Effectiveness of a purified type I collagen matrix plus the antimicrobial polyhexamethylene biguanide for use in cutaneous wounds: analysis of a population of three combined registries.

INTRODUCTION: Chronic wounds represent a significant burden to the health care system and patients. OBJECTIVE: This study determined the effectiveness of a wound scaffold comprised of PCMP for use in nonhealing, cutaneous wounds; this study analyzes pooled data from the population of 3 combined registries. MATERIALS AND METHODS: A total of 3 combined registry populations were pooled from a single-center study of 41 patients, a single-center study of 86 patients, and the RESPOND Registry of 307 patients treated at 28 centers. All 434 patients received PCMP and were followed for up to 48 weeks. Male and female patients 18 years or older with wounds between 0.2 cm2 and 200 cm2 were included. RESULTS: In total, there were 95 VLUs, 78 DFUs, 90 PIs, 73 PSWs, and 98 wounds of other etiologies analyzed. The mean baseline area, depth, and volume of all 434 wounds was 15.1 cm2, 4.9 mm, and 7.2 cm3, respectively. K-M median time to wound closure for all wounds was 19 weeks. At weeks 20, 24, 28, and 48, the frequency of wound closure for all wounds was 51%, 56%, 62%, and 72%, respectively. The median time to closure by wound type was 22 weeks for VLUs, 24 weeks for DFUs, 23 weeks for PIs, 12 weeks for PSWs, and 14 weeks for other wounds. The proportion of wounds closed were 72% (VLUs), 52% (DFUs), 63% (PIs), 95% (PSWs), and 67% (other etiologies). CONCLUSIONS: This 434-patient PCMP cohort analysis showed 72% wound closure and median time to wound closure of 19 weeks. PCMP demonstrated effectiveness for use in multiple wound types.

Effectiveness of type I collagen matrix plus polyhexamethylene biguanide antimicrobial for the treatment of pressure injuries.

INTRODUCTION: The first prospective noninterventional registry study (RESPOND) evaluated the clinical effectiveness of a native type I collagen matrix plus polyhexamethylene biguanide antimicrobial barrier (PCMP) in various nonhealing wounds. This product is intended for the management of partial- and full-thickness wounds and acts as an effective barrier to reduce microbes penetrating through the dressing. The RESPOND study demonstrated that PCMP has clinically meaningful benefits in managing a variety of wounds. OBJECTIVE: The authors describe the effects of PCMP in the subgroup of patients with pressure injuries (PIs) from the RESPOND registry. MATERIALS AND METHODS: The prospective, noninterventional study was designed to collect information regarding the use of PCMP in a real-world situation. Eligibility included male and female patients aged 18 years and older with target wounds (partial- or full-thickness) suitable for the use of PCMP. Enrolled patients were followed approximately weekly for up to 32 weeks. All wounds and the subgroups were analyzed to determine the frequency and median time to wound closure using Kaplan-Meier methods. RESULTS: The patients with PIs were older adults with a mean age of 69 years and a mean BMI of 27 kg/m2. At baseline, the mean measured wound length was 3 cm, the mean depth was 8.0 mm, the mean volume was 12.6 cm3, and the mean area was 10.5 cm2. Complete wound closures were evident in 5% of patients (n = 2) at week 4, and were achieved in 39% of patients (n = 18) by week 16, in 49% (n = 22) by week 24, and in 62% (n = 28) by week 32. The median time to wound closure was 32 weeks. For all 45 PIs managed with PCMP, the incidence of achieving greater than 60% reduction in baseline area and depth was 78% (n = 35) and 64% (n = 29), respectively, with approximately 82% (n = 37) of wounds showing a reduction in volume greater than 75%. CONCLUSIONS: It appears that PCMP is a useful adjunct in managing chronic deep wounds such as PIs.

A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies

COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery. At 15-120 days post-virus clearance, histologic evaluation identified subpleural lesions containing collagen, proliferative fibroblasts, and chronic inflammation with tertiary lymphoid structures. Longitudinal spatial transcriptional profiling identified global reparative and fibrotic pathways dysregulated in diseased regions, similar to human COVID-19. Populations of alveolar intermediate cells, coupled with focal upregulation of pro-fibrotic markers, were identified in persistently diseased regions. Early intervention with antiviral EIDD-2801 reduced chronic disease, and early anti-fibrotic agent (nintedanib) intervention modified early disease severity. This murine model provides opportunities to identify pathways associated with persistent SARS-CoV-2 pulmonary disease and test countermeasures to ameliorate PASC.

Autosomal recessive cardiomyopathy and sudden cardiac death associated with variants in MYL3.

PURPOSE: Variants in genes encoding sarcomeric proteins are the most common cause of inherited cardiomyopathies. However, the underlying genetic cause remains unknown in many cases. We used exome sequencing to reveal the genetic etiology in patients with recessive familial cardiomyopathy. METHODS: Exome sequencing was carried out in three consanguineous families. Functional assessment of the variants was performed. RESULTS: Affected individuals presented with hypertrophic or dilated cardiomyopathy of variable severity from infantile- to early adulthood-onset and sudden cardiac death. We identified a homozygous missense substitution (c.170C>A, p.[Ala57Asp]), a homozygous translation stop codon variant (c.106G>T, p.[Glu36Ter]), and a presumable homozygous essential splice acceptor variant (c.482-1G>A, predicted to result in skipping of exon 5). Morpholino knockdown of the MYL3 orthologue in zebrafish, cmlc1, resulted in compromised cardiac function, which could not be rescued by reintroduction of MYL3 carrying either the nonsense c.106G>T or the missense c.170C>A variants. Minigene assay of the c.482-1G>A variant indicated a splicing defect likely resulting in disruption of the EF-hand Ca2+ binding domains. CONCLUSIONS: Our data demonstrate that homozygous MYL3 loss-of-function variants can cause of recessive cardiomyopathy and occurrence of sudden cardiac death, most likely due to impaired or loss of myosin essential light chain function.