Do one-stage indications predict success following two-stage arthroplasty for chronic periprosthetic joint infection?

Introduction: The 2018 International Consensus Meeting (ICM) proposed criteria for one-stage exchange arthroplasty in treating periprosthetic joint infection (PJI). Our study aimed to determine what proportion of PJI patients met the 2018 ICM criteria and how this affected infection-free survivorship for patients. Methods: All chronic PJI patients treated with two-stage exchange within our institution between 2017–2020 were retrospectively reviewed. Included cases met 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI and had a 2-year minimum follow-up. Treatment success was defined as Tier 1A in the 2019 MSIS working group definition. ICM one-stage criteria included non-immunocompromised host, absence of sepsis, adequate soft tissue for closure, known preoperative pathogen, and susceptibility. Immunocompromised host was analyzed as two separate definitions. Kaplan–Meier survivorship, Cox regression, and univariate analyses were performed. Results: A total of 293 chronic PJI patients were included. Overall, treatment failure occurred in 64/293 (21.8 %) patients. Only 13 % (n=37) met ICM criteria definition no. 1 for one-stage exchange; 12 % (n=33) met definition no. 2. In both definitions, infection-free survivorship at 2 years did not differ between patients who met and did not meet criteria (p&gt;0.05). Cox proportional hazard regression analyses demonstrated that the only variable predicting treatment failure was knee joint involvement (p=0.01). Conclusions: We found that a very limited number of chronic PJI patients were suitable for a one-stage exchange. Furthermore, the supposition that healthier hosts with known pathogens (the basis of the ICM criteria) yield better PJI treatment outcomes was not observed. These results justify the ongoing multicenter randomized control trial comparing one-stage versus two-stage treatment for chronic PJI.</p

Synthesis of silver nanoparticles using Ulva lactuca, Sargassum denticulatum, Spirulina platensis and Chlorella vulgaris

Nowadays, we need to develop eco-friendly nanoparticles synthesis process that does not use toxic chemicals in the synthesis methods. Biological synthesis of nanomaterials is cheaper, innovative and environmental friendly. From this point, the present study focused on the synthesis of silver nanoparticles from the extracts of Ulva lactuca, Sargassum denticulatum, Spirulina platensis and Chlorella vulgaris. Characterizations were performed by UV-Visible Spectroscopy (UV-Vis), X-ray Diffraction (XRD) and particle morphology, and size of silver nanoparticles were observed by transmission electron microscope (TEM) It was found spherical shaped nanoparticles sizes with average diameter of approximately 20,78.8, 31 and 50 nm from the extracts of the four algal species (Ulva lactuca, Sargassum denticulatum, Chlorella vulgaris and Spirulina platensis), respectively. So, the extracts from algae were screened for phytochemicals analysis followed by FT-IR to know the present chemical functional groups. Therefore, the present study illustrates silver nanoparticles can play an influential role in nanobiotechnology field in future

Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier

Neuroblastoma (NB) is the most common extracranial solid tumor often diagnosed in childhood. Despite intense efforts to develop a successful treatment, current available therapies are still challenged by high rates of resistance, recurrence and progression, most notably in advanced cases and highly malignant tumors. Emerging evidence proposes that this might be due to a subpopulation of cancer stem cells (CSCs) or tumor-initiating cells (TICs) found in the bulk of the tumor. Therefore, the development of more targeted therapy is highly dependent on the identification of the molecular signatures and genetic aberrations characteristic to this subpopulation of cells. This review aims at providing an overview of the key molecular players involved in NB CSCs and focuses on the experimental evidence from NB cell lines, patient-derived xenografts and primary tumors. It also provides some novel approaches of targeting multiple drivers governing the stemness of CSCs to achieve better anti-tumor effects than the currently used therapeutic agents

Midterm Survivorship and Complications of Total Knee Arthroplasty in Patients with Dwarfism

Background Dwarfism is associated with skeletal dysplasias and joint deformities that frequently result in osteoarthritis requiring treatment with total knee arthroplasty (TKA). These surgeries can be challenging because of alignment deformities, poor bone stock, and smaller components. This study aims to compare TKA implant survivorship and complications between dwarf and nondwarf patients. Methods A retrospective case-control study was performed from 1997-2014 evaluating 115 TKAs in patients under the height threshold of 147.32 cm. This cohort was compared with 164 patients of normal height. Medical records were reviewed for demographics, surgical characteristics, and outcomes. All cases had 2-year minimum follow-up. Results The revision rate was 8.7% in dwarfs compared with 3.7% in controls (P = .08). The 2-, 5-, and 10-year implant survivorship in dwarfs was 96.4%, 92.5%, and 90.2%, respectively; and 96.6%, 95.6%, and 94.8% for controls, respectively (P = .24). Dwarfs underwent significantly more manipulations for arthrofibrosis (P = .002). There was greater femoral (17.4% vs 2.1%, P < .01) and tibial (6.5% vs 2.7%, P < .01) component overhang in dwarfs compared with controls. Conclusion Despite a 2-fold increase in the revision rate of the dwarf cohort, the midterm survivorship is comparable between the dwarf and nondwarf patients. However, dwarfs were more likely to become stiff and undergo manipulation; the increased propensity for stiffness may be associated with oversized components, as evidenced by greater component overhang. Surgeons should be aware of this increased risk and may consider using smaller or customized implants to account for the morphological differences in this patient population

Comparison of new and emerging SARS-CoV-2 variant transmissibility through active contact testing. A comparative cross-sectional household seroprevalence study

Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding

Proposed quality indicators and recommended standard reporting items in performance of EBUS bronchoscopy: An official world association for bronchology and interventional pulmonology expert panel consensus statement

Background: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. Methods: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. Results: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. Conclusion: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres

Assessment of treatment burden and its impact on quality of life in dialysis-dependent and pre-dialysis chronic kidney disease patients

Background The management of chronic kidney disease (CKD) and its complications places a significant burden on patients, resulting in impairment of their health-related quality of life (HR-QOL). Little is known about treatment-related burden in pre-dialysis and hemodialysis (HD) CKD patients. Objective This study aimed to investigate the magnitude of treatment-related burden and its impact on HR-QOL among patients with CKD. Methods This was a prospective, cross-sectional study to assess treatment-related burden and HR-QOL among patients with CKD in Qatar. Treatment-related burden and HR-QOL were assessed quantitatively using the Treatment Burden Questionnaire (TBQ) and the Kidney Disease Quality of Life (KDQOL™) questionnaire, respectively. The total TBQ score ranges from 0 to 150, with a higher score indicating higher treatment burden, while the range of total possible scores for the KDQOL™ are from 0 to 3600 with higher transformed score indicating better QOL. Pre-dialysis and hemodialysis (HD) CKD patients who had regular follow-up appointments at Fahad Bin Jassim Kidney Center in Qatar were enrolled. Data were analyzed descriptively and inferentially using SPSS version-24. Results Two hundred-eighty CKD patients (HD = 223 and pre-dialysis = 57) were included in the analyses (response rate 60.9%). Approximately 35% of the participants reported moderate to high treatment-related burden (TBQ global score 51–150). HD patients experienced significantly higher treatment burden compared to pre-dialysis patients with a median (IQR) score of 45 (36) versus 25 (33), respectively (p < 0.001). Medication burden and lifestyle changes burden were the highest perceived treatment-related burden. Overall, the perceived median (IQR) HR-QOL measured using the KDQOL-36™ among the participants was 2280.6 (1096.2) compared to the maximum global score of 3600. Similarly, the HD patients demonstrated significantly lower HR-QOL compared to the pre-dialysis patients [median (IQR) score of 2140 (1100) vs. 2930 (995), respectively; p < 0.001). There was a strong negative correlation between TBQ score and KDQOL-36™ score [rs (251) = −0.616, p < 0.001], signifying that HR-QOL decreases as treatment burden increases. Conclusions This study suggests that a considerable proportion of CKD patients suffered from treatment-related burden and deterioration in HR-QOL at a varying degree of seriousness. HD patients experienced significantly higher burden of treatment and lower HR-QOL compared to pre-dialysis patients and that HR-QOL declines as treatment burden increases. Therefore, treatment-related burden should be considered in CKD management and factors that increase it should be considered when designing healthcare interventions directed to CKD patients.This research was funded by Qatar University under Student Grant number QUST-CPH-SPR/2017-19 [Approved amount QAR 20,000.00 (~US$ 5,480)]. The funders had no role in the design, planning, and implementation of the study. The content is the sole responsibility of the authors.Scopu

Characterization and mitigation of gene expression burden in mammalian cells

Despite recent advances in circuit engineering, the design of genetic networks in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here, we demonstrate that transiently expressed genes in mammalian cells compete for limited transcriptional and translational resources. This competition results in the coupling of otherwise independent exogenous and endogenous genes, creating a divergence between intended and actual function. Guided by a resource-aware mathematical model, we identify and engineer natural and synthetic miRNA-based incoherent feedforward loop (iFFL) circuits that mitigate gene expression burden. The implementation of these circuits features the use of endogenous miRNAs as elementary components of the engineered iFFL device, a versatile hybrid design that allows burden mitigation to be achieved across different cell-lines with minimal resource requirements. This study establishes the foundations for context-aware prediction and improvement of in vivo synthetic circuit performance, paving the way towards more rational synthetic construct design in mammalian cells

Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles

Hypoxia has been shown to be a key factor inhibiting the successful treatment of solid tumours. Existing strategies for reducing hypoxia, however, have shown limited efficacy and/or adverse side effects. The aim of this study was to investigate the potential for reducing tumour hypoxia using an orally delivered suspension of surfactant-stabilised oxygen nanobubbles. Experiments were carried out in a mouse xenograft tumour model for human pancreatic cancer (BxPc-3 cells in male SCID mice). A single dose of 100 μL of oxygen saturated water, oxygen nanobubbles or argon nanobubbles was administered via gavage. Animals were sacrificed 30 minutes post-treatment (3 per group) and expression of hypoxia-inducible-factor-1α (HIF1α) protein measured by real time quantitative polymerase chain reaction and Western blot analysis of the excised tumour tissue. Neither the oxygen saturated water nor argon nanobubbles produced a statistically significant change in HIF1α expression at the transcriptional level. In contrast, a reduction of 75% and 25% in the transcriptional and translational expression of HIF1α respectively (p<0.001) was found for the animals receiving the oxygen nanobubbles. This magnitude of reduction has been shown in previous studies to be commensurate with an improvement in outcome with both radiation and drug-based treatments. In addition, there was a significant reduction in the expression of vascular endothelial growth factor (VEGF) in this group and corresponding increase in the expression of arrest-defective protein 1 homolog A (ARD1A)

Comparison of new and emerging SARS-CoV-2 variant transmissibility through active contact testing. A comparative cross-sectional household seroprevalence study.

Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding