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Chronic visceral pain (CVP) is one of the common symptoms of many diseases triggered by underlying diseases of the internal organs of the human body. Its causes include vascular mechanisms, mechanical factors, persistent inflammation, and unexplained functional mechanisms. Although the pathogenesis is unclear, more and more research has begun to shift from the neuronal aspect to the glial cells in recent years. Some data highlight that the spinal glial cells, particularly the microglia and astrocytes, play an essential role in CVP. Based on this, we highlight the mechanisms of microglia and astrocytes in CVP concerning the release of cytokines, chemokines, and neuroactive substances and alterations in intracellular signaling pathways during the process. Finally, because CVP is widespread in various diseases, we present future perspectives targeting microglia and astrocytes for treatment.

Благодаря прогрессу в области интенсивной терапии многие пациенты с тяжелой патологией выписываются из отделений интенсивной терапии. Однако у части больных сохраняется длительное слабой степени воспаление, восстановление является затяжным, и у них развивается хроническое критическое состояние. Кроме того, у некоторых пациентов наряду с устойчивым воспалением возникают иммуносупрессия и катаболизм. В 2012 году это состояние было выделено в отдельный синдром, который может наблюдаться после тяжелой травмы и ожогов, сепсиса, некротического панкреатита. Один из ведущих клинических проявлений при этом — значительная потеря мышечной массы тела, плохо поддающаяся коррекции. При использовании литературы из базы MedLine описываются современные представления о механизмах саркопении при синдроме устойчивого воспаления, иммуносупрессии и катаболизма и возможные пути оптимальной анаболической поддержки.

Objective:Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.Methods:263 individuals were categorized into four groups: HIV− non-cannabis users (n= 65), HIV+ non-cannabis users (n= 105), HIV+ moderate cannabis users (n= 62), and HIV+ daily cannabis users (n= 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.Results:HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p= .015;p= .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (allps < .05).Conclusions:Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

Aim. Determination of informativeness of leukocyte indices in patients with bronchial asthma, who have comorbid diseases in clinical remission of asthma. Materials and methods. The work based on a single examination of 225 patients with bronchial asthma. Criteria for inclusion in the study are following: the presence of a verified diagnosis of bronchial asthma, the phase of clinical remission. The patients have been divided into 4 groups, taking into account the type of comorbid diseases: the 1 group (53 patients) bronchial asthma was combined with lesions of the upper gastrointestinal tract; the 2 group (73 patients) with allergic rhinitis; the 3 group (76 patients) with hypertension; the 4 group (23 patients) comparison group: the patients without comorbid pathology. According to the clinical blood analysis, 10 leukocyte indices were calculated for each group of patients and their values were analyzed taking into account the frequency and severity of deviations from the reference values. Mathematical processing of the material was carried out using the statistical software package SPSS13.0 for Windows. Results. Using leukocyte indices, it has been revealed that even during the period of clinical remission, almost all examined patients with BA have endogenous intoxication, the severity of which increases in comorbid diseases. Intoxication was inflammatory in nature and, according to the data of leukocyte indices, was due to the presence of persistent inflammation (local and systemic) and during clinical remission. Violation of immunological reactivity has been revealed in most of the examined patients. The presence of correlation relationships of leukocyte indices with a number of biochemical and immunological indicators allows one to exclude the latter from the plan of examination of patients without reducing the quality of their examination: for example, in the conditions of polyclinics, small hospitals, and resorts. Eight leukocyte indices that are the most informative at BA have been selected. Conclusion. Additional information about the condition of BA patients who have comorbid diseases during clinical remission can be used to develop programs for their comprehensive treatment and rehabilitation.

Introduction: Scalp rosacea is scarcely reported in the literature, but it is probably not uncommon. Trichoscopic findings have not been specifically established for this entity. Case Presentation: We report 4 cases of chronic scalp rosacea with trichoscopic evidence of peripilar scaling that resolved without scarring after treatment. Discussion/Conclusion: Chronic and persistent inflammation around the isthmus produced in scalp rosacea may form peripilar scaling resembling that found in lichen planopilaris.

Clinical and morphological manifestation of periodontitis is associated with persistent inflammation of the gingiva, loss of connective tissue attachment, formation of a periodontal pocket and loss...

Hypertrophic scars, resulting from alterations in the normal processes of cutaneous wound healing, are characterized by proliferation of dermal tissue with excessive deposition of fibroblast-derived extracellular matrix proteins, especially collagen, over long periods, and by persistent inflammation and fibrosis. Hypertrophic scars are among the most common and frustrating problems after injury. As current aesthetic surgical techniques become more standardized and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results. However, hypertrophic scars remain notoriously difficult to eradicate because of the high recurrence rates and the incidence of side effects associated with available treatment methods. This review explores the various treatment methods for hypertrophic scarring described in the literature including evidence-based therapies, standard practices, and emerging methods, attempting to distinguish those with clearly proven efficiency from anecdotal reports about therapies of doubtful benefits while trying to differentiate between prophylactic measures and actual treatment methods. Unfortunately, the distinction between hypertrophic scar treatments and keloid treatments is not obvious in most reports, making it difficult to assess the efficacy of hypertrophic scar treatment.

