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1.
Plast Reconstr Surg ; 153(1): 55-64, 2024 01 01.
Article in English | MEDLINE | ID: mdl-36877624

ABSTRACT

BACKGROUND: Outpatient plastic surgery at office-based surgery facilities (OBSFs) and ambulatory surgery centers (ASCs) has become increasingly prevalent over the past 30 years. Importantly, historical data are inconsistent regarding the safety outcomes of these venues, with advocates for both citing supporting studies. This investigation's purpose is to provide a more definitive comparative evaluation of outcomes and safety for outpatient surgery performed in these facilities. METHODS: The most common outpatient procedures were identified using the Tracking Operations and Outcomes for Plastic Surgeons database between 2008 and 2016. Outcomes were analyzed for OBSFs and ASCs. Patient and perioperative information was also analyzed using regression analysis to identify risk factors for complications. RESULTS: A total of 286,826 procedures were evaluated, of which 43.8% were performed at ASCs and 56.2% at OBSFs. Most patients were healthy, middle-aged women categorized as American Society of Anesthesiologists class I. The incidence of adverse events was 5.7%, and most commonly included antibiotic requirement (1.4%), dehiscence (1.3%), or seroma requiring drainage (1.1%). Overall, there was no significant difference in adverse events between ASCs and OBSFs. Age, American Society of Anesthesiologists class, body mass index, diabetes, smoking history, general anesthesia, certified registered nurse anesthetist involvement, operative duration, noncosmetic indications, and body region were associated with adverse events. CONCLUSIONS: This study provides an extensive analysis of common plastic surgery procedures performed in an outpatient setting in a representative population. With appropriate patient selection, procedures are safely performed by board-certified plastic surgeons in ambulatory surgery centers and office-based settings, as evidenced by the low incidence of complications in both environments. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Subject(s)
Plastic Surgery Procedures , Surgery, Plastic , Middle Aged , Humans , Female , Ambulatory Surgical Procedures/adverse effects , Ambulatory Surgical Procedures/methods , Outpatients , Retrospective Studies
2.
Plast Reconstr Surg Glob Open ; 11(9): e5290, 2023 Sep.
Article in English | MEDLINE | ID: mdl-38152714

ABSTRACT

ChatGPT is a cutting-edge language model developed by OpenAI with the potential to impact all facets of plastic surgery from research to clinical practice. New applications for ChatGPT are emerging at a rapid pace in both the scientific literature and popular media. It is important for clinicians to understand the capabilities and limitations of these tools before patient-facing implementation. In this article, the authors explore some of the technical details behind ChatGPT: what it is, and what it is not. As with any emerging technology, attention should be given to the ethical and health equity implications of this technology on our plastic surgery patients. The authors explore these concerns within the framework of the foundational principles of biomedical ethics: patient autonomy, nonmaleficence, beneficence, and justice. ChatGPT and similar intelligent conversation agents have incredible promise in the field of plastic surgery but should be used cautiously and sparingly in their current form. To protect patients, it is imperative that societal guidelines for the safe use of this rapidly developing technology are developed.

