Checkpoints: it takes more than time to heal some wounds.
Ontology highlight
ABSTRACT:
SUBMITTER: Rhind N
PROVIDER: S-EPMC2861551 | biostudies-other | 2000 Dec 14-28
REPOSITORIES: biostudies-other
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Project description:BackgroundCOVID-19 has been associated with persistent symptoms and functional changes, especially in those surviving severe disease.MethodsWe conducted a prospective multicenter study in patients with severe COVID-19 to determine respiratory sequelae. Patients were stratified into two groups: ward admission (WA) and intensive care unit (ICU) admission. In each follow-up visit, the patients where inquired about cough and dyspnea, and performed spirometry, lung volumes, carbon monoxide diffusion capacity (DLCO), 6-minute walk test (6MWT), and respiratory muscle strength (MIP and MEP). Results of pulmonary function tests at 45 days and 6 months after hospital admission were compared using paired analysis.Results211 patients were included, 112 in WA and 99 in ICU. Dyspnea persisted in 64.7% in the WA and 66.7% in the ICU group after 6 months. Lung function measures showed significant improvement between 45 days and 6 months, both in WA and ICU groups in VC, FVC, FEV1, total lung capacity, and 6MW distance measures. The improvement in the proportions of the altered functional parameters was significant in the ICU group for VC (44.2% 45 d; 20.8% 6 m; p = 0,014), FVC (47.6% 45 d; 28% 6 m; p = 0,003), FEV1 (45.1% 45 d; 28% 6 m; p = 0,044), DLCO (33.8% 45 d; 7.7% 6 m; p < 0,0001).ConclusionSix months follow-up of patients with the severe forms of COVID-19 showed significant improvement in the lung function measures compared to 45 days post hospital discharge. The difference was more evident in those requiring ICU admission.
| S-EPMC9042802 | biostudies-literature
Project description:COVID-19, as a crucial public health crisis, has affected our lives in nearly every aspect. Besides its major health threats, COVID-19 brings severe secondary impacts, one of which is the rise of social stigma. Although numerous studies have examined the antecedents and outcomes of COVID-19-related stigma, we still lack a systematic understanding of who is being stigmatized during the COVID-19 pandemic, what exacerbates COVID-19-related stigma, and what impacts COVID-19-related stigma has on victims. Therefore, this review aims to provide a systematic overview of COVID-19-related stigma. With 93 papers conducted with 126,371 individuals in more than 150 countries and territories spanning five continents, we identify three targets that have received the most research: Chinese/Asian people, (suspected) patients and survivors, and healthcare workers. Furthermore, we find that for each stigma target, characteristics of the stigmatized, stigmatizer, and context contribute to COVID-19-related stigma and that this stigma negatively influences victims' health and non-health outcomes. We call for future research to provide a more integrative, balanced, and rigorous picture of COVID-19-related stigma via conducting research on neglected topics (e.g., contextual factors that contribute to stigma toward HCWs) and stigma interventions and using a longitudinal design. In practice, we urge governments and institutions (e.g., ministries of public health, hospitals) to pay close attention to stigma issues and to promote safe and inclusive societies.
