Hematologic malignant neoplasms after drug exposure in rheumatoid arthritis

BACKGROUND: Rheumatoid arthritis is a severe inflammatory polyarthritis that requires long-term treatment with disease-modifying antirheumatic drugs. There is increasing concern about the influence of rheumatoid arthritis therapy on the risk for hematologic malignant neoplasms. METHODS: We used a case-control design nested in a cohort of 23,810 patients with rheumatoid arthritis assembled from administrative databases covering the population of Quebec, Canada. The study was carried out from January 1, 1980, through December 31, 2003. Case patients having hematologic malignant neoplasms were ascertained from physician billing and hospitalization records; each case patient was matched for age and sex with 10 control subjects. Adjusting for clinical variables and concomitant medications, we used conditional logistic regression to analyze potential associations between disease-modifying antirheumatic drug exposures and risk for hematologic malignant neoplasms. We estimated rate ratios attributable to each disease-modifying antirheumatic drug exposure. RESULTS: During the study, hematologic malignant neoplasms developed in 619 patients, including lymphomas in 346 patients, leukemia in 178 patients, and multiple myelomas in 95 patients. The unadjusted rate ratios for hematologic malignant neoplasms after drug exposures were as follows: methotrexate, 1.18 (95% confidence interval [CI], 0.99-1.40); azathioprine, 1.44 (95% CI, 1.01-2.03); and cyclophosphamide, 2.21 (95% CI, 1.52-3.20). Because biologic agents first appeared in the Régie d'Assurance Maladie du Quebec formulary in 2002, there were few exposures to these drugs. Adjusted estimates suggested that hematologic cancer risk was most elevated after exposure to cyclophosphamide (rate ratio, 1.84; 95% CI, 1.24-2.73). For lymphomas only, the adjusted rate ratio after cyclophosphamide exposure was 2.12 (95% CI, 1.33-3.54). CONCLUSIONS: In this large cohort of patients with rheumatoid arthritis, the greatest relative risk for hematologic malignant neoplasms was noted after use of cyclophosphamide. Assessments of risk related to newer and emerging therapies should carefully consider previous and concomitant medication exposures.     

Large Subchorionic Hematoma: Breus' Mole

A case of large subchorionic hematoma complicated by intrauterine growth retardation and oligohydramnios diagnosed at 32 weeks' gestation with twin pregnancy after ICSI is reported below. The patient was on clexane injection during pregnancy for mitral valve replacement. She was managed with tocolysis using progesterone therapy and antibiotic with followup until delivery. At 34 weeks, a male baby weighing was delivered without complication by caesarean section because of single fetal demise of twin pregnancy.     

Immunohistochemical Evaluation of Leptin Role in Skin Tags

Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of loose fibrous tissue. However, their exact etiology is not fully understood. Leptin is a major player in the biology and pathology of the skin and its appendages. It is linked to cell differentiation, proliferation, migration, and survival with pronounced effects on angiogenesis, blood flow, and tissue perfusion. This study aimed at investigating the possible role of leptin in STs pathogenesis and correlating its expression with different clinical and histopathological parameters. Using immunohistochemical techniques, we examined 90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and Body Mass Index-matched normal subjects as a control group.

Leptin was overexpressed in STs compared with normal skin (p?p?p?H score was significantly associated with female gender (p?=?.004) and haphazard collagen arrangement (p?H score was significantly associated with smooth skin tags (p?=?.01), dilated blood vessels (p?=?.04), presence of mast cells (MCs) (p?=?.002), presence of inflammatory cells (p?=?.004), and haphazard collagen arrangement (p?相似文献   

Coated silver nanoparticles: synthesis,cytotoxicity, and optical properties

Coated silver nanoparticles (AgNPs) have recently become a topic of interest due to the fact that they have several applications such as in electronic, antimicrobial, industrial, optical, and medical fields as biosensors and drug delivery systems. However, the use of AgNPs in medical fields remains somewhat limited due to their probable cytotoxic effect. Researchers have succeeded in reducing the toxicity of silver particles by coating them with different substances. Generally, the coating of AgNPs leads to change in their properties depending on the type of the coating material as well as the layer thickness. This review covers the state-of-the-art technologies behind (a) the synthesis of coated AgNPs including coating methods and coating materials, (b) the cytotoxicity of coated AgNPs and (c) the optical properties of coated AgNPs.

Coated silver nanoparticles (AgNPs) have recently become a topic of interest due to the fact that they have several applications such as in electronic, antimicrobial, industrial, optical, and medical fields as biosensors and drug delivery systems.     