3.
Adv Skin Wound Care ; 36(7): 385-391, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37224465

ABSTRACT

OBJECTIVE: The management of cranioplasty infections has historically been explantation followed by delayed reimplantation/reconstruction. This treatment algorithm necessitates surgery, tissue expansion, and prolonged disfigurement. In this report, the authors describe a treatment approach consisting of serial vacuum-assisted closure (VAC) with hypochlorous acid (HOCl) solution (Vashe Wound Solution; URGO Medical) as a salvage strategy. METHODS: A 35-year-old man who sustained head trauma, neurosurgical complications, and severe syndrome of the trephined (SOT; devastating neurologic decline treated by cranioplasty) underwent titanium cranioplasty with free flap. Three weeks postoperation, he presented with pressure-related wound dehiscence/partial flap necrosis, exposed hardware, and bacterial infection. Given the severity of his precranioplasty SOT, hardware salvage was critical. He was treated with serial VAC with HOCl solution for 11 days followed by VAC for 18 days and definitive split-thickness skin graft placement over resulting granulation tissue. Authors also conducted a literature review of cranial reconstruction infection management. RESULTS: The patient remained healed 7 months postoperatively without recurrent infection. Importantly, his original hardware was retained, and his SOT remained resolved. Findings from the literature review support the use of conservative modalities to salvage cranial reconstructions without hardware removal. CONCLUSIONS: This study investigates a new strategy for managing cranioplasty infections. The VAC with HOCl solution regimen was effective in treating the infection and salvaging the cranioplasty, thus obviating the complications associated with explantation, new cranioplasty, and recurrence of SOT. There is limited literature on the management of cranioplasty infections using conservative treatments. A larger study to better determine the efficacy of VAC with HOCl solution is underway.


Subject(s)
Negative-Pressure Wound Therapy , Male , Humans , Adult , Negative-Pressure Wound Therapy/methods , Treatment Outcome , Surgical Wound Infection/therapy , Wound Healing , Surgical Flaps , Postoperative Complications
4.
Ann Plast Surg ; 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36752563

ABSTRACT

BACKGROUND: Nipple-areolar complex (NAC) necrosis is a known risk of breast surgery, particularly mastectomy. Disruption of the underlying blood supply to the NAC can lead to ischemia and subsequent necrosis. Nitroglycerin paste is currently used to combat NAC ischemia but has limited efficacy and an unfavorable side effect profile. Topical dimethyl sulfoxide (DMSO) has been shown to increase tissue perfusion in microsurgery and various skin flaps, but its role in the treatment and prevention of NAC ischemia has not been reported. Through a prospective case series, this study aims to introduce DMSO as a safe treatment for NAC ischemia after breast surgery. METHODS: Patients treated by 2 breast surgeons and a single plastic surgeon who underwent nipple-sparing mastectomy or breast reduction and developed NAC ischemia were identified via a prospectively maintained database. Ischemic changes were diagnosed, and treatment to the affected NAC with DMSO was initiated at the conclusion of the procedure, or postoperative day 1 in most cases, and continued 4 times daily until ischemic changes had resolved clinically. Collected demographic, surgical, and outcome variables were analyzed using descriptive statistics. RESULTS: Eleven patients with a mean age of 47.8 ± 9.5 years (range, 35-61 years) and mean body mass index of 26.0 ± 4.4 kg/m2 (range, 20.7-33.4 kg/m2) were identified. The mean duration of time between surgery and the clinical diagnosis of NAC ischemia was 1.3 ± 2.8 days (range, 0-7 days). The average length of time from DMSO initiation to clinical improvement or resolution of NAC ischemia was 7.5 ± 2.5 days (range, 5-12 days). All patients demonstrated significant improvement or complete resolution of NAC ischemia following serial topical DMSO application. CONCLUSIONS: This study demonstrates DMSO is a safe treatment for threatened NACs. All patients in this series showed either dramatic improvement or resolution of NAC ischemia after DMSO application, and threatened NACs of all 11 patients were successfully salvaged. These promising results set the basis for ongoing randomized controlled studies to determine the efficacy of DMSO treatment for NAC ischemia.

