Abstract - Prosthetic joint infection (PJI) still remains a significant problem. In line with the forecasted rise in joint replacement procedures, the number of cases of PJI is also anticipated to ...rise. The formation of biofilm by causative pathogens is central to the occurrence and the recalcitrance of PJI. The subject of microbial biofilms is receiving increasing attention, probably as a result of the wide acknowledgement of the ubiquity of biofilms in the natural, industrial, and clinical contexts, as well as the notorious difficulty in eradicating them. In this review, we discuss the pertinent issues surrounding PJI and the challenges posed by biofilms regarding diagnosis and treatment. In addition, we discuss novel strategies of prevention and treatment of biofilm-related PJI.
Studies report high burnout prevalence among resident physicians, with little consensus on methods to effectively reduce it.
This systematic literature review explores the efficacy of interventions ...in reducing resident burnout.
PubMed, Embase, and Web of Science were searched using these key words:
and
,
, or
. We excluded review articles, editorials, letters, and non-English-language articles. We abstracted data on study characteristics, population, interventions, and outcomes. When appropriate, data were pooled using random effects meta-analysis to account for between-study heterogeneity. Study quality was assessed using Newcastle-Ottawa Scale (cohort studies) and Jadad scale (randomized control trials RCTs).
Of 1294 retrieved articles, 19 (6 RCTs, 13 cohort studies) enrolling 2030 residents and examining 12 interventions met criteria, with 9 studying the 2003 and 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour restrictions. Work hour reductions were associated with score decrease (mean difference, -2.73; 95% confidence interval (CI) -4.12 to -1.34;
< .001) and lower odds ratio (OR) for residents reporting emotional exhaustion (42%; OR = 0.58; 95% CI 0.43-0.77;
< .001); a small, significant decrease in depersonalization score (-1.73; 95% CI -3.00 to -0.46;
= .008); and no effect on mean personal accomplishment score (0.93; 95% CI -0.19-2.06;
= .10) or for residents with high levels of personal accomplishment (OR = 1.01; 95% CI 0.67-1.54;
= .95). Among interventions, self-care workshops showed decreases in depersonalization scores, and a meditation intervention reduced emotional exhaustion.
The ACGME work hour limits were associated with improvement in emotional exhaustion and burnout.
Genome integrity relies on the accuracy of DNA metabolism, but as appreciated for more than four decades, transcription enhances mutation and recombination frequencies. More recent research provided ...evidence for a previously unforeseen link between RNA and DNA metabolism, which is often related to the accumulation of DNA–RNA hybrids and R-loops. In addition to physiological roles, R-loops interfere with DNA replication and repair, providing a molecular scenario for the origin of genome instability. Here, we review current knowledge on the multiple RNA factors that prevent or resolve R-loops and consequent transcription–replication conflicts and thus act as modulators of genome dynamics.
The discovery of epigenetic modulators (writers, erasers, readers, and remodelers) has shed light on previously underappreciated biological mechanisms that promote diseases. With these insights, ...novel biomarkers and innovative combination therapies can be used to address challenging and difficult to treat disease states. This review highlights key mechanisms that epigenetic writers, erasers, readers, and remodelers control, as well as their connection with disease states and recent advances in associated epigenetic therapies.
Background Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This was the first ...systematic review with the objective of summarizing evidence on HZ burden in adults with asthma. Methods A global systematic literature review (SLR) and meta-analysis was conducted (Medline and Embase, 2003–2024), on HZ burden (incidence, risk, complications) in adults (≥18 years) with asthma. Results There were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% confidence interval CI 4.68–6.96) in ≥18-year-olds (4.20 3.09–5.70 in <60-year-olds versus 10.33 9.17–11.64 in ≥60-year-olds). The pooled rate ratio for developing HZ was 1.23 1.11–1.35 in ≥18-year-olds, and 1.36 1.15–1.61 in ≥50-year-olds. The risk of HZ was higher in people with asthma using systemic corticosteroids; long-acting beta-agonists plus inhaled corticosteroids; and “add-on therapy”. Asthma was also associated with an increased risk of post-herpetic neuralgia (odds ratio, OR 1.21 1.06–1.37) and HZ ophthalmicus (OR 1.9 1.1–3.2). Differences in study design, setting, case definitions, and follow-up durations led to heterogeneity. Conclusions This SLR and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups, and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care.
The humoral immune system comprises B cells and plasma cells, which play important roles in organ transplantation, ranging from the production of both protective and injurious antibodies as well as ...cytokines that can promote operational tolerance. Recent data from conditions outside of transplantation have identified a novel human B-cell subset that expresses the transcription factor T-bet and exerts pleiotropic functions by disease state. Here, we review the generation, activation, and functions of the T-bet+ B-cell subset outside of allotransplantation, and consider the relevance of this subset as mediators of allograft injury.
Regulatory T cells (Treg), a subset of CD4+ T cells, are potent regulators of immune reactions, which have been shown to be a promising therapeutic alternative to toxic immunosuppressive drugs. Data ...support the utility of Treg in managing immunopathologies, including solid organ transplant rejection, graft-versus-host disease, and autoimmune disorders. Notably, reports suggest that interleukin-2 (IL-2) is critical to survival of Treg, which constitutively express high levels of CD25, that is, the IL-2 receptor α-chain, and are exquisitely sensitive to IL-2, even at very low concentrations in contrast to effector T cells, which only upregulate IL-2 receptor α-chain on activation. This has led to the notion of using low doses of exogenous IL-2 therapeutically to modulate the immune system, specifically Treg numbers and function. Here, we summarize developments of clinical experience with low-dose IL-2 (LD-IL-2) as a therapeutic agent. So far, no clinical data are available to support the therapeutic use of LD-IL-2 therapy in the solid organ transplant setting. For the latter, fine-tuning by biotechnological approaches may be needed because of the narrow therapeutic window and off-target effects of LD-IL-2 therapy and so to realize the therapeutic potential of this molecule.
Patients with decompensated end-stage liver disease (ESLD) are at increased risk for mortality, and only liver transplantation (LT) offers meaningful hope for survival. These patients are at risk for ...kidney dysfunction through the continuum of care for ESLD including LT. We discuss the role of accurate estimation and measurement of baseline glomerular filtration rate in assessment of kidney dysfunction among those with ESLD. Optimizing kidney function is a vital goal in the management of these patients before LT. In this review, we summarize salient aspects of assessing and optimizing kidney function in this patient population. Precipitating factors and different causes of acute kidney injury are discussed, including hepatorenal syndrome. We further review treatment options for acute kidney injury including volume management. The role of vasopressor therapy, renal replacement therapy, and transjugular intrahepatic portosystemic shunting are discussed.
Through the effective targeting of the adaptive immune system, solid organ transplantation became a life-saving therapy for organ failure. However, beyond 1 y of transplantation, there is little ...improvement in transplant outcomes. The adaptive immune response requires the activation of the innate immune system. There are no modalities for the specific targeting of the innate immune system involvement in transplant rejection. However, the recent discovery of innate allorecognition and innate immune memory presents novel targets in transplantation that will increase our understanding of organ rejection and might aid in improving transplant outcomes. In this review, we look at the latest developments in the study of innate allorecognition and innate immune memory in transplantation.
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