Immune profiling of SARS-CoV-2 epitopes in asymptomatic and symptomatic pediatric and adult patients.

BACKGROUND: The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unpredictable manifestations of coronavirus disease (COVID-19) and variable clinical course with some patients being asymptomatic whereas others experiencing severe respiratory distress, or even death. We aimed to evaluate the immunoglobulin G (IgG) response towards linear peptides on a peptide array containing sequences from SARS-CoV-2, Middle East respiratory syndrome-related coronavirus (MERS) and common-cold coronaviruses 229E, OC43, NL63 and HKU1 antigens, in order to identify immunological indicators of disease outcome in SARS-CoV-2 infected patients. METHODS: We included in the study 79 subjects, comprising 19 pediatric and 30 adult SARS-CoV-2 infected patients with increasing disease severity, from mild to critical illness, and 30 uninfected subjects who were vaccinated with one dose of SARS-CoV-2 spike mRNA BNT162b2 vaccine. Serum samples were analyzed by a peptide microarray containing 5828 overlapping 15-mer synthetic peptides corresponding to the full SARS-CoV-2 proteome and selected linear epitopes of spike (S), envelope (E) and membrane (M) glycoproteins as well as nucleoprotein (N) of MERS, SARS and coronaviruses 229E, OC43, NL63 and HKU1 (isolates 1, 2 and 5). RESULTS: All patients exhibited high IgG reactivity against the central region and C-terminus peptides of both SARS-CoV-2 N and S proteins. Setting the threshold value for serum reactivity above 25,000 units, 100% and 81% of patients with severe disease, 36% and 29% of subjects with mild symptoms, and 8% and 17% of children younger than 8-years reacted against N and S proteins, respectively. Overall, the total number of peptides in the SARS-CoV-2 proteome targeted by serum samples was much higher in children compared to adults. Notably, we revealed a differential antibody response to SARS-CoV-2 peptides of M protein between adults, mainly reacting against the C-terminus epitopes, and children, who were highly responsive to the N-terminus of M protein. In addition, IgG signals against NS7B, NS8 and ORF10 peptides were found elevated mainly among adults with mild (63%) symptoms. Antibodies towards S and N proteins of other coronaviruses (MERS, 229E, OC43, NL63 and HKU1) were detected in all groups without a significant correlation with SARS-CoV-2 antibody levels. CONCLUSIONS: Overall, our results showed that antibodies elicited by specific linear epitopes of SARS-CoV-2 proteome are age dependent and related to COVID-19 clinical severity. Cross-reaction of antibodies to epitopes of other human coronaviruses was evident in all patients with distinct profiles between children and adult patients. Several SARS-CoV-2 peptides identified in this study are of particular interest for the development of vaccines and diagnostic tests to predict the clinical outcome of SARS-CoV-2 infection.

A Single Center's Clinical Experience With Ergonomix Breast Implants.

BACKGROUND: This retrospective study reports on the early experience of a private surgical center with Motiva Ergonomix SilkSurface breast implants. OBJECTIVES: The aim of this study was to examine the incidence of complications and satisfaction levels in women who received primary and revision breast augmentation or augmentation-mastopexy with Ergonomix SilkSurface breast implants. METHODS: A total of 356 consecutive patients received Ergonomix SilkSurface breast implants between April 2014 and October 2018 by 3 different surgeons and were followed-up for a minimum of 12 months. Complications were assessed by measuring the rate of rupture, capsular contracture, malposition, late seroma, double capsule, reoperation, symmastia, ptosis, extrusion, and infection. Satisfaction with aesthetic results was assessed on a Likert scale by both surgeon and patient. RESULTS: Only 6 major complications were observed in these 356 patients (712 implants): 1 unilateral implant ptosis ("bottoming out") at 12 months (0.14%) and 2 capsular contractures (0.28%), 1 at 14 months and 1 at 2 years. At all time points, 98% of the patients were "extremely satisfied or very satisfied" with the aesthetic results, and the surgeons categorized the outcomes as "very important or important improvement" in 96% of the cases. CONCLUSIONS: Motiva Ergonomix SilkSurface devices provided high patient satisfaction up to more than 5 years postoperatively with very few complications. These data are consistent with other reports in the literature. The observed favorable outcomes might be attributed, at least in part, to the bioengineered "cell-friendly" surface of these implants.

Facial Aging Surgery: Healing Time, Duration Over the Years, and the Right Time to Perform a Facelift.