Evaluation of the performance of the N95-companion: effects of filter penetration and comparison with other aerosol instruments

Fit factor is the ratio of the particle concentration outside (C(out)) to the inside (C(in)) of the respirator and assumes that filter penetration is negligible. For Class-95 respirators, concerns were raised that filter penetration could bias fit test measurements. The TSI N95-Companion was designed to overcome this limitation by measuring only 40-60 nm size particles. Recent research has shown that particles in this size range are the most penetrating for respirators containing electrostic filter media. The goal of this study was to better understand the performance of the N95-Companion by assessing the impact of filter penetration and by comparing C(out)/C(in) ratios measured by other aerosol instruments (nano-Differential Mobility Analyzer/Ultrafine Condensation Particle Counter (nano-DMA/UCPC) and the TSI PortaCount Plus) using N95 filtering facepiece respirators sealed to a manikin and with intentionally created leaks. Results confirmed that 40-60 nm-diameter size room air particles were most penetrating for the respirators tested. A nonlinear relationship was found between the N95-Companion-measured C(out)/C(in) ratios and the other instruments at the sealed condition and at the small leak sizes because the N95-Companion measures only charged particles that are preferentially captured by the electrostic filter media, while the other instrument configurations also measure uncharged particles, which are captured less efficiently. The C(out)/C(in) ratios from the N95-Companion for experiments conducted under sealed condition suggest that filter penetration of negatively charged 40-60 nm size particles was less than 0.05%. Thus, the N95-Companion measured C(out)/C(in) ratios are due primarily to particle penetration through leakage, not through filter media, while the C(out)/C(in) ratios for the PortaCount, nano-DMA/UCPC, and UCPC result from a combination of face seal leakage and filter penetration.     

African League Against Rheumatism (AFLAR) preliminary recommendations on the management of rheumatic diseases during the COVID-19 pandemic

Objectives

To develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic.

Method

A task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and recommendations were pruned down according to predefined criteria. Each statement was rated between 1 and 9 with 1–3, 4–6 and 7–9 representing disagreement, uncertainty and agreement, respectively. The levels of agreement on the statements were stratified as low, moderate or high according to the spread of votes. A statement was retired if it had a mean vote below 7 or a ‘low’ level of agreement.

Results

A total of 126 initial statements of recommendations were drafted, and these were reduced to 22 after the two rounds of voting.

Conclusions

The preliminary statements of recommendations will serve to guide the clinical practice of rheumatology across Africa amidst the changing practices and uncertainties in the current era of COVID-19. It is recognized that further updates to the recommendations will be needed as more evidence emerges.

Efficacy and tolerance of infliximab in children and adolescents with Crohn's disease

Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn's disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3-17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8-7.3) of infliximab during a median time period of 4 months (1-17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey-Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn's disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment.     

Divergent immune responses in male and female mice after trauma-hemorrhage: dimorphic alterations in T lymphocyte steroidogenic enzyme activities.

Immune responses are suppressed in males, but not in proestrous females, after trauma-hemorrhage. Testosterone and 17beta-estradiol appear to be responsible for divergent immune effects. There is considerable evidence to suggest sex steroid hormone involvement in immune functions. As formation of active steroid depends on the activity of androgen- and estrogen-synthesizing enzymes, expression and activity of 5alpha-reductase, aromatase, and 3beta- and 17beta- hydroxysteroid dehydrogenases were determined in spleen and T lymphocytes of male and proestrous female mice after trauma-hemorrhage. All of the enzymes were present in spleen, specifically in T lymphocytes. 5alpha-Reductase expression and activity increased in male T lymphocytes, whereas aromatase activity, but not expression, increased in female T lymphocytes. Increased 5alpha-reductase activity in male T lymphocytes is immunosuppressive because of increased 5alpha-dihydrotestosterone synthesis, whereas in females increased aromatase activity triggering 17beta-estradiol synthesis is immunoprotective. This study also demonstrates the importance of 17beta-hydroxysteroid dehydrogenase oxidative and reductive functions. The immunoprotection of proestrous females is associated with enhanced reductase function of the enzyme. In males, decreased expression of oxidative isomer type IV, which impairs catabolism of 5alpha-dihydrotestosterone, probably augments immunosuppression. This study provides evidence for the involvement of intracrine sex steroid synthesis in gender dimorphic immune responses after trauma-hemorrhage.