ABSTRACT
Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and triglycerides. AGPATs demonstrate unique physiological roles despite a similar biochemical function. AGPAT3 is highly expressed in the testis, kidney, and liver, with intermediate expression in adipose tissue. Loss of AGPAT3 is associated with reproductive abnormalities and visual dysfunction. However, the role of AGPAT3 in adipose tissue and whole body metabolism has not been investigated. We found that male Agpat3 knockout (KO) mice exhibited reduced body weights with decreased white and brown adipose tissue mass. Such changes were less pronounced in the female Agpat3-KO mice. Agpat3-KO mice have reduced plasma insulin growth factor 1 (IGF1) and insulin levels and diminished circulating lipid metabolites. They manifested intact glucose homeostasis and insulin sensitivity despite a lean phenotype. Agpat3-KO mice maintained an energy balance with normal food intake, energy expenditure, and physical activity, except for increased water intake. Their adaptive thermogenesis was also normal despite reduced brown adipose mass and triglyceride content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3-deficient cells. We conclude that AGPAT3 regulates adipogenesis and adipose development. It is possible that adipogenic impairment in Agpat3-deficient cells potentially leads to reduced adipose mass. Findings from this work support the unique role of AGPAT3 in adipose tissue.NEW & NOTEWORTHY AGPAT3 deficiency results in male-specific growth retardation. It reduces adipose tissue mass but does not significantly impact glucose homeostasis or energy balance, except for influencing water intake in mice. Like AGPAT2, AGPAT3 is upregulated during adipogenesis, potentially by peroxisome proliferator-activated receptor gamma (PPARγ). Loss of AGPAT3 impairs adipocyte differentiation, which could be rescued by pioglitazone. Overall, AGPAT3 plays a significant role in regulating adipose tissue mass, partially involving its influence on adipocyte differentiation.
Subject(s)
1-Acylglycerol-3-Phosphate O-Acyltransferase , Adipocytes , Mice, Knockout , Animals , Female , Male , Mice , 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics , 1-Acylglycerol-3-Phosphate O-Acyltransferase/metabolism , Adipocytes/metabolism , Adipogenesis/genetics , Adipogenesis/physiology , Adipose Tissue, Brown/metabolism , Cell Differentiation , Energy Metabolism/genetics , Insulin Resistance/genetics , Mice, Inbred C57BL , Phenotype , Thermogenesis/genetics , Thinness/metabolism , Thinness/geneticsABSTRACT
BACKGROUND: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels. CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Everolimus/administration & dosage , Kidney Neoplasms/drug therapy , Phenylurea Compounds/administration & dosage , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Quinolines/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Renal Cell/mortality , Everolimus/adverse effects , Female , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Phenylurea Compounds/adverse effects , Progression-Free Survival , Protein Kinase Inhibitors/therapeutic use , Quinolines/adverse effects , Sunitinib/adverse effects , Sunitinib/therapeutic use , Survival AnalysisABSTRACT
A growing body of evidence suggests that cardiometabolic risk factors play a significant role in Alzheimer's disease (AD). Diabetes, obesity and hypertension are highly prevalent and can accelerate neurodegeneration and perpetuate the burden of AD. Insulin resistance and enzymes including insulin degrading enzymes are implicated in AD where breakdown of insulin is prioritised over amyloid-ß. Leptin resistance and inflammation demonstrated by higher plasma and central nervous system levels of interleukin-6 (IL-6), IL-1ß and tumour necrosis factor-α, are mechanisms connecting obesity and diabetes with AD. Leptin has been shown to ameliorate AD pathology and enhance long-term potentiation and hippocampal-dependent cognitive function. The renin-aldosterone angiotensin system, involved in hypertension, has been associated with AD pathology and neurotoxic reactive oxygen species, where angiotensin binds to specific angiotensin-1 receptors in the hippocampus and cerebral cortex. This review aims to consolidate the evidence behind putative processes stimulated by obesity, diabetes and hypertension, which leads to increased AD risk. We focus on how novel knowledge can be applied clinically to facilitate recognition of efficacious treatment strategies for AD.