BACKGROUND: The "time variable" assumes paramount importance, especially regarding facial rejuvenation procedures. Questions regarding the length of recovery time before returning to work, how long the results will last, and the ideal time (age) to undergo this particular type of surgery are the most commonly asked by patients during the initial consultation. OBJECTIVES: The authors endeavored to determine the healing time, optimal age to perform the surgery, and duration of the results after cosmetic face surgery. METHODS: A 35-year observational study of 9313 patients who underwent facial surgeries was analyzed. The principal facial rejuvenation interventions were divided into 2 subgroups: (1) eyelid and periorbital surgery, including eyebrow lift, blepharoplasty, and its variants and midface lift; and (2) face and neck lift. Significant follow-ups were conducted after 5, 10, and 20 years. To evaluate the course of convalescence, the degree of satisfaction with the intervention, and the stability of the results, a questionnaire survey was administered to a sample of 200 patients who underwent face and neck lifts. RESULTS: The answers given indicated that surgery performed according to rigorous standards allowed for a relatively rapid recovery, and the positive results were stable up to 10 years after surgery. The level of patient satisfaction also remained high even after 20 years. CONCLUSIONS: The "right time" for a facelift, taking into account age, recovery time, and the longevity of the results, is an important consideration for both the patient and the cosmetic surgeon.

Hypoxia-Regulated miRNAs in Human Mesenchymal Stem Cells: Exploring the Regulatory Effects in Ischemic Disorders.

Human mesenchymal/stromal stem cells (hMSC) are the most promising cell source for adult cell therapies in regenerative medicine. Many clinical trials have reported the use of autologous transplantation of hMSCs in several disorders, but with limited results. To exert their potential, hMSCs could exhibit efficient homing and migration toward lesion sites among other effects, but the underlying process is not clear enough. To further increase the knowledge, we studied the co-regulation between hypoxia-regulated genes and miRNAs. To this end, we investigated the miRNA expression profile of healthy hMSCs in low oxygen/nutrient conditions to mimic ischemia and compared with cells of patients suffering from critical limb ischemia (CLI). miRNAs are small, highly conserved, non-coding RNAs, skilled in the control of the target's expression level in a fine-tuned way. After analyzing the miRNOme in CLI-derived hMSC cells and healthy controls, and intersecting the results with the mRNA expression dataset under hypoxic conditions, we identified two miRNAs potentially relevant to the disease: miR-29b as a pathological marker of the disease and miR-638 as a therapeutic target. This study yielded a deeper understanding of stem cell biology and ischemic disorders, opening new potential treatments in the future.

"Dynamic Canthopexy" Drill Hole Canthal Repositioning.

BACKGROUND: Canthopexies can be performed to modify the eye slant, both when the lateral canthus is lower than the medial one (congenital defect) or in case the patient asks for an almond-shaped eye (cosmetic indication). OBJECTIVES: This peculiar type of canthopexy can be defined as "dynamic canthopexy," meaning that the lateral canthus is released from its original insertion and raised to a higher position. The goal of this study is to demonstrate the differences and the efficacy of the dynamic cantoplasty. METHODS: The authors reviewed 30 patients treated with a "dynamic canthopexy" between January 2005 and March 2015. Eighteen patients were affected by true downslanting palpebral fissure, and 12 patients had a normal eye shape but were wishing for a more "Asian" look. Dynamic canthopexy involves a total modification of the canthal suspension system and its careful reconstruction at a higher level inside the orbital rim. To obtain a permanent result, canthal ligament and tendon had to be anchored to drill holes in the orbital rim bone with nonabsorbable sutures. Symmetry was very carefully assessed. The average surgical time was 1 hour. RESULTS: This surgery proved extremely effective in all cases. Patients must be warned, though, that an initial hypercorrection is necessary to achieve the desired canthal position. About 6 months after surgery the result of this operation can be considered permanent. Severe complications are rare. CONCLUSIONS: Dynamic canthopexy can provide stable correction of anti-Mongolian slant. It can also be effectively employed to obtain permanent slant eyes when required by purely cosmetic patients. If precisely carried out, this technique can yield very rewarding outcomes.

HOTAIR role in melanoma progression and its identification in the blood of patients with advanced disease.

