Clinical manifestations of COVID-19 breakthrough infections: A systematic review and meta-analysis.

To provide a comparative meta-analysis and systematic review of the risk and clinical outcomes of coronavirus 2019 (COVID-19) infection between fully vaccinated and unvaccinated groups. Eighteen studies of COVID-19 infections in fully vaccinated ("breakthrough infections") and unvaccinated individuals were reviewed from Medline/PubMed, Scopus, Embase, and Web of Science databases. The meta-analysis examined the summary effects and between-study heterogeneity regarding differences in the risk of infection, hospitalization, treatments, and mortality between vaccinated and unvaccinated individuals. he overall risk of infection was lower for the fully vaccinated compared to that of the unvaccinated (relative risk [RR] 0.20, 95% confidence interval [CI]: 0.19-0.21), especially for variants other than Delta (Delta: RR 0.29, 95% CI: 0.13-0.65; other variants: RR 0.06, 95% CI: 0.04-0.08). The risk of asymptomatic infection was not statistically significantly different between fully vaccinated and unvaccinated (RR 0.56, 95% CI: 0.27-1.19). There were neither statistically significant differences in risk of hospitalization (RR 1.06, 95% CI: 0.38-2.93), invasive mechanical ventilation (RR 1.65, 95% CI: 0.90-3.06), or mortality (RR 1.19, 95% CI: 0.79-1.78). Conversely, the risk of supplemental oxygen during hospitalization was significantly higher for the unvaccinated (RR 1.40, 95% CI: 1.08-1.82). Unvaccinated people were more vulnerable to COVID-19 infection than fully vaccinated for all variants. Once infected, there were no statistically significant differences in the risk of hospitalization, invasive mechanical ventilation, or mortality. Still, unvaccinated showed an increased need for oxygen supplementation. Further prospective analysis, including patients' risk factors, COVID-19 variants, and the utilized treatment strategies, would be warranted.

Extensive Polyostotic Craniofacial Fibrous Dysplasia With Optic Nerve Impingement.

ABSTRACT: Fibrous dysplasia is a benign overgrowth of metaplastic fibrous material resulting in disorganized deposition of bony matrix. Surgical intervention is the primary treatment modality. Here the authors present the case of a 36-year-old male with extensive and severe fibrous dysplasia of the calvarium, orbit, sphenoid, and facial bones causing significant facial distortion and impingement of his optic nerve. Combined operative treatment with craniofacial plastic surgery and neurosurgery was performed. Repair consisted of extensive intra- and extracranial resection and contouring of involved bones followed by reconstruction of the superior orbital rims, forehead, orbital roof, and calvarium with custom polyetheretherketone (PEEK) implant. The authors discuss the advantages of using computer assisted design/modeling, intraoperative neuronavigation, and custom prosthetic cranioplasty for surgical treatment of extensive fibrous dysplasia; a review of the current surgical literature is provided.

MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair.

Myocardial infarction (MI) remains a major cause of mortality worldwide. Despite significant advances in MI treatment, many who survive the acute event are at high risk of chronic cardiac morbidity. Here we developed a cell-free therapeutic that capitalizes on the antifibrotic effects of micro(mi)RNA-101a and exploits the multi-faceted regenerative activity of mesenchymal stem cell (MSC) extracellular nanovesicles (eNVs). While the majority of MSC eNVs require local delivery via intramyocardial injection to exert therapeutic efficacy, we have developed MSC eNVs that can be administered in a minimally invasive manner, all while remaining therapeutically active. When loaded with miR-101a, MSC eNVs substantially decreased infarct size (9.2 ±â€¯1.7% vs. 20.0 ±â€¯6.5%) and increased ejection fraction (53.6 ±â€¯7.6% vs. 40.3 ±â€¯6.0%) and fractional shortening (23.6 ±â€¯4.3% vs. 16.6 ±â€¯3.0%) compared to control. These findings are significant as they represent an advance in the development of minimally invasive cardio-therapies.

