Evidence-based opioid prescribing guidelines after lung resection: a prospective, multicenter analysis.

Background: Opioid prescribing guidelines have significantly decreased overprescribing and post-discharge use after cardiac surgery; however, limited recommendations exist for general thoracic surgery patients, a similarly high-risk population. We examined opioid prescribing and patient-reported use to develop evidence-based, opioid prescribing guidelines after lung cancer resection. Methods: This prospective, statewide, quality improvement study was conducted between January 2020 to March 2021 and included patients undergoing surgical resection of a primary lung cancer across 11 institutions. Patient-reported outcomes at 1-month follow-up were linked with clinical data and Society of Thoracic Surgery (STS) database records to characterize prescribing patterns and post-discharge use. The primary outcome was quantity of opioid used after discharge; secondary outcomes included quantity of opioid prescribed at discharge and patient-reported pain scores. Opioid quantities are reported in number of 5-mg oxycodone tablets (mean ± standard deviation). Results: Of the 602 patients identified, 429 met inclusion criteria. Questionnaire response rate was 65.0%. At discharge, 83.4% of patients were provided a prescription for opioids of mean size 20.5±13.1 pills, while patients reported using 8.2±13.0 pills after discharge (P<0.001), including 43.7% who used none. Those not taking opioids on the calendar day prior to discharge (32.4%) used fewer pills (4.4±8.1 vs. 11.7±14.9, P<0.001). Refill rate was 21.5% for patients provided a prescription at discharge, while 12.5% of patients not prescribed opioids at discharge required a new prescription before follow-up. Pain scores were 2.4±2.5 for incision site and 3.0±2.8 for overall pain (scale 0-10). Conclusions: Patient-reported post-discharge opioid use, surgical approach, and in-hospital opioid use before discharge should be used to inform prescribing recommendations after lung resection.

Treatment of locally advanced parotid malignancies with parotidectomy and temporal bone resection.

PURPOSE: In this study we review our institution's experience and outcomes with temporal bone resection and parotidectomy in the treatment of advanced parotid malignancies. METHODS: Patients undergoing lateral temporal bone resection and parotidectomy from 2007-2013 were identified in the EPIC electronic medical record. Primary tumor location, staging, surgical procedure, and patient demographic and outcome data were collected retrospectively. RESULTS: Fifteen patients underwent combined temporal bone resection and parotidectomy for parotid malignancy. Carcinoma ex-pleomorphic and squamous cell carcinoma were the most common pathologies. Two year disease free survival was 40%. Distant metastases were the most common site of disease recurrence. Only nodal disease was predictive of reduced disease free survival, though pre-operative facial paralysis showed a trend towards significance. Margin status and operating for recurrent tumor did not influence outcome in our series. CONCLUSION: Local and regional tumor controls are attainable with combined skull base approaches to advanced parotid malignancies. Unfortunately these cases have a high rate of distant recurrence despite negative margins and local control.

Mucormycosis Causing Ludwig Angina: A Unique Presentation.

Mucormycosis is a rare fungal infection with a yearly incidence of 1.7 cases per million in the United States. It usually occurs in patients with metabolic abnormalities or who are immunocompromised with prolonged neutropenia. However, it can also occur in patients without any underlying disease process. The treatment of choice is surgical debridement of necrotic tissue and systemic antifungal therapy, including amphotericin B. A dilemma for the surgeon when faced with head and neck mucormycosis is the morbidity of surgical debridement from both a functional and cosmetic standpoint. There have been multiple case reports of a form of cutaneous mucormycosis in the head and neck involving the oral mucosa and the mandible, but no reports in the literature of a fungal infection causing Ludwig angina. This report describes one such case. The morbid clinical implications of mucormycosis causing Ludwig angina become apparent when considering the defect caused by adequate surgical debridement.

Impact of Ultrafiltration on Kidney Injury After Cardiac Surgery: The Michigan Experience.

