Developing an interprofessional team to support patients prescribed long-term high-dose opioid therapy.

Despite decreases in US opioid prescribing rates, daily morphine milligram equivalents (MME) prescribed per person remains three times higher than in 1999. An interprofessional team (IPT) was developed to support pain management for patients prescribed long-term high-dose opioids (HDO) in a Federally Qualified Health Center. The IPT utilized a clinical pharmacist, addiction nurse, medical director, and another physician or nurse practitioner to manage adults prescribed long-term HDO, defined as exceeding 50 daily MME. Visits focused on patient education including risks associated with long-term HDO use and effective pain management. The IPT engaged in supportive, individualized care planning for safer, evidence-based pain management, which included, but was not limited to opioid tapers, adjuvant non-opioid pain medications (NOPM), non-pharmacological therapy (NPT), and naloxone co-prescribing. The IPT saw 90% (n = 19) of eligible patients. Excluding outliers, the cohort demonstrated an average 18% ± 24.9 decrease in daily MME. The most common NOPM were acetaminophen, NSAIDs, and pregabalin, and the most common NPT were physical, aquatic, and behavioral therapy. Shared decision-making, collaborative teamwork, and simple patient-centered goals are key to moving patients toward safer, evidence-based therapy.

Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates.

Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee), carnivores (Siberian tiger, clouded leopard), cetartiodactyls (humpback whale, giraffe) and primates (human, common chimpanzee). Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317) of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant) and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967) and rodents (Palay and Chan-Palay, 1974), although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures.

Recurrent laryngeal nerve monitoring during mediastinoscopy: predictors of injury.

BACKGROUND: Recurrent nerve injuries occur during mediastinoscopy despite assiduous technique. We evaluated mediastinoscopy by monitoring laryngeal nerve stimulation during the surgery. These techniques utilize sensing electrodes on laryngeal masks to evaluate stimulus of the larynx, and are used to identify recurrent nerves during redo neck surgery. METHODS: Fifteen patients were monitored during the entire mediastinoscopy. The laryngeal sensor was placed just before intubation. All patients had a suprasternal incision, digital dissection along the anterior wall of the trachea, and harvest of the nodes in the left paratracheal (4L), right paratracheal (4R), and subcarinal (7) positions. Cautery was used when needed in the subcarinal space and the right paratracheal groove. RESULTS: Surprisingly, 14 of 15 patients demonstrated intense recurrent nerve stimulation during digital dissection along the anterior wall of the trachea. This dissection activated the right and left recurrent nerves. Though the use of cautery on the left caused significant laryngeal nerve activity, cautery in the subcarinal space and on the right caused very little activity. One patient was found to have a (transient) recurrent nerve injury after surgery. She demonstrated intense activity both during dissection along the anterior wall of the trachea, and during removal of a left paratracheal node. CONCLUSIONS: Our data demonstrate that traction in the anterior mediastinum causes the greatest stimulation to the nerves, even greater than direct stimulation with current. Thus, these data suggest that injuries could result only from traction. Traction on both recurrent nerves can occur with dissection along the trachea. Laryngeal nerve monitoring can be used to direct biopsies in the left paratracheal groove.

Postoperative respiratory failure.

This analysis differentiates the causes of postoperative respiratory failure. Respiratory failure in thoracic patients is broken down into two distinct groups, aspiration and pneumonia, promoting actions to prevent respiratory failure. The goal is to develop different strategies to avoid postoperative respiratory failure using an active approach (what can be done in the management of patients undergoing lung resection to prevent problems) rather than passive approach (what patient factors caused problems after surgery). Before that analysis, the operative risks after lung resections (lobectomies, pneumonectomies, elderly patients) and esophagectomies are reviewed to understand the data.

Ectopic adrenocorticotropic hormone hypersecretion due to a primary pulmonary paraganglioma.

OBJECTIVE: To present a rare case of primary paraganglioma of the lung, which caused the syndrome of ectopic adrenocorticotropic hormone (ACTH) hypersecretion. METHODS: The clinical, biochemical, and imaging findings in this case are described, and the pathologic features of the resected tumor tissue are depicted. In addition, the related literature on paragangliomas is reviewed. RESULTS: In a 39-year-old woman with hypertension, weight gain, and easy bruising, laboratory studies showed hypercortisolemia, high plasma ACTH levels, and suppression of cortisol by high-dose dexamethasone. An indium-labeled octreotide whole-body scan disclosed a tumor in the left lower lung field. Thoracoscopic wedge resection of the pulmonary mass was performed. Postoperative microscopic findings and immunohistochemical stains revealed nests of rounded and polyhedral cells and S-100 protein-positive sustentacular (supporting) cells, charac- CONCLUSION: This unusual case of Cushing's syndrome was attributable to an ACTH-secreting primary pulmonary paraganglioma.

Significance of p63 amplification and overexpression in lung cancer development and prognosis.

The fight against lung cancer is greatly compromised by the lack of effective early detection strategies. Genomic abnormalities and specifically the amplification of chromosomal region 3q26-3qter in lung cancer represent a major signature of neoplastic transformation. Here, we address the significance of p53 homologue p63 mapping to 3q27 in lung tumorigenesis. We analyzed p63 gene copy number (CN) by fluorescence in situ hybridization and expression by immunohistochemistry in tissue microarrays of 217 non-small cell lung cancers (NSCLCs) and correlated them with survival. We additionally characterized our findings in a subset of 24 NSCLCs by reverse transcription-PCR and Western blotting. We analyzed p63 CN and protein expression in 41 preinvasive squamous lesions. The p63 genomic sequence was amplified in 88% of squamous carcinomas, in 42% of large cell carcinomas, and in 11% of adenocarcinomas of the lung. The predominant splice variant of p63 expressed was DeltaNp63alpha. Western analyses revealed DeltaNp63alpha expression in normal bronchus and squamous carcinomas but not in normal lung or in adenocarcinomas. Furthermore, p63genomic amplification and protein staining intensity associated with better survival. We found a significant increase in CN in preinvasive lesions graded severe dysplasia or higher. Our data demonstrate that there is early and frequent genomic amplification of p63 in the development of squamous carcinoma of the lung and that patients with NSCLC showing amplification and overexpression of p63 have prolonged survival. These observations suggest that p63 genomic amplification has an early role in lung tumorigenesis and deserves additional evaluation as a biomarker for lung cancer progression.

A training-testing approach to the molecular classification of resected non-small cell lung cancer.

PURPOSE: RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance. EXPERIMENTAL DESIGN: In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray. RESULTS: Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous. High alpha-actinin-4 expression was identified as highly correlated with poor prognosis. CONCLUSIONS: These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.

Proteomic patterns of tumour subsets in non-small-cell lung cancer.

BACKGROUND: Proteomics-based approaches complement the genome initiatives and may be the next step in attempts to understand the biology of cancer. We used matrix-assisted laser desorption/ionisation mass spectrometry directly from 1-mm regions of single frozen tissue sections for profiling of protein expression from surgically resected tissues to classify lung tumours. METHODS: Proteomic spectra were obtained and aligned from 79 lung tumours and 14 normal lung tissues. We built a class-prediction model with the proteomic patterns in a training cohort of 42 lung tumours and eight normal lung samples, and assessed their statistical significance. We then applied this model to a blinded test cohort, including 37 lung tumours and six normal lung samples, to estimate the misclassification rate. FINDINGS: We obtained more than 1600 protein peaks from histologically selected 1 mm diameter regions of single frozen sections from each tissue. Class-prediction models based on differentially expressed peaks enabled us to perfectly classify lung cancer histologies, distinguish primary tumours from metastases to the lung from other sites, and classify nodal involvement with 85% accuracy in the training cohort. This model nearly perfectly classified samples in the independent blinded test cohort. We also obtained a proteomic pattern comprised of 15 distinct mass spectrometry peaks that distinguished between patients with resected non-small-cell lung cancer who had poor prognosis (median survival 6 months, n=25) and those who had good prognosis (median survival 33 months, n=41, p<0.0001). INTERPRETATION: Proteomic patterns obtained directly from small amounts of fresh frozen lung-tumour tissue could be used to accurately classify and predict histological groups as well as nodal involvement and survival in resected non-small-cell lung cancer.

Minimally invasive surgery in the treatment of empyema: intraoperative decision making.