5.
Aesthet Surg J ; 42(12): NP763-NP774, 2022 12 14.
Article in English | MEDLINE | ID: mdl-35961054

ABSTRACT

BACKGROUND: Paradoxical adipose hyperplasia (PAH), a rare side effect of CoolSculpting (cryolipolysis), is characterized by fatty enlargement of the treatment area occurring months after the procedure. OBJECTIVES: The purpose of this study was to report a retrospective case series of patients diagnosed with PAH at the authors' institution, increase the collective understanding of this complication and subsequent management, and raise the question of who should ethically perform cryolipolysis. METHODS: All participants diagnosed with PAH by a plastic surgeon at a large academic medical center were identified. Demographic information, medical history, procedure details, time to PAH diagnosis, and corrective surgical intervention details were collected. Mean duration of time from cryolipolysis treatment to diagnosis of PAH was calculated, along with other descriptive statistics. A scoping review of all PAH literature published in PubMed, Embase, and Web of Science was also conducted. RESULTS: Four patients diagnosed with PAH after cryolipolysis were identified for inclusion in this study. The calculated incidence of PAH at our center was 0.67%. All patients requested therapy for PAH and subsequently underwent either liposuction, abdominoplasty, or both. The mean duration of in-person follow-up time after final surgical treatment of PAH was 13.8 + 19.8 months (range, 2.8-43.5). Fortunately, no patients showed signs of PAH recurrence, and 3 out of 4 patients did not show signs of residual deformity. CONCLUSIONS: Findings from this patient cohort and scoping review provide evidence that although revisions may be required, conventional body contouring methods, not in the armamentarium of non-plastic surgeon practitioners, effectively alleviated PAH.


Subject(s)
Lipectomy , Subcutaneous Fat , Humans , Subcutaneous Fat/pathology , Hyperplasia/etiology , Retrospective Studies , Lipectomy/adverse effects , Lipectomy/methods , Adiposity , Obesity/surgery
6.
Hand Clin ; 38(2): 129-139, 2022 05.
Article in English | MEDLINE | ID: mdl-35465931

ABSTRACT

This review discusses the anatomy and biomechanics of the thumb carpometacarpal (CMC) joint. This articulation between the trapezium and first metacarpal is integral for opposition and other complex movements necessary for pinch and grasp maneuvers. Fortunately, this joint is well equipped to handle the extreme forces imposed by these movements, as it is stabilized by an elaborate arrangement of ligaments and muscles. Without this stability, thumb subluxation would occur with loading during pinch and grasp, and human prehension would be impossible. Understanding the interactions occurring within this joint is essential for adequately treating pathology arising in this crucial joint.


Subject(s)
Carpometacarpal Joints , Metacarpal Bones , Trapezium Bone , Biomechanical Phenomena , Humans , Thumb/physiology , Trapezium Bone/surgery
7.
Plast Reconstr Surg Glob Open ; 9(12): e3997, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34909358

ABSTRACT

We report successful restoration of quadriceps function following contralateral obturator to lateral branch of the femoral nerve transfer (with intervening autograft) in two patients with multilevel lumbosacral root avulsions, resulting in severe unilateral motor and sensory deficits. Three years postoperatively, patient 1 had regained Medical Research Council grade 3 knee extension with the ability to extend against 10 pounds of resistance. At 28 months postoperatively, patient 2 had regained Medical Research Council grade 2 knee extension. Treatment options for severe lumbosacral plexus injuries with multiple root avulsions are limited. This approach offers a new option for these devastating injuries.

8.
World J Pediatr ; 17(5): 527-535, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34546541

ABSTRACT

BACKGROUND: Little is known regarding risk factors specific to pediatric upper extremity firearm injuries. The purpose of this study is to evaluate pediatric patients treated for these injuries to identify at-risk populations and recurring mechanisms of injury. METHODS: A 20-year retrospective review was conducted. Patients 17 years of age and younger, with upper extremity injuries related to a firearm, were included. Analysis involved Fisher's exact and Chi-square tests. RESULTS: One hundred and eighty patients were included. The mean age was 12.04 ± 4.3 years. Most included patients were male (85%). Interestingly, females were more frequently victims of assault (P = 0.03), and males were more frequently injured due to accidental discharge (P < 0.001). The most affected race/ethnicity was White-not Hispanic or Latino (48%). The hand was the most frequent location injured (31%) and was more likely to be accidental than proximal injuries (P = 0.003). Air rifles were the most common firearm type used (56%). Pistols were implicated in 47 (26%) cases, rifles in 17 (9%), and shotguns in 10 (6%). Ninety-nine (55%) patients had procedures in the operating room. The most frequent procedure was foreign body removal (55%). CONCLUSIONS: Risk factors such as male sex, White-not Hispanic or Latino race/ethnicity, and adolescent age were attributed to increased risk for injury. Male sex was associated with increased risk of injury by accidental discharge and female sex with intentional assault. Air rifles were the most common firearm type overall, although female sex was associated with increased risk for injury by powder weapon.