BACKGROUND: This study examines the relationship between the use and volume of conventional ultrafiltration (CUF) and the risk of acute kidney injury (AKI) after isolated on-pump coronary artery bypass graft surgery. METHODS: A total of 6,407 consecutive patients underwent isolated on-pump coronary artery bypass graft surgery between 2010 and 2013 at 21 medical centers participating in the PERFusion Measures and Outcomes (PERForm) registry. We assessed the effect of CUF use on AKI and other postoperative sequelae using a generalized linear mixed-effect model with a logit link. We also modeled the effect of increasing volume of CUF per weight on AKI, and tested for any modification by a patient's preoperative kidney function. RESULTS: Patients having CUF were more likely to have diabetes, vascular disease, chronic obstructive pulmonary disease, congestive heart failure, history of a myocardial infarction, or an intraaortic balloon pump (p < 0.05). They had lower preoperative and nadir hematocrits, creatinine clearance, and ejection fraction (p < 0.05). Patients exposed to CUF had higher adjusted risk of AKI (adjusted odds ratio, 1.36; p = 0.002), although similar rates of death, stroke, and reoperation for bleeding (p > 0.05). The risk of AKI was modified by a patient's preoperative kidney function (p < 0.0004). Among patients with a creatinine clearance of less than 99.6 mL/min (95% confidence interval, 67.6 to 137.5), increasing volume of CUF was associated with a higher risk of AKI. CONCLUSIONS: Patients exposed to CUF had a higher adjusted risk of AKI. Clinical teams should consider lower volumes of CUF among patients with low creatinine clearance to minimize the risk of AKI.

Rare and Other Notable Complications in Endoscopic Sinus Surgery.

This article focuses on the rare and obscure complications of endoscopic sinus surgery. The majority of surgeons will not encounter these complications in their practice, but should be aware of their possibility. With knowledge of these rare complications, the surgeon can understand the possible avoidance as well as urgent management of these problems.

Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses.

OBJECTIVE: Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, then treatment involves only nonspecific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar after disparate infections with similar mortalities. DESIGN: Prospective, randomized controlled study. SETTING: Animal laboratory in a university medical center. INTERVENTIONS: Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple time points. MEASUREMENTS AND MAIN RESULTS: The host response was dependent on the causative organism as well as kinetics of mortality, but the pro-inflammatory and anti-inflammatory responses were independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of five distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary macrophage inflammatory peptide-2 and interleukin-10 with progression of infection, whereas elevated plasma tumor necrosis factor sr2 and macrophage chemotactic peptide-1 were indicative of fulminant disease with >90% mortality within 48 hrs. CONCLUSIONS: Septic mice have distinct local and systemic responses to Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses induced by distinct bacterial infections could represent a potential therapeutic approach in the treatment of sepsis.

Discovery of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine scaffold as a novel, potent and selective GABA(A) alpha5 inverse agonist series.

Through iterative design cycles we have discovered a number of novel new classes where the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine was deemed the most promising GABA(A) alpha5 inverse agonist class with potential for cognitive enhancement. This class combines a modest subtype binding selectivity with inverse agonism and has the most favourable molecular properties for further lead optimisation towards a central nervous system (CNS) acting medicine.

Effects of the novel 5-HT(6) receptor antagonist RO4368554 in rat models for cognition and sensorimotor gating.

