Chamaecyparis lawsoniana and Its Active Compound Quercetin as Ca2+ Inhibitors in the Contraction of Airway Smooth Muscle.

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.

Examination of the Novel National Institutes of Health-Supported Relative Citation Ratio, a Measure of Research Productivity, Among Academic Plastic Surgeons.

BACKGROUND: Considerable interest has been devoted to quantifying research productivity for the purposes of academic appointment and promotion in plastic surgery. A novel bibliometric, the relative citation ratio (RCR), integrates features unavailable in prior metrics, such as the h-index, including the ability to compare researchers in distinct fields. This investigation examines the RCR in relation to established measures of academic productivity and provides the benchmark data in plastic surgery. METHODS: Online sources were queried to identify the characteristics of 955 academic plastic surgeons from 94 programs, ie, academic rank, gender, degrees, and fellowships. Bibliometric data were acquired using the iCite and Scopus databases. Comparative and correlational analyses of variables were performed. RESULTS: Academic plastic surgeons were exceptionally productive, with a mean RCR of 1.20 (interquartile range, 0.79-1.67) and a weighted RCR of 17.68 (interquartile range, 5.14-52.48). Increased mean RCR was significantly associated with advanced academic rank and fellowship training. Increased weighted RCR was significantly associated with advanced academic rank, male gender, PhD acquisition, publication experience, and fellowship training. The h-index was weakly correlated with mean RCR but strongly correlated with weighted RCR and publication experience. CONCLUSIONS: The RCR was associated with established markers of academic productivity, indicating its validity as a reliable field-normalized measure for the evaluation of plastic surgery faculty. Because scholarly output is a potential factor with respect to decisions of hiring, promotion, and allocation of funding, this modality of standardized comparison is paramount for plastic surgeons who exist within a larger general surgery department.

Outcomes of Ventral Hernia Repair After Orthotopic Liver Transplant Using Component Separation and Onlay Biologic Mesh.

INTRODUCTION: The management of ventral hernias (VHs) after orthotopic liver transplant (OLT) can be uniquely challenging because of immunosuppression coupled with large laparotomy size that can compromise the quality of the abdominal wall. The component separation with multipoint suture onlay acellular dermis fixation technique has proven to be effective in high-risk abdominal wall reconstructions. The goal of this study was to elucidate the factors that affect safety and efficacy of VH repair in post-OLT patients. METHODS: A retrospective review of 345 patients who underwent repair of VH with compartment separation and onlay acellular dermal matrix reinforcement from a single surgeon from 2012 to 2020 was conducted. Of these, 27 patients were identified with a history of OLT and were stratified based on whether the defect was a initial or recurrent hernia repair. The majority of patients had a standard chevron incision (70%). Data abstraction was performed for preoperative risk factors, hernia characteristics, surgical site complications, and postoperative course including hernia recurrence. RESULTS: A majority of cases in the study period were initial hernia repairs (59%) with no significant differences in the patient demographics and size of VH defects (190 ± 112.69 cm 2 ). Comorbidities were similar between the groups with the exception of a significantly higher baseline creatinine levels and higher history of smoking in the recurrent hernia repair group ( P < 0.05). Of the 27 cases, there were no demonstrable hernia recurrences noted and an overall 11% complication rate. Univariate analysis noted a statistically significant difference in surgical site complication rate ( P = 0.017), with the initial hernia repair group having the lowest rate of surgical site complications. CONCLUSIONS: In complex post-OLT patients with large VH, modified component separation with onlay acellular mesh was shown to have acceptable medium-term results. Further studies investigating the factors leading to postoperative complications are necessary to reduce recurrence in this evolving patient population.

Pediatric Cranioplasty Patients With Hostile Reconstructive Environments: Split Calvarial Versus Prosthetic Implant.

INTRODUCTION: Pediatric cranial defects can be preceded by prior infection, radiation therapy, failed prior cranioplasty, or cerebrospinal fluid leak, leading to a complex reconstructive environment. The primary aim of this study was to investigate differences in outcomes between pediatric patients with hostile reconstructive environments who received split-calvarial autologous grafts as opposed to prosthetic grafts in cranioplasty. METHODS: We performed an institutional review board-approved retrospective chart review of 51 patients younger than 18 years who underwent cranioplasty with a hostile setting between 1998 and 2020. Patients were then stratified into prosthetic (45%) and autologous groups (54%). The primary outcome measured was postoperative complication, defined as requirement of a subsequent surgery or revision. RESULTS: Overall, there were no significant differences in age, sex, type of hostile setting, etiology of cranial defect, or side of the cranial defect between the 2 groups. Complication rate among the 2 graft groups was 18%. However, there were no significant differences in complications, defined as infection, failure or resorption of the graft, wound breakdown or necrosis, resulting bone defect, or hematoma, between the 2 populations. There was a significant difference in etiology between patients with complications, with patients who required a cranioplasty due to previous hemicraniectomy being nearly 5 times as likely to face a complication ( P = 0.045). CONCLUSIONS: In our study, there was no significant difference observed in complications between prosthetic and split-thickness autologous grafts in pediatric patients with hostile settings. It does, however, seem that patients who had a previous hemicraniectomy are more likely to face complications as a result of cranioplasty.

A Systematic Review of Microsurgical Pedicle Lengthening in Free Tissue Transfer.

INTRODUCTION: Traumatic injuries that require free tissue flaps for reconstruction may require vascular pedicle extension between the flap and recipient vessels to form a clear anastomosis. Currently, a variety of techniques are used, each with their own potential benefits and harms. In addition, reports in the literature conflict on the reliability of pedicle extensions of vessels in free flap (FF) surgery. The objective of this study is to systematically assess the available literature about outcomes of pedicle extensions in FF reconstruction. METHODS: A comprehensive search was performed for relevant studies published up to January 2020. Study quality was assessed using the Cochrane Collaboration risk of bias assessment tool and a set of predetermined parameters was extracted by 2 investigators independently for further analysis. The literature review yielded 49 studies investigating pedicled extension of FF. Studies meeting inclusion criteria underwent data extraction focusing on demographics, conduit type, microsurgical technique, and postoperative outcomes. RESULTS: The search yielded 22 retrospective studies totaling 855 procedures from 2007 to 2018 in which 159 complications (17.1%) were reported in patients aged between 39 and 78 years. Overall heterogeneity of articles included in this study was high. Free flap failure and thrombosis were the 2 most prevalent major complications noted: vein graft extension technique had the highest rate of flap failure (11%) in comparison with the arterial graft (9%) and arteriovenous loops (8%). Arteriovenous loops had a rate of thrombosis of 5% versus 6% in arterial grafts and 8% in venous grafts. Bone flaps maintained the highest overall complication rates per tissue type at 21%. The overall success rate of pedicle extensions in FFs was 91%. Arteriovenous loop extension resulted in a 63% decrease in the odds of vascular thrombosis and a 27% decrease in the odds of FF failure when compared with venous graft extensions (P < 0.05). Arterial graft extension resulted in a 25% decrease in the odds of venous thrombosis and a 19% decrease in the odds of FF failure when compared with venous graft extensions (P < 0.05). CONCLUSIONS: This systematic review strongly suggests that pedicle extensions of the FF in a high-risk complex setting are a practical and effective option. There may be a benefit to using arterial versus venous conduits, although further examination is warranted given the small number of reconstructions reported in the literature.

Do Socioeconomic Status and Race Impact the Safety and Efficacy of Breast Reconstruction?