Background:Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases.Methods:This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases.Results:Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models.Conclusion:Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

Syndrome of persistent inflammation, the immune suppression and catabolism in surgery

Treatment modalities developed in intensive care units in recent years have led to the reduction of premature deaths from multiple organ failure (MOF). In patients with late period of MOF, the Chronic Critical Patient symptoms caused by the imbalance between Systemic Inflammatory Response syndrome and Compensatory Anti-inflammatory Response syndrome are observed frequently. Persistent Inflammation, Immunosuppression and Catabolism syndrome (PICS) have been defined in today’s intensive care practice as a catabolic patient group with recurrent episodes of infection with insuppressible inflammatory process. PICS should all be taken into consideration in the presence of persistent inflammation (C-reactive protein >150 μgr/dL), retinol binding protein 10% weight loss or body mass index

Significance: Chronic skin wounds are a significant health problem around the world, often leading to amputation and even death. Although persistent inflammation is a hallmark of these poorly heali...

Keloids and hypertrophic scars (HTS) are pathological scars that occur as a result of dermal injury and are characterized by persistent inflammation and fibrosis and excessive deposition of collagen and other fibroblast-derived extracellular matrix(ECM) proteins during skin healing.. Keloids Also hypertrophic scars representable an unreasonable tissue light of dermal damage described Toward nearby fibroblast burgeoning Furthermore overproduction of collagen. The point of this fill in is on analyze between the viability for intralesional versus topical anesthesia botulinum poison a joined together with fragmentary co2 laser in the medication of hypertrophic scars and keloids. This prospective clinical investigation included 10 patients with Keloids Also HTSs with no historical backdrop about medication six months former of the contemplate. Those whole scar lese greatness might have been partitioned under two halves. Person A large portion might have been dealt with with intralesional infusion for botulinum poison sort a once An month to an aggregate time of two months. The an alternate A large portion of the scar might have been approached with An course about two sessions from claiming co2 laser help at particular case month trailed Eventually Tom's perusing topical anesthesia requisition from claiming botulinumtoxin a for a catch up time of four months. Advanced photographas might have been performed for each tolerant previously, then after medicine.

Las bronquiectasias son un síndrome clínico, frecuente en nuestro medio, resultado de una serie de condiciones de inflamación persistente con daño estructural bronquial. Sus causas son múltiples, las que incluyen las secuelas de Tuberculosis Pulmonar. En el presente simposio, se considera su fisiopatología y clasificación con una explicación concisa de los mecanismos que la producen. En el apartado de diagnóstico, se enfoca sobre las características de las pruebas de imágenes que apoyan su definición; asimismo en las indicaciones de las pruebas de función pulmonar. Finalmente, en el apartado del tratamiento, se hará un resumen de las propuestas con evidencia científica que se tienen hasta al momento actual.

Persistent inflammation is the key aggravator in many cardiovascular diseases, including atherosclerosis, aneurysm, injury/reperfusion, thrombosis, and neointimal hyperplasia following surgical or percutaneous interventions. Resolution is an active process orchestrated by specialized pro-resolving lipid mediators (SPMs) which tamp down acute inflammatory signals, promote healing and facilitate a return to homeostasis. SPMs are endogenously derived from poly-unsaturated fatty acids, and their biologic activity is mediated via specific G-protein coupled receptor binding. The potency of SPM in regulating the inflammatory response has encouraged investigation into their therapeutic and diagnostic use in cardiovascular pathologies. Herein we describe the translational groundwork which has established the synthesis and interactions of SPM in cardiovascular and hematologic cells, the therapeutic effects of SPM in animal models of cardiovascular disease, and some early technologies that harness and attempt to optimize SPM delivery and "resolution pharmacology". Further studies are required to precisely determine the mechanisms of resolution in the cardiovascular system and to determine the clinical settings in which SPM can be utilized to optimize patient outcomes.

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Although sepsis is characterized by early hypercoagulability and delayed hypocoagulability, coagulopathy during chronic critical illness is not fully understood. The objective of this study was to determine whether sepsis-induced PICS is associated with coagulation abnormalities. Using our previously described murine PICS model, outbred mice underwent cecal ligation and puncture, and coagulability was characterized after 8 days. We found that during PICS the spleen became markedly enlarged with increased splenocytes and splenic megakaryocytes without a concomitant increase in circulating platelets. Microscopy revealed a nearly sevenfold increase in pulmonary microvascular thrombi in PICS mice, along with significantly decreased pulmonary tidal volumes and inspiratory times and with significantly increased respiratory rates. Thromboelastometry showed that PICS mice had significantly delayed clot initiation time but increased clot firmness. Finally, PICS mice displayed delayed thrombin production and decreased overall thrombin concentrations. All together, these data demonstrate a general dysregulation of coagulation resulting in microthrombus formation and compromised lung function. On the basis of these findings, we propose that consumptive coagulopathy constitutes another cardinal feature of PICS and may contribute to the ongoing tissue damage and multiple organ failure that can occur in chronic critical illness.