| S-EPMC9752089 | biostudies-literature
Project description:BACKGROUND:Thalamic dysfunction has been implicated in overall chronic neurological dysfunction after traumatic brain injury (TBI), however little is known about the underlying histopathology. In experimental diffuse TBI (dTBI), we hypothesize that persisting histopathological changes in the ventral posteromedial (VPM) nucleus of the thalamus is indicative of progressive circuit reorganization. Since circuit reorganization in the VPM impacts the whisker sensory system, the histopathology could explain the development of hypersensitivity to whisker stimulation by 28days post-injury; similar to light and sound hypersensitivity in human TBI survivors. METHODS:Adult, male Sprague-Dawley rats underwent craniotomy and midline fluid percussion injury (FPI) (moderate severity; 1.8-2.0atm) or sham surgery. At 1d, 7d, and 28days post-FPI (d FPI) separate experiments confirmed the cytoarchitecture (Giemsa stain) and evaluated neuropathology (silver stain), activated astrocytes (GFAP), neuron morphology (Golgi stain) and microglial morphology (Iba-1) in the VPM. RESULTS:Cytoarchitecture was unchanged throughout the time course, similar to previously published data; however, neuropathology and astrocyte activation were significantly increased at 7d and 28d and activated microglia were present at all time points. Neuron morphology was dynamic over the time course with decreased dendritic complexity (fewer branch points; decreased length of processes) at 7d FPI and return to sham values by 28d FPI. CONCLUSIONS:These data indicate that dTBI results in persisting thalamic histopathology out to a chronic time point. While these changes can be indicative of either adaptive (recovery) or maladaptive (neurological dysfunction) circuit reorganization, they also provide a potential mechanism by which maladaptive circuit reorganization could contribute to the development of chronic neurological dysfunction. Understanding the processes that mediate circuit reorganization is critical to the development of future therapies for TBI patients.
| S-EPMC5491365 | biostudies-literature
Project description:BackgroundHyperbaric oxygen therapy (HBOT) is used to treat various wound types. However, the possible beneficial and harmful effects of HBOT for acute wounds are unclear.MethodsWe undertook a systematic review to evaluate the effectiveness of HBOT compared to other interventions on wound healing and adverse effects in patients with acute wounds. To detect all available randomized controlled trials (RCTs) we searched five relevant databases up to March 2010. Trial selection, quality assessment, data extraction, and data synthesis were conducted by two of the authors independently.ResultsWe included five trials, totaling 360 patients. These trials, with some methodologic flaws, included different kinds of wound and focused on different outcome parameters, which prohibited meta-analysis. A French trial (n = 36 patients) reported that significantly more crush wounds healed with HBOT than with sham HBOT [relative risk (RR) 1.70, 95% confidence interval (CI) 1.11-2.61]. Moreover, there were significantly fewer additional surgical procedures required with HBOT (RR 1.60, 95% CI 1.03-2.50), and there was significantly less tissue necrosis (RR 1.70, 95% CI 1.11-2.61). In one of two American trials (n = 141) burn wounds healed significantly quicker with HBOT (P < 0.005) than with routine burn care. A British trial (n = 48) compared HBOT with usual care. HBOT resulted in a significantly higher percentage of healthy graft area in split skin grafts (RR 3.50, 95% CI 1.35-9.11). In a Chinese trial (n = 145) HBOT did not significantly improve flap survival in patients with limb skin defects.ConclusionsHBOT, if readily available, appears effective for the management of acute, difficult to heal wounds.
| S-EPMC3032900 | biostudies-literature
Project description:Child welfare involvement reflects childhood adversity and is associated with increased adult mortality, but it remains unclear how this association changes over the life course. Drawing on the Stockholm Birth Cohort Multigenerational Study (Sweden) and the National Childhood Development Study (Great Britain) this study examines whether inequalities within these cohorts diverge or converge. Involvement with child welfare services (ICWS) is divided into two levels ('child welfare contact' and 'out-of-home care'). For each cohort, we quantify absolute health inequalities as differences in cumulative probabilities of death (18-58 years) and temporary life expectancy; and relative inequalities as hazard ratios in ten-year intervals and ratios of lifetime lost. Persistently, ICWS was associated with premature mortality. The strength of the association varied by age, sex and level of ICWS. Consistently across both countries, the most robust relationship was between out-of-home care and mortality, with statistically significant age-specific hazard ratios ranging between 1.8 and 3.4 for males and 1.8-2.1 for females. Child welfare contact that did not result in out-of-home placement showed less consistent results. Among females the mortality gap developed later compared to males. Estimates attenuate after controlling for family socioeconomic and other background variables but patterns remain intact. Our results show that absolute inequalities widen with increasing age, while relative inequalities might peak in early adulthood and then stabilize in midlife. The relative disadvantage among looked-after children in early adulthood is heightened by overall low rates of mortality at this age. Absolute inequality increases with age, highlighting the weight of the accumulation of disadvantage in mortality over time. The bulk of excess deaths that could be attributed to ICWS occurs from midlife onwards. Mechanisms that uphold the disadvantage after childhood experiences require further exploration. This study highlights that the association between out-of-home care and premature mortality seems to transcend welfare systems.
