Tumor suppressor protein p53 and anti-p53 autoantibodies in pediatric rheumatological diseases

The tumor suppressor protein p53 plays an important role in cell cycle regulation. One of the major features in rheumatic diseases is the abnormal proliferation of lymphocytes. p53 expression in peripheral blood mononuclear cells (by flowcytometry) and serum anti-p53 antibodies (by ELISA) were therefore measured in 18 children and adolescents with juvenile rheumatoid arthritis (JRA) and 17 with systemic lupus erythematosus (SLE) in comparison to 20 healthy controls, to determine their role. p53 expression in patients was insignificantly higher than that of controls (2.28 ± 2.71% vs. 1.08 ± 1.02%, respectively, p > 0.05) with 29.4% of the patients showing values above a cut-off level of 2.55% (95th percentile of controls). SLE patients with active disease had significantly higher p53 expression compared to controls and to patients with quiescent disease although no significant correlation with ESR or complement 3 was detected. Seropositivity to anti-p53 antibodies was observed in none of controls but in 22.8% of patients, all of whom, except one, had active disease. Seropositivity to anti-p53 antibodies was more prominent in lupus nephritis than in other presentations of SLE (p < 0.05). The mean p53 expression in seropositive patients was insignificantly higher than in seronegatives. p53 expression and seropositivity to anti-p53 were slightly higher in SLE than in JRA and were not significantly affected by the mode of therapy. Thus, the overexpression of p53 in some patients with active SLE and JRA might explain the abnormal proliferation of autoreactive lymphocytes that perpetuates the inflammatory response. The presence of anti-p53 antibodies might cause malfunctioning of p53 protein interfering with its regulatory functions.     

Are Doctors the Best People to Manage Gout? Is There a Role for Nurses and Pharmacists?

Purpose of Review

To discuss alternate models of long-term gout management

Recent Findings

Nurse-led care of gout appears to improve the uptake of and adherence to urate-lowering treatment in a research setting. Less impressive improvements were achieved with pharmacist-led remote management of gout; however, both strategies were more effective than usual primary care provider management of gout.

Summary

Individualised education about gout, patient involvement in decision-making, and access to trained support in managing side-effects and gout flares can improve the uptake of fine and adherence to urate-lowering treatment. This may be best achieved with nurse-led care of gout. However, further research is required to evaluate if the model of nurse-led care of gout can be implemented in routine clinical practice and in different healthcare systems.

     

Non–C. difficile Clostridioides Bacteremia in Intensive Care Patients,France

Usually responsible for soft tissue infections, Clostridioides species can also cause bacteremia, life-threatening infections often requiring intensive care unit (ICU) admission. We conducted a multicenter retrospective study to investigate Clostridioides bacteremia in ICUs to describe the clinical and biologic characteristics and outcomes in critically ill patients. We identified 135 patients with Clostridioides bacteremia, which occurred almost exclusively (96%) in patients with underlying conditions. Septic shock and digestive symptoms were the hallmarks of Clostridioides bacteremia in the ICU. We identified 16 different species of Clostridioides, among which C. perfringens accounted for 31% of cases. Despite the high sensitivity of Clostridioides to common antimicrobial drugs, mortality rates were high: 52% for ICU patients and 71% overall at 3 months. In multivariate analysis, the most important factor associated with increased risk for death was the presence of hemolysis. Clostridioides bacteremia often leads to multiple organ failures, which have high mortality rates.     

Orthopedic Surgery and Anesthesiology Surgical Improvement Strategies Project—Phase II Outcomes

BackgroundOur institution previously initiated a perioperative surgical home initiative to improve quality and efficiency across the hospital arc of care of primary total knee arthroplasty and total hip arthroplasty patients. Phase II of this project aimed to (1) expand the perioperative surgical home to include revision total hip arthroplasties and total knee arthroplasties, hip preservation procedures, and reconstructions after oncologic resections; (2) expand the project to include the preoperative phase; and (3) further refine the perioperative surgical home goals accomplished in phase I.MethodsPhase II of the Orthopedic Surgery and Anesthesiology Surgical Improvement Strategies project ran from July 2018 to July 2019. The evaluated arc of care spanned from the preoperative surgical consult visit through 90 days postoperative in the expanded population described above.ResultsMean length of stay decreased from 2.2 days to 2.0 days (P < .001), 90-day readmission decreased from 3.0% to 1.6% (P < .001), and Press-Ganey scores increased from 77.1 to 79.2 (97th percentile). Mean and maximum pain scores and opioid consumption remained unchanged (lowest P = .31). Annual surgical volume increased by 10%. Composite changes in surgical volume and cost reductions equaled $5 million.ConclusionApplication of previously successful health systems engineering tools and methods in phase I of Orthopedic Surgery and Anesthesiology Surgical Improvement Strategies enabled additional evolution of an orthopedic perioperative surgical home to encompass more diverse and complex patient populations while increasing system-wide quality, safety, and financial outcomes. Improved process and outcomes metrics reflected increased efficiency across the episode of care without untoward effects.Level of EvidenceIII Therapeutic.     