Highlights • Physiological properties of RVM pain-modulating neurons were described in female rats. • ON- and OFF-cells in females have fundamental properties comparable to those in males. • As in males, RVM neuron output is altered in persistent inflammation and by morphine. • This work provides a foundation for future studies of RVM in females., Functional pain disorders disproportionately impact females, but most pain research in animals has been conducted in males. While there are anatomical and pharmacological sexual dimorphisms in brainstem pain-modulation circuits, the physiology of pain-modulating neurons that comprise a major functional output, the rostral ventromedial medulla (RVM), has not been explored in female animals. The goal of this study was to identify and characterize the activity of RVM cells in female, compared to male, rats. ON- and OFF-cells were identified within the RVM in females, with firing properties comparable to those described in males. In addition, both ON- and OFF-cells exhibited a sensitized response to somatic stimuli in females subjected to persistent inflammation, and both ON- and OFF-cells responded to systemically administered morphine at a dose sufficient to produce behavioral antinociception. These data demonstrate that the ON-/OFF-cell framework originally defined in males is also present in females, and that as in males, these neurons are recruited in females in persistent inflammation and by systemically administered morphine. Importantly, this work establishes a foundation for the use of female animals in studies of RVM and descending control.

Introduction: The persistent inflammation that characterizes COPD and affects its natural course also impacting on symptoms has prompted research to find molecules that can regulate the inflammatory process but still available anti-inflammatory therapies provide little or no benefit in COPD patients. Consequently, numerous anti-inflammatory molecules that are effective in animal models of COPD have been or are being evaluated in humans. Areas covered: In this article we describe several classes of drugs that target the cellular components of inflammation under clinical development for COPD. Expert opinion: Although the results of many clinical trials with new molecules have often been disappointing, several studies are underway to investigate whether some of these molecules may be effective in treating specific subgroups of COPD patients. Indeed, the current perspective is to apply a more personalized treatment to the patient. This means being able to better define the patient’s inflammatory state and treat it in a targeted manner. Unfortunately, the difficulty in translating encouraging experimental data into human clinical trials, the redundancy in the effects induced by signal-transmitting substances and the nonspecific effects of many classes that are undergoing clinical trials, do not yet allow specific inflammatory cell types to be targeted.

Keratinized mucosa (KM) is regarded as a key factor in peri-implant health. A lack of KM has been associated with discomfort, higher plaque accumulation, and mucosal inflammation. Persistent inflammation might lead to progressive peri-implant bone loss. Several approaches to manage peri-implantitis have been advocated. Despite the effectiveness shown by surgical therapeutic modalities, soft tissue conditioning seems pivotal for long-term peri-implant health and stability. Free epithelial grafts have been demonstrated to efficiently augment the band of KM. Nevertheless, morbidity, dynamic soft tissue changes, and longer healing periods are shortcomings to be considered. The purpose of this technical note is to provide an alternative therapeutic modality for the surgical management of peri-implantitis combined with simultaneous soft tissue conditioning by means of pedicle flaps. Three main clinical scenarios are provided to conceive pedicle epithelial or connective tissue flaps, combined or not with collagen matrices, as predictable approaches to augment KM in the surgical therapy of peri-implantitis.

Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many patients will not rapidly recover, but instead will go on to develop chronic critical illness (CCI) and experience dismal long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets for immunomodulatory therapy.

Nociceptor sensitization following nerve injury or inflammation leads to chronic pain. An increase in the nociceptor hyperpolarization-activated current, Ih, is observed in many models of pathological pain. Pharmacological blockade of Ih prevents the mechanical and thermal hypersensitivity that occurs during pathological pain. Alterations in the Hyperpolarization-activated Cyclic Nucleotide-gated ion channel 2 (HCN2) mediate Ih-dependent thermal and mechanical hyperalgesia. Limited knowledge exists regarding the nature of these changes during chronic inflammatory pain. Modifications in HCN2 expression and post-translational SUMOylation have been observed in the Complete Freund’s Adjuvant (CFA) model of chronic inflammatory pain. Intra-plantar injection of CFA into the rat hindpaw induces unilateral hyperalgesia that is sustained for up to 14 days following injection. The hindpaw is innervated by primary afferents in lumbar DRG, L4-6. Adjustments in HCN2 expression and SUMOylation have been well-documented for L5 DRG during the first 7 days of CFA-induced inflammation. Here, we examine bilateral L4 and L6 DRG at day 1 and day 3 post-CFA. Using L4 and L6 DRG cryosections, HCN2 expression and SUMOylation were measured with immunohistochemistry and proximity ligation assays, respectively. Our findings indicate that intra-plantar injection of CFA elicited a bilateral increase in HCN2 expression in L4 and L6 DRG at day 1, but not day 3, and enhanced HCN2 SUMOylation in ipsilateral L6 DRG at day 1 and day 3. Changes in HCN2 expression and SUMOylation were transient over this time course. Our study suggests that HCN2 is regulated by multiple mechanisms during CFA-induced inflammation.

