Characterizing Conformational Change of a Thermoresponsive Polymeric Nanoparticle with Raman Spectroscopy.

Molecular conformational changes in the collapsing and reswelling processes occurring during the phase transition at the lower critical solution temperature (LCST) of the polymer are not well understood. In this study, we characterized the conformational change of Poly(oligo(Ethylene Glycol) Methyl Ether Methacrylate)-144 (POEGMA-144) synthesized on silica nanoparticles using Raman spectroscopy and zeta potential measurements. Changes in distinct Raman peaks associated with the oligo(Ethylene Glycol) (OEG) side chains (1023, 1320, and 1499 cm-1) with respect to the methyl methacrylate (MMA) backbone (1608 cm-1) were observed and investigated under increasing and decreasing temperature profiles (34 °C to 50 °C) to evaluate the polymer collapse and reswelling around its LCST (42 °C). In contrast to the zeta potential measurements that monitor the change in surface charges as a whole during the phase transition, Raman spectroscopy provided more detailed information on vibrational modes of individual molecular moieties of the polymer in responding to the conformational change.

Long-Term Voice Outcomes Following Cricotracheal Resection for Subglottic Stenosis: A Retrospective Analysis.

OBJECTIVES/HYPOTHESIS: Cricotracheal resection (CTR) is an effective treatment for refractory idiopathic subglottic stenosis (iSGS) but is associated with persistent dysphonia. Outcomes were measured longitudinally to characterize how patients' voices and self-perceived voice handicaps changed after CTR. STUDY DESIGN: Retrospective case-series. METHODS: We conducted a retrospective cohort study of patients with refractory iSGS treated by CTR from 2006 to 2017. Voice Handicap Index (VHI), Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V), and acoustic analysis were prospectively collected preoperatively and postoperatively at 1, 3, 6, 12, and 24-month intervals. A linear mixed model was used to evaluate temporal change. RESULTS: Thirty-three patients (97% female) were included. VHI scores increased significantly from baseline preoperative score (27.2 ± 22.7) to a mean value of 44.3 ± 25.6 (P < .001) 1-month postoperatively but decreased below preoperative scores after 2 years (18.8 ± 11.9, P = .795). Mean fundamental frequency (F0) values in speech decreased significantly from 192.0 ± 24.9 Hz preoperatively to 167.1 ± 19.8 Hz at a 2-year follow-up (P = .002), with a nadir value at 1-month postoperatively (148.4 ± 20.5, P < .001). CAPE-V scores increased significantly from preoperative to 1-month postoperative (3.0 ± 2.3 vs. 21.9 ± 17.3, P < .001) but returned toward baseline values at 24 months after CTR (6.9 ± 4.8, P = .027). CAPE-V measurements postoperatively were correlated with VHI and F0 (Pearson coefficient = 0.54 (VHI), -0.46 (F0), P < .001). CONCLUSIONS: Following CTR, mean F0 values were significantly and consistently lower but did increase over time, correlating with patients' improving VHI and CAPE-V scores. VHI values indicate that patient's perception of their voice is not significantly impacted in long term. These results provide a framework to counsel patients about long term voice expectations. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1054-1060, 2022.

Neural Antibody Testing for Autoimmune Encephalitis: A Canadian Single-Centre Experience.

Neural antibodies have emerged as useful biomarkers in suspected autoimmune encephalitis. We reviewed results of neural antibody testing (anti-N-methyl D-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein (LGI1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid type B receptor (GABA(B)R), dipeptidyl-peptidase-like protein-6 (DPPX), IgLON family member 5 (IgLON5) and glutamic acid decarboxylase-65 (GAD65)) using cell-based assays (CBAs) and tissue indirect immunofluorescence (TIIF) at our centre. Our findings suggest increased clinical sensitivity of CBA compared to TIIF. However, this may come at some expense to clinical specificity, as evidenced by possible false-positive results when weak serum positivity by CBA was observed for certain antibodies (i.e. anti-NMDAR, CASPR2). In such cases, correlation with serum TIIF, as well as CSF CBA and TIIF, aids in identifying true-positive results.

An unusual case of massive hemoptysis due to Bacillus cereus necrotizing pneumonia.

Bacillus cereus is a gram-positive bacillus that is ubiquitously present in the environment, often regarded as a contaminant when isolated in clinical testing. Cases of B. cereus causing lower respiratory tract infections are sparse, with less than 20 reported in the literature, and even fewer as a cause of massive hemoptysis. The majority of cases occur in the setting of an immunosuppressed patient. We describe a case of a 59-year-old male with esophageal adenocarcinoma undergoing chemotherapy presenting with a right upper lobe necrotizing pneumonia secondary to B. cereus with consequent massive hemoptysis.

Evaluation of an electronic health record structured discharge summary to provide real time adverse event reporting in thoracic surgery.

BACKGROUND: The reporting of adverse events (AE) remains an important part of quality improvement in thoracic surgery. The best methodology for AE reporting in surgery is unclear. An AE reporting system using an electronic discharge summary with embedded data collection fields, specifying surgical procedure and complications, was developed. The data are automatically transferred daily to a web-based reporting system. METHODS: We determined the accuracy and sustainability of this electronic real time data collection system (ERD) by comparing the completeness of record capture on procedures and complications with coded discharge data (administrative data), and with the standard of chart audit at two intervals. All surgical procedures performed for 2 consecutive months at initiation (Ti) and 1 year later (T1yr) were audited by an objective trained abstractor. A second abstractor audited 10% of the charts. RESULTS: The ERD captured 71/72 (99%) of charts at Ti and 56/65 (86%) at T1yr. Comparing the presence/absence of complications between ERD and chart audit demonstrated at Ti a high sensitivity and specificity, positive predictive value (PPV) of 95.5%, negative predictive value (NPV) of 93.9% with a kappa of 0.872 (95% CI 0.750 to 0.994), and at T1yr a sensitivity, specificity, PPV and NPV of 100% with a kappa of 1.0 (95% CI 1.0). Comparing the presence/absence of complications between administrative data and chart audit at Ti demonstrated a low sensitivity, high specificity and a kappa of 0.471 (95% CI 0.256 to 0.686), and at T1yr a low sensitivity, high specificity of 85% and a kappa of 0.479 (95% CI 0.245 to 0.714). CONCLUSIONS: We found that the ERD can provide accurate real time AE reporting in thoracic surgery, has advantages over previous reporting methodologies and is an alternative system for surgical clinical teams developing AE reporting systems.

Glucose responsiveness in a novel adult-derived GnRH cell line, mHypoA-GnRH/GFP: involvement of AMP-activated protein kinase.

Glucose regulates energy homeostasis and reproductive function within the hypothalamus. The underlying mechanisms responsible for glucose regulation of GnRH gene transcription were investigated using a novel murine immortalized, adult-derived hypothalamic cell line, mHypoA-GnRH/GFP. Analysis of GnRH mRNA synthesis and secretion following agonist treatment demonstrated that the mHypoA-GnRH/GFP cell line is a representative model of in vivo GnRH neurons. c-fos mRNA levels, following glucose exposure, indicated that these neurons were responsive to low (0.5mM) and high (5mM) glucose, and high glucose stimulated GnRH mRNA transcription in a metabolism-dependent manner. Glucose inhibited AMPK activity, and was linked to the downstream stimulation of GnRH mRNA levels. The effect was confirmed with an AMPK antagonist, Compound C. Collectively, these findings demonstrate that glucose can directly regulate GnRH transcription, while implicating the AMPK pathway as an essential mediator of nutritional signaling in a novel GnRH neuronal cell model.

Cellular leptin resistance impairs the leptin-mediated suppression of neuropeptide Y secretion in hypothalamic neurons.

Evidence shows that neuropeptide Y (NPY) neurons are involved in mediating the anorexigenic action of leptin via neuronal circuits in the hypothalamus. However, studies have produced limited data on the cellular processes involved and whether hypothalamic NPY neurons are susceptible to cellular leptin resistance. To investigate the direct regulation of NPY secretion by leptin, we used novel NPY-synthesizing, immortalized mHypoA-NPY/green fluorescent protein and mHypoA-59 hypothalamic cell lines derived from adult hypothalamic primary cultures. We report that leptin treatment significantly suppressed NPY secretion in the cells by approximately 20%. We found a decrease in c-fos expression upon leptin exposure, indicating deactivation or hyperpolarization of the neurons. Protein analysis indicated that leptin inhibits AMP-activated protein kinase (AMPK) activity and activates acetyl-coenzyme A carboxylase in NPY neurons, supporting the hypothesis of an AMPK-dependent mechanism. Inhibiting both AMPK with Compound C or phosphatidylinositol 3 kinase (PI3K) with 2-(4-morpholinyl)-8-phenyl-1(4H)-1-benzopyran-4-one hydrochloride prevented the leptin-mediated decrease in NPY secretion, indicating both AMPK- and PI3K-mediated mechanisms. Further, NPY secretion was stimulated by 30% by the AMPK activator, aminoimidazole carboxamide ribonucleotide. Importantly, prolonged leptin exposure in the mHypoA-NPY/green fluorescent protein cells prevented leptin-induced changes in AMPK phosphorylation and suppression of NPY secretion, indicating that NPY neurons are susceptible to leptin resistance. Our studies indicate that AMPK and PI3K pathways are involved in leptin action in NPY neurons and that leptin resistance blocks the feedback response likely required to maintain energy homeostasis.

