Tag: nevin manimala

RMD Open. 2021 Jun;7(2):e001662. doi: 10.1136/rmdopen-2021-001662.

ABSTRACT

OBJECTIVES: Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.

METHODS: 15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.

RESULTS: Disease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.

CONCLUSIONS: TCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.

PMID:34112702 | DOI:10.1136/rmdopen-2021-001662

Clin Cancer Res. 2021 Jun 10:clincanres.0732.2021. doi: 10.1158/1078-0432.CCR-21-0732. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effect of sulindac, a non-selective anti-inflammatory drug, for activity to reduce breast density (BD), a risk factor for breast cancer.

EXPERIMENTAL DESIGN: An open-label Phase 2 study was conducted to test the effect of 12 months’ daily sulindac at 150 mg bid on change in percent BD in postmenopausal hormone receptor-positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by non-contrast MRI and reported as change in MRI percent BD (MRPD). A non-randomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12-months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated (SHG) microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy.

RESULTS: In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% (95% CI, -14.6 to -4.7) at 12 months; an absolute decrease of -1.4% (95% CI, -2.5 to -0.3). A significant decrease in mean breast tissue collagen fiber straightness (p=0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI only observation group (N = 40).

CONCLUSIONS: This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.

PMID:34112707 | DOI:10.1158/1078-0432.CCR-21-0732

Clin Cancer Res. 2021 Jun 10:clincanres.0474.2021. doi: 10.1158/1078-0432.CCR-21-0474. Online ahead of print.

ABSTRACT

PURPOSE: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC patients to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce.

EXPERIMENTAL DESIGN: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR) and overall response rate (ORR) were analyzed.

RESULTS: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR).

CONCLUSION: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.

PMID:34112711 | DOI:10.1158/1078-0432.CCR-21-0474

Science. 2021 Jun 11;372(6547):1192-1196. doi: 10.1126/science.abg8102.

ABSTRACT

Extending the framework of statistical physics to the nonequilibrium setting has led to the discovery of previously unidentified phases of matter, often catalyzed by periodic driving. However, preventing the runaway heating that is associated with driving a strongly interacting quantum system remains a challenge in the investigation of these newly discovered phases. In this work, we utilize a trapped-ion quantum simulator to observe the signatures of a nonequilibrium driven phase without disorder-the prethermal discrete time crystal. Here, the heating problem is circumvented not by disorder-induced many-body localization, but rather by high-frequency driving, which leads to an expansive time window where nonequilibrium phases can emerge. Floquet prethermalization is thus presented as a general strategy for creating, stabilizing, and studying intrinsically out-of-equilibrium phases of matter.

PMID:34112691 | DOI:10.1126/science.abg8102

Hosp Pediatr. 2021 Jun 10:hpeds.2020-001974. doi: 10.1542/hpeds.2020-001974. Online ahead of print.

ABSTRACT

OBJECTIVES: To analyze factors associated with the initiation of long-acting reversible contraception (LARC) among adolescent patients in inpatient settings in the United States.

METHODS: This study is a secondary data analysis of the national Kids’ Inpatient Database 2016 data (N = 4200 hospitals). Eligible patients were hospitalized girls 10 to 20 years old. The primary outcome was initiation of LARC (ie, subdermal implant and/or intrauterine device [IUD]) while hospitalized. Covariables included age, race or ethnicity, insurance type, postpregnancy status, geographic region, hospital type (rural or urban), hospital size, and children’s hospital status. Bivariable statistics were calculated by using survey-weighted analysis, and a design-based logistic regression model was used to determine the adjusted odds of LARC initiation and of implant versus IUD initiation.

RESULTS: LARC initiation occurred in 0.4% (n = 3706) of eligible hospital admissions (n = 874 193). There were differences in LARC initiation by patient age, insurance type, race or ethnicity, postpregnancy status, hospital type, and hospital status (all P < .01). In the adjusted model, older age, public insurance, nonwhite race or ethnicity, postpregnancy status, and urban, teaching or larger hospitals were independently associated with LARC initiation (all P < .01). Smaller hospital size and postpregnancy status increased the odds of implant versus IUD initiation after stratifying by hospital region.

CONCLUSIONS: LARC initiation occurred in <1% of adolescent hospitalizations, with 90% of those occurring in postpregnancy adolescents. Addressing LARC capacity in rural, nonteaching, and smaller hospitals is important in increasing access. Future research is needed to identify and close gaps in the number of adolescents desiring and initiating LARC in hospital settings.

