Chronic kidney disease (CKD) affects over 10% of the global population and poses significant challenges for societies and health care systems worldwide. To illustrate these challenges and inform ...cost-effectiveness analyses, we undertook a comprehensive systematic scoping review that explored costs, health-related quality of life (HRQoL) and life expectancy (LE) amongst individuals with CKD. Costs were examined from a health system and societal perspective, and HRQoL was assessed from a societal and patient perspective. Papers published in English from 2015 onward found through a systematic search strategy formed the basis of the review. All costs were adjusted for inflation and expressed in US$ after correcting for purchasing power parity. From the health system perspective, progression from CKD stages 1-2 to CKD stages 3a-3b was associated with a 1.1-1.7 fold increase in per patient mean annual health care cost. The progression from CKD stage 3 to CKD stages 4-5 was associated with a 1.3-4.2 fold increase in costs, with the highest costs associated with end-stage renal disease at $20,110 to $100,593 per patient. Mean EuroQol-5D index scores ranged from 0.80 to 0.86 for CKD stages 1-3, and decreased to 0.73-0.79 for CKD stages 4-5. For treatment with renal replacement therapy, transplant recipients incurred lower costs and demonstrated higher HRQoL scores with longer LE compared to dialysis patients. The study has provided a comprehensive updated overview of the burden associated with different CKD stages and renal replacement therapy modalities across developed countries. These data will be useful for the assessment of new renal services/therapies in terms of cost-effectiveness.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The fear-avoidance model of chronic pain holds that individuals who catastrophize in response to injury are at risk for pain-related fear and avoidance behavior, and ultimately ...prolonged pain and disability.
Purpose
Based on the hypothesis that the predictive power of the fear-avoidance model would be enhanced by consideration of positive psychological constructs, the present study examined inclusion of pain resilience and self-efficacy in the model.
Methods
Men and women (N = 343) who experienced a recent episode of back pain were recruited in a longitudinal online survey study. Over a 3-month interval, participants repeated the Pain Resilience Scale, Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia, Pain Self-Efficacy Questionnaire, the McGill Pain Questionnaire, and NIH-recommended measures of pain, depressive symptoms, and physical dysfunction. Structural equation modeling assessed the combined contribution of pain resilience and pain catastrophizing to 3-month outcomes through the simultaneous combination of kinesiophobia and self-efficacy.
Results
An expanded fear-avoidance model that incorporated pain resilience and self-efficacy provided a good fit to the data, Χ2 (df = 14, N = 343) = 42.09, p = .0001, RMSEA = 0.076 (90% CI: 0.05, 0.10), CFI = 0.97, SRMR = 0.03, with higher levels of pain resilience associated with improved 3-month outcomes on measures of pain intensity, physical dysfunction, and depression symptoms.
Conclusions
This study supports the notion that the predictive power of the fear-avoidance model of pain is enhanced when individual differences in both pain-related vulnerability (e.g., catastrophizing) and pain-related protective resources (e.g., resilience) are considered.
Pain resilience protects against development of fear following acute back injury and is longitudinally associated with less pain, distress, and disability after three months.
Abstract Introduction Kinematic alignment in TKA seeks to more anatomically align the knee prosthesis in order to promote more physiologic kinematics. However, there are questions about the ...durability, function, and complication rate of a non-mechanically aligned TKA. Therefore, the purpose of this study is to perform a systematic review and meta-analysis to evaluate early outcomes following kinematic alignment. Materials and Methods Two independent reviewers performed a systematic review of the English literature using both the MEDLINE and EMBASE databases searching for studies on kinematic TKA. Out of the initial 839 published reports, 9 studies were included in the review. Four randomized controlled trials comparing outcomes of kinematic and conventional alignment TKA were identified. Data was extracted and aggregated using inverse variance and Mantel-Haenszel fixed effects meta-analysis. Results Of an aggregated 877 kinematic TKAs, the cumulative survivorship was 97.4% at weighted mean follow-up of 37.9 months. The most common reasons for revision were patellofemoral problems in 8 patients (1.2 percent). We found no difference in complication rate between the 229 kinematic and 229 conventional TKA patients (3.9% vs. 4.4%, p=0.83). The kinematic TKA group had a higher combined postoperative Knee Society Score than the conventional TKA group (mean difference 9.1 points, 95% CI 5.2-13.0 points, p<0.001). Conclusions Small deviations from the traditional mechanical axis alignment in TKA do not appear to impact overall survivorship or complication rates at short-term follow-up. Functional outcome as measured by the Knee Society Score favored kinematic alignment. These preliminary results illustrate the concept that there may be more than a single alignment target for all patients undergoing primary TKA.