The molecular mechanisms responsible for the metastatic progression of melanoma have not been fully defined yet. We have recently shown that an important role in this process is certainly played by HOX genes, whose regulation is under control of particular non-coding RNAs, some of which are present within the HOX locus. HOTAIR is the most studied among them, whose aberrant expression is associated with the metastatic progression of many malignancies. The aim of this study was to verify the role played by HOTAIR in metastatic progression of melanoma and to evaluate the circulating levels of HOTAIR in the blood of patients with metastatic melanoma. A series of melanocytic lesions were selected to evaluate the potential changes in the expression of HOTAIR during the evolution of the disease through in situ and molecular approaches. None of the benign melanocytic lesions showed the presence of HOTAIR. The staining of HOTAIR resulted very weak in the primary pT1 lesions, while it was very strong in all pairs of primary tissues and corresponding metastases. Surprisingly, we found the presence of HOTAIR in some intratumoral lymphocytes, while this positivity decreased in lymphocyte component further away from the tumor. HOTAIR was also detected in the serum of selected metastatic patients. These data allowed us to speculate on the fundamental role played by HOTAIR in tumor evolution of melanoma. Its presence in intratumoral lymphocytes might suggest that its involvement in the modulation of tumor microenvironment and the detection in the serum could be used in the management of melanoma patients.

Facelift 2015.

Among the current topics, one that is more commonly discussed is that of the mini-invasive or "soft" techniques that seem to attract doctors and patients more than real surgery. We instead propose a relatively aggressive technique that can really rejuvenate the faces and necks of our patients. Are we not in step with the times? The problem is, unfortunately, that until now there is nothing that, without anesthesia, swelling, bruising, and so forth, can magically bring about the result of a well-done facelift. There are no "thread lifts" or fillings or endopeels or weird devices using radiofrequency, ultrasound, or shock waves-the list could go on forever-that can compare with a properly performed facelift. But how should a good facelift be done? For many years, we have been using the protocol described in this article, and the request for facelifts has not dropped, despite never having used advertising in our practice. We want to give our patients natural and long-lasting results, and for this purpose we must use an effective and individualized technique, even if it implies a relatively long down time. In this article, we describe the technical choices that we have made based on a long clinical experience and on detailed anatomical studies. Most difficulties that are encountered with this type of surgery concern finding the proper dissection plane and the proper amount of traction to be applied to the different tissue layers. It is indeed not at all easy, especially for a beginner, to be sure that one has reached the proper depth of dissection, which will allow the elevation of the superficial musculo-aponeurotic system (SMAS) in a risk-free manner even in the area which is medial to the anterior border of the parotid gland where the facial nerve is no longer protected by the gland itself. We will nevertheless try to provide precise indications concerning every important detail needed to perform the operation safely.

Chin Microgenia: A Clinical Comparative Study.

BACKGROUND: The aesthetic relevance of the chin and its relatively simple correction through different approaches make genioplasty one of the most performed aesthetic procedures of the face. Sliding genioplasty is extremely rewarding, particularly when performed as an adjunction to rhinoplasty, rhytidectomy, or jaw surgery. In the scientific literature, many different surgical techniques are described, but the biological implications and the economical impact can shape the surgeon's decision on which can be the best treatment: surgical correction with osteotomy, chin implants, or with fillers. OBJECTIVE: The authors propose a decision making protocol for correcting chin microgenia based on a revision of 345 treated cases. METHODS: A retrospective review of 345 cases of chin microgenia was undertaken to understand the proper preoperative assessment and therapeutic planning. A total of 135 patients were treated with surgical sliding genioplasty (group A): 60 patients (group B) have been grafted with alloplastic implants and the remaining 150 patients (group C) with hyaluronic acid. We recorded clinical indications, complications, and long-term aesthetic results at 3-year follow-up. RESULTS: The analysis of the results based on the entity of the chin's sagittal defect, the chin soft-tissue thickness, the patient's age, and self-judgment allows for simplified treatment planning for sagittal chin deformities showing a greater predictability and a more stable long-term aesthetic result regarding sliding genioplasty compared to alloplastic implant placement and fillers. CONCLUSIONS: Our proposal for a simple and versatile protocol of chin microgenia aims to simplify the therapeutic indications for a predictable and a stable long-term aesthetic result. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Stem cell therapy for arterial restenosis: potential parameters contributing to the success of bone marrow-derived mesenchymal stromal cells.