PMID:34112700 | DOI:10.1542/hpeds.2020-001974

J World Fed Orthod. 2021 Jun 7:S2212-4438(21)00020-5. doi: 10.1016/j.ejwf.2021.05.001. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the rate of tooth movement and the periodontal tissue status over a period of 90 days with and without micro-osteoperforation (MOP).

METHOD: Thirty-three adults of the 19 to 25 age group undergoing labial fixed orthodontic treatment with bilateral maxillary first premolar extraction, requiring individual canine retraction as a part of the treatment plan, were recruited for this split-mouth randomized clinical trial. While performing micro-implant-assisted canine retraction in the maxillary arch, the experimental side received three MOPs each on the mesial and distal aspects of the canine root. The amount of tooth movement was measured clinically at every 15 days interval for 90 days; the periodontal status was assessed clinically (probing depth, relative attachment level) and tomographically (canine root length, alveolar bone level) at the 1st day and 90th day of retraction. The data were subjected to appropriate statistical analyses.

RESULTS: A statistically significant difference in tooth movement on the MOP side was observed in the first 45 days, amounting to 1.5 times more than that of the control side. However, during 45 to 90 days, the difference in the rate of tooth movement between the sides was not statistically significant. Changes in periodontal variables were also insignificant between the sides except for the distal alveolar bone level.

CONCLUSION: An increase in the rate of tooth movement can be achieved without any periodontal adverse effects in the first 45 days of the MOP procedure. The effectiveness of the MOP procedure on the rate of tooth movement gradually declined thereafter.

TRIAL REGISTRATION: CTRI/2019/07/020403.

PMID:34112627 | DOI:10.1016/j.ejwf.2021.05.001

BMJ Open. 2021 Jun 10;11(6):e043444. doi: 10.1136/bmjopen-2020-043444.

ABSTRACT

INTRODUCTION: English is the lingua franca of science. How well doctors understand English is therefore crucial for their understanding of scientific articles. However, only 5% of the world’s population have English as their first language.

METHODS: Objectives: To compare doctors’ comprehension of a scientific article when read in their first language (Norwegian) versus their second language (English). Our hypothesis was that doctors reading the article in Norwegian would comprehend the content better than those reading it in English.

DESIGN: Parallel group randomised controlled trial. We randomised doctors to read the same clinical review article in either Norwegian or English, before completing a questionnaire about the content of the article.

SETTING: Conference in primary care medicine in Norway, 2018.

PARTICIPANTS: 130 native Norwegian-speaking doctors, 71 women and 59 men. One participant withdrew before responding to the questionnaire and was excluded from the analyses.

INTERVENTIONS: Participants were randomly assigned to read a review article in either Norwegian (n=64) or English (n=66). Reading time was limited to 7 min followed by 7 min to answer a questionnaire.

MAIN OUTCOME MEASURES: Total score on questions related to the article content (potential range -9 to 20).

RESULTS: Doctors who read the article in Norwegian had a mean total score of 10.40 (SD 3.96) compared with 9.08 (SD 3.47) among doctors who read the article in English, giving a mean difference of 1.32 (95% CI 0.03 to 2.62; p=0.046). Age was independently associated with total score, with decreased comprehension with increasing age.

CONCLUSION: The difference in comprehension between the group who read in Norwegian and the group who read in English was statistically significant but modest, suggesting that the language gap in academia is possible to overcome.

PMID:34112640 | DOI:10.1136/bmjopen-2020-043444

Int Orthod. 2021 Jun 7:S1761-7227(21)00070-X. doi: 10.1016/j.ortho.2021.05.002. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this in vitro study was to evaluate the effects of enamel deproteinization on the shear bond strength of a self-etching primer Transbond Plus™(TBP), with different application times of sodium hypochlorite (NaOCl 5.25%), primarily and secondarily on the adhesive remnant index score.

MATERIALS AND METHODS: One hundred twenty-five freshly extracted human premolars were randomly and blindly divided into five groups according to the enamel surface preparation, as follows (n=25): group 1(control): Etching with 37% phosphoric acid for 15seconds+Bonding; group 2 (control): TBP™ without NaOCl, group 3: 60seconds NaOCl+TBP™, group 4: 30seconds NaOCl+TBP™, group 5: 15seconds NaOCl+TBP™. The same composite resin was used (Transbond XT™) to bond the orthodontic metal brackets. After the immersion of the teeth in distilled water at 37°C for 24hours the shear bond strength was measured using the universal testing machine and the adhesive remnant index score (ARI) was evaluated under an optical microscope (25×).

RESULTS: The mean SBS values (inMPa) of the groups were respectively: group 1: 13.03±5.36; group 2: 12.28±3.06; group 3: 12.38±4.55; group 4: 12.98±5.76; and group 5: 11.73±5.67. Enamel deproteinization increased the SBS for groups 3 and 4, but no statistically significant difference was found between the five groups (P=0.883). Group 1 showed the highest ARI scores, with 52% of the teeth retaining all the adhesive (score 3). However, for all the other groups, scores 0 and 1 were predominant, with less than half of the adhesive or no adhesive at all remaining on the teeth.

CONCLUSIONS: Enamel deproteinization with sodium hypochlorite (5.25%) and the variation of its application time has no effect on the SBS of the self-etching primer Transbond Plus ™.

PMID:34112607 | DOI:10.1016/j.ortho.2021.05.002

J Formos Med Assoc. 2021 Jun 7:S0929-6646(21)00242-4. doi: 10.1016/j.jfma.2021.05.027. Online ahead of print.

ABSTRACT

BACKGROUND/PURPOSE: To investigate the clinical characteristics of intraocular lymphoma and to evaluate two protocols of intravitreal methotrexate injection.

METHODS: A retrospective chart review was conducted of newly-diagnosed intraocular lymphoma patients between January 2013 and January 2018 at National Taiwan University Hospital. Patients were divided into two groups. In Group A, intravitreal methotrexate was administered weekly for the initial 8 weeks, every 2 weeks for the following 12 weeks, and then monthly for 7 months. In Group B, intravitreal methotrexate was administered twice a week for the initial 2 weeks, weekly for the subsequent 2 weeks, once every 2 weeks for the next 1 month, and monthly for the last 10 months.

RESULTS: A total of 12 patients were analyzed in the study; seven of these patients were allocated to Group A. Differences in the overall survival and progression-free survival between the two groups did not yield statistical significance. The median visual acuity was improved from LogMAR 0.46 to LogMAR 0.30 with borderline significance in Group A (p = 0.053). Two of seven patients in Group A and five of five patients in Group B developed punctate keratitis during intravitreal methotrexate injection treatment.

CONCLUSION: Intravitreal methotrexate is an effective and repeatable treatment for intraocular lymphoma. A new protocol with reduced frequency of intravitreal injections as shown in this study could potentially produce similar results without a worse prognosis, along with a decrease in the incidence of keratitis.

PMID:34112589 | DOI:10.1016/j.jfma.2021.05.027

Semergen. 2021 Jun 7:S1138-3593(21)00124-6. doi: 10.1016/j.semerg.2021.03.008. Online ahead of print.

ABSTRACT

BACKGROUND: Inhibitors of proprotein convertase subtilisin/kexin type9 (PCSK9 inhibitors) are a treatment option for those patients with familial hypercholesterolemia or in secondary prevention who do not reach the LDL-C target with other therapeutic measures. The aim of this study is to assess the effectiveness and safety of these drugs.

METHODS: Retrospective, multicentric, descriptive study. We collected data from all patients that have started PCSK9 inhibitors treatment in three hospitals in Asturias since the beginning of its use in 2016. We analysed changes in lipid profile with PCSK9 inhibitors and its side effects.

RESULTS: We registered 98 patients, 75 of them affected by familial hypercholesterolemia (FH) and 23 unaffected. Two months after the beginning of PCSK9 inhibitors treatment, a 61% reduction rate in LDL-C in patients with FH and 52% in those without this condition was observed. This statistically significant reduction remained stable during follow-up. A significant decrease in total cholesterol was observed, without significant changes in HDL-C and triglycerides. 96% of patients had no complications.

CONCLUSIONS: PCSK9 inhibitors are safe drugs that rapidly achieve significant reductions in LDL-C after the beginning of treatment, which are maintained over time. Hence, the use of PCSK9 inhibitors is an alternative for the control of LDL-C in those patients in which the LDL-C target is not reached with other therapeutic measures.

PMID:34112592 | DOI:10.1016/j.semerg.2021.03.008