Chronic rhinosinusitis (CRS) is a clinical syndrome stemming from persistent inflammation of the sinonasal mucosa. Phenotypically, it is traditionally and widely described according to the presence or absence of polyps. While this distinction is simple to use, it has little bearing on prognosis and treatment, for CRS is essentially an inflammatory disease resulting from dysregulated interaction between a multitude of host and environmental factors. Allergy is merely one of them and, like many of the proposed aetiologies, has been subject to much debate which will be discussed here. As our understanding of CRS continues to evolve, previous so-called conventional wisdom about phenotypes (e.g. CRS with nasal polyps is associated with Type 2 inflammation) is being challenged, and new phenotypes are also emerging. In addition, there is growing interest in defining the endotypes of CRS to deliver precise and personalised treatment, especially pertaining to the development of biologics for the group of severe, difficult-to-treat CRS patients. A proposed model of precision medicine tailored to management of CRS will also be introduced to readers, which can be continually modified to adapt to new discoveries about this exciting condition.

Inflammation is a response to an injury and infection by the immune system. Based on visual observation the ancients characterized inflammation by five cardinal signs, namely, redness, swelling, heat, pain, and loss of function. Persistent inflammation can lead to undesired health effects, including cancer. Hence, it is necessary to neutralize redness. Medicinal plants such as herbs and spices play a vital role in treating pathologies associated with inflammatory reactions. Spices possess antiinflammatory activity and have a long history of quick remedy in terms of inflammatory conditions, including fevers, migraine, and arthritis. Many of the diseases in the modern world are to be due to inflammation; consequently, spices, namely, turmeric (Curcuma longa) and ginger (Zingiber officinale), help to cure inflammatory conditions. The active chemical compounds have proved a broad spectrum of pharmacological activities either in the form of powder, extracts, or in its isolated compounds with minimum side effects. This paper reviews the antiinflammatory activity of turmeric (C. longa) and ginger (Z. officinale).

In the conditions of steadily increasing urbanization and emerging negative microclimates, there is increase the morbidity of children in megacities. The damaging effect of environmental factors causes the development of “minimal persistent inflammation” of mucosa. We had studied 55 children in age 1–8 years suffering from recurrent ARVI associated with different chronic HVI (HSV I/II, EBV, CMV, HHV VI) and chronic recurrent bacterial diseases. The comparison group was 40 conditionally healthy children, comparable by sex and age. Clinical and immunological methods: ELISA, PCR, cytofluorimetry were used. We studied 2 groups of children: 1 group – 1–4 years old (early children) and 2 group – 5–8 years old, suffering from recurrent ARVI of a high rate of frequency. Clinical and anamnestic data showed that the incidence of ARVI was in 1 group – 7–15 and in 2 groups – 7–24 or more episodes per year, and the duration of these episodes was: 7.5 and 15.8 days, respectively. In all children, repeated ARI in combination with chronic respiratory diseases with frequent exacerbations were associated with recurrent and/or mono- and mixed HVI. Comparative analysis showed that in the children from group 1 demonstrate deficient in IFN-α, serum IgA and various NG disorders. However more severe disorders in IFN-α, NK-cells, NG system were detected in group 2, which is associated with a greater age of infectious history. Our study revealed the urgency to create new approaches for targeted immunoprophylaxis for immunocompromised children living in the megapolis.

Chronic endometritis is a persistent inflammation of the endometrium, characterized by plasma cell infiltration of endometrial stroma [1].

Many small molecules (mostly lipids derived from polyunsaturated fatty acids) and proteins (e. g., cytokines and chemokines) are labeled as inflammatory mediators for their role in eliciting physiological responses to injury. While acute inflammatory events are controlled by anti-inflammatory drugs, lasting damage to the tissues as a result of persistent inflammation is increasingly viewed as the root cause of many chronic diseases that include cardiovascular, neurological, and metabolic disorders, rheumatoid arthritis, and cancer. Interestingly, some of the “inflammatory” mediators also participate in normal developmental physiology without eliciting inflammation. Anti-inflammatory drugs that target the biosynthesis of these mediators are too indiscriminate to distinguish their two divergent physiological roles. A more precise definition of these two physiological processes partaken by the “inflammatory” mediators is warranted to identify their differences. The new paradigm is named “unalamation” ('ə‘n'əlAmāSH(ə)n) to distinguish from inflammation and to identify appropriate intervention strategies to mitigate inflammation associated pathophysiology without affecting the normal developmental physiology.