Can preoperative computed tomography of the chest predict completeness of the major pulmonary fissure at surgery?

BACKGROUND: An incomplete major pulmonary fissure can make anatomic lung resection technically more difficult and may increase the risk of complications, such as prolonged postoperative air leak. The objective of this study was to determine if preoperative computed tomography (CT) of the chest could accurately predict the completeness of the major pulmonary fissure observed at the time of surgery. METHODS: From October 2008 to June 2009, patients at a single university institution were enrolled if they underwent surgery for a pulmonary nodule, mass or known cancer. At the time of surgery, completeness of the major pulmonary fissure was graded 1 if pulmonary lobes were entirely separate, 2 if the visceral cleft was complete with an exposed pulmonary artery at the base with some parenchyma fusion, 3 if the visceral cleft was only evident for part of the fissure without a visible pulmonary artery and 4 if the fissure was absent. The preoperative CT scan of each patient was graded by a single, blinded chest radiologist using the same scale. We used the Pearson χ2 test with 2-tailed significance to test the independence of the operative and radiologic grading. RESULTS: In 48% (29 of 61) of patients, the radiologic and operative grading were the same. Of those graded differently, 94% (30 of 32) were within 1 grade. Despite this agreement, we observed no statistically significant correlation between the operative and radiologic grading (p = 0.24). CONCLUSION: The major fissure can often be well-visualized on a preoperative CT scan, but preoperative CT cannot accurately predict the completeness of the major pulmonary fissure discovered at surgery.

Thoracic surgery training in Canada according to the residents: the thoracic surgery resident survey, of the Canadian thoracic manpower and education study (T-Med).

OBJECTIVE: The resident component of the Canadian Thoracic Manpower and Education Study (T-MED) was conducted to understand the basic demographic of Canadian thoracic surgery residents, the factors influencing their selection of training programs, current work conditions, training and competencies, and opinions in regard to the manpower needs for the specialty. DESIGN: A modified Delphi process was used to develop a survey applicable to thoracic surgery residents. In May and June 2009, residents completed the voluntary anonymous Internet-based survey. All Canadian residents participated in the survey, providing a 100% response rate. RESULTS: Most respondents were male (11/12), and the average age was 34 years old with an anticipated debt greater than $50,000 on graduation. All residents worked more than 70 hours per week, with most doing 1 : 3 or 1 : 4 on-call. Two-thirds of respondents reported being satisfied or very satisfied with their training program. Rates of anticipated competence in performing various thoracic surgeries on graduation differed between residents and program directors. Two-thirds (8/12) of residents planned to practice thoracic surgery exclusively, and hoped to practice in an academic setting. Most residents (10/12) agreed or strongly agreed that not enough jobs are available in Canada for graduating trainees and that the number of residency positions should reflect the predicted availability of jobs. CONCLUSIONS: This study has provided detailed information on thoracic surgery resident demographics and training programs. Most thoracic surgery residents are satisfied with their current training program but have concerns about their job prospects on graduation, and they believe that the number of training positions should reflect potential job opportunities. This survey represents the first attempt to characterize the current state of thoracic surgery training in Canada from the resident's perspective and may help in directing educational and manpower planning.

Resolution of chronic diarrhea after resection of a localized pulmonary carcinoid tumor.

Pulmonary carcinoid tumors are rarely associated with symptoms of the carcinoid syndrome, such as flushing and diarrhea. When present, these symptoms virtually always represent extensive hepatic metastases. In this article we describe the presentation, perioperative management, and presumed mechanisms of a patient with a localized pulmonary carcinoid with associated chronic diarrhea that resolved after operation.

Weather and chinook winds in relation to spontaneous pneumothoraces.

BACKGROUND: Spontaneous pneumothorax (SP) results from the rupture of blebs or emphysematous bullae. Rapid changes in weather may precipitate this process. The city of Calgary is well suited to examine the effects of weather and specifically the rapid changes in weather associated with a chinook event and the occurrence of SP. METHODS: We performed a retrospective chart review of all cases of SP in the Calgary Health Region from 2001 to 2005. We obtained local hourly weather data over the same period from Environment Canada. We then compared the rates of SP on chinook and nonchinook days. Further, we compared mean daily temperature, humidity, wind speed and atmospheric pressure on chinook and nonchinook days. RESULTS: In all, 220 SP events from 149 patients occurred during the 4.5-year study period. There was no significant difference in the rate of SP on chinook days versus nonchinook days (p = 0.80). Similarly, there was no significant difference in the rate of SP in each of the 4 seasons (p = 0.30). We observed significantly higher average wind speed and lower mean atmospheric pressure on days with SP versus days without (p = 0.009, p = 0.020, respectively). There was no difference in mean temperature or mean relative humidity when comparing days with SP versus days without. CONCLUSION: We found no association between SP and chinook events. We observed significantly higher wind speeds and lower atmospheric pressures on days with SP versus days without.