Epidemiology, Socioeconomic Analysis, and Specialist Involvement in Dog Bite Wounds in Adults.

Dog bites have been well described and characterized in the pediatric population. Comparatively, dog-bite injuries in adults and the settings in which surgeons become involved are less studied. An electronic hospital database identified all patients 18 years or older who were treated for dog bites from 2010 to 2014. Demographics, injury information, intervention type, and payer source were collected. Socioeconomic analysis was performed using Geographic Information Systems mapping. A total of 189 adults presented to the emergency department with dog-bite-related injuries. The most common injury location was the hand (n = 62, 32.8%), followed by the head and neck (n = 36, 19.1%). Of the 189 patients, 33 adults (17.5%) were forwarded to a surgical subspecialist for repair. A head and neck injury was significantly more likely to be repaired by a surgical specialist (P = 0.011). The most common breed of dog identified was pit bull (n = 29, 47.5%). The majority of pit bull attacks involved the extremities (65.5%) compared to other breeds of dogs. Pit bull victims were noted to have a lower average annual income compared to other breed victims ($64,708 versus $75,004; P = 0.16). Annual income between intervention group and no intervention group was not significantly different (P = 0.26). This study is the 1st to perform a socioeconomic analysis in the adult dog-bite population and encourages the use of a surgical specialist in the setting of a head and neck bite.

Depression and cigarette smoking behavior: A critical review of population-based studies.

BACKGROUND: Smoking and depression are both leading causes of disability, mortality and morbidity around the world. Using epidemiologic data to study the association between depression and the severity, course, and persistence of smoking in the general population is important for understanding the scope of the problem of smoking among people with depression. OBJECTIVES: The current paper aims to critically review existing epidemiologic research on the smoking behaviors of persons with depressive symptoms and disorders and to identify gaps in the literature that warrant further study. METHODS: Literature searches of Medline and EMBASE were used to identify articles that analyzed epidemiologic data and examined an aspect of smoking behavior in persons with depressive symptoms or disorders. Six hundred ninety-three abstracts were reviewed and 45 studies met all of the inclusion criteria to be included in the review. RESULTS: Persons with depression, compared to those without depression, are more likely to smoke, and meet criteria for nicotine dependence, are less likely to quit smoking, and are more likely to relapse. Little is known about the association between depression and smoking behavior by age, socioeconomic status, or race/ethnicity or with regard to the use of tobacco products other than cigarettes. CONCLUSION: Persons with depression are more likely to smoke cigarettes and have greater difficulty quitting smoking. Community-based and public health approaches may need to begin considering the links between depression and smoking in order to best target the current smokers in the population and develop more effective tobacco control campaigns.

Deconstructing negative pressure wound therapy.

Since its introduction 20 years ago for the treatment of chronic wounds, negative pressure wound therapy use has expanded to a variety of other wound types. Various mechanisms of action for its efficacy in wound healing have been postulated, but no unifying theory exists. Proposed mechanisms include induction of perfusion changes, microdeformation, macrodeformation, exudate control and decreasing the bacterial load in the wound. We surmise that these different mechanisms have varying levels of dominance in each wound type. Specifically, negative pressure wound therapy is beneficial to acute open wounds because it induces perfusion changes and formation of granulation tissue. Post-surgical incisional wounds are positively affected by perfusion changes and exudate control. In the context of chronic wounds, negative pressure wound therapy removes harmful and corrosive substances within the wounds to affect healing. When skin grafts and dermal substitutes are used to close a wound, negative pressure wound therapy is effective in promoting granulation tissue formation, controlling exudate and decreasing the bacterial load in the wound. In this review, we elucidate some of the mechanisms behind the positive wound healing effects of negative pressure wound therapy, providing possible explanations for these effects in different wound types.

Vascularized Fibular Epiphyseal Transfer for Pediatric Limb Salvage: Review of Applications and Outcomes.