| S-EPMC8010861 | biostudies-literature
Project description:Despite advances in diabetic wound care, the significant number of amputations that occur every year demands more effective therapeutics. Herein, we offer an aminated polyethersulfone nanofiber-expanded human umbilical cord blood-derived CD34+ cells (henceforth CD34+ cells) effective therapy, tested in cutaneous wounds developed in streptozotocin-induced diabetic NOD/SCID mice. We show that systemic administration of CD34+ cells homed to the wound site and significantly accelerated wound closure. Wound closure was associated with improved re-epithelialization and increased neovascularization; and with decreased sustained pro-inflammatory activity of NF-κB and its downstream effector molecules TNF-α, IL-1β, and IL-6 at the wound bed. This finding was further supported by the observation of a decreased number of myeloperoxidase positive neutrophils, and concomitantly increased levels of IL-10. In addition, improved granulation tissue formation was observed along with higher collagen deposition and myofibroblasts and decreased expressions of MMP-1. Mechanistically, CD34+ cells reduced the level of MMP-1 expression by inhibiting recruitment of NF-κB to the MMP-1 promoter site in dermal fibroblasts. In summary, we provide evidence of a novel nanofiber-expanded CD34+ stem cell therapeutic development for treating diabetic wounds by defining their cellular and molecular mechanisms.
| S-EPMC6557810 | biostudies-other
Project description:Basic mechanisms by which cellular barriers sense and respond to integrity disruptions remain poorly understood. Despite its tenuous structure and constitutive exposure to disruptive strains, the vascular endothelium exhibits robust barrier function. We show that in response to micrometer-scale disruptions induced by transmigrating leukocytes, endothelial cells generate unique ventral lamellipodia that propagate via integrins toward and across these "micro-wounds" to close them. This novel actin remodeling activity progressively healed multiple micro-wounds in succession and changed direction during this process. Mechanical probe-induced micro-wounding of both endothelia and epithelia suggests that ventral lamellipodia formed as a response to force imbalance and specifically loss of isometric tension. Ventral lamellipodia were enriched in the Rac1 effectors cortactin, IQGAP, and p47Phox and exhibited localized production of hydrogen peroxide. Together with Apr2/3, these were functionally required for effective micro-wound healing. We propose that barrier disruptions are detected as local release of isometric tension/force unloading, which is directly coupled to reactive oxygen species-dependent self-restorative actin remodeling dynamics.
| S-EPMC3639391 | biostudies-literature
Project description:BackgroundA lack of longitudinal studies has hampered the understanding of the development of posttraumatic stress symptoms (PTSS) in parents of children diagnosed with cancer. This study examines level of PTSS and prevalence of posttraumatic stress disorder (PTSD) from shortly after diagnosis up to 5 years after end of treatment or child's death, in mothers and fathers.MethodsA design with seven assessments (T1-T7) was used. T1-T3 were administered during treatment and T4-T7 after end of treatment or child's death. Parents (N = 259 at T1; n = 169 at T7) completed the PTSD Checklist Civilian Version. Latent growth curve modeling was used to analyze the development of PTSS.ResultsA consistent decline in PTSS occurred during the first months after diagnosis; thereafter the decline abated, and from 3 months after end of treatment only minimal decline occurred. Five years after end of treatment, 19% of mothers and 8% of fathers of survivors reported partial PTSD. Among bereaved parents, corresponding figures were 20% for mothers and 35% for fathers, 5 years after the child's death.ConclusionsFrom 3 months after end of treatment the level of PTSS is stable. Mothers and bereaved parents are at particular risk for PTSD. The results are the first to describe the development of PTSS in parents of children diagnosed with cancer, illustrate that end of treatment is a period of vulnerability, and that a subgroup reports PTSD 5 years after end of treatment or child's death.