Subject(s)
Firearms , Wounds, Gunshot , Adolescent , Child , Ethnicity , Female , Humans , Male , Retrospective Studies , Upper Extremity , Wounds, Gunshot/epidemiology
9.
Oral Oncol ; 116: 105195, 2021 05.
Article in English | MEDLINE | ID: mdl-33618103

ABSTRACT

INTRODUCTION: Current research is elucidating how the addition of depth of invasion (DOI) to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging for oral cavity squamous cell carcinoma influences its prognostic accuracy. However, there is limited research on survival in pT3N0M0 oral tongue SCC (OTSCC) patients when stratifying by DOI. OBJECTIVES: Determine 5-year overall survival (OS), and cancer-specific survival (CSS) for patients with pT3N0M0 oral OTSCC based on shallow DOI (<10 mm) and deep DOI (10-20 mm). METHODS: Retrospective review involving three tertiary care cancer centers in North America. cT3N0M0 OTSCC patients receiving primary surgical treatment from 2004 to 2018 were identified. Inclusion: age > 18 years old and confirmation of pT3N0M0 OTSCC on surgical pathology. Exclusion: patients undergoing palliative treatment or previous head and neck surgery/radiotherapy. Analysis comprised two groups: shallow pT3 (tumor diameter > 4 cm, DOI < 10 mm) and deep pT3 (DOI 10 mm-20 mm). RESULTS: One hundred and four patients with pT3N0M0 OTSCC were included. Mean age was 59.1 years (range: 18-80.74). Age, gender, and Charlson Comorbidity Index were similar between the two groups (p > 0.05). Recurrence, LVI, PNI, and positive margins were more common in deep T3 tumors (P < 0.05). 5-year OS (50% vs 26%, p = 0.006) and CSS (72% vs 24%, p = 0.005) were worse in deep pT3 tumors. Deep pT3 disease was an independent predictor of OS (p = 0.004) and CSS (p = 0.01) on Cox-Regression analysis. CONCLUSION: DOI is an independent predictor of poor survival in pT3N0M0 OTSCC patients. Consideration should be given to escalating adjuvant therapy for deep pT3N0M0 OTSCC patients.


Subject(s)
Squamous Cell Carcinoma of Head and Neck , Tongue Neoplasms , Adult , Humans , Middle Aged , Neoplasm Invasiveness , Retrospective Studies , Survival Rate , Tongue Neoplasms/surgery
10.
Am J Otolaryngol ; 42(1): 102793, 2021.
Article in English | MEDLINE | ID: mdl-33130532

ABSTRACT

PURPOSE: Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) treatment outcomes are re-defining management. Traditional margins, the role of extranodal extension (ENE) and adjuvant treatment intensity continue to be debated. This study aimed to determine the impact of margins, ENE and adjuvant therapy on survival following transoral robotic surgery (TORS). METHODS: Patients treated with TORS at an academic center were retrospectively identified (2013-2019). Survival outcomes were evaluated using Kaplan-Meier curves. RESULTS: 48 patients were included. 40 (83%) were male. Mean age was 61.2 years. 43 (90%) were stage I. 22 (45.8%) had ENE. 31 (65%) had margins >1 mm. 38 (79%) had indications for radiation therapy; 9 (24%) refused. Chemotherapy was recommended in 36 (75%) patients; 24 (67%) refused. Locoregional control was 98%, metastasis-free survival was 96%, and disease-specific survival was 100% at 5-years. Overall survival was 95%. CONCLUSIONS: Given the high survival rate seen after TORS, it is likely that margins, ENE and adjuvant treatment may not significantly contribute to outcomes.