Background:Systemic lupus erythematosus (SLE) patients run a higher risk of having low bone mass due to multifactorial events that include physical inactivity, persistent inflammation, low vitamin D levels, and glucocorticoid treatment. This study aimed at obtaining a comparison between bone involvement in SLE patients and healthy matched subjects (HS). Methods:A total of 40 SLE females (average age 54.1 +/- 16.3 years) and 40 age-gender matched HS (average age 54.2 +/- 15.9 years) were enrolled after having obtained informed written consent. Bone mineral density (BMD, g/cm(2)) of the lumbar spine (L1-L4) was analyzed by a dual-energy X-ray absorptiometry (DXA) scan (GE, Lunar Prodigy). The lumbar spine trabecular bone score (TBS) was derived for each spine DXA examination by the TBS index (TBS iNsight Medimaps). Results:The lumbar spine TBS score was statistically significantly lower in SLE patients than in HS (0.797 +/- 0.825 vs. 1.398 +/- 0.207,p< 0.001, as was BMD (p< 0.001) in all areas examined. Conclusions:SLE is associated with significant low bone mass as evidenced by DXA and TBS. This study emphasizes the importance of using DXA and TBS in the evaluation of the different aspects of bone architecture.

Peri-implant diseases are prevalent with a weighted mean prevalence rate of 43% across Europe and 22% across South and North America. Although the main etiologic agent is bacterial biofilm, a myriad of factors influence the initiation and progression of the disease. Unfortunately, the treatment of peri-implant diseases is at best favorable in the short term with a high rate of persistent inflammation and recurrence. Therefore, it is sensible to consider and control all potential factors that may predispose an implant to peri-implant tissue inflammation in an attempt to avoid the disease. This paper reviews recent evidence on factors that may predispose implants to peri-implantitis and measures that can be taken to prevent it.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium which colonizes the human stomach. The ability of H. pylori to evade the host defense system and the emergence of antibiotic resistant strains result in bacteria persistence and chronic inflammation, which leads to both severe gastric and extra-gastric diseases. Consequently, innovative approaches able to overcome H. pylori clinical outcomes are needed. In this work, we develop a novel non-toxic therapy based on the synergistic action of H. pylori phage and lactoferrin adsorbed on hydroxyapatite nanoparticles, which effectively impairs bacteria colonization and minimizes the damage of the host pro-inflammatory response.

Persistent inflammation, immunosuppression and catabolism syndrome (PIICS) often occur after critical care. Disseminated intravascular coagulation (DIC) is expected to be associated independently with PIICS development. We retrospectively analyzed 5397 patients admitted to the Hitachi General Hospital emergency and critical care center during four years. We classified PIICS as C-reactive protein &gt, 3.0 mg/dL or albumin &lt, 3.0 g/dL or lymphocyte count &lt, 800/&mu, L on day 14. Prolonged hospital stay (&gt, 14 days) without PIICS and early recovery (discharged alive within 14 days) were assigned as non-PIICS. Early death (death within 14 days) was identified. We analyzed the association between the International Society on Thrombosis and Haemostasis overt DIC and PIICS outcomes. Results revealed 488 PIICS, 416 early death and 4493 non-PIICS cases. Analyses showed DIC as associated significantly with mortality, the Barthel index at discharge and PIICS development. Multivariate regression analysis and a generalized structural equation model identified DIC on admission as an independent risk factor for PIICS in surviving patients.

Associations among inflammatory cytokines, erythropoietin (EPO), and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased EPO would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume.Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ΔHb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ΔHb (AdjΔHb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with AdjΔHb of greater than 0 (positive AdjΔHb, n = 18) were compared with patients with AdjΔHb of less than or equal to 0 (negative AdjΔHb, n = 24).Plasma tumor necrosis factor α, granulocyte colony-stimulating factor, interleukin (IL)-6, IL-8, EPO, erythrocyte mean corpuscular volume, and serum transferrin receptor were measured on days 0, 1, 4, 7, and 14. Patients with negative AdjΔHb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p0.05), IL-8 (39.1 vs. 18.2 pg/mL, p = 0.01), and granulocyte colony-stimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower AdjΔHb was associated with higher day 14 levels of IL-6 (r = 0.22, p0.01), IL-8 (r = 0.10, p = 0.04), stromal cell-derived factor 1 (r = 0.14, p = 0.02), and tumor necrosis factor α (r = 0.13, p = 0.02), but not EPO. Patients with negative AdjΔHb had significantly lower mean corpuscular volume on days 4 (89.6 vs. 93.2 fL/cell, p = 0.04), 7 (92.3 vs. 94.9 fL/cell, p = 0.04), and 14 (92.1 vs. 96.0 fL/cell, p = 0.03) but similar serum transferrin receptor levels.Persistent elevation of inflammatory cytokines was associated with iron-restricted anemia among critically ill septic patients, occurring in the absence of systemic iron deficiency, independent of endogenous EPO.Prognostic study, level II.

