Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

Continuous transversus abdominis plane block catheter analgesia for postoperative pain control in renal transplant.

PURPOSE: Continuous transversus abdominis plane (TAP) block using a catheter has proven its usefulness in reducing opioid requirements and pain scores after lower abdominal surgery. However, there are no reports of its successful use after renal transplant. We tested the hypothesis that continuous TAP block would retrospectively reduce opioid requirement, nausea score and hospital stay after renal transplant surgery. METHODS: In a retrospective study, we reviewed the data from 63 adult renal transplant recipients-31 with patient-controlled TAP analgesia with standing orders for intravenous as well as oral opioids as needed and 32 with intravenous patient-controlled analgesia. The TAP catheter was inserted preoperatively using an ultrasound-guided technique. Infusion of ropivacaine 0.2 % at 8 ml basal, 12 ml bolus and a lockout interval of 60 min were maintained for 48 h postoperatively. The primary outcome was total morphine-equivalent dose during the 48-h postoperative period. Secondary outcomes were pain and nausea scores for the 48-h postoperative period. RESULTS: The mean 48-h postoperative morphine-equivalent doses [95 % confidence interval] for patient-controlled intravenous analgesia and TAP catheter were 197 [111, 349] and 50 [28, 90], respectively, which were significantly different (P = 0.002). The mean 48-h average verbal response pain scores were 2.94 [2.39, 3.50] and 2.49 [1.93, 3.06], respectively, which were not significantly different (P = 0.26). The mean nausea scores were 0.66 [0.46, 0.87] and 0.60 [0.40, 0.81], respectively, which were not significantly different (P = 0.69). There was no difference regarding hospital stay. CONCLUSION: The use of continuous TAP analgesia for postoperative analgesia after renal transplant was effective in reducing the morphine-equivalent requirements.

Practical recommendations on incorporating new oral anticoagulants into routine practice.

The use of new oral anticoagulants (NOACs) is expected to rise significantly in upcoming years. Therefore, it is important to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages over warfarin, including a rapid onset and offset of action, fewer drug interactions, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their ease of administration and the advantage of eliminating the requirement for regular coagulation monitoring. NOACs work to prevent and treat thrombosis by targeting either thrombin (as with dabigatran) or factor Xa (as with rivaroxaban and apixaban). In this review, we discuss practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.

Exploration of C-H and N-H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines.

The synthesis of 1,2,3-trisubstituted indoles was investigated. More specifically, straightforward synthetic routes towards 1-(1,2-diarylindol-3-yl)-N-PG-THIQs (PG = protecting group, THIQ = tetrahydroisoquinoline) employing transition metal-catalyzed C-H and N-H-bond functionalization were explored. It was found that the synthesis of the target compounds is strongly dependent on the order of events. Hence, depending on the requirements of a synthetic problem the most suitable and promising pathway can be chosen. Additionally, a new synthetic approach towards 1,2-diarylindoles starting from 1-arylindole could be established in the course of our investigation by using a palladium-catalyzed protocol. Such 1,2-diarylindoles were successfully reacted with N-Boc-THIQ to furnish 1,2,3-trisubstituted indoles as target compounds. Furthermore, regioselective N-arylation of protected and unprotected 1-(indol-3-yl)-THIQs was successfully conducted using either simple iron or copper salts as catalysts.

Effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery.

BACKGROUND: The authors tested the primary hypothesis that perioperative IV lidocaine administration during spine surgery (and in the postanesthesia care unit for no more than 8 h) decreases pain and/or opioid requirements in the initial 48 postoperative hours. Secondary outcomes included major complications, postoperative nausea and vomiting, duration of hospitalization, and quality of life. METHODS: One hundred sixteen adults having complex spine surgery were randomly assigned to perioperative IV lidocaine (2 mg·kg·h) or placebo during surgery and in the postanesthesia care unit. Pain was evaluated with a verbal response scale. Quality of life at 1 and 3 months was assessed using the Acute Short-form (SF) 12 health survey. The authors initially evaluated multivariable bidirectional noninferiority on both outcomes; superiority on either outcome was then evaluated only if noninferiority was established. RESULTS: Lidocaine was significantly superior to placebo on mean verbal response scale pain scores (P < 0.001; adjusted mean [95% CI] of 4.4 [4.2-4.7] and 5.3 [5.0-5.5] points, respectively) and significantly noninferior on mean morphine equivalent dosage (P = 0.011; 55 [36-84] and 74 [49-111] mg, respectively). Postoperative nausea and vomiting and the duration of hospitalization did not differ significantly. Patients given lidocaine had slightly fewer 30-day complications than patients given placebo (odds ratio [95% CI] of 0.91 [0.84-1.00]; P = 0.049). Patients given lidocaine had significantly greater SF-12 physical composite scores than placebo at 1 (38 [31-47] vs. 33 [27-42]; P = 0.002) and 3 (39 [31-49] vs. 34 [28-44]; P = 0.04) months, postoperatively. CONCLUSION: IV lidocaine significantly improves postoperative pain after complex spine surgery.