Abstract Background As outpatient total hip (THA) and knee arthroplasty (TKA) increases in popularity, concerns exist about the safety of discharging patients home the same day. The purpose of this ...study is to determine the complications associated with outpatient total joint arthroplasty and to identify high-risk patients who should be excluded from these protocols. Methods We queried the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database for all patients who underwent primary TKA or THA from 2011 to 2014. Demographic variables, medical comorbidities, and 30-day complication, readmission, and reoperation rates were compared between outpatient and traditional inpatient procedures. A multivariate logistic regression analysis was then performed to identify independent risk factors of poor short-term outcomes. Results Of the total 169,406 patients who underwent TJA, 1,220 were outpatient (0.7%). The outpatient and inpatient groups had an overall complication rate of 8% and 16%, respectively. Patients over age 70, those with malnutrition, cardiac history, smoking history, or diabetes mellitus are at higher risk for readmission and complications (all p<0.05). Surprisingly, outpatient TJA alone did not increase the risk of readmission (OR 0.652, 95% CI 0.243-1.746, p=0.395) or reoperation (OR 1.168, 95% CI 0.374-3.651, p=0.789), and was a negative independent risk factor for complications (OR 0.459, 95% CI 0.371-0.567, p<0.001). Conclusion With the resources available in a hospital setting, outpatient TJA may be a safe option, but only in select, healthier patients. Care should be taken to extrapolate these results to an outpatient facility, where complications may be more difficult to manage.
Class II tetramer reagents for eleven common DR alleles and a DP allele prevalent in the world population were used to identify SARS-CoV-2 CD4+ T cell epitopes. A total of 112, 28 and 42 epitopes ...specific for Spike, Membrane and Nucleocapsid, respectively, with defined HLA-restriction were identified. Direct ex vivo staining of PBMC with tetramer reagents was used to define immunodominant and subdominant T cell epitopes and estimate the frequencies of these T cells in SARS-CoV-2 exposed and naïve individuals. Majority of SARS-CoV-2 epitopes identified have <67% amino acid sequence identity with endemic coronaviruses and are unlikely to elicit high avidity cross-reactive T cell responses. Four SARS-CoV-2 Spike reactive epitopes, including a DPB1*04:01 restricted epitope, with ≥67% amino acid sequence identity to endemic coronavirus were identified. SARS-CoV-2 T cell lines for three of these epitopes elicited cross-reactive T cell responses to endemic cold viruses. An endemic coronavirus Spike T cell line showed cross-reactivity to the fourth SARS-CoV-2 epitope. Three of the Spike cross-reactive epitopes were subdominant epitopes, while the DPB1*04:01 restricted epitope was a dominant epitope. Frequency analyses showed Spike cross-reactive T cells as detected by tetramers were present at relatively low frequency in unexposed people and only contributed a small proportion of the overall Spike-specific CD4+ T cells in COVID-19 convalescent individuals. In total, these results suggested a very limited number of SARS-CoV-2 T cells as detected by tetramers are capable of recognizing ccCoV with relative high avidity and vice versa. The potentially supportive role of these high avidity cross-reactive T cells in protective immunity against SARS-CoV-2 needs further studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A dysregulated proinflammatory cytokine response is characteristic of severe coronavirus infections caused by SARS-CoV-2, yet our understanding of the underlying mechanism responsible for this ...imbalanced immune response remains incomplete. Processing bodies (PBs) are cytoplasmic membraneless ribonucleoprotein granules that control innate immune responses by mediating the constitutive decay or suppression of mRNA transcripts, including many that encode proinflammatory cytokines. PB formation promotes turnover or suppression of cytokine RNAs, whereas PB disassembly corresponds with the increased stability and/or translation of these cytokine RNAs. Many viruses cause PB disassembly, an event that can be viewed as a switch that rapidly relieves cytokine RNA repression and permits the infected cell to respond to viral infection. Prior to this submission, no information was known about how human coronaviruses (CoVs) impacted PBs. Here, we show SARS-CoV-2 and the common cold CoVs, OC43 and 229E, induced PB loss. We screened a SARS-CoV-2 gene library and identified that expression of the viral nucleocapsid (N) protein from SARS-CoV-2 was sufficient to mediate PB disassembly. RNA fluorescent in situ hybridization revealed that transcripts encoding TNF and IL-6 localized to PBs in control cells. PB loss correlated with the increased cytoplasmic localization of these transcripts in SARS-CoV-2 N protein-expressing cells. Ectopic expression of the N proteins from five other human coronaviruses (OC43, MERS, 229E, NL63 and SARS-CoV) did not cause significant PB disassembly, suggesting that this feature is unique to SARS-CoV-2 N protein. These data suggest that SARS-CoV-2-mediated PB disassembly contributes to the dysregulation of proinflammatory cytokine production observed during severe SARS-CoV-2 infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose of Review
Despite significant progress in recent years, the diagnosis of periprosthetic joint infection (PJI) remains a challenge and no gold standard test exists. A combination of ...serological, synovial, microbiological, histological, and radiological investigations is performed that are expensive, often invasive, and imperfect. Novel biomarkers and molecular methods have shown promise in recent years. The purpose of this review is to provide an update about the diagnostic recommendations for PJI and cover a selection of emerging diagnostic tools.