Chronic inflammatory disorders are rising worldwide. The implication of the microbiota in persistent inflammation has been studied for years, but a direct causal relationship has not yet been stablished. Intestinal epithelial cells (IECs) form a protective barrier against detrimental luminal components. Indeed, a decrease in epithelial integrity may trigger a severe inflammatory reaction due to the infiltration of potentially harmful molecules and microorganisms. Bacterial imbalance, more commonly known as dysbiosis, occurs during inflammation and several strategies have been proposed to counteract this condition. Probiotics have been widely used to positively alter the inherited microbial composition and recover a eubiotic status. Nevertheless, probiotics are thought to impair the return of the indigenous microbiome, and to aggravate inflammation in compromised patients. In contrast, postbiotics-bacterial-free metabolites secreted by probiotic strains-have been proposed as a better and safer strategy. Recent scientific studies that have demonstrated the immunomodulatory properties and epithelial protection of postbiotics are summarized in this review, with an emphasis on the available methods that are currently in use to better understand the role of postbiotics in health and nutrition.

Summary Background Appropriate protein delivery amounts during the acute phase of critical care are unknown. Along with nutrition, early mobilization and the combination are important. We conducted a randomized controlled trial during critical care to assess high-protein and medium-protein delivery under equal total energy delivery with and without active early rehabilitation. Methods ICU patients of August 2018–September 2019 were allocated to a high-protein group (target energy 20 kcal/kg/day, protein 1.8 g/kg/day) or a medium-protein group (target energy 20 kcal/kg/day, protein 0.9 g/kg/day) with the same nutrition protocol by day 10. By dividing the study period, standard rehabilitation was administered during the initial period. Rehabilitation with belt-type electrical muscle stimulation was given from day 2 in the latter as a historical comparison. Femoral muscle volume was evaluated on day 1 and day 10 using computed tomography. Results This study analyzed 117 eligible patients with similar characteristics assigned to a high-protein or medium-protein group. Total energy delivery was around 20 kcal/kg/day in both groups, but protein delivery was 1.5 g/kg/day and 0.8 g/kg/day. As a primary outcome, femoral muscle volume loss was 12.9 ± 8.5% in the high-protein group and 16.9 ± 7.0% in the medium-protein group, with significant difference (p = 0.0059). Persistent inflammation, immunosuppression, and catabolism syndrome were significantly less frequent in the high-protein group. Muscle volume loss was significantly less in the high-protein group only during the electrical muscle stimulation period. Conclusions For critical care, high protein delivery provided better muscle volume maintenance, but only with active early rehabilitation. Registration University Hospital Medical Information Network, UMIN000033783 Registered on 16 Aug 2018. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038538 .

As early as the 1990s, chronic critical illness, a distinct syndrome of persistent high-acuity illness requiring management in the ICU, was reported under a variety of descriptive terms including the "neuropathy of critical illness," "myopathy of critical illness," "ICU-acquired weakness," and most recently "post-intensive care unit syndrome." The widespread implementation of targeted shock resuscitation, improved organ support modalities, and evidence-based protocolized ICU care has resulted in significantly decreased in-hospital mortality within surgical ICUs, specifically by reducing early multiple organ failure deaths. However, a new phenotype of multiple organ failure has now emerged with persistent but manageable organ dysfunction, high resource utilization, and discharge to prolonged care facilities. This new multiple organ failure phenotype is now clinically associated with the rapidly increasing incidence of chronic critical illness in critically ill surgery patients. Although the underlying pathophysiology driving chronic critical illness remains incompletely described, the persistent inflammation, immunosuppression, and catabolism syndrome has been proposed as a mechanistic framework in which to explain the increased incidence of chronic critical illness in surgical ICUs. The purpose of this review is to provide a historic perspective of the epidemiologic evolution of multiple organ failure into persistent inflammation, immunosuppression, and catabolism syndrome; describe the mechanism that drives and sustains chronic critical illness, and review the long-term outcomes of surgical patients who develop chronic critical illness.

Intestinal microbial dysbiosis has been described in individuals with an HIV-1 infection and may underlie persistent inflammation in chronic infection, thereby contributing to disease progression. Herein, we induced an HIV-1-like intestinal dysbiosis in rhesus macaques (Macaca mulatta) with vancomycin treatment and assessed the contribution of dysbiosis to SIV disease progression. Dysbiotic and control animals had similar disease progression, indicating that intestinal microbial dysbiosis similar to that observed in individuals with HIV is not sufficient to accelerate untreated lentiviral disease progression.