Vascularized fibular epiphyseal transfer (VFET) offers a functional advantage in pediatric limb salvage due to the preservation of growth potential and an articular surface for remodeling. This review summarizes the available evidence on the clinical characteristics and outcomes of pediatric reconstruction applying VFET at different recipient sites and with varying techniques. VFET was used to reconstruct the proximal humerus, distal radius or ulna, proximal femur, distal fibula, calcaneus, and mandible. Although most often harvested on the anterior tibial artery, VFET has also been performed using the peroneal artery, the inferior lateral genicular artery, and a dual pedicle. Recipient site flap inset most often involved fixation with plates and/or screws as well as soft tissue reconstruction using a retained slip of biceps femoris tendon. Outcomes included limb growth, range of motion, and strength. The most common reported complications were bone flap fracture and peroneal nerve palsy. The anterior tibial artery was the most applied pedicle with reliable limb growth, but with the added risk of postoperative peroneal palsy. Bone flap fracture most often occurred at the proximal humerus and femur recipient sites. Plate fixation and the combined use of allograft had lower instances of bone flap fracture. This review highlights how the anticipated dynamic growth and remodeling this free flap offers in the long term must be weighed against its complexity and potential complications.

Wisconsin Card Sorting Task-64 performance among HIV+ Black/African American and Latinx adults compared to normative samples and by sociocultural and health variables.

Many people living with HIV experience cognitive impairment, and HIV disproportionately affects racial/ethnic minority groups. Independent of HIV, racial/ethnic minority individuals perform worse than White individuals on cognitive tasks, even after accounting for education. Our goals were to (1) compare WCST-64 scores between HIV+ Black/African American (Black/AA) (n = 45) and Latinx (n = 41) urban-dwelling adults; (2) compare our total sample to the WCST-64 manual's normative (N) and clinical normative (CN) groups; and (3) explore relationships between WCST-64 performance and sociocultural/health variables. In our sample, employment (12%), mean annual income (<$10,000), and mean education (<12 years) were low, while mean medication adherence rates were high for both Black/AA (90%) and Latinx (87%). WCST-64 scores were similar between groups (p > .05). Percentages of "below average" and "mildly impaired" scores in our sample were higher than the N group, and similar to the CN group. Lifetime heroin use, dementia, and longer HIV illness duration were significantly associated with worse WCST-64 performance (ps < .05). The observed low scores in our asymptomatic sample are likely due to the intersectionality of sociocultural and medical burden, highlighting complexities in interpreting neuropsychological data in real-world HIV+ clinics. Executive deficits are linked to poorer outcomes, and routine cognitive screening may be clinically indicated.

Association of Neighborhood Income with Clinical Outcomes Among Pregnant Patients with Cardiac Disease.

Cardiovascular disease is the leading cause of pregnancy mortality. Socioeconomic and racial disparities in pregnancy are well established. Despite this, little is known about the impact of social determinants of health in pregnant patients with heart disease. This study aims to determine whether pregnant patients with heart disease living in lower income neighborhoods and managed at cardio-obstetrics programs have higher rates of cardiac events or preterm deliveries compared with those living in higher income neighborhoods. This is a retrospective cohort study of 206 patients between 2010 and 2020 at a quaternary care hospital in Northern California. The exposure was household income level based on neighborhood defined by the US Census data. Patients in lower income neighborhoods (N = 103) were 45% Hispanic, 34% White, and 14% Asian versus upper income neighborhoods (N = 103), which were 48% White, 31% Asian, and 12% Hispanic (p < 0.001). There was no significant difference in the rates of intrapartum cardiac events (10% vs. 4%; p = 0.16), postpartum cardiac events (14% vs. 17%; p = 0.7), and preterm delivery (24% vs. 17%; p = 0.23). The rates of antepartum hospitalization were higher for lower income neighborhoods (42% vs 22%; p = 0.004). While there is no significant difference in cardiac events and preterm delivery rates between patients from low versus high income neighborhoods, patients from lower income neighborhoods have higher antepartum hospitalization rates. Earlier identification of clinical deterioration provided by a cardio-obstetrics team may contribute to increased hospitalizations, which might mitigate socioeconomic disparities in outcomes for these pregnant patients with heart disease.