Subject(s)
Carcinoma, Squamous Cell/surgery , Chemoradiotherapy, Adjuvant , Margins of Excision , Oral Surgical Procedures/methods , Oropharyngeal Neoplasms/surgery , Papillomavirus Infections/complications , Robotic Surgical Procedures/methods , Adult , Aged , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/etiology , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Retrospective Studies , Survival Rate , Treatment Outcome
11.
J Cyst Fibros ; 19(5): 677-687, 2020 09.
Article in English | MEDLINE | ID: mdl-32522463

ABSTRACT

As CFTR modulator therapy transforms the landscape of cystic fibrosis (CF) care, its lack of uniform access across the globe combined with the shift towards a new standard of care creates unique challenges for the development of future CF therapies. The advancement of a full and promising CF therapeutics pipeline remains a necessary priority to ensure maximal clinical benefits for all people with CF. It is through collaboration across the global CF community that we can optimize the evaluation and approval process of new therapies. To this end, we must identify areas for which harmonization is lacking and for which efficiencies can be gained to promote ethical, feasible, and credible study designs amidst the changing CF care landscape. This article summarizes the counsel from core advisors across multiple international regions and clinical trial networks, developed during a one-day workshop in October 2019. The goal of the workshop was to identify, in consideration of the highly transitional era of CFTR modulator availability, the drug development areas for which global alignment is currently uncertain, and paths forward that will enable advancement of CF therapeutic development.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/drug effects , Cystic Fibrosis/drug therapy , Drug Development/organization & administration , International Cooperation , Cystic Fibrosis/genetics , Humans
13.
Public Health ; 173: 9-16, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31207426

ABSTRACT

OBJECTIVES: During the 2014-2016 West Africa Ebola outbreak, the Centers for Disease Control and Prevention recommended daily monitoring and surveillance of persons arriving in the United States (US) from impacted areas through either active monitoring (phone calls, online platforms, and so on) or direct active monitoring (in-person or electronic visualization). Intensiveness of policies implemented by state/local jurisdictions varied markedly. To study the experiences and perceptions of active monitoring versus direct active monitoring on former persons under monitoring (FPUMs) in the US, we compared two jurisdictions that utilized distinct polices: the District of Columbia (DC) and Indiana (IN). STUDY DESIGN: Retrospective assessment survey of FPUMs. METHODS: FPUMs from both jurisdictions (DC 826 and IN 246) monitored from October 2014 to September 2015 were surveyed regarding their overall perception of monitoring, communications with jurisdictional staff, negative consequences experienced, and risk for and concern about Ebola virus disease. A total of 294 DC FPUMs and 52 IN FPUMs responded. RESULTS: Directly actively monitored FPUMs in IN were more likely to report monitoring was difficult (P < 0.01), not being allowed to return to work (P = 0.01), and faster response times when reaching out to their assigned health department (P < 0.01). Overall all FPUMs, regardless of the monitoring method they underwent, perceived little risk and reported they felt monitoring protected public health. CONCLUSIONS: Our results display that while FPUMs preferred active monitoring, both polices equally reduced their concern, suggesting that less intensive polices achieve the same level of perceived effectiveness by those monitored while also reducing the amount of negative consequences they may face.