| S-EPMC5033007 | biostudies-literature
Project description:Objective:To determine the concentration of thiobarbituric acid reactive substances (TBARS) in erythrocytes and blood plasma, and the activities of selected antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in erythrocytes in patients receiving hyperbaric oxygen (HBO) treatment due to difficult-to-heal "skin wounds". Material and Methods. Indices of oxidative stress were assessed in venous blood taken from 23 patients three times: immediately before HBO procedure, approx. 5 minutes after leaving the hyperbaric chamber, and after 25 HBO procedures. Moreover, selected blood counts were measured in the collected material two times: prior to treatment and after 25 HBO procedures. Results:A statistically significant positive correlation between the CAT activity and the TBARS concentration in the erythrocytes of patients was found before treatment in the hyperbaric chamber (r = 0.394; P ? 0.05). No statistically significant changes in the TBARS concentration in erythrocytes and blood plasma were observed both after the first HBO procedure and after 25 procedures. No statistically significant changes in the activities of CAT, SOD, and GPx were noted. Platelet count decreased by 18.7% (P ? 0.05) after 25 HBO procedures. Granulocyte count decreased by approx. 21% (P ? 0.05), and granulocyte percentage by 11.8% (P ? 0.01). In turn, the percentage of lymphocytes and monocytes increased after the treatment by 16.6% (P < 0.05) and 16.4% (P < 0.05), respectively. Conclusions:Exposure to HBO due to difficult-to-heal skin wounds does not significantly affect the levels of oxidative stress in the peripheral blood of patients and, from the point of view of oxidation-reduction processes, appears to be a safe therapeutic method for the treatment of chronic wounds.
| S-EPMC7415099 | biostudies-literature
Project description:IntroductionExtracellular vesicles from mesenchymal stromal cells (MSC-EVs) have shown promise in wound healing. Their use in diabetic wounds specifically, however, remains pre-clinical and their efficacy remains uncertain less clear. A systematic review of preclinical studies is needed to determine the efficacy of MSC-EVs in the treatment of diabetic wounds to accelerate the clinical translation of this cell-based therapy.MethodsPubMed and Embase were searched (to June 23, 2020). All English-language, full-text, controlled interventional studies comparing MSC-EVs to placebo or a "no treatment" arm in animal models of diabetic wounds were included. Study outcomes, including wound closure (primary outcome), scar width, blood vessel number and density, and re-epithelialisation were pooled using a random effects meta-analysis. Risk of bias (ROB) was assessed using the SYRCLE tool for pre-clinical animal studies.ResultsA total of 313 unique records were identified from our search, with 10 full text articles satisfying inclusion criteria (n = 136 animals). The administration of MSC-EVs improved closure of diabetic wounds compared to controls with a large observed effect (Standardized Mean Difference (SMD) 5.48, 95% Confidence Interval (CI) 3.55-8.13). Healing was further enhanced using MSC-EVs enriched in non-coding RNAs or microRNAs compared to controls (SMD 9.89, 95%CI 7.32-12.46). Other outcomes, such as blood vessel density and number, scar width, and re-epithelialisation were improved with the administration of MSC-EVs, with a large effect. ROB across studies was unclear.ConclusionMSC-EVs, particularly following enrichment for specific RNAs, are a promising treatment for diabetic wounds in pre-clinical studies and translation to the clinical domain appears warranted.RegistrationPROSPERO #CRD42020199327 [248]. Forest plot demonstrating increased wound closure rates of diabetic wounds receiving genetically modified MSC-EVs that were enriched for specific RNAs. DFO = deferoxamine. Control groups were inactive (no treatment or saline) except for 3 studies which used hydrogels without MSC-EVs as control (Li M 2016; Shi 2017; Tao 2016).
| S-EPMC8064883 | biostudies-literature