INTRODUCTION: Immediate breast reconstruction after mastectomy has increased in recent years when compared with delayed reconstruction. Despite this encouraging trend, racial and socioeconomic disparities in the receipt of postmastectomy breast reconstruction have been well documented. We sought to assess the effect of race, socioeconomic status, and patient comorbidities on muscle sparing transverse rectus abdominis myocutaneous outcomes at our safety net hospital institution in the southeast. METHODS: The database of a tertiary referral center was queried for patients who received free transverse rectus abdominis myocutaneous flaps for immediate reconstruction after mastectomy meeting inclusion criteria from 2006 to 2020. Patient demographics and outcomes were compared based on socioeconomic status. The primary outcome (reconstructive success) was defined as breast reconstruction without flap loss. Statistical analysis included analysis of variance and χ2 tests were appropriate using Rstudio. RESULTS: Three-hundred fourteen patients were included in the study, with 76% White, 16% Black, and 8% other. Overall complication rate at our institution was 17% and reconstructive success was 94%. Non-White race, older age at time of breast cancer diagnosis, higher body mass index, and presence of comorbid conditions including current smoking and hypertension were all associated with low socioeconomic status. Despite this, surgical complication rates were not predicted by non-White race, older age, or presence of diabetes mellitus. When analyzing major and minor complications based on radiation received or reconstructive success, there was no significant difference regardless of radiation treatment with the group overall achieving a 94% success rate (P = 0.229). CONCLUSIONS: This study aimed to characterize the impact of socioeconomic status and race/ethnic status of patients on breast reconstruction outcomes at an institution in the South. We found that despite the greater morbidity in low income and ethnic/minority patients that when treated by a comprehensive safety net institution, they had excellent reconstructive outcomes due to low complications and minimal reoperations.

Hypoxic Effects on Matrix Metalloproteinases' Expression in the Tumor Microenvironment and Therapeutic Perspectives.

The tumor microenvironment (TME) is characterized by an acidic pH and low oxygen concentrations. Hypoxia induces neoplastic cell evasion of the immune surveillance, rapid DNA repair, metabolic reprogramming, and metastasis, mainly as a response to the hypoxic inducible factors (HIFs). Likewise, cancer cells increase matrix metalloproteinases' (MMPs) expression in response to TME conditions, allowing them to migrate from the primary tumor to different tissues. Since HIFs and MMPs are augmented in the hypoxic TME, it is easy to consider that HIFs participate directly in their expression regulation. However, not all MMPs have a hypoxia response element (HRE)-HIF binding site. Moreover, different transcription factors and signaling pathways activated in hypoxia conditions through HIFs or in a HIF-independent manner participate in MMPs' transcription. The present review focuses on MMPs' expression in normal and hypoxic conditions, considering HIFs and a HIF-independent transcription control. In addition, since the hypoxic TME causes resistance to anticancer conventional therapy, treatment approaches using MMPs as a target alone, or in combination with other therapies, are also discussed.

Phytoestrogen-Based Hormonal Replacement Therapy Could Benefit Women Suffering Late-Onset Asthma.

It has been observed that plasmatic concentrations of estrogens, progesterone, or both correlate with symptoms in asthmatic women. Fluctuations in female sex steroid concentrations during menstrual periods are closely related to asthma symptoms, while menopause induces severe physiological changes that might require hormonal replacement therapy (HRT), that could influence asthma symptoms in these women. Late-onset asthma (LOA) has been categorized as a specific asthmatic phenotype that includes menopausal women and novel research regarding therapeutic alternatives that might provide relief to asthmatic women suffering LOA warrants more thorough and comprehensive analysis. Therefore, the present review proposes phytoestrogens as a promising HRT that might provide these females with relief for both their menopause and asthma symptoms. Besides their well-recognized anti-inflammatory and antioxidant capacities, phytoestrogens activate estrogen receptors and promote mild hormone-like responses that benefit postmenopausal women, particularly asthmatics, constituting therefore a very attractive potential therapy largely due to their low toxicity and scarce side effects.

Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.

To preserve ionic homeostasis (primarily Ca2+, K+, Na+, and Cl-), in the airway smooth muscle (ASM) numerous transporters (channels, exchangers, and pumps) regulate the influx and efflux of these ions. Many of intracellular processes depend on continuous ionic permeation, including exocytosis, contraction, metabolism, transcription, fecundation, proliferation, and apoptosis. These mechanisms are precisely regulated, for instance, through hormonal activity. The lipophilic nature of steroidal hormones allows their free transit into the cell where, in most cases, they occupy their cognate receptor to generate genomic actions. In the sense, estrogens can stimulate development, proliferation, migration, and survival of target cells, including in lung physiology. Non-genomic actions on the other hand do not imply estrogen's intracellular receptor occupation, nor do they initiate transcription and are mostly immediate to the stimulus. Among estrogen's non genomic responses regulation of calcium homeostasis and contraction and relaxation processes play paramount roles in ASM. On the other hand, disruption of calcium homeostasis has been closely associated with some ASM pathological mechanism. Thus, this paper intends to summarize the effects of estrogen on ionic handling proteins in ASM. The considerable diversity, range and power of estrogens regulates ionic homeostasis through genomic and non-genomic mechanisms.

Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015-2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.

Outcomes of Cranioplasty Strategies for High-Risk Complex Cranial Defects: A 10-Year Experience.

INTRODUCTION: Although the literature contains reports of the risks and complications of calvarial vault reconstruction for acquired defects, there are few publications addressing the specific patient population who require such reconstructions in cases preceded by prior infection, radiation, massive associated soft tissue trauma, and so on. We define such clinical presentations as a hostile environment for large surface area reconstruction. Our objective is to compare the safety and efficacy of autologous bone and alloplastic reconstruction in hostile cranial defects. METHODS: An institutional review board-approved retrospective review of patients who underwent cranioplasty of a hostile site at the University of Alabama at Birmingham between January 2008 and December 2018 was performed. The patients were stratified into 3 groups based on the type of implant used: autogenous (bone), alloplastic (polyetheretherketone [PEEK], titanium, polymethyl methacrylate), or mixed (combination of bone and prosthetic). The primary outcome metric was a complication in the year after cranioplasty, identified by implant failure, necrosis, or infection. Statistical analysis included t tests and χ2 tests where appropriate using SPSS. RESULTS: There were 55 total cases in this period: 27 autogenous, 23 alloplastic, and 5 mixed. The purely autogenous group had the highest complication rate (44%), and the alloplastic group had the lowest complication rate (38%), which was not statistically different between the 3 groups (P = 0.121). When stratified by specific material used for reconstruction (27 bone, 14 PEEK, 10 titanium, and 5 polymethyl methacrylate), overall complication rate was statistically significant (P = 0.009, χ2 test), with PEEK implants having the lowest complication rate (21%). CONCLUSIONS: This analysis interestingly found that in the setting of hostile cranial defects, cranioplasties would benefit from the use of prosthetic implants instead of autologous bone grafts, not only for avoidance of donor site morbidity but also for a decrease in overall complications.

The Safety of Fat Grafting: An Institutional Retrospective Review.

BACKGROUND: Autologous fat grafting is a popular technique for volume replacement in the breast and face. The efficacy, safety, and complication rate of this technique at the division of plastic surgery at the University of Alabama at Birmingham will be described in this review. METHODS: An institutional review board-approved retrospective review of patients undergoing fat grafting procedures from January 2015 to July 2018 was performed. Records were reviewed for fat graft recipient site, donor site, amount grafted, and complications. Continuous variables were compared using either a t test or one-way analysis of variance test. Categorical data were compared using χ2 test. A P value of 0.05 or less was considered statistically significant for all comparisons. RESULTS: A total of 396 patients who underwent fat grafting procedures of the face and body from January 2015 through July 2018 met inclusion criteria. Average amount of fat grafted for all grafts was 124.4 +/- 6.74 grams. Two hundred fifty of the grafts (62.7%) involved the bilateral breasts with an average of 140.6 +/- 93.97 g used, 70 per side. Of the 396 patients, 110 (27.8%) experienced complications. Forty three of the complications (10.9%) were considered to be major, which included hematomas/seromas, fat necrosis, dermatitis/cellulitis, and infection. No statistical differences were seen among recipient site complication rate. Types of minor complications were statistically significant per recipient sites with bilateral breasts more likely to experience asymmetry than the other recipient sites (20% for bilateral breasts vs 16% overall, P < 0.05). Fifty nine of the 110 patients (53.6%) had the complications reported to be resolved. CONCLUSIONS: Fat grafting is a reliable method for volumization of the breasts and face. Minor complications were not infrequent in this case series; however, no life-threatening complications were observed. Continued work needs to be done to use fat grafting beyond traditional measures.