Subject(s)
Alzheimer Disease , Hypertension , Obesity , Humans , Alzheimer Disease/metabolism , Obesity/complications , Obesity/metabolism , Cardiometabolic Risk Factors , Diabetes Mellitus/metabolism , Renin-Angiotensin System/physiology , Insulin Resistance/physiologyABSTRACT
OBJECTIVE: The authors of this study aimed to investigate independent prognostic factors of survival with a particular focus on comparing the safety and efficacy of endoscopic endonasal versus open approaches in the surgical management of skull base chordoma. METHODS: A retrospective National Cancer Database review of skull base chordoma patients was performed to capture resection cases from 2010 to 2020, evaluating overall survival (OS), early postoperative mortality, readmission rates, and hospital length of stay (LOS) between surgical approaches and the independent prognostication of death utilizing Cox multivariate regression analysis. RESULTS: Among the 736 patients included in the cohort, 456 patients (62.0%) and 280 patients (38.0%) underwent endoscopic endonasal and open resection, respectively. These values represent a rate of change over the study period of +4.1 versus -0.14 cases per year, respectively. Gross-total resection was achieved in 32.5% of cases. A positive margin status was found in 51.8% of cases. There was no association between extent of resection and surgical approach (p = 0.257). There was no difference in OS (p = 0.562), 30- and 90-day mortality (p = 0.209 and 0.126, respectively), and 30-day readmission (p = 0.438) between the two surgical groups. The mean LOS was reduced by 2.1 days in the endoscopic cohort (p = 0.013) compared with the open approach cohort. Finally, multivariate analysis revealed a tumor size ≥ 4 cm (HR 4.03, p = 0.005) and public insurance (HR 2.76, p = 0.004) as negative predictors of survival and treatment at an academic center (HR 0.36, p = 0.043) as a positive prognosticator of survival. CONCLUSIONS: The endoscopic endonasal approach has been increasingly utilized over time and touts noninferiority with respect to safety and efficacy with a marked improvement in LOS, which carries substantial implications for both healthcare costs and enhanced patient recovery. Future prospective studies are necessary to further delineate trends and surgical outcomes for skull base chordoma.
Subject(s)
Chordoma , Databases, Factual , Skull Base Neoplasms , Humans , Chordoma/surgery , Skull Base Neoplasms/surgery , Male , Female , Middle Aged , Retrospective Studies , Aged , Adult , Length of Stay/statistics & numerical data , Neuroendoscopy/methods , Treatment Outcome , Neurosurgical Procedures/methods , Patient Readmission/statistics & numerical dataABSTRACT
BACKGROUND: While nasal epistaxis balloons are generally seen as safe and routinely utilized by both surgical and nonsurgical providers, the complication profile related to this type of device has not been well defined. OBJECTIVE: The objective of this study was to utilize the FDA MAUDE (Manufacturer and User Facility Device Experience) database to better assess adverse events (AE) related to use of nasal epistaxis balloons. Reports were individually tabulated and events were categorized with special attention to AEs. METHODS: The FDA MAUDE database was queried for all medical device reports (MDR) related to nasal epistaxis balloon devices from January 2012 to November 2022. RESULTS: 19 MDRs met inclusion criteria. 5 MDRs were classified as device related (26.3 %); two events were reported for balloon leak and deflation, two events were reported for device breakage, and one device related event was unknown. 14 MDRs (73.7 %) were classified as patient related. Two documented MDRs were patient deaths due to exsanguination. Additional serious AEs included balloon ingestion and subsequent small bowel perforation (n = 1), cerebrospinal fluid leak (n = 1), skull base violation and intracranial placement of the device (n = 1), and respiratory distress (n = 3). CONCLUSION: Though epistaxis control with nasal balloons is generally seen as a safe procedure, there have been several concerning AEs reported. While two reports of death due to exsanguination were the most severe AEs, multiple other life-threatening AEs were also documented. Increased awareness of associated complications can be used to better counsel patients during the informed consent process as well as providers in their clinical decision making.
