Citations

All-natural cross-linked nanoemulsions provide effective treatment of wound biofilm infections.

Abstract The role of thoracic CT (computerized tomography) in monitoring disease course of COVID-19 is controversial. The purpose of this study is to investigate the risk factors and predictive value of deterioration on repeatedly performed CT scan during hospitalization. All COVID-19 patients treated in our isolation ward, from January 22, 2020 to February 7, 2020, were reviewed. Patients included were categorized into RD (Radiological Deterioration) group or NRD (No Radiological Deterioration) group according to the manifestation on the CT routinely performed during the hospitalization. All clinical data and CT images were analyzed. Forty three patients were included in our study. All are moderate cases with at least 4 CT scans each. Eighteen (42.9%) patients had radiological deteriorations which were all identified in CT2 (the first CT after admission). Patients in RD group had lower leukocyte count (P = .003), lymphocyte count (P = .030), and higher prevalence (P = .012) of elevated C-reactive protein (CRP) at admission. NRD patients had a lower prevalence of reticulations (P = .034) on baseline CT (CT1, performed within 2 days before admission) and a longer duration between symptom onset and the time of CT2 (P < .01). There was no significant difference in hospital stay or fibrotic change on CT4 (follow-up CT scan performed 4 weeks after discharge) between 2 groups. Shorter duration between symptom onset and CT2 time (odds ratio [OR], 0.436; 95% confidence interval: 0.233–0.816; P < .01) and lower leukocyte count in baseline evaluation (OR, 0.316; 95% CI: 0.116–0.859; P < .05) were associated with increased odds of radiological deterioration on CT image during hospitalization. For moderate COVID-19 patients, the value of routinely performed CT during the treatment is limited. We recommend avoiding using CT as a routine monitor in moderate COVID-19 patients.

Introduction: Retinal vascular features predict cognitive performance and retinal imaging is a non-invasive tool to study brain health. Patients with Alzheimer’s disease (AD)-related cognitive disorders exhibit both retinal vascular abnormalities and intraretinal accumulation of amyloid-beta (Aβ) plaque. Curcumin-enhanced retinal fluorescence imaging (CRFI) was recently translated as a safe imaging tool for retinal Aβ plaque quantification. In this study, we sought to determine whether and which retinal arterial and venous parameters are predictive of retinal Aβ burden and cognitive Z-scores. Methods: We used scanning laser ophthalmoscopy with RetiaTM (Centervue, Inc) to obtain CRFI in a cohort of patients with cognitive decline. Retinal blood vessels were segmented in a predefined circumpapillary region of interest. For each centerline, vessel tortuosity index (VTI), vessel inflection index (VII), and branching angle (VBA) were quantified, independently for arteries and veins. Additionally, we automatically quantified retinal amyloid count in the supero-temporal quadrant and its subregions: posterior pole (PP), proximal mid-periphery (PMP), and distal mid-periphery (DMP). All quantifications were done blinded to the subjects’ clinical characteristics. Linear regression models were used to assess the correlations between retinal vascular and amyloid parameters. Results: 29 subjects (55% female, mean age 64±6 years) were included in the analysis: 11 had normal cognition, 16 mild cognitive impairment and 2 probable AD. Venous VTI was the only vascular parameter significantly different across levels of Clinical Dementia Rate scores and between cognitively normal and impaired. Venous VBA was a significant predictor of DMP amyloid count (p=0.03). Arterial VII significantly predicted PP amyloid count (p=0.02). VBA predicted Wechsler Adult Intelligence Scale Z-score (p=0.08). The combined VTI-PMP amyloid index significantly predicted Wechsler Memory Scale, California Verbal Learning Test and SF-36 mental component score Z-scores (p<0.05). Conclusion: Retinal venous tortuosity discriminates across cognitive scores and in combination with PMP amyloid count may predict verbal memory and related quality-of-life scores.

Major pretibial degloving injuries are complex wounds, which can be challenging to treat. Despite recent advances in reconstructive options, most of these injuries still require a prolonged healing period and may result in amputation. Few reports have been published on the management of these complex traumatic injuries. In this article, we present a case of an octogenarian, frail patient with a major pretibial degloving injury. Treatment included serial surgical debridements in combination with negative pressure wound therapy aimed at salvaging the avulsed tissue. Subsequently, a fenestrated-type artificial dermis and negative pressure wound therapy were used as combined therapy so as to obtain adequate soft tissue coverage. The patient made an unremarkable recovery and was discharged on day 22 after injury. The wound healed by secondary intention without need for skin grafting.