Comorbidity Trends in Patients Requiring Sternectomy and Reconstruction: Updated Data Analysis From 2005 to 2020.

INTRODUCTION: Comorbidity trends after median sternectomy were studied at our institution by Vasconze et al (Comorbidity trends in patients requiring sternectomy and reconstruction. Ann Plast Surg. 2005;54:5). Although techniques for sternal reconstruction have remained unchanged, the patient population has become more complex in recent years. This study offers insight into changing trends in this patient population. METHODS: A retrospective review was performed of patients who underwent median sternectomy followed by flap reconstruction at out institution between 2005 and 2020. Comorbidities, reconstruction method, average laboratory values, and complications were analyzed. RESULTS: A total of 105 patients were identified. Comorbidities noted were diabetes (27%), immunosuppression (16%), hypertension (58%), renal insufficiency (23%), chronic obstructive pulmonary disease (16%), and tobacco utilization (24%). The most common reconstruction methods were omentum (45%) or pectoralis major flaps (34%). Thirty-day mortality rates were 10%, and presence of at least 1 complication was 34% (hematoma, seroma, osteomyelitis, dehiscence, wound infection, flap failure, and graft exposure). Univariate analysis demonstrated that sex (P = 0.048), renal insufficiency, surgical site complication, wound dehiscence, and flap failure (P < 0.05) had statistically significant associations with mortality. In addition, body mass index, creatinine, and albumin had a significant univariate association with mortality (P < 0.05). CONCLUSIONS: Similar to the original study, there is an association between renal insufficiency and mortality. However, the mortality rate is decreased to 10%, likely because of improved medical management of patients with increasing comorbidities (80% with greater than one comorbidity). This has led to the increased use of omentum as a first-line option. Subsequent wound dehiscence and flap failure demonstrate an association with mortality, suggesting that increasingly complex patients are requiring a method of reconstruction once used a last resort as a first-line option.

Could Lower Testosterone in Older Men Explain Higher COVID-19 Morbidity and Mortalities?

The health scourge imposed on humanity by the COVID-19 pandemic seems not to recede. This fact warrants refined and novel ideas analyzing different aspects of the illness. One such aspect is related to the observation that most COVID-19 casualties were older males, a tendency also noticed in the epidemics of SARS-CoV in 2003 and the Middle East respiratory syndrome in 2012. This gender-related difference in the COVID-19 death toll might be directly involved with testosterone (TEST) and its plasmatic concentration in men. TEST has been demonstrated to provide men with anti-inflammatory and immunological advantages. As the plasmatic concentration of this androgen decreases with age, the health benefit it confers also diminishes. Low plasmatic levels of TEST can be determinant in the infection's outcome and might be related to a dysfunctional cell Ca2+ homeostasis. Not only does TEST modulate the activity of diverse proteins that regulate cellular calcium concentrations, but these proteins have also been proven to be necessary for the replication of many viruses. Therefore, we discuss herein how TEST regulates different Ca2+-handling proteins in healthy tissues and propose how low TEST concentrations might facilitate the replication of the SARS-CoV-2 virus through the lack of modulation of the mechanisms that regulate intracellular Ca2+ concentrations.

Theophylline: Old Drug in a New Light, Application in COVID-19 through Computational Studies.

Theophylline (3-methyxanthine) is a historically prominent drug used to treat respiratory diseases, alone or in combination with other drugs. The rapid onset of the COVID-19 pandemic urged the development of effective pharmacological treatments to directly attack the development of new variants of the SARS-CoV-2 virus and possess a therapeutical battery of compounds that could improve the current management of the disease worldwide. In this context, theophylline, through bronchodilatory, immunomodulatory, and potentially antiviral mechanisms, is an interesting proposal as an adjuvant in the treatment of COVID-19 patients. Nevertheless, it is essential to understand how this compound could behave against such a disease, not only at a pharmacodynamic but also at a pharmacokinetic level. In this sense, the quickest approach in drug discovery is through different computational methods, either from network pharmacology or from quantitative systems pharmacology approaches. In the present review, we explore the possibility of using theophylline in the treatment of COVID-19 patients since it seems to be a relevant candidate by aiming at several immunological targets involved in the pathophysiology of the disease. Theophylline down-regulates the inflammatory processes activated by SARS-CoV-2 through various mechanisms, and herein, they are discussed by reviewing computational simulation studies and their different applications and effects.

