Inflammasomes are a group of protein complexes built around several proteins, including NLRP3, NLRC4, AIM2 and NLRP6. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase-1, which subsequently induces secretion of potent pro-inflammatory cytokines and a form of cell death called pyroptosis. Inflammasome-mediated processes are important during microbial infections and also in regulating both metabolic processes and mucosal immune responses. We review the functions of the different inflammasome complexes and discuss how aberrations in them are implicated in the pathogenesis of human diseases.

https://www.weizmann.ac.il/immunology/elinav/sites/immunology.elinav/files/2012_elinav_nature_b.pdf

Inflammasomes in health and disease

Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis

Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1β, TNFα, IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.

/pdf/the-role-of-inflammatory-and-anti-inflammatory-cytokines-in-3au3sectyv.pdf

The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis.

Osteoarthritis (OA) has traditionally been classified as a noninflammatory arthritis; however, the dichotomy between inflammatory and degenerative arthritis is becoming less clear with the recognition of a plethora of ongoing immune processes within the OA joint and synovium. Synovitis is defined as inflammation of the synovial membrane and is characteristic of classical inflammatory arthritidies. Increasingly recognized is the presence of synovitis in a significant proportion of patients with primary OA, and based on this observation, further studies have gone on to implicate joint inflammation and synovitis in the pathogenesis of OA. However, clinical OA is not one disease but a final common pathway secondary to many predisposing factors, most notably age, joint trauma, altered biomechanics, and obesity. How such biochemical and mechanical processes contribute to the progressive joint failure characteristic of OA is tightly linked to the interplay of joint damage, the immune response to perceived damage, and the subsequent state of chronic inflammation resulting in propagation and progression toward the phenotype recognized as clinical OA. This review will discuss a wide range of evolving data leading to our current hypotheses regarding the role of immune activation and inflammation in OA onset and progression. Although OA can affect any joint, most commonly the knee, hip, spine, and hands, this review will focus primarily on OA of the knee as this is the joint most well characterized by epidemiologic, imaging, and translational studies investigating the association of inflammation with OA.

/pdf/role-of-inflammation-in-the-pathogenesis-of-osteoarthritis-2aaujdkp8y.pdf

Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations

This review describes the features of modern infrared imaging technology and the standardization protocols for thermal imaging in medicine. The technique essentially uses naturally emitted infrared radiation from the skin surface. Recent studies have investigated the influence of equipment and the methods of image recording. The credibility and acceptance of thermal imaging in medicine is subject to critical use of the technology and proper understanding of thermal physiology. Finally, we review established and evolving medical applications for thermal imaging, including inflammatory diseases, complex regional pain syndrome and Raynaud's phenomenon. Recent interest in the potential applications for fever screening is described, and some other areas of medicine where some research papers have included thermal imaging as an assessment modality. In certain applications thermal imaging is shown to provide objective measurement of temperature changes that are clinically significant.

https://iopscience.iop.org/article/10.1088/0967-3334/33/3/R33/pdf

Infrared thermal imaging in medicine

Background: Digital infrared thermal imaging is a means of measuring the heat radiated from the skin surface. Our goal was to develop and assess the reproducibility of serial infrared measurements of the knee and to assess the association of knee temperature by region of interest with radiographic severity of knee Osteoarthritis (rOA).

Methods: A total of 30 women (15 Cases with symptomatic knee OA and 15 age-matched Controls without knee pain or knee OA) participated in this study. Infrared imaging was performed with a Meditherm Med2000™ Pro infrared camera. The reproducibility of infrared imaging of the knee was evaluated through determination of intraclass correlation coefficients (ICCs) for temperature measure- ments from two images performed 6 months apart in Controls whose knee status was not expected to change. The average cutaneous temperature for each of five knee regions of interest was extracted using WinTes software. Knee x-rays were scored for severity of rOA based on the global Kellgren-Lawrence grading scale.

Results: The knee infrared thermal imaging procedure used here demonstrated long-term reproducibility with high ICCs (0.50–0.72 for the various regions of interest) in Controls. Cutaneous temperature of the patella (knee cap) yielded a significant correlation with severity of knee rOA (R = 0.594, P = 0.02).

Conclusion: The skin temperature of the patellar region correlated with x-ray severity of knee OA. This method of infrared knee imaging is reliable and as an objective measure of a sign of inflammation, temperature, indicates an interrelationship of inflammation and structural knee rOA damage.

https://journals.sagepub.com/doi/pdf/10.4137/CMAMD.S5916

Patellar Skin Surface Temperature by Thermography Reflects Knee Osteoarthritis Severity

Objective To estimate the incidence of and define risk factors for postpartum infectious complications after vaginal birth after cesarean (VBAC) complicated by chorioamnionitis. Study Design A secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Cesarean Registry was performed. The primary outcome was a composite of postpartum infection: endometritis, sepsis, pelvic abscess, urinary tract infection, necrotizing fasciitis, and septic pelvic thrombophlebitis. Peripartum predictors were compared using parametric and nonparametric tests, as appropriate, and multivariate predictors assessed using logistic regression. Results A total of 559 subjects had chorioamnionitis in labor and a successful VBAC. Twenty-four (4.3%) subjects experienced the primary outcome, mainly due to endometritis (19/24). Significant factors included preterm delivery Conclusion Nearly 5% of women with chorioamnionitis had a postpartum infectious complication after vaginal delivery, with higher rates in those delivering at

Chorioamnionitis and Infectious Complications after Vaginal Delivery.

