Hubbardlocklear1027
Immune checkpoint inhibitors (CPI) have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events (irAEs), wherein the skin and its appendages are the most frequent targets. Cutaneous irAEs (irCAEs) include a diverse group of inflammatory reactions, with maculopapular rash (MPR), pruritus, and lichenoid dermatitis being the most prevalent subtypes. irCAEs occur early, with MPR presenting within the first six weeks after the initial CPI dose. Management involves the use of topical corticosteroids for mild-moderate (grade 1-2) rash, addition of oral corticosteroids for severe (grade 3) rash, and permanent discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid-like eruptions, vitiligo-like depigmentation, and psoriasiform dermatitis are more often attributed to PD-1/PD-L1 inhibitors. The treatment of bullous pemphigoid-like eruptions is similar to that of MPR and lichenoid dermatitis, with the addition of rituximab in grade 3-4 rash. Vitiligo-like depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform dermatitis may be managed with vitamin D3 analogues, narrow-band ultraviolet B phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other very severe irCAEs, although rare, have also been associated with checkpoint blockade.Objective Our understanding of the origin of allergic diseases has increased in recent years, highlighting the importance of microbial dysbiosis and epithelial barrier dysfunction in affected tissues. Exploring the microbial-epithelial-immune crosstalk underlying the mechanisms of allergic diseases will allow the development of novel prevention and treatment strategies of allergic diseases. Data sources This review summarizes recent advances in microbial, epithelial, and immune interactions in atopic dermatitis, allergic rhinitis, chronic rhinosinusitis and asthma. Study selections We performed a literature search, identifying relevant recent primary articles and review articles. Results Dynamic crosstalk between the environmental factors and microbial, epithelial, and immune cells in the development of atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, and asthma underlies the pathogenesis of these disease. There is substantial evidence in the literature suggesting that environmental factors directly affect barrier function of epithelium. In addition, T helper 2 cells, type 2 innate lymphoid cells and their cytokine IL-13 damage skin and lung barriers. The effects of environmental factors may at least in part be mediated by epigenetic mechanisms.Histondeacetylase activation by type 2 immune response has a major effect on leaky barriers and blocking of histone deacetylase activity corrects the defective barrier in human air-liquid interface cultures and mouse models of allergic asthma with rhinitis. We also present and discuss a novel device to detect and monitor skin barrier dysfunction, which provides an opportunity to rapidly and robustly assess disease severity. Conclusion A complex interplay between environmental factors, epithelium, and the immune system is involved in the development of systemic allergic diseases.A significant amount of clinical and research interest in thrombosis is focused on large vessels (eg, stroke, myocardial infarction, deep venous thrombosis, etc.); however, thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of organ injury in this disease. In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation. In this review, we discuss endogenous regulatory mechanisms that prevent thrombosis in the microcirculation, experimental approaches to induce microvascular thrombi, and clinical conditions associated with microvascular thrombosis. A greater understanding of the links between inflammation and thrombosis in the microcirculation is anticipated to provide optimal therapeutic targets for patients with diseases accompanied by microvascular thrombosis.This study aimed to describe perioperative care after anatomical lung resection in the Netherlands, before publication of Enhanced Recovery After Surgery/European Society of Thoracic Surgeons (ERAS/ESTS) guidelines in 2019. An online survey was sent to all 43 Dutch lung surgical centers in December 2017, addressing topics in the 4 phases of perioperative care (preoperative, admission, perioperative, postoperative). Respondents were requested to report care that would be delivered to a standardized patient without perioperative complications. To compare current care with ERAS/ESTS guidelines, we assigned an ERAS/ESTS score per hospital, weighted for evidence level per recommendation. Higher scores indicate higher application of recommendations. Response rate of centers was 100%, median response rate per question was 98% (interquartile range 94-100). Some perioperative recommendations are commonly applied (>85%), such as minimally invasive surgery and regional anesthesia; others, such as admission carbohydrate drinks, are not ( less then 35%). Wide variation was observed regarding patient counselling, pre- and postoperative admission logistics, anemia correction, fluid management, pain management, and chest drain management. Median 62% (interquartile range 53%-72%) of the maximum ERAS/ESTS score was achieved. Large variation in ERAS/ESTS score between hospitals were found in all phases (preoperative 6.0 [6.5-10.5] points, admission 5.0 [1.0-6.0] points, perioperative 21.5.0 [16.0-22.5] points, postoperative 8.0 [5.0-8.5] points). Large variation exists in perioperative care after