Background: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease with progressive course affecting articular and extra-articular structures resulting in pain, disability and mortality. Persistent inflammation leads to erosive joint damage and functional impairment in the vast majority of patients. The onset of disease is not similar in all patients but varies in regard to type, number, and the pattern of joint involvement. The course of disease may be also different according to the presence or absence of several variables including genetic background, frequency of swollen joints, autoantibody in the serum and the severity of inflammatory process. Objective: The aim of this study was to demonstrate the role of Ultrasonography and Power Doppler in diagnosis of activity of rheumatoid arthritis in the hands and wrist joints among different aged population, compared with the laboratory investigations. Patients and Methods: This study was carried out in Radiology department of Ain Shams university hospitals. Twenty-five patients known patients with rheumatoid arthritis suspecting activity will underwent assessment by ultrasonography and power Doppler of both wrist and hand joints. Result: US & PD are highly sensitive and specific in detection of activity of the Rheumatoid Arthritis in correlation to laboratory investigations. So, they can be used as non-invasive methods in detection of RA activity changes in wrist and hand joints. Conclusion: Both ultrasonography and power doppler are good predicators for activity in rheumatoid arthritis patients

While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed outcomes of people with rheumatoid arthritis (RA), a proportion of patients are refractory to multiple bDMARDs. Definitions of refractory RA thus far have been arbitrary, and outcome data and impact of such cohorts remain limited. Extrapolation from randomised controlled trial and some real-life data suggest approximately 20% progress onto a third bDMARD with a more modest proportion failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA disease and proposes key principles to accurately identify refractory cohorts. These include demonstrating presence of persistent inflammation despite multiple therapies and acknowledging development of antidrug antibody. Potential basis of refractory disease is summarised, and suggestions for an initial approach in the future evaluation of refractory disease are offered. Specific investigation of refractory RA disease is necessary to inform the clinical need and provide a basis for robust investigation of underlying mechanisms.

Der Morbus Whipple ist eine seltene infektiose Erkrankung, die verschiedene Organsysteme betreffen kann. Aufgrund der haufig auftretenden Arthritiden wird die Erkrankung des Ofteren als seronegative rheumatoide Arthritis fehldiagnostiziert. In seltenen Fallen kann eine Infektion mit Tropheryma whipplei auch Hautveranderungen wie subkutane Knoten, Erythema nodosum oder eine Vaskulitis hervorrufen. Die Kasuistik beschreibt eine 77-jahrige Patientin mit erosiven Gelenkveranderungen, persistierend erhohten serologischen Entzundungszeichen und rezidivierenden ulzerierenden Hautveranderungen an den unteren Extremitaten, welche initial ebenfalls als rheumatoide Vaskulitis fehldiagnostiziert wurden. Bei klinischem Verdacht auf eine Infektion mit Tropheryma whipplei sollte daher zeitnah eine bioptische Abklarung der betroffenen Organsysteme zum Erregernachweis erfolgen.

Objective To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage. Methods In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases. Results In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68; p < 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4; p = 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (βadd, 16.3; 95% confidence interval [CI], 4.6–28.0; p < 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; βadd, 30.4; 95% CI, 15.6–45.2; p < 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (βadd, 1.1; 95% CI, 0.3–1.9; p < 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center: p = 0.004 and p = 0.0002, respectively). Conclusion Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.

Skin chronic wounds are associated with a state of persistent inflammation and often with infection, originating a specific microenvironment characterized by increased temperature, alkaline pH, elevated enzymatic activity, and high levels of reactive oxygen species (ROS). These alterations can be explored as intrinsic triggers in the design of stimuli-responsive biomaterials for the release of bioactive molecules at the wound microenvironment. Stimuli-responsive biomaterials may not only prolong the bioactivity of the therapeutic agents but also synchronize it with the healing stages, tuning the wound treatment. In addition, the high activity of enzymes, such as lysozyme in infected chronic wounds, as well as the shift to a more alkaline pH may be used as biomarkers for early detection of infected and/or non-healing wounds. Overall, although a few shortcomings still need to be addressed before clinical translation, the bioengineered smart formulations highlighted in this review stand out as a new generation of therapies to manage skin chronic wounds. This work was supported by Portuguese funds through FCT-MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project “AntINFECT“ (POCI-01-0145-FEDER-031781, PTDC/NAN-MAT/31781/2017). FCT-MCTES is further acknowledged for funding LAQV-REQUIMTE Research Unit (UIDB/50006/2020). P.A. thanks FCT-MCTES for the doctoral grant SFRH/BD/145471/2019 financially supported by national and European Union funds (ESF – European Social Fund through “Programa Operacional Regional Norte”).

To explore clinical characteristics and long-term quality of life (QOL) in severe acute pancreatitis (SAP) patients with persistent inflammation-immunosuppression and catabolism syndrome (PICS).SAP patients admitted to ICU were eligible for the retrospective cohort study if they needed prolonged intensive care (14days). Post-ICU QOL was assessed by a questionnaire, including 36-item Short Form Health Survey (SF-36) and record of re-work in a long-term follow-up.214 SAP patients were enrolled, in which 149 (69.6%) patients met the criteria of PICS. PICS patients had more complications and ICU days compared to non-PICS patients (P0.001), and their post-ICU mortality was higher (P=0.046). When adjusted for confounders, PICS was independently associated with higher post-ICU mortality (hazard ratio 4.5; 95% CI, 1.2 to 16.3; P=0.024). The 36-item Short Form Health Survey (SF-36) score was lower for PICS group in six subscales (P0.001). Only 28.8% patients in the PICS group returned to work compared to 60% patients in the non-PICS group (P=0.001) CONCLUSIONS: SAP patients with prolonged ICU stay had a high morbidity of PICS, which was a risk factor for the post-ICU mortality and poor long-term QOL.