Recent Findings
Recent literature highlights a new evidence-based definition for diagnosing hip and knee PJI that shows excellent performance on formal external multi-institutional validation. There is also increasing evidence to support the measurement of selected biomarkers in serum and synovial fluid, such as alpha-defensin, D-dimer, and interleukin-6. Finally, the emerging utility of next-generation sequencing for pathogen identification is discussed.
Summary
In summary, we describe current recommendations and emerging tests for the diagnosis of PJI. Residual limitations and directions for future research are also discussed.
Developing and applying a novel and sustainable energy crop is essential to reach an efficient and economically feasible technology for bioenergy production. In this study, plant tissue culture, also ...referred to as in vitro culture, is introduced as one of the most promising and environmentally friendly methods for the sustainable supply of biofuels. The current study investigates the potential of in vitro -grown industrial hemp calli obtained from leaf, root, and stem explants as a new generation of energy crop. For this purpose, the in vitro grown explants were first fully characterized in terms of elemental and chemical composition. Secondly, HTL experiments were designed by Design Expert 11 with a particular focus on biocrude. Finally, the chemical components, functional groups, and petroleum-like hydrocarbons present in the biocrude were identified by PY-GCMS. A 22.61 wt.% biocrude was produced for the sample grown through callogenesis of the leaf (CL). The obtained biocrude for CL consisted of 19.55% acids, 0.42% N compounds, 15.44% ketones, 16.03% aldehydes, 2.21% furans, 20.01% aromatics, 5.2% alcohols, and 19.88% hydrocarbons. To the best of the authors' knowledge, this is the first report that in vitro -grown biomass is hydrothermally liquefied toward biocrude production; the current work paves the way for integrating plant tissue culture and thermochemical processes for the generation of biofuels and value-added chemicals.
Amphibian skin is a mucosal surface in direct and continuous contact with a microbially diverse and laden aquatic and/or terrestrial environment. As such, frog skin is an important innate immune ...organ and first line of defence against pathogens in the environment. Critical to the innate immune functions of frog skin are the maintenance of physical, chemical, cellular, and microbiological barriers and the complex network of interactions that occur across all the barriers. Despite the global decline in amphibian populations, largely as a result of emerging infectious diseases, we understand little regarding the cellular and molecular mechanisms that underlie the innate immune function of amphibian skin and defence against pathogens. In this review, we discuss the structure, cell composition and cellular junctions that contribute to the skin physical barrier, the antimicrobial peptide arsenal that, in part, comprises the chemical barrier, the pattern recognition receptors involved in recognizing pathogens and initiating innate immune responses in the skin, and the contribution of commensal microbes on the skin to pathogen defence. We briefly discuss the influence of environmental abiotic factors (natural and anthropogenic) and pathogens on the immunocompetency of frog skin defences. Although some aspects of frog innate immunity, such as antimicrobial peptides are well-studied; other components and how they contribute to the skin innate immune barrier, are lacking. Elucidating the complex network of interactions occurring at the interface of the frog's external and internal environments will yield insight into the crucial role amphibian skin plays in host defence and the environmental factors leading to compromised barrier integrity, disease, and host mortality.
The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals ...program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, we show that microbiota-derived stimulator of interferon genes (STING) agonists induce type I interferon (IFN-I) production by intratumoral monocytes to regulate macrophage polarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation with a high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved the efficacy of immune checkpoint blockade (ICB). We validated our findings in individuals with melanoma treated with ICB and showed that the predicted intratumoral IFN-I and immune compositional differences between responder and non-responder individuals can be transferred by fecal microbiota transplantation. Our study uncovers a mechanistic link between the microbiota and the innate TME that can be harnessed to improve cancer therapies.
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•Microbiota-induced type I IFN programs antitumorigenic mononuclear phagocytes (MPs)•Monocytes in the TME produce type I IFN in response to microbial STING agonists•High-fiber diet induces type I IFN, remodels MPs in the TME, and improves ICB efficacy•Microbiota from ICB responders induces IFN-I and shapes the MP landscape in the TME
The gut microbiota tunes the pro/anti-tumorigenic balance of the tumor microenvironment via a STING-type I IFN-dependent mechanism. Feeding a high-fiber diet or transferring the fecal microbiota from immune checkpoint blockade (ICB) responder melanoma individuals triggers this pathway and programs intratumoral mononuclear phagocytes to promote anticancer immunity and ICB efficacy.
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