Subject(s)
Epistaxis , Exsanguination , Humans , United States , Epistaxis/etiology , Epistaxis/therapy , Databases, FactualABSTRACT
Air guns, particularly BB (ball-bearing or bullet ball) guns, have gained significant power and velocity over the last few decades. More than 145,000 pediatric patients suffered injuries attributed to air guns in the United States between 2001 and 2011, and approximately 22,000 pediatric emergency department visits are attributed to air gun-related injuries annually (Hyak et al., 2020 [1]). This study aims to describe an effective surgical technique in addressing maxillofacial injuries caused by BB gun projectiles in the pediatric population. We present a detailed surgical approach for endoscopic endonasal retrieval of a transorbital projectile in a 13-year-old male who sustained a maxillofacial BB gun injury, with the goal of restoring sinonasal function in a minimally invasive fashion.
Subject(s)
Firearms , Wounds, Gunshot , Male , Humans , Child , United States , Adolescent , Wounds, Gunshot/diagnostic imaging , Wounds, Gunshot/surgery , Wounds, Gunshot/epidemiology , Multimedia , Emergency Service, HospitalABSTRACT
STUDY DESIGN: Systematic, scoping literature review and case presentation. OBJECTIVE: The goal of this study is to review current literature on management trends and outcomes of pediatric intranasal lobular capillary hemangioma (ILCH). CASE PRESENTATION: A 14-year-old male patient presented with a 15-month history of unilateral epistaxis, nasal congestion, and mouth breathing. Further workup revealed a pale nasal mass obstructing the right nasal cavity. The patient was successfully treated using a minimally invasive endoscopic endonasal approach for mass resection and nasal floor free mucosal graft for septal reconstruction. METHODS: Independent queries of the PubMed Central, MEDLINE, and Bookshelf databases were performed; articles from 1990 to 2023 were abstracted. All studies that described pediatric ILCH using the Boolean method and relevant search term combinations, including "Intranasal," "Lobular capillary hemangioma," "Pyogenic granuloma," "Pediatric," "Outcome," and "Management," were collected for subsequent analysis. RESULTS: A total of 407 relevant unique articles were identified for analysis. Of these, 19 articles were deemed appropriate for inclusion in this literature review. Twenty-two pediatric ILCH cases were identified with a mean age at diagnosis of 10.5 years. The majority of cases occurred in males and presented with recurrent epistaxis and nasal obstruction. Most lesions originated from the anterior nasal septum and were resected using an endoscopic endonasal approach with no recurrence at last follow-up. CONCLUSIONS: Pediatric ILCH, a benign vascular neoplasm, often presents with unilateral nasal obstruction and severe, refractory epistaxis. This comprehensive review aims to highlight the importance of including this lesion in the differential diagnosis for unilateral nasal obstruction and epistaxis in young children.
Subject(s)
Granuloma, Pyogenic , Humans , Male , Adolescent , Granuloma, Pyogenic/surgery , Granuloma, Pyogenic/diagnosis , Nose Neoplasms/surgery , Nose Neoplasms/diagnosis , Multimedia , Rhinoplasty/methodsABSTRACT
RVU valuations need to be revisited regularly as procedure complexity and patient care pathways continue to evolve. The NSQIP-P database was queried for craniofacial procedures performed in North America between 2012 and 2019. Multivariate regression was performed to determine correlation coefficients of perioperative variables deemed to reflect procedure severity, including procedure duration, blood transfusion, length of stay, serious adverse events, related readmission, and related reoperation. CPT 21159 Le Fort III with forehead advancement remains the craniofacial procedure with the highest RVUs using our model at 33.93 units. The most underestimated procedure is CPT 42235 Repair of anterior palate, including vomer flap, with a suggested change of +8.27 units, which is a 194% increase from current compensation. Adjusted RVUs based on quantitative and nationally representative perioperative variables that reflect procedure severity might be a better alternative for procedure valuation over current survey methods to determine appropriate insurance compensation.