Clinical factors associated with a positive postpartum depression screen in people with cardiac disease during pregnancy.

Background: While people with cardiac disease are known to be at increased lifetime risk of depression, little is known about postpartum depression rates in this population. Describing rates of positive postpartum depression screens and identifying risk factors that are unique to cardiac patients may help inform risk reduction strategies. Methods: This retrospective cohort study included pregnant patients with congenital and/or acquired cardiac disease who delivered at a single institution between 2014 and 2020. The primary outcome was a positive postpartum depression screen, defined as Edinburgh Postpartum Depression Score (EPDS) ≥10. Potential exposures were selected a priori and compared between patients with and without a positive postpartum depression screen using Wilcoxon rank-sum and Fisher's exact tests. Secondary outcomes were responses to a longitudinal follow-up survey sent to English-speaking patients evaluating cardiac status, mental health, and infant development. Results: Of 126 eligible cardiac patients, 23 (18.3%) had a positive postpartum depression screen. Patients with a positive postpartum depression screen were more likely to have had antepartum anticoagulation with heparin or enoxaparin (56.5% versus 26.2%, p=0.007), blood transfusion during delivery (8.7% versus 0%, p=0.032), and maternal-infant separation postpartum (52.2% versus 28.2%, p=0.047) compared to patients with a negative screen. Among 29 patients with a positive screen who responded to the follow up survey, 50% reported being formally diagnosed with anxiety or depression and 33.3% reported child development problems. Conclusions: Our results highlight the importance of screening for postpartum depression in patients with cardiac disease, especially those requiring antepartum anticoagulation or maternal-infant separation postpartum.

Addressing postpartum contraception practices utilizing a multidisciplinary Pregnancy Heart Team approach.

BACKGROUND: Cardiovascular disease has emerged as the leading cause of maternal morbidity and mortality, making planned pregnancy, and thereby reliable contraception among people with cardiovascular disease, vital. OBJECTIVE: This study aimed to compare postpartum contraceptive practices among people with cardiovascular disease (cardiac cohort) cared for by a Pregnancy Heart Team to people with other chronic comorbidities (high-risk cohort), and people without comorbidities (low-risk cohort). We hypothesized that the Pregnancy Heart Team influenced baseline contraception counseling and practices among those with cardiovascular disease. STUDY DESIGN: This was a retrospective cohort study comparing postpartum contraceptive practices between a cardiac cohort who received care by a multidisciplinary team between 2012 and 2020 and high-risk and low-risk cohorts delivering at a single academic center between 2016 and 2019. We investigated presence of a contraceptive plan (at birthing admission, discharge, and postpartum visit) and uptake of reliable contraception by 8 weeks postpartum. RESULTS: We included 1464 people: 189 with cardiovascular disease, 197 with other chronic comorbidities, and 1078 low-risk people. At birth hospitalization admission, reliable contraception was planned among 42% of the cardiac cohort, 40% of the high-risk cohort, and 31% of the low-risk cohort, with similar distributions at the time of discharge and at 8 weeks postpartum. Compared with the cardiac cohort, by 8 weeks postpartum, the high-risk cohort had similar odds of using highly reliable forms of contraception (39% vs 36%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.21) and similar odds of having a plan to use the most reliable forms of contraception (intrauterine device, implant, bilateral tubal ligation) at the time of birthing admission (42% vs 40%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.22), discharge (47% vs 45%; adjusted odds ratio, 0.95; 95% confidence interval, 0.61-1.48), and postpartum visit (35% vs 29%; adjusted odds ratio, 0.76; 95% confidence interval, 0.49-1.17). The low-risk cohort had lower odds of using a reliable form of contraception (39% vs 27%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37-0.75) and was less likely to have a plan for reliable contraception at the time of birthing admission (42% vs 31%; adjusted odds ratio, 0.54; 95% confidence interval, 0.38-0.76), discharge (47% vs 33%; adjusted odds ratio, 0.58; 95% confidence interval, 0.4-0.82), and postpartum visit (35% vs 21%; adjusted odds ratio, 0.50; 95% confidence interval, 0.35-0.71). CONCLUSION: People with cardiovascular disease cared for by a Pregnancy Heart Team had higher odds of reliable postpartum contraception planning and uptake compared with a low-risk cohort and similar odds compared with a high-risk cohort. Pregnancy could serve as a critical period for contraception counseling and family planning among people with cardiovascular disease. A multidisciplinary team should be used to address postpartum contraception as a modifiable risk factor to reduce maternal morbidity and mortality among those with cardiovascular disease.