Surfactants are widely used as detergents, emulsifiers, wetting agents, foaming agents and dispersants in the cosmetics, hygiene, food and oil industries. Their use in a clinical setting is also common, particularly within the field of wound care. Many wound cleansers contain surfactants and subsequently there is available data that shows the growing potential of these wound cleansers in the enhancement of wound closure. The presence of microorganisms in wounds has been recognised as a significant factor that delay healing. In complex or chronic wounds that are complicated by biofilms, persistent inflammation or the production of non-viable tissue and slough, the use of surfactants has been shown to aid in the removal of these barriers to wound healing. The use of concentrated surfactant(poloxamer) based wound dressings represent an important component of wound management. Consequently, this article will discuss the effect of clinically used surfactants, with specific focus on a concentrated poloxamer for use against wound biofilm.

Biofilms are complex microbial architectures that attach to surfaces and encase microorganisms in a matrix composed of self-produced hydrated extracellular polymeric substances (EPSs). In biofilms, microorganisms become much more resistant to antimicrobial treatments, harsh environmental conditions, and host immunity. Biofilm formation by microbial pathogens greatly enhances survival in hosts and causes chronic infections that result in persistent inflammation and tissue damages. Currently, it is believed over 80% of chronic infectious diseases are mediated by biofilms, and it is known that conventional antibiotic medications are inadequate at eradicating these biofilm-mediated infections. This situation demands new strategies for biofilm-associated infections, and currently, researchers focus on the development of antibiofilm agents that are specific to biofilms, but are nontoxic, because it is believed that this prevents the development of drug resistance. Here, we review the most promising antibiofilm agents undergoing intensive research and development.

Summary Inflammation, an essential tissue response to extrinsic/intrinsic damage, is a very dynamic process in terms of complexity and extension of cellular and metabolic involvement. The aim of the inflammatory response is to eliminate the pathogenic initiator with limited collateral damage of the inflamed tissue, followed by a complex tissue repair to the preinflammation phenotype. Persistent inflammation is a major contributor to the pathogenesis of many musculoskeletal diseases including ageing-related pathologies such as osteoporosis, osteoarthritis, and sarcopaenia. The translational potential of this article : Understanding the mechanisms of inflammation and its resolution is therefore critical for the development of effective regenerative, and therapeutic strategies in orthopaedics.

Purpose: To evaluate the clinical outcomes of ruptured dermoid cysts. Methods: A multicenter, retrospective study of all cases of periorbital and orbital dermoid cysts with histopathological evidence of rupture, including those with clinical rupture, was performed over a 10-year period. Demographics and clinical outcomes of ruptured dermoid cysts were recorded. Persistent inflammation was defined as the presence of edema, erythema, and discomfort for at least 28 days. Results: Eighty-six cases of dermoid cysts were identified. Median age was 5.5 (range, 1–63) years. Location of cyst was either periorbital (n = 60, 70%) or orbital (n = 26, 30%). There were 29 cases with clinically apparent rupture: 27 surgically ruptured (93%) and 2 spontaneous rupture (7%). Persistent inflammation was found in 1 spontaneous cyst rupture case (50%) and 1 surgically ruptured cyst (3.7%). Older age (p = 0.01) and bony attachment (p = 0.001) were significant factors for cyst rupture, while there was no influence from cyst location (p = 0.14). Conclusions: Persistent inflammation is uncommon after surgical rupture of dermoid cysts, but likely after spontaneous rupture. Older age and bony attachment are risk factors for cyst rupture.

Introduction Hyperbilirubinemia may have deleterious effects on many organs, even after the neonatal age. Blood purification is effective in the treatment of hyperbilirubinemia. Recently some reports suggest the potential role of hemoadsorption columns in this setting. Methods We present the case of a 6-year-old child with severe hyperbilirubinemia due to congestive liver dysfunction, complicated by persistent inflammation, immunosuppression and catabolism syndrome (PICS). The patient was treated with a hemoadsorption column (Lixelle®) in combination with continuous veno-venous hemodiafiltration (CVVHDF). Results During treatment, a significant and rapid decrease in total bilirubin (TB) and other indices of cholestasis was observed. Furthermore, a progressive reduction in the inflammatory biomarkers (Procalcitonin, C-reactive protein) occurred. These results persisted at the discontinuation of therapy. Conclusions To our knowledge this is the first case in which hemoadsorption with the Lixelle® adsorbing column in combination with CVVHDF has been used to manage pediatric hyperbiliribinemia secondary to cardiogenic liver injury.