Direct functionalization of (un)protected tetrahydroisoquinoline and isochroman under iron and copper catalysis: two metals, two mechanisms.

A highly facile, straightforward synthesis of 1-(3-indolyl)-tetrahydroisoquinolines was developed using either simple copper or iron catalysts. N-protected and unprotected tetrahydroisoquinolines (THIQ) could be used as starting materials. Extension of the substrate scope of the pronucleophile from indoles to pyrroles and electron-rich arenes was realized. Additionally, methoxyphenylation is not limited to THIQ but can be carried out on isochroman as well, again employing iron and copper catalysis.

Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping).

OBJECTIVES: The aim of this report is to describe the lung biopsy findings in vaping-associated pulmonary illness. METHODS: Lung biopsies from eight patients with vaping-associated pulmonary illness were reviewed. RESULTS: The biopsies were from eight men (aged 19-61 years) with respiratory symptoms following e-cigarette use (vaping). Workup for infection was negative in all cases, and there was no evidence for other etiologies. Imaging showed diffuse bilateral ground-glass opacities in all patients. Most recovered with corticosteroid therapy, while one died. Lung biopsies (seven transbronchial, one surgical) showed acute lung injury, including organizing pneumonia and/or diffuse alveolar damage. Common features were fibroblast plugs, hyaline membranes, fibrinous exudates, type 2 pneumocyte hyperplasia, and interstitial organization. Some cases featured a sparse interstitial chronic inflammatory infiltrate. Although macrophages were present within the airspaces in all cases, this feature was not prominent, and findings typical of exogenous lipoid pneumonia were absent. CONCLUSIONS: The histopathology of acute pulmonary illness related to e-cigarette use (vaping) is characterized by acute lung injury patterns, supporting the contention that vaping can cause severe lung damage.

An efficient, one-pot synthesis of various ceramide 1-phosphates from sphingosine 1-phosphate.

An efficient, one-pot procedure for the synthesis of ceramide 1-phosphates with varying N-acyl substituents, to serve as tool compounds for analytical and biological investigations, was developed. Sphingosine 1-phosphate was silylated in situ to increase its solubility and to protect the 3-hydroxy functionality and then allowed to react with activated acid derivatives in the presence of diisopropylethylamine. Simultaneous cleavage of the silyl protecting groups and separation from reagents and by-products was achieved by medium pressure chromatography on reversed phase material. Thus, ceramide 1-phosphates with various fatty acid chains and with fluorescent and affinity labels attached to the sphingoid backbone were prepared in good yields.

Models to Estimate the Probability of Malignancy in Patients with Pulmonary Nodules.

Pulmonary nodules are a common clinical problem. The goals of their evaluation are to expedite the diagnosis and treatment of patients with malignant nodules and to minimize testing in patients with benign nodules. The approach to lung nodule evaluation is directed by the probability that the nodule is malignant. Estimation of the probability of malignancy can be performed subjectively with intuition and clinical experience or by using validated probability models that combine patient clinical characteristics with nodule imaging features to estimate a probability of malignancy. The accuracy and the generalizability of probability models depend on the clinical profile and the prevalence of malignancy in the population in which they were derived. In this article, we review available validated models to estimate the probability of malignancy in patients with pulmonary nodules and outline how they were derived, their limitations, and how they compare with each other and physician judgment. We conclude with a brief discussion of advances in probability models.

The Effects of Dexmedetomidine and Remifentanil on Hemodynamic Stability and Analgesic Requirement After Craniotomy: A Randomized Controlled Trial.