Surgical Treatment of Pediatric Dog-bite Wounds: A 5-year Retrospective Review.

INTRODUCTION: Dog bites are a significant health concern in the pediatric population. Few studies published to date have stratified the injuries caused by dog bites based on surgical severity to elucidate the contributing risk factors. METHODS: We used an electronic hospital database to identify all patients ≤17 years of age treated for dog bites from 2013-2018. Data related to patient demographics, injury type, intervention, dog breed, and payer source were collected. We extracted socioeconomic data from the American Community Survey. Data related to dog breed was obtained from public records on dog licenses. We calculated descriptive statistics as well as relative risk of dog bite by breed. RESULTS: Of 1,252 injuries identified in 967 pediatric patients, 17.1% required consultation with a surgical specialist for repair. Bites affecting the head/neck region were most common (61.7%) and most likely to require operating room intervention (P = 0.002). The relative risk of a patient being bitten in a low-income area was 2.24, compared with 0.46 in a high-income area. Among cases where the breed of dog responsible for the bite was known, the dog breed most commonly associated with severe bites was the pit bull (relative risk vs German shepherd 8.53, relative risk vs unknown, 3.28). CONCLUSION: The majority of injuries did not require repair and were sufficiently handled by an emergency physician. Repair by a surgical specialist was required <20% of the time, usually for bites affecting the head/neck region. Disparities in the frequency and characteristics of dog bites across socioeconomic levels and dog breeds suggest that public education efforts may decrease the incidence of pediatric dog bites.

Management Modalities and Outcomes Following Acute Scaphoid Fractures in Children: A Quantitative Review and Meta-Analysis.

BACKGROUND: Early evaluation and appropriate management of pediatric scaphoid fractures are necessary to avoid complications. To date, current management of pediatric fractures varies among providers. The objective of this study was to compare clinical outcomes following different treatment modalities. METHODS: A PubMed literature search identified studies involving acute scaphoid fractures in children. Studies were evaluated for treatment provided and their respective effects on union rate, wrist range of motion, and wrist pain. Data were pooled across studies, and quantitative statistical analysis was conducted to compare outcomes. RESULTS: Seventeen studies representing 812 acute pediatric scaphoid fractures were included in the current analysis. We found 93.5% of scaphoid fractures were treated with cast immobilization vs 6.5% treated surgically as 13 of 17 authors treated all fractures with immobilization vs 4 of 17 studies who offered surgical intervention. We found pediatric scaphoid fractures had excellent bone union rates (96.2%) with no difference between the cast immobilization and surgery groups ( P value NS). Long- and short-arm thumb spica immobilization protocols were commonly employed; however, we found no difference in the rates of union ( P value NS). At follow-up, 99.0% of patients treated nonoperatively had normal wrist range of motion and 96.8% were pain free. CONCLUSIONS: Pediatric scaphoid fractures have excellent outcomes. Nonoperative treatment results in a high rate of union with few posttreatment wrist symptoms. Nonsurgical treatment represents an adequate treatment modality in a majority of acute pediatric scaphoid fractures, wherein the role for surgery needs to be better defined.

