Navigating obstacles impacting the sustainability of Medicare-funded wound care pricing.

CONCLUSION: With more effective oversight, Medicare costs can be reduced, while stabilising a portion of its trust fund, disincentivising non-compliance and improving outcomes for the growing population of US beneficiaries with hard-to-heal wounds.

Dehydrated human amnion/chorion membrane use in emergent craniectomies shows minimal dural adhesions.

Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exploration of posterior lumbar interbody fusion operations which require entry into the epidural space. The purpose of this study was to evaluate whether or not the use of DHACM in the setting of emergent craniectomies decreased the rate of dural adhesion formation and subsequent cranioplasty complications. Patients (n=7) who underwent emergent craniectomy and intraoperative placement of DHACM were evaluated during replacement of either an autologous skull cap or a custom-made implant, at which point the degree of adhesions was qualitatively assessed. Placement of DHACM below and on top of the dura resulted in negligible adhesion being found during the defect exposure, and there were no intraoperative complications during cranioplasties. Reported estimated blood loss across the seven patients averaged 64.2ml, total operative time averaged 79.2 minutes, and time dedicated to exposing defect for bone flap placement was <3 minutes.

Specialty specific quality measures needed to improve outcomes in wound care.

Despite the health care community's best efforts, 20% of diabetic patients who develop a diabetic foot ulcer will require some form of amputation. Those undergoing a major lower extremity amputation risk an increase in their five-year mortality rate to 56.6%, which is comparable to or higher than many forms of cancer. Given this perspective, quality measures need to be considered at each patient inflection point to drive increased compliance with best practices in order to redirect patients whose therapies fail. Medicare limited datasets (October 2015 through October 2019) retrospectively analyzed patients with diabetes receiving care for chronic lower extremity diabetic ulcers (LEDUs). The analysis demonstrated that only 21% of Medicare patients with hard-to-heal LEDUs received sharp debridement at intervals of every 7 days and less, while only 40% received sharp debridement at intervals of every 8 to 14 days. This is despite landmark prospective randomized controlled trials showing the benefits of frequent sharp debridement to patients with LEDUs. According to the Medicare data, when patients received debridement at intervals of 7 days or less with concurrently applied skin substitutes, observed amputation rates dropped by 65% to the lowest levels identified among Medicare LEDU episodes (2.1%). Optimal use of debridement and adjunctive use of skin substitutes significantly improves outcomes and lowers the use of healthcare resources. Another unexpected finding highlighted in the Medicare data analysis was that wound care providers have not been applying skin substitutes early enough. Clinical guidelines related to LEDUs have long relied on the seminal Sheehan marker study, which identified that diabetic ulcers that have not progressed to at least 53% healing after four weeks of conservative care have only a 9% chance of proceeding to closure by 12 weeks. It is therefore vital that patients move to advanced therapies within 30 to 45 days after initiation of failed conservative care; however, the Medicare claims data shows this is not happening regularly enough (average time to first skin substitute application >69 days) to benefit both the patient and the healthcare system. There is a demonstrable need for quality measures that encourage (1) frequent and adequate debridement throughout wound treatment, (2) earlier adoption of advanced treatments, such as skin substitutes, for LEDUs to align with clinical guidelines, (3) the application of skin substitutes to better align with medical evidence, which is associated with improved patient outcomes, as well as (4) expansion of best practices across all demographic and socioeconomic populations.

Whole genome sequences of Treponema pallidum subsp. endemicum isolated from Cuban patients: The non-clonal character of isolates suggests a persistent human infection rather than a single outbreak.

Bejel (endemic syphilis) is a neglected non-venereal disease caused by Treponema pallidum subsp. endemicum (TEN). Although it is mostly present in hot, dry climates, a few cases have been found outside of these areas. The aim of this work was the sequencing and analysis of TEN isolates obtained from "syphilis patients" in Cuba, which is not considered an endemic area for bejel. Genomes were obtained by pool segment genome sequencing or direct sequencing methods, and the bioinformatics analysis was performed according to an established pipeline. We obtained four genomes with 100%, 81.7%, 52.6%, and 21.1% breadth of coverage, respectively. The sequenced genomes revealed a non-clonal character, with nucleotide variability ranging between 0.2-10.3 nucleotide substitutions per 100 kbp among the TEN isolates. Nucleotide changes affected 27 genes, and the analysis of the completely sequenced genome also showed a recombination event between tprC and tprI, in TP0488 as well as in the intergenic region between TP0127-TP0129. Despite limitations in the quality of samples affecting breadth of sequencing coverage, the determined non-clonal character of the isolates suggests a persistent infection in the Cuban population rather than a single outbreak caused by imported case.

Circulating tumor cells are transcriptionally similar to the primary tumor in a murine prostate model.

The abundance of circulating tumor cells (CTC) indicates patient prognosis. Molecular characterization of CTCs may add additional information about a patient's disease. However, currently available methods are limited by contamination with blood cells. We describe a study using a modified CTC-chip to capture CTCs from an orthotopic xenograft model. Using laser capture microscopy to collect CTCs from the chip, we compared transcripts from purified CTCs with those from primary and metastatic tissue. Transcriptional profiles showed strong concordance among primary, metastatic, and CTC sources. Moreover, cells captured on the chip were viable and could be expanded in culture. We conclude that the CTC-chip is a useful tool to further characterize animal models of cancer and that viable CTCs can be isolated and show transcriptional similarity to solid tumors.

Techniques for the isolation and use of conditionally expressed antisense RNA to achieve essential gene knockdowns in Staphylococcus aureus.

This chapter provides methods and insights into the use of antisense RNA as a molecular genetic tool. Posttranscriptional inhibition of specific gene expression can be achieved by antisense RNA fragments under control of a conditional promoter. Effective titration of gene expression can cause an apparent null mutation or can be modulated to levels of interest in comparison with wild type. Validation of antisense RNA can be achieved by both RNA and protein quantitation techniques. Applications include phenotypic studies of genes in response to specific stimuli, environments, or the contribution of genes in regulatory networks. This chapter will focus on shotgun-cloned antisense for comprehensive gene identification and cell-based hypersensitivity assays for antibiotic screening. Antisense RNA strategies have high utility when the target gene is essential for survival and needs to be compared with wild type.