BACKGROUND: Pneumonia, parapneumonic effusions, and empyema continue to be significant health problems, especially in elderly individuals. Minimally invasive thoracic surgery in the treatment of empyema has been demonstrated but has not been well defined. Furthermore, it has not been determined how to choose patients who can be treated with thoracoscopy versus thoracotomy. We report the results of a strategy in which all patients were initially approached with thoracoscopy and converted to open decortication only if the lung could not be inflated to fill the chest. METHODS: A total of 172 patients underwent decortication for empyema over a 5-year period. Thoracoscopic decortication was attempted in all patients; patients were converted to open decortication if access to the pleural space was not possible, or if the lung could not be mobilized sufficiently to reach both the chest wall and the diaphragm. Proportions were compared using the chi(2) test. RESULTS: Of the 172 patients, 66 successfully underwent decortication with thoracoscopic techniques only. The remaining 106 patients required complete thoracotomy. No difference was found in the reoperation rate; 3 of 106 open thoracotomy patients underwent reexploration for recurrent empyema, whereas two of 66 thoracoscopy patients required reoperation for hemothorax (p = 0.347). There was a tendency for thoracoscopic patients to require reoperation for bleeding (p = 0.08); both patients taken back to the operation room for bleeding had undergone thoracoscopic pleurectomy. Eleven of 166 patients (all explored with open thoracotomy) died after decortication, for a mortality rate of 6.6%. All of these patients had gone to surgery from the intensive care unit. CONCLUSIONS: Using the criteria of complete expansion of the lung surface to the chest wall and diaphragm allowed accurate selection of patients who could undergo complete thoracoscopic decortication without risk of recurrent empyema. Computed tomographic scans did not help to predict which patients would require open procedures. Thoracoscopic patients were more likely to require reoperation for bleeding if thoracoscopic pleurectomy was performed.

Bilateral diaphragmatic agenesis in an adult complicated by a paraduodenal hernia.

Diaphragmatic agenesis is an extremely rare clinical entity and has only been reported five previous times in the English literature. We report a patient with bilateral diaphragmatic agenesis complicated by a paraduodenal hernia. Diaphragmatic agenesis is rarely diagnosed preoperatively. Most diagnoses will likely be made during exploration for suspected bowel obstruction or other gastrointestinal emergency. When they are found repair seems warranted if contamination from associated procedures such as bowel resection is minimal. Repair of diaphragmatic agenesis can be approached much like the creation of a neodiaphragm after diaphragmatic resection. The diagnosis of paraduodenal hernia can usually be confirmed radiologically. Many cases of paraduodenal hernias have been reported and repair is uniformly recommended.

A modified bronchial anastomosis technique for lung transplantation.

BACKGROUND: Low rates of major complications have been reported for the intussuscepting bronchial anastomotic technique but stenosis, malacia, and granulation tissue at the anastomosis may cause clinically important morbidity. We hypothesized that a modification of the telescoping technique that improves bronchial wall apposition might be associated with improved bronchial healing and clinical outcomes. METHODS: The telescoping horizontal mattress "U-stitch" suture technique was modified to incorporate figure-of-eight sutures placed in the cartilaginous wall between each of three intussuscepting U stitches. Serial videotape records of 152 individual anastomoses (99 modified, 53 telescoped) in 118 consecutive operative survivors were retrospectively reviewed by examiners blinded with respect to technique used. Stenosis, airway instability, mucosa quality, and devascularized luminal tissue were graded at 4 to 14 days (initial), 4 to 12 weeks (early), and 6 to 12 months (late) after transplantation. RESULTS: The incidence of anastomotic stenosis was significantly lower using the modified technique at the initial (p = 0.025) and late (p = 0.015) observations. In the initial phase airway instability (p = 0.015) and devascularization grades (p = 0.001) were also significant lower in the modified group. There were no significant differences in mucosal condition between techniques. The modified telescoping technique was associated with significant survival advantage (mean 17.7%; p = 0.029) by multivariate analysis. The incidence of major airway complications (dehiscences and stenoses required stents) tended to be lower (3% versus 6%) in the modified group. CONCLUSIONS: The modified telescoping bronchial anastomosis technique is associated with improved early and late bronchial healing and higher 5-year survival without increased major airway complications.