ABSTRACT
Tryptophan (TRP) is an essential amino acid catabolized mainly through the kynurenine pathway, and part of it is catabolized in the brain. The abnormal depletion of TRP and production of kynurenine (KYN) by two enzymes, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), have been linked to various neurological diseases. The ratio of TRP/KYN in plasma is a valuable measure for IDO/TDO activity and the prognosis of disease conditions. The 4-vinylphenylboronic acid (4-VPBA) was evaluated as a novel stationary phase for OT-CEC-MS/MS. TRP, KYN, and 3-hydroxykynurenine were separated using optimum conditions of 15 mM (NH4 )2 CO3 at pH 8 as a background electrolyte and 25 kV separation voltage on a 90 cm column. The usefulness of the 4-VPBA column for simple, fast, repeatable, and sensitive CEC-ESI-MS/MS application was demonstrated for the quantitation of TRP and KYN in the plasma of healthy human subjects and neuroinflammation subjects. The plasma sample was extracted on a zirconia-based ion-exchange cartridge for simultaneous protein precipitation and phospholipid removal. The method of standard addition, in combination with the internal standards approach, was used to prepare the calibration curve to overcome matrix matching and eliminate procedural errors. The developed quantitation method was validated according to FDA guidelines for sensitivity, accuracy, precision, and extraction recovery. The measured plasma level of TRP and KYN in healthy humans is aligned with the human metabolome database for the same two metabolites.
Subject(s)
Capillary Electrochromatography , Tryptophan , Humans , Tryptophan/chemistry , Kynurenine , Tandem Mass Spectrometry/methodsABSTRACT
BACKGROUND: Eustachian tube dysfunction (ETD) is common in children. Over the past decade, eustachian tube balloon dilation (ETBD) has become a more widespread treatment for this condition. Data has been encouraging in the adult population, but data among the pediatric population has been sparser. This comprehensive review aims to assess current evidence for ETBD in pediatric patients. REVIEW: Studies relevant to ETBD in the pediatric population were identified by utilizing the PubMed MEDLINE database. While multiple retrospective studies were found, this search yielded two systematic reviews focused on the pediatric population as the highest level of evidence assessing ETBD in children. There was overlap of included studies, but each review contained a unique set of studies. These reviews found that ETBD was safe in children. BEST PRACTICE SUMMARY: Overall, ETBD appears safe and efficacious in children with refractory ETD. Future prospective trials confirming this conclusion are warranted. At this time, there appears to be a role for ETBD with or without ventilation tube placement in children with refractory ETD.
Subject(s)
Ear Diseases , Eustachian Tube , Adult , Humans , Child , Dilatation , Retrospective Studies , Endoscopy , Catheterization , Ear Diseases/therapyABSTRACT
OBJECTIVE: To review and summarize reported adverse events related to the use of porcine small intestine submucosal grafts (Biodesign™) in otologic procedures. STUDY DESIGN: Retrospective cross-sectional analysis. SETTING: Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database. MATERIAL AND METHODS: The MAUDE database was queried for all medical device reports (MDR) related to otologic use of Biodesign™ (Cook Medical, Bloomington, IN) from January 2016 to November 2022. Adverse events (AEs) were identified by reviewing all reports with the basic search term "Biodesign" and "Biodesign, Otologic". Reports were individually reviewed and categorized with special attention to AEs. RESULTS: A total of 500 reports were reviewed. Since FDA approval of Biodesign™ in 2016, there have been 5 adverse events reported for use of Biodesign™ during otologic surgery (tympanoplasty, n = 3; stapes surgery, n = 2). All reported events described patient injury, and all cases required at least one revision surgery. Four cases described significant foreign body inflammatory reactions. Complications included hearing loss (n = 3), severe otalgia (n = 2), persistent perforation (n = 2), vertigo (n = 2), and facial paralysis (n = 1). CONCLUSION: The use of porcine small intestinal submucosal graft has been thought to be a safe and effective option for otologic surgery, with the advantage of availability without graft harvest in minimally invasive endoscopic surgery. However, foreign body or granulomatous reactions have been documented and should be considered prior to its use in otologic surgery.