anatomical lung resection in the Netherlands. Given previously published data linking variation in perioperative care to variation in outcomes, standardization of perioperative care in lung surgery, preferably based on the ERAS/ESTS guidelines, may be warranted but requires further study.Fighting the current COVID-19 pandemic, we must not forget to prepare for the next. Since elderly and frail people are at high risk, we wish to predict their vulnerability, and intervene if possible. For example, it would take little effort to take additional swabs or dried blood spots. Such minimally-invasive sampling, exemplified here during screening for potential COVID-19 infection, can yield the data to discover biomarkers to better handle this and the next respiratory disease pandemic. Longitudinal outcome data can then be combined with other epidemics and old-age health data, to discover the best biomarkers to predict (i) coping with infection & inflammation and thus hospitalization or intensive care, (ii) long-term health challenges, e.g. deterioration of lung function after intensive care, and (iii) treatment & vaccination response. this website Further, there are universal triggers of old-age morbidity & mortality, and the elimination of senescent cells improved health in pilot studies in idiopathic lung fibrosis & osteoarthritis patients alike. Biomarker studies are needed to test the hypothesis that resilience of the elderly during a pandemic can be improved by countering chronic inflammation and/or removing senescent cells. Our review suggests that more samples should be taken and saved systematically, following minimum standards, and data be made available, to maximize healthspan & minimize frailty, leading to savings in health care, gains in quality of life, and preparing us better for the next pandemic, all at the same time.Background While endoscopy is recommended at one year after colorectal cancer (CRC) resection to detect locally recurrent CRC, prior work at our Veterans Affairs (VA) facility demonstrated that 35% of patients achieve this metric. Study design The interdisciplinary team used quality improvement methods to standardize processes and implement a gastroenterology-managed virtual surveillance clinic. The intervention clinic was implemented in August 2014. Veterans who underwent resection for stage I-III CRC at a single VA facility from January 2010 - December 2017 were included, with those undergoing resection between January 2010 - July 2014 considered pre-intervention and those undergoing resection between August 2014 - December 2017 considered post-intervention. The primary outcome was the proportion of eligible patients for whom endoscopy was completed within 1 year of resection. Secondary outcomes were the proportion who completed endoscopy within 18 months of resection or at any time post-resection, and time to surveillance endoscopy. Results A total of 186 patients underwent resection for stage I-III CRC from 2010-2017; of these 160 (86%) were eligible for endoscopy at 1-year post-resection (98 pre-intervention and 62 post-intervention). In the pre-intervention period, 30/98 (30.6%) underwent surveillance endoscopy within one year versus 31/62 (50.0%) post-intervention (P=0.031). When evaluated at 18 months after resection, 56/98 (57.1%) in the pre-intervention group versus 52/62 (83.9%) in the post-intervention group underwent surveillance endoscopy (P=0.001). Median time from resection to endoscopy decreased over the study period, from 1.19 years pre-intervention (Interquartile range [IQR] 0.93, 1.74) to 1.0 years post-intervention (IQR 0.93, 1.09) (P=0.006). Conclusions Implementation of a virtual surveillance clinic with standardized processes was associated with increased guideline-concordant endoscopic surveillance after CRC resection.Purpose This study aimed to compare lamina cribrosa (LC) parameters obtained by spectral-domain optical coherence tomography (SD-OCT) of eyes with exfoliation syndrome (PXS), exfoliation glaucoma (PXG) and healthy subjects. Methods In this cross-sectional comparative study, 206 eyes of 206 subjects were included. The Bruch's membrane opening distance (BMOd), the anterior and posterior borders of the LC (LC thickness) and the anterior laminar depth (ALD) were imaged using the enhanced depth imaging (EDI) mode of SD-OCT. Results There were 96 eyes in the PXG group, 55 eyes in the PXS group, and 55 eyes in the control group. The LC thickness was the thinnest in the PXG group (151.10 ± 51.18 µm), followed in the PXS group (158.76 ± 49.62 µm), and the thickest in the control group (181.00 ± 39.10 µm) (p = 0.002). In PXG cases where LC was observed in the deepest location, the ALD value was highest (423.92 ± 111.75 µm) in the PXG group, followed by the control group (403.08 ± 63.56 µm), and PXS group (357.43 ± 80.87 µm) (p less then 0.001). The BMOd values were largest in the PXG group (1542.43 ± 152.99 µm), followed by the control group (1506.52 ± 169.09 µm) and PXS group (1435.74 ± 141.06 µm) (p less then 0.001). In the PXG group, peripapillary retinal nerve fiber layer (pRNFL) thickness, BCVA, and cup to disc (C/D) ratio were also statistically different from the other groups (p less then 0.001). Conclusion We found thinner LC thickness in PXG and PXS cases relative to the control group. Although its severity is associated with the diagnosis and severity of glaucoma, LC thinning can be encountered as an isolated condition in the presence of exfoliation.