Retrospective analysis of the clinical performance of anterior mediastinotomy.

BACKGROUND: Accurate staging of patients with lung cancer is imperative in generating an appropriate treatment strategy. This study examined the clinical performance of anterior mediastinotomy in staging patients with suspected left upper lobe non-small cell lung cancer. METHODS: This study was designed as a retrospective cohort. All patients with suspected left upper lobe cancer and otherwise normal computed tomography scan results were eligible. Patients with clinically unresectable disease (advanced disease or not fit for surgery) were excluded. After exclusions, 151 patients were stratified into two groups: 117 patients had cervical and anterior mediastinotomy as part of preoperative staging, and 34 had cervical mediastinoscopy only. The primary outcome was rate of preventable thoracotomy defined as thoracotomy during which either metastases to aortopulmonary or paraaortic lymph nodes, or mediastinal invasion was identified. RESULTS: The rate of preventable thoracotomy for the anterior mediastinotomy arm was 4 (3.4%) of 117, compared with 1 (2.9%) of 34 for cervical mediastinoscopy-only arm (p = 0.99). The rate of morbidity in the anterior mediastinotomy arm was 8 (6.8%) of 117, compared with 2 (5.8%) of 34 for the cervical mediastinoscopy-only arm (p = 0.99). Anterior mediastinotomy patients stayed in hospital 1 day longer (p = 0.008). Anterior mediastinotomy was successful at harvesting one or more lymph nodes in 67% of patients. Five patients (4.3%) who underwent anterior mediastinotomy were spared a thoracotomy by identification of metastases to aortopulmonary lymph nodes. CONCLUSIONS: In patients with suspected left upper lobe lung cancer and otherwise normal computed tomography scan results, anterior mediastinotomy does not significantly reduce the rate of preventable thoracotomy.

Levels of evidence and grades of recommendations in general thoracic surgery.

OBJECTIVES: To determine the grades of recommendations and levels of evidence available if the formal practice of evidence-based medicine is applied to general thoracic surgery. METHODS: Three general thoracic surgeons, by consensus, developed a sample of 10 clinically important questions. The first 3 steps of evidence-based medicine (creation of answerable clinical questions, search for best external evidence, and critical appraisal of literature) were performed. Abstracts and appropriate articles were identified through Medline from January 1999 through December 2001. A hierarchical series of search strategies was employed to identify the best level of evidence. The best evidence found was categorized according to the Oxford Centre for Evidence-Based Medicine into 4 grades of recommendations (A-D) and 5 levels of evidence (1-5). RESULTS: The best evidence found for the 10 sample questions was categorized as grade A recommendations in 5 and grade B, also in 5 questions. The levels of evidence found were la in 3 studies, 1b in 5, and 2b in 2. CONCLUSIONS: A formal evidence-based-medicine approach to general thoracic surgery found the grades of recommendation and levels of evidence for a sample of clinically important questions to be high.

Functional results and quality of life after tracheal resection for locally invasive thyroid cancer.

BACKGROUND: Local invasion of the upper aerodigestive tract by thyroid cancer, although uncommon, is a serious cause of morbidity and mortality. The impact of aerodigestive tract resection on the functional status and quality of life of the patient has not previously been investigated. METHODS: Patients with locally invasive thyroid cancer were included in a prospective surgical protocol. Swallowing function was assessed with barium swallow at 7 days and 1 month postoperatively. Postoperative quality of life (QOL) was measured using a validated head and neck QOL instrument. RESULTS: Seven patients underwent airway resection for locally invasive recurrent thyroid cancer in the period 1999 to 2001. At 1 week postoperative 3 of 7 (43%) had no evidence of aspiration on barium swallow. At 4 weeks 6 of 7 (86%) had no aspiration. Postoperative QOL scores in the domains of eating function (85.2) and emotional status (78.6) were significantly better than those of a comparison group undergoing treatment for cancers of the oropharynx, P = 0.012 and P = 0.0077, respectively. CONCLUSIONS: Tracheal resection for locally invasive thyroid cancer is associated with a return to full dietary intake within 4 weeks of surgery in most cases. Function and QOL after this type of surgery are acceptable.

Clostridium perfringens pleuropulmonary infection and septic shock: case report and population-based laboratory surveillance study.

We report a rare case of necrotizing pneumonia, empyema, and septic shock caused by Clostridium perfringens. Population-based laboratory surveillance was subsequently conducted that identified an annual incidence of invasive C. perfringens disease of 0.83 per 100,000 population with a striking age-related increased risk for acquisition.