Subject(s)
Disease Outbreaks/prevention & control , Hemorrhagic Fever, Ebola/prevention & control , Population Surveillance/methods , Public Health Surveillance/methods , Travel , Africa, Western/epidemiology , Centers for Disease Control and Prevention, U.S. , Communication , District of Columbia/epidemiology , Female , Health Policy , Hemorrhagic Fever, Ebola/epidemiology , Humans , Indiana/epidemiology , Male , Public Health , Retrospective Studies , Risk Assessment , Surveys and Questionnaires , United States
14.
Science ; 358(6370): 1579-1583, 2017 12 22.
Article in English | MEDLINE | ID: mdl-29038372

ABSTRACT

Gravitational waves have been detected from a binary neutron star merger event, GW170817. The detection of electromagnetic radiation from the same source has shown that the merger occurred in the outskirts of the galaxy NGC 4993, at a distance of 40 megaparsecs from Earth. We report the detection of a counterpart radio source that appears 16 days after the event, allowing us to diagnose the energetics and environment of the merger. The observed radio emission can be explained by either a collimated ultrarelativistic jet, viewed off-axis, or a cocoon of mildly relativistic ejecta. Within 100 days of the merger, the radio light curves will enable observers to distinguish between these models, and the angular velocity and geometry of the debris will be directly measurable by very long baseline interferometry.

15.
Clin Exp Allergy ; 47(11): 1478-1490, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28756642

ABSTRACT

BACKGROUND: Allergen immunotherapy uses pharmaceutical preparations derived from naturally occurring source materials, which contain water-soluble allergenic components responsible for allergic reactions. The success of in vivo and in vitro diagnoses in allergen sensitization and allergen immunotherapy largely depends on the quality, composition and uniformity of allergenic materials used to produce the active ingredients, and the formulation employed to prepare finished products. OBJECTIVES: We aimed to examine the factors influencing batch-to-batch consistency of Jack Jumper (Myrmecia pilosula) ant venom (JJAV) in the form of active pharmaceutical ingredient (AI) and informed whether factors such as temperature, artificial light and container materials influence the quality of JJAV AIs. We also aimed to establish handling and storage requirements of JJAV AIs to ensure preservation of allergenic activities during usage in the diagnosis of allergen sensitization and in allergen immunotherapy. METHODS: The quality and consistency of JJAV AIs were analysed using a combination of bicinchoninic acid assay for total protein quantification, HPLC-UV for JJAV allergen peptides quantification, ELISA inhibition for total allergenic potency, SDS-PAGE, AU-PAGE and immunoblot for qualitative assessment of JJAV components, and Limulus Amebocyte Lysate assay for the quantification of endotoxin concentration. API-ZYM and Zymogram assays were used to probe the presence of enzymatic activities in JJAV. RESULTS: Pharmaceutical-grade JJAV for allergen immunotherapy has good batch-to-batch consistency. Temporary storage at 4°C and light exposure do not affect the quality of JJAV. Exposure to temperature above 40°C degrades high MW allergens in JJAV. Vials containing JJAV must be stored frozen and in upright position during long-term storage. CONCLUSIONS AND CLINICAL RELEVANCE: We have identified factors, which can influence the quality and consistency of JJAV AIs, and provided a framework for appropriate handling, transporting and storage of JJAV to be used for the diagnosis of allergen sensitization and in AIT.


Subject(s)
Allergens/immunology , Ant Venoms/immunology , Desensitization, Immunologic , Hypersensitivity/diagnosis , Hypersensitivity/immunology , Hypersensitivity/therapy , Allergens/administration & dosage , Allergens/chemistry , Animals , Ant Venoms/administration & dosage , Ant Venoms/chemistry , Desensitization, Immunologic/methods , Enzyme Activation , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/standards , Humans , Immunization , Light , Preservation, Biological , Reproducibility of Results , Temperature
16.
Clin Pharmacol Ther ; 101(2): 209-219, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28019026

ABSTRACT

Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing antiinflammatory agents. We propose that psychedelics exert therapeutic effects for psychiatric disorders by acutely destabilizing local brain network hubs and global network connectivity via amplification of neuronal avalanches, providing the occasion for brain network "resetting" after the acute effects have resolved. Antiinflammatory effects may hold promise for efficacy in treatment of inflammation-related nonpsychiatric as well as potentially for psychiatric disorders. Serotonergic psychedelics operate through unique mechanisms that show promising effects for a variety of intractable, debilitating, and lethal disorders, and should be rigorously researched.