Subject(s)
Foreign Bodies , Otologic Surgical Procedures , Humans , Swine , Animals , United States , Retrospective Studies , Cross-Sectional Studies , Otologic Surgical Procedures/adverse effects , Endoscopy , Databases, FactualABSTRACT
BACKGROUND: The purpose of this study was to evaluate the epidemiology and perioperative complications of different reconstructive strategies to correct cleft nasal deformity, with particular attention paid to type and timing of cartilage grafting. METHODS: Retrospective cohort study was conducted of cleft rhinoplasty performed between 2012 and 2017 in North America utilizing the American College of Surgeons National Surgical Quality Improvement Program- Pediatric hospital network. Medical/surgical complications, reoperations, and readmissions within 30 days postoperatively were analyzed with appropriate statistics. RESULTS: During the study interval, 3317 pediatric patients underwent cleft rhinoplasty, with 8.0% involving the use of cartilage grafts. Ear cartilage was significantly more commonly used for intermediate repair, whereas rib cartilage was more commonly used for late repair (P=0.006). Overall, rhinoplasties with ear cartilage grafts had shorter procedure durations than those without cartilage grafts (P=0.005), whereas those with rib cartilage grafts had increased procedure duration (P<0.001). The use of cartilage grafts was not associated with increased complications in either intermediate or late cleft rhinoplasty. Patients with bilateral clefts were more likely to undergo rhinoplasty with cartilage grafts overall (P=0.047) and with cartilage grafts for late reconstruction (P=0.039). CONCLUSIONS: Ear cartilage is most frequently utilized for intermediate repair, whereas rib cartilage is most frequently utilized for late repair during cleft rhinoplasty. Ear cartilage grafts are associated with significantly decreased procedure duration, whereas rib cartilage grafts are associated with significantly increased procedure duration. Not surprisingly, cleft rhinoplasty is relatively safe, with a 2% overall short-term complication rate.
Subject(s)
Cleft Lip , Costal Cartilage , Rhinoplasty , Child , Cleft Lip/surgery , Costal Cartilage/transplantation , Ear Cartilage/surgery , Humans , Nose/surgery , Retrospective Studies , Rhinoplasty/methodsABSTRACT
Acute lung injury (ALI) is an acute inflammatory process arises from a wide range of lung insults. A major cause of ALI is dysfunction of the pulmonary vascular endothelial barrier but the mechanisms involved are incompletely understood. The therapeutic potential of histone deacetylase (HDAC) inhibitors for the treatment of cardiovascular and inflammatory diseases is increasingly apparent, but the mechanisms by which HDACs regulate pulmonary vascular barrier function remain to be resolved. We found that specific Class IIa HDACs inhibitor, TMP269, significantly attenuated the lipopolysaccharide (LPS)-induced human lung microvascular endothelial cells (HLMVEC) barrier compromise in vitro and improved vascular barrier integrity and lung function in murine model of ALI in vivo. TMP269 decreased LPS-induced myosin light chain phosphorylation suggesting the role for Class IIa HDACs in LPS-induced cytoskeleton reorganization. TMP269 did not affect microtubule structure and tubulin acetylation in contrast to the HDAC6-specific inhibitor, Tubastatin A suggesting that Class IIa HDACs and HDAC6 (Class IIb) regulate endothelial cytoskeleton and permeability via different mechanisms. Furthermore, LPS increased the expression of ArgBP2 which has recently been attributed to HDAC-mediated activation of Rho. Depletion of ArgBP2 abolished the ability of LPS to disrupt barrier function in HLMVEC and both TMP269 and Tubastatin A decreased the level of ArgBP2 expression after LPS stimulation suggesting that both Class IIa and IIb HDACs regulate endothelial permeability via ArgBP2-dependent mechanism. Collectively, our data strongly suggest that Class IIa HDACs are involved in LPS-induced ALI in vitro and in vivo via specific mechanism which involved contractile responses, but not microtubule reorganization.
Subject(s)
Acute Lung Injury/chemically induced , Acute Lung Injury/enzymology , Histone Deacetylases/metabolism , Acute Lung Injury/physiopathology , Adaptor Proteins, Signal Transducing/metabolism , Animals , Cell Membrane Permeability/drug effects , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endotoxins , Heart Rate/drug effects , Histone Deacetylase Inhibitors/pharmacology , Lipopolysaccharides , Lung/drug effects , Lung/pathology , Lung/physiopathology , Mice, Inbred C57BL , Microvessels/pathology , Models, Biological , Oxygen/metabolism , Pneumonia/complications , Pneumonia/pathology , Signal Transduction/drug effects , rho GTP-Binding Proteins/metabolismABSTRACT
Analysis of food is essential for safety, quality control, government regulations, and recommendations to answer basic research questions. Capillary electrophoresis-mass spectrometry (CE-MS) is a powerful hyphenated technique in food, beverages, and foodomics for analytes ranging from small organic ions and biochemical compounds to macromolecules. Advantages of CE-MS for food analysis include high efficiency, high resolution, low cost of reagent consumption, fast and green approach in various food research areas. This review offers a comprehensive evaluation of CE-MS application for food analysis published in the open literature in the last decade (July 2010-October 2020). The principles of various CE-MS modes, CE-inductively coupled plasma mass spectrometry, ionization interfaces, and sample preparation methods for multiple types of liquid and solid food analysis are compiled. The latest advances and potential trends are outlined in several food analysis areas where CE-MS could be beneficial.