Mandibular Distraction Osteogenesis as a Primary Intervention in Infants With Pierre Robin Sequence.

BACKGROUND: Pierre Robin sequence (PRS) is a triad of congenital facial abnormalities that can present as a syndrome (syndromic PRS [sPRS]) or an isolated entity (isolated PRS [iPRS]). Patients with PRS can develop airway and feeding problems that may result in failure to thrive. Mandibular distraction osteogenesis (MDO) is a method for improving the functional issues associated with breathing and feeding. There is a Paucity of literature evaluating the outcomes of MDO between sPRS and iPRS patients. METHODS: An institutional review board-approved retrospective review of PRS patients managed by a single surgeon and treated with MDO between January 2015 and December 2019 at a tertiary referral hospital was performed. The patients were stratified into iPRS or sPRS based on gene testing. Airway outcome measures included avoidance of tracheostomy, relief of sleep apnea, and oxygen saturation improvement. Primary feeding measures included achievement of full oral feeds and growth/weight gain. Statistical analysis included t tests and χ2 tests where appropriate using SPSS. RESULTS: Over the study period, of the 29 infants with PRS, 55% identified as iPRS and 45% as sPRS. There were no significant differences in the patient characteristics, apnea-hypoxia index (22.27 ± 12.27) and laryngeal view (3 ± 0.79) pre-MDO. After MDO, 83% of the subjects achieved a positive feeding outcome and 86% achieved a positive airway outcome with no statistical significance between sPRS and iPRS (P = 0.4369). There was a statistically significant change post-MDO in apnea-hypoxia index (5.24 ± 4.50, P = 0.02) and laryngeal view (1.59 ± 1.00, P = 0.01). CONCLUSIONS: Our recent experience would lead us to believe that sPRS patients have greater morbidities and challenging clinical developments that, when properly evaluated, can be managed by MDO. There is a potential role for MDO in reducing the need for traditional surgical interventions for respiratory and feeding problems in both iPRS and sPRS patients.

Reconstructive Management of Gunshot Wounds to the Frontal Sinus: An Urban Trauma Center's Perspective.

INTRODUCTION: In the last decade, we have seen a steady increase in the incidence of frontal sinus trauma due to gunshot wounds and a decrease in motor vehicle trauma. Penetrating gunshot wounds to the frontal sinus present a unique challenge to the reconstructive surgeon because they require careful consideration of the management principles of plastic surgery. Despite previous reviews on frontal sinus trauma, there are no studies examining the management techniques of frontal sinus fractures due specifically to gunshot wounds. In this study, we aim to retrospectively evaluate the use of a variety of tissue flaps in intervention and associated outcomes. METHODS: A retrospective chart review was completed on all patients with gunshot wound(s) to the frontal sinus from January 2010 to January 2018 at a single institution. The patients were classified based on the fracture pattern (anterior vs posterior table vs both), degree of displacement, presence of nasofrontal outflow tract injury, and evidence of cerebrospinal fluid leak. Patients were then stratified according to the type of reconstruction performed (cranialization, obliteration and need for free flap) and evaluated for major and minor complications after reconstruction. RESULTS: In this study, we present outcome data from 28 cases of frontal sinus trauma due to gunshot wounds. There was a statistically significant difference (P = 0.049) in the type reconstructive strategy employed with each type of flap, with pericranial flaps primarily used in cranialization, temporal grafts were more likely to be used in obliteration, and free flaps were more likely to be used in cranialization. The overall major complication rate was 52% (P = 0.248), with the most common acute major complication was cerebrospinal fluid leak (39%) and major chronic was abscess (23.5%). CONCLUSIONS: This report explores the management of frontal sinus trauma and presents short-term outcomes of treatment for penetrating gunshot wounds at a tertiary referral center.

