The response of IH to an ACEi supports a critical role for the RAS in IH and represents a paradigm shift in the understanding and treatment of this enigmatic condition.
The trauma and sepsis that follow open fractures and wounds may lead to the production of various cytokines. Understanding wound healing requires a direct knowledge of the specific cytokines and the respective wound fluid levels that are present at the wound site. An animal model was designed that mimics the open fracture and the clinical repair of the human, high-energy open fracture. Canine right tibiae were fractured with a penetrating, captive-bolt device, then repaired in a standard clinical fashion using an interlocking intramedullary nail. Before primary wound closure, microdialysis probes were placed at the fracture site and in a muscle located at a contralateral site. Canines received one of the following experimental protocols: (1) tibial fracture (n = 5); (2) tibial fracture plus Staphylococcus aureus inoculation at the fracture site (n = 5); and (3) tibial fracture, S. aureus inoculation, and a rotational gastrocnemius muscle flap (n = 5). Microdialysis fluid samples were collected intermittently for 7 days. Tumor necrosis factor alpha (TNFalpha) levels at the fracture site were significantly elevated 3 to 34-fold (p<0.02), as compared with respective serum levels at all time points for all treatment groups. Fracture site TNFalpha levels were elevated (p<0.02) in days 1 through 6, as compared with the baseline and contralateral in all treatment groups. At days 1 through 6, the TNFalpha levels of the muscle flap group fracture site were significantly decreased by approximately 50 percent (p<0.05), as compared with the fractures without muscle flaps and regardless of additional S. aureus inoculation. On day 7, fracture site TNFalpha levels in all animal groups were similar, yet remained well above those of baseline TNFalpha. These results demonstrate that S. aureus does not further elevate TNFalpha levels in the presence of an open fracture and that a muscle flap reduces pro-inflammatory TNFalpha levels during early wound healing. This experimental model allows for the characterization of specific biological signals and cellular pathways that are influenced by bacterial infection and surgical closure. These data provide a scientific framework on which to judge or validate therapeutic regimens for open-fracture wound healing.
◥Metastasis of human tumors to lymph nodes (LN) is a universally negative prognostic factor. LN stromal cells (SC) play a crucial role in enabling T-cell responses, and because tumor metastases modulate their structure and function, this interaction may suppress immune responses to tumor antigens. The SC subpopulations that respond to infiltration of malignant cells into human LNs have not been defined. Here, we identify distinctive subpopulations of CD90 þ SCs present in melanoma-infiltrated LNs and compare them with their counterparts in normal LNs. The first populationcorresponds to fibroblastic reticular cells that express various T-cell modulating cytokines, chemokines, and adhesion molecules. The secondSCs embedded in collagenous structures, such as the capsule and trabeculae, that predominantly produce extracellular matrix. We also demonstrated that these two SC subpopulations are distinct from two subsets of human LN pericytes, CD90 þ CD146 þ CD36 þ NG2 À pericytes in the walls of high endothelial venules and other small vessels, and CD90 þ CD146 þ NG2 þ CD36 À pericytes in the walls of larger vessels. Distinguishing between these CD90 þ SC subpopulations in human LNs allows for further study of their respective impact on T-cell responses to tumor antigens and clinical outcomes.
Background/Objectives: Merkel cell carcinomais an aggressive neuroendocrine skin cancer. Australian studies report high incidence and poor survival rates compared internationally. While New Zealand has a comparable UV index and racial composition to Australia, survival outcomes are currently unknown. The role of Merkel cell polyoma virus in oncogenesis of Merkel cell carcinoma is an active area of research. We describe the incidence and survival of Merkel cell carcinoma in New Zealand with correlation to demographic and clinical factors including regional polyoma virus prevalence.Methods: Retrospective study of population-based data from the New Zealand Cancer Registry. Incidence rates were directly standardised to the US standard 2000 population. Survival was investigated using Kaplan-Meier and multivariable Cox regression models.Results: Six hundred and one cases were diagnosed in New Zealand between 2000 and 2015. The overall incidence rate was 0.96/100 000 population. Merkel cell carcinoma is more common in males, elderly and on sun-exposed areas. Eighteen percent of patients were diagnosed with distant metastasis at time of presentation. The overall 5-year survival rate and relative 5-year survival rate were 31% and 45%, respectively. Mortality was 1.9 and 2.5 times higher for stage III and IV disease, respectively, relative to stage I/II disease. Patients over age 80 had twice the mortality compared to those aged 60-69. Conclusions: New Zealand has a high incidence ofMerkel cell carcinoma and poor survival outcomes when compared internationally. We have the highest proportion of distant metastatic disease at time of diagnosis. Further research into the role of nonpolyoma-related Merkel cell carcinoma is warranted to improve Merkel cell carcinoma outcomes in New Zealand and abroad.
Backgrounds: Surgical site infections (SSIs) represent one of the most common and potentially preventable sources of morbidity and healthcare cost escalation associated with skin cancer surgery. There is a lack of data reporting organisms cultured from SSIs in skin surgery, with guidelines for antibiotic prophylaxis based on common skin pathogens rather than actual cultured organisms. In this study, we sought to define the cultured microbiology of SSIs specific to skin cancer surgery and test these against empiric treatment guidelines. Methods: All consenting patients presenting to the Auckland regional skin cancer treatment centre over a 6-month period were included. Patients receiving any form of antibiotics within a week prior to surgery were excluded. All wounds were assessed postoperatively, with clinically significant infections identified as those with a standardized wound infection score of 4 (range 0-7) and/or prescribed post-operative antibiotics within 3 weeks of surgery. Wound cultures were recorded. Results: About 104 clinically significant SSIs were identified from 333 lesions treated, with cultures available in 27%. Cultured organisms included MSSA (79%), MRSA (14%), coagulase-negative Staphylococci (11%), and 'skin flora' (14%). Empiric guidelines inaccurately predicted effective treatment in 14% of cases, exclusively due to MRSA. Conclusion: To our knowledge this is the first comprehensive report of SSI microbiology following skin cancer surgery. The overwhelmingly predominant organisms were Staphylococcus sp. (76%), with the rate of MRSA approaching prevalence warranting empiric firstline treatment. These data help inform effective rationalized empiric antibiotic treatment, when indicated, for optimal outcome following skin surgery.
Background Melanoma is the most lethal skin cancer. Excision biopsy is generally recommended for clinically suspicious pigmented lesions; however, a proportion of cutaneous melanomas are diagnosed by shave biopsy. A systematic review was undertaken to investigate the impact of shave biopsy on tumor staging, treatment recommendations, and prognosis. Methodology The MEDLINE, Embase, and Cochrane Library databases were searched for relevant articles. Data on deep margin status on shave biopsy, tumor upstaging, and additional treatments on wide local excision (WLE), disease recurrence, and survival effect were analyzed across studies. Results Fourteen articles from 2010 to 2020 were included. In total, 3713 patients had melanoma diagnosed on shave biopsy. Meta-analysis revealed a positive deep margin in 42.9% of shave biopsies. Following WLE, change in tumor stage was reported in 7.7% of patients. Additional treatment was recommended for 2.3% of patients in the form of either further WLE and/or sentinel lymph node biopsy. There was high heterogeneity across studies in all outcomes. Four studies reported survival, while no studies found any significant difference in disease-free or overall survival between shave biopsy and other biopsy modalities. Conclusions Just over 40% of melanomas diagnosed on shave biopsy report a positive deep margin; however, this translated into a change in tumor stage or treatment recommendations in relatively few patients (7.7% and 2.3%, respectively), with no impact on local recurrence or survival among the studies analyzed.
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