PURPOSE: Restenosis is a complex and heterogeneous pathophysiological phenomenon occurring in patients submitted to revascularization procedures. Previous studies proved the antirestenotic properties of injected allogenic mesenchymal stromal cells (MSCs) in an experimental model of rat carotid (re)stenosis induced through arteriotomy. In this study we describe some of the effects subsequent to MSC treatment of rats submitted to carotid arteriotomy and possibly responsible for their antirestenotic effect. METHODS: Rat MSCs were isolated from bone marrow, expanded in vitro and characterized. Subsequently, we evaluated the effects of MSC administration via tail vein at 3 and 7 days after carotid arteriotomy both in rat serum and in injured carotids, focusing on DNA oxidative damage (8-oxo-dG detection), cell proliferation index (BrdU incorporation assay), apoptotic index (TUNEL assay), the expression of inflammation- and proliferation-related genes (RT-PCR), the release of growth factors and of inflammation-related cytokines (antibody arrays and ELISA). RESULTS: MSC administration induced a greater cell proliferation in carotids after arteriotomy, together with an increased level of VEGF in the serum and with the higher expression of VEGF mRNA in injured carotids. Serum analysis also revealed a decreased level of the pro-inflammatory cytokines CXCL1, CXCL5, L-Selectin, ICAM-1 and LIX, and of TIMP1 and SDF-1alpha in MSC-treated rats. The MSC immunomodulatory activity was confirmed by the decreased expression of TLR2 and TLR4 in injured carotids. CONCLUSIONS: MSCs play an immunomodulatory paracrine role when injected in rats submitted to carotid arteriotomy, accompanied by the release of VEGF, possibly contributing to the accelerated repair of the injured vascular wall.

Liporeduction: A Faster and Safer Breast Remodeling Technique.

BACKGROUND: Breast reduction is a time-consuming procedure with a relatively high complication rate. Furthermore, recurrent breast enlargement can occur in case of postoperative weight gain. The authors describe a breast reduction technique based on liposuction, followed mostly by skin resection alone, which makes this operation easier, faster, and safer, with more stable results. METHODS: Two hundred thirty-three patients were treated by breast liporeduction between 2006 and 2017, with an age range of 18 to 70 years (average age, 42 years). The patients were selected after careful clinical and instrumental assessment among those in whose breasts the fat component was prevalent over the gland. Most of the soft-tissue reduction consisted of fat aspiration. The follow-up ranged from 12 months to 9 years (average, 4.5 years). RESULTS: The results of this study have been extremely satisfactory. Most of the patients healed uneventfully and were happy with the final outcome. Very few complications were encountered, among which were small steatonecroses and partial nipple-areola complex necroses. CONCLUSIONS: For the past 15 years, all four authors have preferred this breast reduction technique over others. Fat only is selectively removed by aspiration with a blunt cannula, sparing the vascular network and easily mobilizing the nipple-areola complex. Liporeduction provides a good stable result because any postoperative weight variation will not change the volume of a breast consisting mainly of glandular and fibrous tissue. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Changing Epidemiology of Acute Viral Respiratory Infections in Hospitalized Children: The Post-Lockdown Effect.

Several reports highlighted how public health measures aimed at limiting severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) circulation have likely contributed to reducing the circulation of other respiratory viruses, particularly during the first year of the COVID-19 pandemic. We evaluated the epidemiology of acute respiratory infections in a large cohort of hospitalized children during the third year of the pandemic (2021−2022). We retrospectively analyzed data from the health records of children (<14 years) hospitalized for acute respiratory infections between 1 July 2021 and 31 March 2022. A total of 1763 respiratory panels were collected. Overall, 1269 (72%) panels hadpositive results for at least one pathogen. Most positive panels (53.8%) belonged to patients aged 1−12 months. The most detected pathogen was respiratory syncytial virus (RSV) (57.8% of positive panels). The RSV peak occurred in November 2021. Nine hundred and forty-five (74.5%) panels were positive for one pathogen while three hundred and twenty-four (25.5%) showed multiple infections. Patients with multiple infections were significantly older than those with a single infection. The 2021−2022 peak of RSV infection in Italy occurred earlier than in the previous pre-pandemic seasons. A high number of children have been hospitalized because of acute viral infections also due to less aggressive viruses.

Detection of SARS-CoV-2 infection in a pediatric population from south Italy without symptoms of Coronavirus Disease 2019.

BACKGROUND: SARS-CoV-2 has had dramatic consequences on the world population in morbidity and mortality and socially. Clinical manifestations range from common cold-like to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. The pediatric population may be infected with SARS-CoV-2, but is less likely to be symptomatic or develop severe symptoms. METHODS: We analyzed a cohort of pediatric subjects from Campania Region, south Italy, without symptoms of SARS-CoV2, to evaluate the distribution of infection in relation to gender and age. Detection on nasopharyngeal swabs was performed with two different RT-PCR methods, a qualitative rapid test (VitaPCRTM SARS-CoV-2 assay) and a quantitative test (SARS-CoV-2 ELITe MGB® assay). RESULTS: Positive subjects were 52.63% male and 47.36% female. Regarding age distribution, we described a consistent increase of detection rate (82.45%) in 0-2 year-old patients. CONCLUSION: The importance of children in transmitting the virus remains uncertain; however our analysis of the distribution of the infection in these subjects may help monitor SARS-CoV2 spread in the general population.

Face Lifting in Bald Male Patients: New Trends and Specific Needs.

