located protooncogene, testis-specific protein Y encoded ( TSPY ), promotes cell proliferation and oncogenesis whereas its X-located homologue, TSPY homologue X ( TSPX ), retards cell cycle and oncogenic progression. Furthermore, TSPX promotes proteasomal degradation of hepatitis B virus–encoded X oncoprotein and hence could serve as a tumor suppressor in virus–associated HCC. Using immunohistochemistry and reverse-transcription polymerase chain reaction analysis, we had examined the expression of TSPY and TSPX with reference to other established biomarkers in HCC and related liver cancers. Our results demonstrated that 55 (19.2%) of 287 male cases were TSPY positive in immunohistochemistry of tissue arrays, and 15 (46.9%) of 32 male cases were TSPY positive in reverse-transcription polymerase chain reaction analysis of clinical samples. TSPY expression was closely associated with the expression of HCC biomarkers, such as glypican 3. In contrast, TSPX expression was down-regulated in 54.5% of total tumor/nontumorous paired samples (18/33) and negatively associated with those of TSPY , glypican 3 , and forkhead box M1 (FOXM1) and was positively associated with that of a tumor suppressor, insulin-like growth factor binding protein 3. The present findings support the hypothesis that the oncogenic events leading to an ectopic activation of the Y-located protooncogene TSPY and/or inactivating mutation/epigenetic silencing of the X-located tumor suppressor gene TSPX could collectively contribute to the sexual dimorphism(s) in HCC and related liver cancers in male-biased manners.
The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus ...influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic.
For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere.
Overall, 116 841 cases were analysed: 76 481 in 2018–19, before the pandemic, and 40 360 in 2020–21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40–0·55), H influenzae (0·51; 0·40–0·66) and N meningitidis (0·26; 0·21–0·31), while no significant changes were observed for S agalactiae (1·02; 0·75–1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145–55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories.
COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies.
Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.
Abstract Objective To prevent iron deficiency, 2014 Canadian recommendations for healthy term infants from 6 to 24 months recommend iron-rich complementary foods such as meat and meat alternatives 2 ...or more times a day. The purpose of our study was to evaluate the association between meat and meat-alternative consumption and iron status in young children and the association between red meat consumption and iron status among children meeting recommendations. Methods Healthy children aged 12 to 36 months were recruited. A cross-sectional study was conducted. Meat and meat-alternative consumption was measured using the NutriSTEP questionnaire. Adjusted multivariable regression analyses were used to evaluate an association between meat consumption and serum ferritin, and iron deficiency (serum ferritin <14 μg/L). Results A total of 1043 children were included. Seventy-three percent of children met the recommended daily intake of meat and meat alternatives, and 66% ate red meat in the past 3 days. Eating meat and meat alternatives was not associated with serum ferritin (0.13 μg/L, 95% confidence interval −0.05, 0.31, P = .16), but it was associated with a decreased odds of iron deficiency (odds ratio 0.97, 95% confidence interval 0.94, 0.99, P = .03). Associations between red meat consumption and iron status were not statistically significant. Statistically significant covariates associated with increased odds of iron deficiency included longer breast-feeding duration, daily cow's milk intake of >2 cups, and a higher body mass index z score. Conclusions Daily cow's milk intake of >2 cups, longer breast-feeding duration, and a higher body mass index z score were modifiable risk factors associated with iron deficiency. Eating meat according to recommendations may be a promising additional target for the prevention of iron deficiency in early childhood.
Systems navigation services provided by a designated provider or team have the potential to address health and social disparities. We conducted an environmental scan of navigation activities in a ...large urban Canadian community to identify and describe: service providers who engage in systems navigation; the clients who require systems navigation support and the issues they face; activities involved; and barriers and facilitators in providing systems navigation support to clients. Using an online survey and convenience sampling, we recruited individuals who self-identified as community navigators or practiced systems navigation activities as part of their role. The majority of respondents (n = 145) were social workers, social services workers, or nurses. Clients of navigators struggled with mental health or addictions issues, disabilities, chronic diseases, and history of trauma or abuse. The most frequently reported activities of navigators were building professional relationships, managing paperwork, and communicating with relevant agencies or organizations. Barriers to navigation were time available in the work day, difficulty partnering due to bureaucratic structures, differing philosophies and ways of working, and a lack of central information repository in the community. Facilitators were a client-centered organization, the availability of multiple community resources in the region, and organizational support. Participants struggled with client waitlists, system issues such as lack of resources and interagency collaboration, and role clarity.
Abstract Objective To determine if there is an association between longer breast-feeding duration and dental caries in healthy urban children. Methods We conducted a cross-sectional study of urban ...children aged 1 to 6 years recruited through The Applied Research Group for Kids (TARGet Kids!) practice-based research network between September 2011 and August 2013. The main outcome measure was parental report of dental caries. Results The adjusted predicted probability of dental caries was 7%, 8%, 11%, and 16% with total duration of breast-feeding duration of 12, 18, 24, and 36 months, respectively. In the adjusted logistic regression analyses, relative to breast-feeding 0 to 5 months, the odds of dental caries with total breast-feeding duration >24 months was 2.75 (95% confidence interval 1.61–4.72). Conclusions Among healthy urban children, longer breast-feeding duration was associated with higher odds of dental caries. These findings support heightened awareness and enhanced anticipatory guidance for preventive dental care, particularly among children who breast-feed beyond 2 years of age.
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