Serotonin(6) (5-HT(6)) receptors are almost exclusively located in the central nervous system. High expression in the hippocampus, nucleus accumbens and striatum is consistent with a potential role in cognition and psychosis. The availability of potent, selective and brain-penetrating 5-HT(6) antagonists such as RO4368554 allows further characterization of the role of the 5-HT(6) receptor in these processes. Herein, we tested RO4368554 in several cognition tasks, as well as sensorimotor gating tests. Using scopolamine-impaired and unimpaired adult male rats, RO4368554 was given in novel object discrimination, social recognition, social discrimination, Morris water maze, passive avoidance and autoshaping procedures. RO4368554 reversed the effects of scopolamine in novel object discrimination (active doses in mg/kg, i.p., 3, 10), social recognition (3, 10), social discrimination (1, 3, 10) and passive avoidance (10, 30 i.p. and 100 p.o.) tasks. In unimpaired rats, RO4368554 enhanced object discrimination (3, 10; 4-h forgetting interval) and autoshaping learning (3), but was inactive in a water maze task (doses tested: 1-10 mg/kg, i.p.). In tests sensitive to antipsychotics, RO4368554 did not reverse sensorimotor gating deficits induced by the psychostimulants dizocilpine and amphetamine (doses tested: 1-30 mg/kg, i.p.) or neonatal lesion of the ventral hippocampus (1-10 mg/kg, i.p.). In conclusion, RO4368554 enhanced learning and memory processes in unimpaired and scopolamine-impaired rats, supporting the notion that the cognitive enhancing effects of 5-HT(6) receptor antagonists involve modulation of cholinergic neurotransmission.

Right atrial papillary elastoma: an uncommon location.

We present a patient with a right atrial mass, which was detected by transthoracic and transesophageal echocardiography. The patient was asymptomatic on presentation. The mass was subsequently confirmed by gross and microscopic examination to be a papillary fibroelastoma. To the best of our knowledge this is only the fourth such report of this tumor in this location.

Influence of the 5-HT6 receptor on acetylcholine release in the cortex: pharmacological characterization of 4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine, a potent and selective 5-HT6 receptor antagonist.

A small series of aryl pyridyl sulfones has been prepared and investigated for its 5-HT(6) receptor binding properties. Thereof, pyrrolidinyl derivative 11 proved to be a very potent (pK(i) 9) and selective 5-HT(6) receptor antagonist. By means of in vivo microdialysis in the frontal cortex and a passive avoidance paradigm, where 11 reversed a scopolamine induced retention deficit, a functional correlation between 5-HT(6) receptors and cholinergic neurotransmission could be shown, supporting the therapeutic potential of 5-HT(6) receptors in the treatment of cognitive deficits.

Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety.

The 5-HT2C antagonist SB-242084 was examined in various anxiety tests at doses based on reversal of mCPP-induced hypoactivity (0.1--3 mg/kg ip). In the elevated plus-maze task, SB-242084 exhibited signs of anxiolysis (time spent, distance travelled, and entries into open arms), but this was potentially confounded by its general increase of locomotion; alprazolam selectively affected open-arm parameters. In a Geller--Seifter conflict test, SB-242084 produced a modest, nonsignificant increase in punished responding compared to the significant effect produced by diazepam. None of the treatments significantly affected unpunished responding. In the conditioned emotional response (CER) test, SB-242084 produced an increase in the suppression ratio (SR, smaller than diazepam). Since this 5-HT2C antagonist also increased lever pressing, an additional test was conducted with amphetamine that stimulated lever pressing but, nonetheless, failed to produce any change in SR. In the fear-potentiated startle task, SB-242084 was inactive in comparison to a significant effect of diazepam. The previously described reduction of schedule-induced polydipsia by fluoxetine and 5-HT2C receptor agonist Ro60-0175 was attenuated by SB-242084 pretreatment, however, the latter compound exhibited a potent increase in polydipsia when given alone. The present results demonstrate an anxiolytic potential of SB-242084, as well as an intrinsic response-enhancing property, however, both of these effects are task dependent.

Considerations of local soil conditions for building siting

Depending upon the area seismicity, site conditions and the nature of the proposed construction a geotechnical site investigation may be necessary to alow adequate definition of seismic hazard and related structure design criteria, In any event, the structural engineer and the geotechnical engineer must effectively cooperate in order to ensure that the building code provisions are adequately extended to effectively address existing geological hazard abd potential for aggravated soil amplification of ground motion or ground failure. This paper provides a summary description of two of the problems introduced by the geotechnical site conditions (liquefaction and resonance) and presents evaluations methods. It is important that the structural engineer realize the importance of the local site conditions on the structural response (AU)