BACKGROUND: Aesthetic surgery has recently become popular also among men. The ever-increasing number of bald men wishing to undergo facial surgery represents a challenge for the surgeon, as the scars cannot be hidden in the hair and must therefore be as short as possible. The authors present their experience in face lifting in bald male patients and propose an innovative technique to handle the skin excess to achieve practically invisible scars. METHODS: A 10-year observational study was carried out on 68 bald male face-lift patients. All patients underwent deep plane lifting with a specific method for handling skin excess. This technique is the innovation presented in this article. Subjective and objective methods were used to evaluate the results. The well-known FACE-Q questionnaire was sent to all the patients together with an explanatory letter. Three ad hoc questions were added to the questionnaire to assess the degree of satisfaction with the scars. The objective method involved the evaluation of preoperative and postoperative photographs by a three-member jury. The average follow-up period was 12 months. RESULTS: All patients showed a high degree of satisfaction with the final appearance of the surgical scars and appreciation of the overall quality of the result, 1 year after face-lift surgery. No patient expressed regret about choosing to undergo this type of surgery. Very high scores were registered for the overall facial appearance and for the various critical areas examined, including scars, from patients and experts alike. CONCLUSION: The face-lifting technique for bald men proposed by the authors, involving a peculiar and innovative way of handling the skin excess, has proven to be reliably effective in obtaining virtually invisible scars.

Detection of Human Papillomaviruses in the Nasopharynx of Breastfed Infants: New Findings and Meta-Analysis.

Vertical transmission of human papillomaviruses (HPVs) from mother to infant is known to occur during labor, delivery or breastfeeding. Infection with mucosal HPV 6 and 11 may cause recurrent respiratory papillomatosis in children, which is a rare and severe respiratory disease. The cutaneous HPV genotypes have also been described to be transmitted from mother to newborn through skin-to-skin contacts and during breastfeeding. To investigate the perinatal transmission of alpha and beta HPVs we collected nasopharyngeal specimens from 0-12-months-old infants born by vaginal delivery and breastfed at the time of sample collection. The mucosal and cutaneous HPVs were searched by nested PCR using the MY09/11-MGPs and CP65/70-CP66/69 primer sets, respectively, and genotypes identified by direct sequencing analysis. Fourteen out of 113 (12.4%) samples tested positive for HPV and sequence analysis allowed us to identify eight beta genotypes (HPV 5b, 20, 25, 100, 107, 124, 152 and RTRX7). Moreover, we performed a comprehensive review of published studies on the prevalence of mucosal and cutaneous HPVs among 5126 newborns and observed that 10% and 53% were positive for alpha and beta HPVs, respectively. In all studies there was an inverse correlation between the rate of alpha HPV positivity and age, while a significant positive trend was observed in beta HPV detection and age with the highest rate among children older than 12 months (Χ2 test for trend of 10.6, p < 0.001). Further studies are needed to confirm the hypothesis that beta HPVs are transmitted to breastfeeding infants through shedding of viruses in the breast milk or on the external breast epithelium.

Author Correction: Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Use of oxidized regenerated cellulose to stop bleeding after a facelift procedure.

A 52-year-old woman came to our department about correcting a severe soft-tissue laxity after a weight loss of 67 kg. We performed a deep-plane face lift under sedation with local anesthesia. Three hours after the operation the patient had significant and diffuse bleeding, which was controlled by a local hemostatic agent made of oxidized regenerated cellulose (Tabotamp). In the weeks after the operation no local pain or skin damage was observed. We believe that oxidized regenerated cellulose could be a good ancillary therapy for controlling local bleeding associated with this kind of surgery.

Characterization of respiratory infection viruses in hospitalized children from Naples province in Southern Italy.

Most acute respiratory infections (ARIs) in children are due to viral etiology, and represent an important cause of mortality and morbidity in children <5 years old in developing countries. The pathogens that cause ARIs vary geographically and by season, and viruses serve a major role. In the present study, the distribution of the seven respiratory viruses that are more prevalent in Southern European countries were retrospectively analyzed in a Southern Italy Hospital, that centralizes pediatric diseases from the Naples province. Viruses were categorized by a FilmArray Respiratory Panel, and demonstrated no substantial differences in sex, age and seasonal viruses distribution. However, all the investigated viruses had a higher detection rate in the surrounding municipalities than in the metropolitan area of Naples. In recent years, the association between air pollution and respiratory infections has become an increasing public health concern. The data in this study support this association in the surrounding areas of Naples extensively contaminated by environmental toxic agents. In these areas, characterization of the epidemiology of ARIs is required to implement a prevention and control program.