Objective Outside pregnancy, nitrofurantoin, ciprofloxacin and sulfamethoxazole-trimethoprim (SMZ-TMP) are first-line therapy (FLT) for lower urinary tract infections (LUTIs). Optimal antibiotics for LUTI have been extrapolated based on expert opinion. Progression to pyelonephritis and adverse obstetric outcomes were compared between women who received FLT and those given alternative antibiotics. Methods This study includes a retrospective cohort of women with LUTI, including asymptomatic bacteriuria and acute cystitis at single health care system from July 2013 to May 2019. Women receiving FLT, defined as nitrofurantoin or SMZ-TMP, were compared with those receiving nonfirst-line therapy (nFLT). Primary outcome was progression to pyelonephritis. Secondary outcomes included pyelonephritis-related anemia, sepsis, length of stay, preterm birth (PTB), and low birth weight (LBW). Logistic regression was used to calculate odds of outcomes. Results Of 476 women, 336 (70.6%) received FLT and 140 (29.4%) received nFLT. Women receiving FLT were more likely having BMI ≥ 40 (p = 0.04). Progression to pyelonephritis did not differ (5.8 vs. 8.2%; p = 0.44), nor did other pyelonephritis-related outcomes. After controlling for confounders, no difference in odds of progression to pyelonephritis was seen (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 0.42, 2.49). FLT was not associated with PTB or LBW (aOR 0.60, 95% CI 0.29, 1.26) after controlling for confounders. Conclusion Receipt of antibiotics other than nitrofurantoin or SMZ-TMP for LUTI in pregnancy was not associated with increased risk of progression to pyelonephritis, PTB, or LBW.

/pdf/beyond-expert-opinion-a-comparison-of-antibiotic-regimens-1x2hey7w10.pdf

Beyond Expert Opinion: A Comparison of Antibiotic Regimens for Infectious Urinary Tract Pathology in Pregnancy

Objective Guidelines for the management of chorioamnionitis include intrapartum antibiotics, while postpartum antibiotics after spontaneous vaginal delivery (SVD) are reserved high-risk women. Our objective is to describe the incidence of and risk factors for postpartum infection after SVD complicated by chorioamnionitis. Study Design This is a retrospective study of SVDs with clinically diagnosed chorioamnionitis at a single center. The primary outcome was a composite of postpartum infection. Women who developed the primary outcome were compared with those who did not using bivariate statistics. Regression models were developed to estimate adjusted odds of outcomes. Results In this cohort, 346 women underwent SVD complicated by chorioamnionitis. Of these, 23 (6.6%) developed postpartum infections (endometritis n = 7, urinary tract infection/pyelonephritis n = 6, sepsis n = 4, and perineal wound infection n = 6). Receipt of antibiotics intra- or postpartum did not differ between groups, but women with postpartum infections were more likely to deliver prior to 32 weeks (17.4 vs. 4.9%, p = 0.04). When controlling for antibiotic use, delivery at  Conclusion Postpartum infections occur in ∼1/15 women delivering vaginally with chorioamnionitis, with those who deliver at

/pdf/risk-factors-for-postpartum-maternal-infection-following-1nvivtl3u0.pdf

Risk Factors for Postpartum Maternal Infection Following Spontaneous Vaginal Delivery Complicated by Chorioamnionitis

Congenital atrioventricular block (CAVB) affects approximately 2% of fetuses of mothers with anti-Ro or anti-La antibodies, regardless of maternal rheumatologic symptoms Anti-Ro and anti-La antibodies are antinuclear antibodies commonly found in autoimmune diseases Congenital atrioventricular block is associated with a relatively high fetal morbidity and mortality, particularly more advanced degrees of block There is significant controversy surrounding surveillance of anti-Ro/La-positive pregnancies and treatment of fetuses diagnosed with CAVB Studies of dexamethasone in the treatment of CAVB have yielded conflicting results, with most suggesting only a limited potential benefit in first- and seconddegree CAVB and in cases complicated by fetal hydrops Larger prospective studies are needed to further evaluate the efficacy of intravenous immunoglobulin in the treatment of CAVB and of intravenous immunoglobulin and hydroxychloroquine in the prevention of CAVB in fetuses of at-risk mothers Surveillance and treatment regimens should be determined on a case-by-case basis, taking into consideration the degree of CAVB, costs, and potential adverse effects of treatment

Controversies in the Management of Isolated Congenital Atrioventricular Block

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