ABSTRACT
PURPOSE OF REVIEW: Over half of all patients with severe asthma have chronic rhinosinusitis (CRS). Although distinct and specialized in function and form, the upper and lower airways share similar and inter-related pathophysiologic mechanisms. The severity of CRS particularly in patients with nasal polyps can correlate with that of asthma and vice versa. The purpose of this review is to elucidate the relationship between these conditions and summarize key elements in the management of these patients. RECENT FINDINGS: Several advances have been made in the evaluation and treatment of patients with CRS and asthma. Further understanding of inflammatory endotypes common to both CRS and severe asthma hopefully will provide appropriate and effective treatments and improve patient outcomes. SUMMARY: CRS significantly impairs quality of life, and therapies are targeted toward improving patient symptoms, and hopefully in the future, treating the underlying immune dysfunction. Management of CRS and severe asthma requires a multidisciplinary approach. Further real-world studies are necessary to determine the best treatment algorithm for these patients.
Subject(s)
Asthma/therapy , Rhinitis/therapy , Sinusitis/therapy , Asthma/complications , Chronic Disease , Comorbidity , Humans , Nasal Polyps , Quality of Life , Rhinitis/complications , Sinusitis/complicationsABSTRACT
We report a case of mycotic thoracic aortic aneurysm managed by staged hybrid repair. A 30-year-old male patient with polysubstance abuse presented with chest pain and elevated white blood cell count. CTA performed showed a rapidly developing mycotic thoracic aortic pseudoaneurysm. He underwent emergent thoracic endovascular aortic repair followed 24 hours later by surgical debridement of the posterior mediastinum. Cultures grew Methicillin-resistant Staphylococcus aureus and patient was placed on long term antibiotics. The patient was asymptomatic on follow up one year after his final operation with complete exclusion of pseudoaneurysm with no endoleak.
Subject(s)
Aneurysm, Infected/surgery , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/surgery , Adult , Aneurysm, Infected/diagnostic imaging , Aneurysm, Infected/microbiology , Anti-Bacterial Agents/therapeutic use , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/microbiology , Debridement , Drug Users , Humans , Male , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Substance Abuse, Intravenous/complications , Treatment OutcomeABSTRACT
BACKGROUND: The ultrasound-guided retroclavicular block (RCB) is a recently described alternative approach to brachial plexus blockade at the level of the cords. Although more distal blockade of the brachial plexus is thought to be associated with a lower incidence of phrenic nerve block, the impact of RCB on ipsilateral diaphragmatic function has not been formally investigated. OBJECTIVE: To compare the effects of supraclavicular and retroclavicular brachial plexus block on diaphragmatic function. SETTING: A single tertiary hospital, study period from December 2017 to May 2019. DESIGN: Double-blinded, randomised study. PATIENTS: A total of 40 patients undergoing upper extremity surgery below the axilla. Exclusion criteria included significant pulmonary disease, BMI more than 40 and contra-indication to peripheral nerve block. INTERVENTIONS: Patients were randomised to supraclavicular or retroclavicular brachial plexus block with ropivacaine 0.5%. OUTCOME MEASURES: Phrenic block was assessed by measuring changes in diaphragmatic excursion using M-mode ultrasound, and maximum inspiratory volume on incentive spirometry from baseline, at 15 and 30âmin postblock, and postoperatively. Comparative assessment of block characteristics included timing and distribution of sensory and motor block onset in the upper extremity, and scanning and block performance times. RESULTS: The incidence of phrenic block in the supraclavicular group was higher by ultrasound imaging (70 vs. 15%) and also by pulmonary function testing (55 vs. 5%), with both diaphragmatic excursion and maximum inspiratory volume decreasing to a greater extent after supraclavicular block (SCB) compared with RCB at 15, 30âmin and postoperative time points (repeated measures analysis of variance, Pâ<â0.001). There was no difference in timing and extent of distal arm block, but suprascapular and axillary nerves were more consistently blocked after SCB than after RCB. CONCLUSION: The current study confirms the hypothesis that a RCB is significantly less likely to affect ipsilateral diaphragmatic function than a SCB. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02631122.