Subject(s)
Brain/drug effects , Hallucinogens/therapeutic use , Mental Disorders/drug therapy , Anxiety/drug therapy , Brain/metabolism , Clinical Trials as Topic , Depression/drug therapy , Dose-Response Relationship, Drug , Hallucinogens/administration & dosage , Hallucinogens/adverse effects , Hallucinogens/pharmacology , Humans , Inflammation/drug therapy , Inflammation/physiopathology , Inflammation Mediators/metabolism , Lysergic Acid Diethylamide/therapeutic use , Mind-Body Therapies/methods , Obsessive-Compulsive Disorder/drug therapy , Psilocybin/therapeutic use , Psychotherapy/methods , Receptor, Serotonin, 5-HT2A/biosynthesis , Serotonin 5-HT2 Receptor Agonists/pharmacology , Severity of Illness Index , Substance-Related Disorders/drug therapy
17.
J Diabetes Res ; 2016: 1527932, 2016.
Article in English | MEDLINE | ID: mdl-27999822

ABSTRACT

Rationale. Cystic fibrosis related diabetes (CFRD) is the most common comorbidity in patients with CF. In spite of increased screening, diagnosis, and treatment of CFRD, the mortality rate in patients with CFRD still far exceeds the mortality rate in those without CFRD. Guidelines suggest that screening for CFRD be performed annually using the 2-hour 75-gram oral glucose tolerance test (OGTT). Adherence to recommended screening has been poor, with only approximately one-quarter of adults with CF undergoing OGTT in 2014. Use of continuous glucose monitoring (CGM) for diagnosis may become an alternative. Objectives. Our objective was to determine whether abnormal CGM predicts subsequent development of CFRD, lung function, and body mass index (BMI) decline and increased rate of CF pulmonary exacerbations in adults with CF. Methods. In a prospective single center pilot trial from September 2009 to September 2010, 21 adult patients due for routine OGTT were recruited to complete simultaneous 3-day CGM and 2-hour 75 gram OGTT. Subsequently, clinical information was reviewed from 2008 to 2015. Conclusions. There was a moderate correlation between interpreted results of 2-hour OGTT and CGM (p = 0.03); CGM indicated a greater level of glucose impairment than OGTT. Glucose >200 mg/dL by CGM predicted development of CFRD (p = 0.0002).


Subject(s)
Blood Glucose/analysis , Cystic Fibrosis/blood , Cystic Fibrosis/complications , Diabetes Mellitus/blood , Glucose Intolerance/blood , Glucose Tolerance Test/methods , Adult , Aged , Blood Glucose Self-Monitoring/methods , Comorbidity , Diabetes Complications/blood , Diabetes Mellitus/diagnosis , Female , Glucose Intolerance/diagnosis , Humans , Male , Mass Screening , Middle Aged , Pilot Projects , Prospective Studies , Treatment Outcome , Young Adult
18.
Gene Ther ; 22(10): 822-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26043872

ABSTRACT

Targeted knockout of genes in primary human cells using CRISPR-Cas9-mediated genome-editing represents a powerful approach to study gene function and to discern molecular mechanisms underlying complex human diseases. We used lentiviral delivery of CRISPR-Cas9 machinery and conditional reprogramming culture methods to knockout the MUC18 gene in human primary nasal airway epithelial cells (AECs). Massively parallel sequencing technology was used to confirm that the genome of essentially all cells in the edited AEC populations contained coding region insertions and deletions (indels). Correspondingly, we found mRNA expression of MUC18 was greatly reduced and protein expression was absent. Characterization of MUC18 knockout cell populations stimulated with TLR2, 3 and 4 agonists revealed that IL-8 (a proinflammatory chemokine) responses of AECs were greatly reduced in the absence of functional MUC18 protein. Our results show the feasibility of CRISPR-Cas9-mediated gene knockouts in AEC culture (both submerged and polarized), and suggest a proinflammatory role for MUC18 in airway epithelial response to bacterial and viral stimuli.