Objective: The aim of this systematic review is to analyze the 30-day postoperative mortality in patients undergoing free flap reconstruction for head and neck cancer published in literature and to identify associated factors. Methods: The authors performed a literature search between January 1950 and February 2020 in PubMed, EMBASE, and Scopus, using a combination of Medical Subject Headings headings and text keywords related to head and neck cancer; microsurgery or free flap reconstruction; and 30-day mortality. Inclusion criteria were: original studies in English reporting on 30-day mortality after head and neck free flap reconstruction in adult population. Results: Thirty-one publications reported on a total of 13,447 patients who underwent head and neck free flap reconstruction. The published 30-day postoperative mortality ranged from 0% to 6.3%, with an average of 1.21%. A number of studies examined the association between mortality and body mass index, American Society of Anesthesiologists, and comorbidity score and age. One study found that underweight patients had significantly higher mortality. Two studies found no association between the American Society of Anesthesiologists score and 30-day postoperative mortality; however, 1 study reported significantly higher mortality with increased comorbidity score. Regarding association with age, 3 studies found significant higher mortality in older patients, while 5 studies found no difference. Conclusions: The average 30-day postoperative mortality in patients undergoing head and neck free flap reconstruction is 1.21% and is; therefore, not negligible. Careful patient selection and preoperative optimization are essential in order to reduce mortality in head neck free flap reconstruction.

Background Complications from prosthetic breast reconstruction are distressing for patients, and their management is challenging. For decades, negative-pressure wound therapy (NPWT) has been successfully used for the closure of complex wounds. This study analyzes the outcomes of NPWT use in the prevention and management of complications from prosthetic breast reconstruction. Method A systematic search of studies published until August 2020 was conducted using the PubMed/MEDLINE, EMBASE, and Ebscohost/CINAHL databases and using the following key words: “negative-pressure wound therapy,” “breast reconstruction,” and “prosthesis” (including breast implants and tissue expanders). Analyzed endpoints were outcomes of NPWT use in prosthetic breast reconstruction compared with conventional dressings. The methodological quality of included studies was assessed independently. Comparative studies were further meta-analyzed to obtain pooled odds ratios (ORs) describing the effectiveness of NPWT in prosthetic breast reconstruction. Results/Discussion Ten studies were included with a total of 787 patients (1230 breasts) undergoing prosthetic breast reconstruction with breast implants or tissue expanders. Three case-control studies focused on preventing breast wound complications. The meta-analysis of the 3 studies included 502 breasts receiving NPWT and 698 breasts receiving conventional wound care. The meta-analysis favored NPWT for less mastectomy flap necrosis (5.6% vs 14.3%; OR, 0.46; 95% confidence interval, 0.27 –0.77; P = 0.004; I 2 = 0%) and less overall wound complications (10.6% vs 21.1%; OR, 0.49; 95% confidence interval, 0.35–0.70; P < 0.00001; I 2 = 0%). In the management of nipple-areolar complex venous congestion, 1 case report demonstrated 85% rescue of nipple-areolar complex after using NPWT (−75 mm Hg) for a total of 12 days. In the management of periprosthetic infections, 2 case series used NPWT with instillation. It accelerated the treatment of infection and maintained the breast cavity for future reconstruction. Conventional NPWT also showed good salvage outcome in four studies. Conclusions Current evidence suggests that prophylactic use of NPWT in prosthetic breast reconstruction reduces the rate of overall wound complications and mastectomy flap necrosis. In the management of complications from prosthetic breast reconstructions, NPWT may be a promising option showing beneficial results. Additional high-quality trials are warranted to corroborate the findings of this systematic review.