Subject(s)
Brachial Plexus Block , Brachial Plexus , Anesthetics, Local , Brachial Plexus/diagnostic imaging , Humans , Ultrasonography , Ultrasonography, InterventionalABSTRACT
BACKGROUND: Parotid gland pathologies requiring resection present with varying effects on surrounding tissue architecture, and we hypothesize that this spectrum of indications confers different risks of adverse events. The purpose of this study is to elucidate the complication profiles of parotidectomy in children across a spectrum of pathologies requiring parotid resection. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Pediatric data set was queried for parotidectomies performed from 2012 through 2017. Indications were subclassified based on International Classification of Diseases, Ninth Revision and Tenth Revision codes. Complications, readmissions, and reoperations were analyzed with appropriate statistics. RESULTS: Parotidectomies in children (n = 208) were mostly performed for neoplasms (47.6%), followed by inflammatory conditions (24.0%). Total parotidectomies took significantly longer (P < 0.001) and remained in the hospital significantly longer than superficial parotidectomies (P < 0.001). There was no significant difference (P = 0.417) between benign neoplasms (29.3%) and malignant neoplasms (37.9%) requiring total parotidectomy. However, there was a significant difference (P = 0.014) across various malformations, with 83.3% of lymphatic malformations requiring total parotidectomy. Although lymphatic malformations required more aggressive resection, these procedures had the lowest rate of adverse events (0%). Despite the unappreciable predilection toward total parotidectomy based on nature of neoplasms, parotidectomy performed for malignant neoplasms had a significantly increased risk of nerve injury (P < 0.001; odds ratio [OR], 3563) and medical complications (P < 0.001; OR, 67.2), whereas those performed for benign neoplasms did not have an increased risk of these complications (all P's > 0.209). Parotidectomy performed for vascular malformations had significantly increased risk of bleeding requiring transfusion (P < 0.001; OR, 14.9) and surgical complications (P < 0.001; OR, 9.2). Bleeding requiring transfusion was significantly related to longer surgical procedures (P < 0.001; 409 vs 191 minutes). CONCLUSIONS: Parotidectomy in pediatric patients for malignant neoplasms is associated with a significantly higher risk of nerve injury compared with parotidectomy for benign neoplasms. Parotidectomy for vascular malformations has a significantly higher risk of bleeding requiring transfusion, whereas parotidectomy for lymphatic malformations is associated with the lowest risk of medical and surgical complications.
Subject(s)
Parotid Neoplasms , Child , Humans , Parotid Gland/surgery , Parotid Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Reoperation , Retrospective StudiesABSTRACT
INTRODUCTION: The precise etiology of Ménière's disease (MD) remains unknown; however, given the association of MD with serum antibodies and human leukocyte antigen (HLA) complex, several studies have proposed a relationship between MD and thyroid disorders. Similarly, multiple hypotheses exist regarding the metabolic disturbances of fluctuating thyroid hormone as a potential contributing agent in the development of MD. METHODS: A total of 171 abstracts were identified and screened by 2 independent reviewers. Based on inclusion and exclusion criteria, 8 studies were selected for final analysis. Due to heterogeneity of clinical data, meta-analysis was not feasible. RESULTS: The prevalence of autoimmune thyroid disease and hypothyroidism in MD varied significantly from 1 to 38%. Notable bias was introduced given the lack of standardization of diagnostic criteria across studies. Articles that described autoimmune thyroid-specific antibodies and HLA types also presented inconclusive results. Multiple studies noted a potential etiologic role of hypothyroidism in MD, which was often confounded by thyroxine supplementation. CONCLUSIONS: Despite a potential correlation in the medical literature between thyroid disorders and MD, there is currently no definitive causal relationship. Although most of the present medical literature focuses on autoimmunity, dysregulated thyroid hormone levels may also be implicated in the association of MD with thyroid disorders.