Possible Beneficial Actions of Caffeine in SARS-CoV-2.

The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Caffeine has been proven to be an effective anti-inflammatory and immunomodulator. In airway smooth muscle, it has bronchodilator effects mainly due to its activity as a phosphodiesterase inhibitor and adenosine receptor antagonist. In addition, a recent published document has suggested the potential antiviral activity of this drug using in silico molecular dynamics and molecular docking; in this regard, caffeine might block the viral entrance into host cells by inhibiting the formation of a receptor-binding domain and the angiotensin-converting enzyme complex and, additionally, might reduce viral replication by the inhibition of the activity of 3-chymotrypsin-like proteases. Here, we discuss how caffeine through certain mechanisms of action could be beneficial in SARS-CoV-2. Nevertheless, further studies are required for validation through in vitro and in vivo models.

Mitochondrial Dysfunction and Alterations in Mitochondrial Permeability Transition Pore (mPTP) Contribute to Apoptosis Resistance in Idiopathic Pulmonary Fibrosis Fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by increased activation of fibroblasts/myofibroblasts. Previous reports have shown that IPF fibroblasts are resistant to apoptosis, but the mechanisms remain unclear. Since inhibition of the mitochondrial permeability transition pore (mPTP) has been implicated in the resistance to apoptosis, in this study, we analyzed the role of mitochondrial function and the mPTP on the apoptosis resistance of IPF fibroblasts under basal conditions and after mitomycin C-induced apoptosis. We measured the release of cytochrome c, mPTP opening, mitochondrial calcium release, oxygen consumption, mitochondrial membrane potential, ADP/ATP ratio, ATP concentration, and mitochondrial morphology. We found that IPF fibroblasts were resistant to mitomycin C-induced apoptosis and that calcium, a well-established activator of mPTP, is decreased as well as the release of pro-apoptotic proteins such as cytochrome c. Likewise, IPF fibroblasts showed decreased mitochondrial function, while mPTP was less sensitive to ionomycin-induced opening. Although IPF fibroblasts did not present changes in the mitochondrial membrane potential, we found a fragmented mitochondrial network with scarce, thinned, and disordered mitochondria with reduced ATP levels. Our findings demonstrate that IPF fibroblasts are resistant to mitomycin C-induced apoptosis and that altered mPTP opening contributes to this resistance. In addition, IPF fibroblasts show mitochondrial dysfunction evidenced by a decrease in respiratory parameters.

Differences in Highly-Cited and Lowly-Cited Manuscripts in Plastic Surgery.

BACKGROUND: There is a paucity of research comparing journal articles that accrue numerous citations with those that accrue few citations over time. Understanding differences between journal articles can help direct investigators in designing and conducting their research. METHODS: Using advanced bibliometric tools, we queried four plastic surgery journals (Journal of Reconstructive Microsurgery, Annals of Plastic Surgery, Plastic and Reconstructive Surgery, and Microsurgery) for primary research articles published between 1998 and 2008 accruing zero or one citations with at least a 10-y lag time. Forty-seven articles were identified as low citation and were compared with an equal number of articles in the same journals that accrued the highest number of citations in the same period as high citation (HC). The data were analyzed using Student t-tests, Wilcoxon rank sum tests, chi-square tests, and Fisher exact tests. The level of significance was established at P < 0.05. RESULTS: When compared with the HC cohort, the low citation articles were more likely to be nonclinical (P < 0.001), have no plastic surgery authors (P = 0.0026), and focus on the field of microsurgery (P = 0.003). The HC cohort was more likely to have higher sample sizes (P = 0.0339), focus on aesthetic/cosmetic surgery (P = 0.003), have a higher number of other disciplines included on authorship (P < 0.001), references (P = 0.0451), manuscript pages (P < 0.001), and words in the abstract (P < 0.001). CONCLUSIONS: A small number of articles published in four plastic surgery journals were uncited during a 10-y period. There are qualitative and quantitative differences between highly and lowly cited articles in the plastic surgery literature. Investigators should consider these differences when designing and conducting studies.