Subject(s)
Genetic Vectors , Lentivirus , Respiratory Mucosa/metabolism , CD146 Antigen/genetics , CD146 Antigen/immunology , CD146 Antigen/metabolism , Clustered Regularly Interspaced Short Palindromic Repeats , Gene Expression , Gene Knockout Techniques , Humans , Inflammation/genetics , Primary Cell Culture , Respiratory Mucosa/immunology
19.
J Cyst Fibros ; 14(2): 228-36, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25466700

ABSTRACT

RATIONALE: Airway inflammation is central to cystic fibrosis (CF) pathophysiology. Pre-clinical models have shown that phosphodiesterase inhibitors (PDEi) like sildenafil have anti-inflammatory activity. PDEi have not been studied in CF subjects. OBJECTIVES: We evaluated the pharmacokinetics, tolerability, and safety of sildenafil in subjects with CF. Sputum biomarkers were used to explore efficacy. METHODS: An open-label pilot study of oral sildenafil administration was conducted in adults with mild to moderate CF lung disease. Subjects received oral sildenafil 20 or 40 mg p.o. t.i.d. for 6 weeks. MEASUREMENTS AND MAIN RESULTS: Twenty subjects completed the study. Estimated elimination rate constants were statistically different in subjects with CF compared to previously published non-CF subjects. Side effects were generally mild. There were no drug-related serious adverse events. Sputum neutrophil elastase activity decreased. CONCLUSIONS: Subjects with CF may eliminate sildenafil at a faster rate than non-CF subjects. Sildenafil administration was safe in subjects with CF and decreased sputum elastase activity. Sildenafil warrants further study as an anti-inflammatory in CF.


Subject(s)
Cystic Fibrosis , Leukocyte Elastase/metabolism , Sildenafil Citrate , Sputum/drug effects , Adult , Biomarkers/metabolism , Cystic Fibrosis/drug therapy , Cystic Fibrosis/metabolism , Cystic Fibrosis/physiopathology , Drug Monitoring/methods , Female , Humans , Inflammation/drug therapy , Lung/metabolism , Lung/physiopathology , Male , Phosphodiesterase 5 Inhibitors/administration & dosage , Phosphodiesterase 5 Inhibitors/adverse effects , Phosphodiesterase 5 Inhibitors/pharmacokinetics , Severity of Illness Index , Sildenafil Citrate/administration & dosage , Sildenafil Citrate/adverse effects , Sildenafil Citrate/pharmacokinetics , Sputum/metabolism , Treatment Outcome
20.
J Cyst Fibros ; 14(2): 219-27, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25228446

ABSTRACT

PURPOSE: To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways. METHODS: A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks. ENDPOINTS: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF. RESULTS: Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14). CONCLUSIONS: NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.


Subject(s)
Acetylcysteine , Cystic Fibrosis , Inflammation , Lung , Oxidative Stress/drug effects , Acetylcysteine/administration & dosage , Acetylcysteine/adverse effects , Administration, Oral , Adolescent , Adult , Antioxidants/administration & dosage , Antioxidants/adverse effects , Child , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Cystic Fibrosis/metabolism , Cystic Fibrosis/physiopathology , Double-Blind Method , Drug Monitoring , Female , Humans , Inflammation/drug therapy , Inflammation/metabolism , Leukocyte Elastase/metabolism , Lung/drug effects , Lung/metabolism , Lung/physiopathology , Male , Respiratory Function Tests/methods , Sputum/drug effects , Sputum/metabolism , Time , Treatment Outcome
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