BACKGROUND: Anesthesia for craniotomies should blunt responses to noxious stimuli, whereas subsequently leaving patients sufficiently alert for early neurological evaluation. The aim was to compare postoperative blood pressure control, pain, and opioid requirement after anesthesia with dexmedetomidine versus remifentanil. We therefore tested 2 primary hypotheses: (1) intraoperative administration of dexmedetomidine provides better control of postoperative blood pressure than remifentanil; and (2) patients given dexmedetomidine have less postoperative pain and use less opioid. MATERIALS AND METHODS: Adults having elective brain tumor excisions under balanced general anesthesia with endotracheal intubation were randomized to an infusion of remifentanil (0.08 to 0.15 µg/kg/min, n=71) or dexmedetomidine (0.2 to 0.7 µg/kg/h, n=68). Patients also received propofol, rocuronium, fentanyl, and sevoflurane. The mean arterial pressure (MAP) and pain were recorded at 15, 30, 45, 60, and 90 postoperative minutes. Outcomes were assessed with joint hypothesis testing, evaluating noninferiority and superiority. RESULTS: Compared with remifentanil, the use of dexmedetomidine was associated with reduced postoperative MAP (88±12 vs. 98±11 mm Hg), with estimated mean difference (97.5% confidence interval) of -10 (-13, -4) mm Hg, P<0.001, and mean visual analog pain score (2.9±2.6 vs. 5.1±2.4 points), with estimated mean difference of -5 (-10, -3) points, P<0.001, and required less median opioid consumption (5 [0, 10] vs. 10 [7, 15] mg morphine equivalents), with estimated median difference of -5 (-10, -3) mg, P<0.001. Dexmedetomidine was both noninferior and superior to remifentanil in maintaining postoperative hemodynamics and providing improved pain control. CONCLUSIONS: Intraoperative dexmedetomidine better controlled postoperative MAP and provided superior analgesia in patients undergoing craniotomy.

Common Congenital Anomalies of the Central Airways in Adults.

The knowledge of airway anatomy is the most fundamental requirement of every bronchoscopist. There are numerous and frequent anatomic variations of the central airways making the examination unique for every individual. It is imperative for every bronchoscopist to be fully cognizant of the common congenital anomalies involving the central airways. Proper identification and reporting of these findings are a matter of the utmost importance, especially when surgical options in a patient with lung cancer or lung transplantation is under consideration. This article focuses on the congenital anomalies of central airway encountered among adults. Each of these anatomic variations has a characteristic appearance, yet requires bronchoscopic acumen for their identification. This review provides a comprehensive description of these anomalies and highlights their clinical implications.

Blood Type O is not associated with increased blood loss in extensive spine surgery.

STUDY OBJECTIVE: To investigate whether Type O blood group status is associated with increased intraoperative blood loss and requirement of blood transfusion in extensive spine surgery. DESIGN: Retrospective comparative study. SETTING: University-affiliated, non-profit teaching hospital. MEASUREMENTS: Data from 1,050 ASA physical status 1, 2, 3, 4, and 5 patients who underwent spine surgeries involving 4 or more vertebral levels were analyzed. Patients with Type O blood were matched to similar patients with other blood types using propensity scores, which were estimated via demographic and morphometric data, medical history variables, and extent of surgery. Intraoperative estimated blood loss (EBL) was compared among matched patients using a linear regression model; intraoperative transfusion requirement in volume of red blood cells, fresh frozen plasma, platelet, cryoprecipitate, cell salvaged blood, volume of intraoperative infusion of hetastarch, 5% albumin, crystalloids, and hospital length of hospital (LOS) were compared using Wilcoxon rank-sum tests. MAIN RESULTS: Intraoperative EBL and requirement of blood product transfusion were similar in patients with Type O blood group and those with other blood groups. CONCLUSION: There was no association between Type O blood and increased intraoperative blood loss or blood transfusion requirement during extensive spine surgery, with similar hospital LOS in Type O and non-O patients.

Facile, solvent and ligand free iron catalyzed direct functionalization of N-protected tetrahydroisoquinolines and isochroman.

An efficient method for an iron catalyzed oxidative indolation and methoxyphenylation of N-protected tetrahydroisoquinolines and isochroman is described including subsequent facile deprotection.

Synthesis and immobilization of erythro-C14-omega-aminosphingosine-1-phosphate as a potential tool for affinity chromatography.

A sphingosine-1-phosphate (S1P) analogue containing a terminal alkyl chain amino group is synthesized in a few steps via olefin cross-metathesis of an optically resolved intermediate and subsequent phosphorylation. Regioselective acylation of this intermediate at its N terminus in solution is demonstrated as a model reaction and provides a biologically active derivative. Finally, the omega-amino intermediate is immobilized on an affinity matrix. The choice of a UV-active phosphate protecting group allows for quantification of resin loading after cleavage which amounted to 66 %.

Synthesis of borondipyrromethene (BODIPY)-labeled sphingosine derivatives by cross-metathesis reaction.

A new efficient and flexible synthesis of fluorescently labeled sphingosine derivatives from commercially available Garner aldehyde (8) is described. For this, appropriate alkenylated borondipyrromethene (BODIPY) dyes were synthesized and used for the first time in a cross-metathesis reaction, the key step of the approach. The labeled sphingosines with appropriate chain length were accepted as substrates by sphingosine kinases (SPHKs), yielding the corresponding phosphorylated products. One of these derivatives (11d) was identified as the first reported selective substrate for SPHK-1.