Carrier-Free CXCR4-Targeted Nanoplexes Designed for Polarizing Macrophages to Suppress Tumor Growth.

INTRODUCTION: Treatment options for cancer metastases, the primary cause of cancer mortality, are limited. The chemokine receptor CXCR4 is an attractive therapeutic target in cancer because it mediates metastasis by inducing cancer cell and macrophage migration. Here we engineered carrier-free CXCR4-targeting RNA-protein nanoplexes that not only inhibited cellular migration but also polarized macrophages to the M1 phenotype. MATERIALS AND METHODS: A CXCR4-targeting single-chain variable fragment (scFv) antibody was fused to a 3030 Da RNA-binding protamine peptide (RSQSRSRYYRQRQRSRRRRRRS). Self-assembling nanoplexes were formed by mixing the CXCR4-scFv-protamine fusion protein (CXCR4-scFv-RBM) with miR-127-5p, a miRNA shown to mediate M1 macrophage polarization. RNA-protein nanoplexes were characterized with regard to their physicochemical properties and therapeutic efficacy. RESULTS: CXCR4-targeting RNA-protein nanoplexes simultaneously acted as a targeting ligand, a macrophage polarizing drug, and a miRNA delivery vehicle. Our carrier-free, RNA-protein nanoplexes specifically bound to CXCR4-positive macrophages and breast cancer cells, showed high drug loading (~ 90% w/w), and are non-toxic. Further, these RNA-protein nanoplexes significantly inhibited cancer and immune cell migration (75 to 99%), robustly polarized macrophages to the tumor-suppressive M1 phenotype, and inhibited tumor growth in a mouse model of triple-negative breast cancer. CONCLUSIONS: We engineered a novel class of non-toxic RNA-protein nanoplexes that modulate the tumor stroma. These nanoplexes are promising candidates for add-ons to clinically approved chemotherapeutics.

The microRNA regulatory landscape of MSC-derived exosomes: a systems view.

Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs. At a system level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis processes in line with observed cardiovascular regenerative effects. Targeted pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-ß and PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and increased angiogenesis in HUVECs. The intrinsic beneficial effects were further improved by virus-free enrichment of MSC exosomes with network-informed regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte proliferation. The data presented here help define the miRNA landscape of MSC exosomes, establish their biological functions through network analyses at a system level, and provide a platform for modulating the overall phenotypic effects of exosomes.

Decreased circulation in the feline choriocapillaris underlying retinal photocoagulation lesions.

PURPOSE: To investigate the effects of argon laser photocoagulation on the choroidal circulation in cats. METHODS: Three sizes of argon laser lesions designed to damage the outer retina were created in six cats: larger than 1 mm, 500 µm, and 200 µm. At least 1 month after the lesions, damage to the choroidal vasculature was studied in two ways. First, scanning laser ophthalmoscopy was used to obtain infrared reflectance (IR) photographs and indocyanine green (ICG) angiograms. Second, fluorescent microspheres (15 µm) were injected into the left ventricle. The globes were fixed, the choroid was flat mounted, and images were taken with a fluorescence microscope. Retinal histology was assessed in comparable lesions. RESULTS: Histology showed that the inner retina was preserved, but the choroid, tapetum, and outer retina were damaged. ICG angiograms revealed choriocapillaris loss in large lesions and in some 500-µm lesions, whereas the larger vessels were preserved; in 200 µm lesions, choriocapillaris loss was not detectable. However, in all lesions, the distribution of microspheres revealed little if any choriocapillaris flow. In larger lesions, the damaged region was surrounded by an area in which the number of microspheres was higher than in the lesion but lower than in the normal retina. CONCLUSIONS: Under lesions that destroyed photoreceptors, the choriocapillaris was also compromised, even when no change could be detected with ICG angiography. Panretinal photocoagulation is designed to increase retinal PO2 by allowing choroidal oxygen to reach the inner retina, but its effectiveness may be limited by damage to the choriocapillaris.