Diagnostic performance of <Superscript>18</Superscript>F-FDG PET/CT and whole-body MRI before and early after treatment of multiple myeloma: a prospective comparative study

Objective

To determine the diagnostic accuracy of WB-MRI and ¹⁸F-FDG PET/CT in detecting infiltration pattern, disease activity, and response to treatment in patients with multiple myeloma (MM).

Materials and methods

Fifty-six patients with confirmed MM were included in the present study for pre-treatment evaluation. Among these individuals, 22 patients were available for the post-treatment evaluation of response to therapy. All patients were imaged with both WB-MRI and ¹⁸F-FDG PET/CT. All radiographic findings of infiltration pattern, disease activity, and response to therapy were compared. The diagnostic performance of both modalities was estimated using bone marrow aspirate and biopsy as the reference test.

Results

For detection of active myelomatous tissue at diagnosis, WB-MRI achieved higher sensitivity (94%) than ¹⁸F-FDG PET/CT (75%) (p?=?0.0039), whereas both modalities achieved the same specificity (80%). For detection of residual myelomatous tissue after treatment, ¹⁸F-FDG PET/CT achieved higher specificity (86%) than WB-MRI (43%) (p?=?0.0081), whereas both modalities achieved the same sensitivity (75%).

Conclusion

WB-MRI is more sensitive than ¹⁸F-FDG PET/CT in the diagnosis of MM before treatment; however, ¹⁸F-FDG PET/CT is more specific than WB-MRI in detecting residual involvement in treated patients.

     

Anticancer therapy and lung injury: molecular mechanisms

Introduction: Chemotherapy and radiation therapy are two mainstream strategies applied in the treatment of cancer that is not operable. Patients with hematological or solid tumor malignancies substantially benefit from chemotherapeutic drugs and/or ionizing radiation delivered to the site of malignancy. However, considerable adverse effects, including lung inflammation and fibrosis, are associated with the use of these treatment modalities.

Areas covered: As we move toward the era of precision health, we are compelled to understand the molecular basis of chemoradiation-induced pathological lung remodeling and to develop effective treatment strategies that mitigate the development of chronic lung disease (i.e. fibrosis) in cancer patients. The review discusses chemotherapeutic agents that are reported to induce or associate with acute and/or chronic lung injury.

Expert commentary: There is a need to molecularly understand how chemotherapeutic drugs induce or associate with respiratory toxicities and whether such characteristics are inherently related to their antitumor effect or are collateral. Once such mechanisms have been identified and/or fully characterized, they may be able to guide disease-management decisions including effective intervention strategies for the adverse effects. In the meantime, radiation oncologists should be judicious on the dose of radiation delivered to the lungs, the volume of lung irradiated, and concurrent use of chemotherapeutic drugs.     

A Germline Mutation in the BRCA1 3’UTR Variant Predicts Susceptibility to Breast Cancer in a Saudi Arabian Population

Purpose: The impact of the BRCA1-3’UTR-variant on BRCA1 gene expression and altered responses to externalstimuli was previously tested in vitro using a luciferase reporter assay. Its ability to predict breast cancer risk in womenwas also assessed but the conclusions were inconsistent. The present study concerns the relationship between theBRCA1-3’UTR germline variant rs8176318G>T and susceptibility to Breast cancer in an ethnic population of SaudiArabia. Methodology: The study included 100 breast cancer patients and 100 sex matched healthy controls fromthe northwestern region (Tabuk) and Dammam of Saudi Arabia were investigated for the BRCA1-3’UTR germlinevariant rs8176318G>T using an allele specific PCR technique. Genotype distributions were then compared. Results:The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian patients were 26%, 8% and 66% andin healthy controls were 45%, 5% and 50%, respectively (p=0.03). Risk of developing breast cancer was found to besignificantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47, 1.11-1.93; P=0.007), GT+TT (OR, 2.32,1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and the T allele (OR 1.62 , 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). Therewere 2.76 and 2.28 fold increase risks of developing breast cancer associated with the TT and GT genotypes in ourcases. A significant correlation was also found between the BRCA1 3’UTR variants with the stage of the disease anddistant metastasis but not with age, grade, and ER, PR and her2/neu status. Conclusion : The rs8176318G/T in the3’untranslated region (UTR) of the BRCA1 gene was found to be associatedwith increased susceptibility to breastcancer in our study population, increased risk being noted with the GT and TT genotypes. Further association studiesare needed to confirm this finding in other regions of Saudi Arabia.