Prodrug strategies use chemical modifications to improve the pharmacokinetic properties and therefore therapeutic effects of parent drugs. Traditional prodrug approaches use endogenous enzymes for activation. Bioorthogonal catalysis uses processes that endogenous enzymes cannot access, providing a complementary strategy for prodrug uncaging. Site-selective activation of prodrugs to drugs (uncaging) using synthetic catalysts is a promising strategy for localized drug activation. We discuss here recent studies that incorporate metal catalysts into polymers and nanoparticle scaffolds to provide biocompatible “enzyme-like” catalysts that can penetrate bacterial biofilms and activate prodrug antibiotics in situ, affording a new strategy to treat bacterial biofilm infections with the potential for reduced off-target effects.

Abstract Background Cancer patients with coronavirus disease 2019 (COVID-19) have been reported to have double the case fatality rate of the general population. Methods A systematic search of PubMed, Embase, and Cochrane Central was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio (OR) and forest plots (random-effects model) were constructed for both primary and secondary outcomes. Results This systematic review of 38 studies and meta-analysis of 181 323 patients from 26 studies included 23 736 cancer patients. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (n = 165 980, OR = 2.54, 95% confidence interval [CI] = 1.47 to 4.42), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated. Among cancer subtypes, the mortality was highest in hematological malignancies (n = 878, OR = 2.39, 95% CI = 1.17 to 4.87) followed by lung cancer (n = 646, OR = 1.83, 95% CI = 1.00 to 3.37). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of comorbidities. There was insufficient data to assess the association of COVID-19–directed therapy and survival outcomes in cancer patients. Conclusion Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19–directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.

Abstract Background: We aimed to analyse clinical characteristics and find potential factors predicting poor prognosis in patients with coronavirus disease 2019 (COVID-19). Methods: We analyzed the demographic and clinical data of COVID-19 patients and detected SARS-CoV-2 RNA in urine sediments collected from 53 COVID-19 patients enrolled in Renmin Hospital of Wuhan University from January 31, 2020 to February 18, 2020 with qRT-PCR analysis, and then classified those patients based on clinical conditions (severe or non-severe syndrome) and urinary SARS-CoV-2 RNA (URNA- or URNA+). Results: We found that COVID-19 patients with severe syndrome (severe patients) showed significantly higher positive rate (11 of 23, 47.8%) of urinary SARS-CoV-2 RNA than non-severe patients (4 of 30, 13.3%, p = 0.006). URNA+ patients or severe URNA+ subgroup exhibited higher prevalence of inflammation and immune discord, cardiovascular diseases, liver damage and renal disfunction, and higher risk of death than URNA- patients. To understand the potential mechanisms underlying the viral urine shedding, we performed renal histopathological analysis on postmortems of patients with COVID-19 and found that severe renal vascular endothelium lesion characterized by increase of the expression of thrombomodulin and von Willebrand factor, markers to assess the endothelium dysfunction. We proposed a theoretical and mathematic model to depict the potential factors determining the urine shedding of SARS-CoV-2. Conclusions: This study indicated that urinary SARS-CoV-2 RNA detected in urine specimens can be used to predict the progression and prognosis of COVID-19 severity.

Abstract One of the greatest barriers to curative treatment of neuroblastoma is its frequent metastatic outgrowth prior to diagnosis, especially in cases driven by amplification of the MYCN oncogene. However, only a limited number of regulatory proteins that contribute to this complex MYCN-mediated process have been elucidated. Here we show that the growth arrest-specific 7 (GAS7) gene, located at chromosome band 17p13.1, is preferentially deleted in high-risk MYCN-driven neuroblastoma. GAS7 expression was also suppressed in MYCN-amplified neuroblastoma lacking 17p deletion. GAS7 deficiency led to accelerated metastasis in both zebrafish and mammalian models of neuroblastoma with overexpression or amplification of MYCN. Analysis of expression profiles and the ultrastructure of zebrafish neuroblastoma tumors with MYCN overexpression identified that GAS7 deficiency led to (i) downregulation of genes involved in cell–cell interaction, (ii) loss of contact among tumor cells as critical determinants of accelerated metastasis, and (iii) increased levels of MYCN protein. These results provide the first genetic evidence that GAS7 depletion is a critical early step in the cascade of events culminating in neuroblastoma metastasis in the context of MYCN overexpression. Significance: Heterozygous deletion or MYCN-mediated repression of GAS7 in neuroblastoma releases an important brake on tumor cell dispersion and migration to distant sites, providing a novel mechanism underlying tumor metastasis in MYCN-driven neuroblastoma. See related commentary by Menard, p. 2815