Vascular Ultrasonography: A Novel Method to Reduce Paracentesis Related Major Bleeding.

Paracentesis is a core competency for hospitalists. Using ultrasound for fluid localization is standard practice and involves a low-frequency probe. Experts recommend a "2-probe technique, " which incorporates a high-frequency ultrasound probe in addition to the low-frequency probe to identify blood vessels within the intended needle path. Evidence is currently lacking to support this 2-probe technique, so we performed a pre- to postintervention study to evaluate its effect on paracentesis-related bleeding complications. From February 2010 to August 2011, procedures were performed using only low-frequency probes (preintervention group), while the 2-probe technique was used from September 2011 to February 2016 (postintervention group). A total of 5777 procedures were performed. Paracentesis-related minor bleeding was similar between groups. Major bleeding was lower in the postintervention group (3 [0.3%], n = 1000 vs 4 [0.08%], n = 4777; P = 0.07). This clinically meaningful trend suggests that using the 2-probe technique might prevent paracentesis-related major bleeding.

Effect of Thoracentesis on Intubated Patients with Acute Lung Injury.

Pleural effusions occur frequently in mechanically ventilated patients, but no consensus exists regarding the clinical benefit of effusion drainage. We sought to determine the impact of thoracentesis on gas exchange in patients with differing severities of acute lung injury (ALI). A retrospective analysis was conducted on therapeutic thoracenteses performed on intubated patients in an adult surgical intensive care unit of a tertiary center. Effusions judged by ultrasound to be 400 mL or larger were drained. Subjects were divided into groups based on their initial P:F ratios: normal >300, ALI 200 to 300, and acute respiratory distress syndrome (ARDS) <200. Baseline characteristics, physiologic variables, arterial blood gases, and ventilator settings before and after the intervention were analyzed. The primary end point was the change in measures of oxygenation. Significant improvements in P:F ratios (mean ± SD) were seen only in patients with ARDS (50.4 ± 38.5, P = 0.001) and ALI (90.6 ± 161.7, P = 0.022). Statistically significant improvement was observed in the pO2 (31.1, P = 0.005) and O2 saturation (4.1, P < 0.001) of the ARDS group. The volume of effusion removed did not correlate with changes in individual patient's oxygenation. These data support the role of therapeutic thoracentesis for intubated patients with abnormal P:F ratios.

Thoracentesis outcomes: a 12-year experience.

BACKGROUND: Despite a lack of evidence in the literature, several assumptions exist about the safety of thoracentesis in clinical guidelines and practice patterns. We aimed to evaluate specific demographic and clinical factors that have been commonly associated with complications such as iatrogenic pneumothorax, re-expansion pulmonary oedema (REPE) and bleeding. METHODS: We performed a cohort study of inpatients who underwent thoracenteses at Cedars-Sinai Medical Center (CSMC) from August 2001 to October 2013. Data were collected prospectively including information on volume of fluid removed, procedure side, whether the patient was on positive pressure ventilation, number of needle passes and supine positioning. Iatrogenic pneumothorax, REPE and bleeding were tracked for 24 h after the procedure or until a clinical question was reconciled. Demographic and clinical characteristics were obtained through query of electronic medical records. RESULTS: CSMC performed 9320 inpatient thoracenteses on 4618 patients during the study period. There were 57 (0.61%) iatrogenic pneumothoraces, 10 (0.01%) incidents of REPE and 17 (0.18%) bleeding episodes. Iatrogenic pneumothorax was significantly associated with removal of >1500 mL fluid (p<0.0001), unilateral procedures (p=0.001) and more than one needle pass through the skin (p=0.001). For every 1 mL of fluid removed there was a 0.18% increased risk of REPE (95% CI 0.09% to 0.26%). There were no significant associations between bleeding and demographic or clinical variables including International Normalised Ratio, partial thromboplastin time and platelet counts. CONCLUSIONS: Our series of thoracenteses had a very low complication rate. Current clinical guidelines and practice patterns may not reflect evidence-based best practices.

Retinal pathology detected by optical coherence tomography in an animal model of Parkinson's disease.

BACKGROUND: Optical coherence tomography (OCT) is a noninvasive procedure for analysis of retinal morphology. Significant changes in the thickness of the peripapillary retinal nerve fiber layer (RNFL) in Parkinson's disease (PD) have been reported, and the current study was performed to examine whether such changes can also be detected in an animal model of PD. METHODS: Optical coherence tomography measurements of peripapillary RNFL thickness, macula volume, and foveal thickness were obtained from 10 normal and five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys with stable Parkinsonian signs. RESULTS: Average RNFL thickness was significantly decreased in Parkinsonian monkeys compared with controls, with statistically significant RNFL thinning found in nasal and inferior quadrants. Macula volume and foveal thickness were also significantly reduced in Parkinsonian animals compared with controls. CONCLUSIONS: As described in PD, RNFL thinning, reduced macula volume, and reduced foveal thickness also occurs in monkeys with MPTP-induced Parkinsonism. These findings pave the way for additional studies in which OCT may be used to track changes in the retina that might be present very early in the PD pathological process, perhaps preceding the onset of motor signs.

Substituted thieno[2,3-d]pyrimidines as adenosine A2A receptor antagonists.

A novel series of benzyl substituted thieno[2,3-d]pyrimidines were identified as potent A2A receptor antagonists. Several five- and six-membered heterocyclic replacements for the optimized methylfuran were explored. Select compounds effectively reverse catalepsy in mice when dosed orally.

Design and characterization of optimized adenosine A2A/A1 receptor antagonists for the treatment of Parkinson's disease.

The design and characterization of two, dual adenosine A(2A)/A(1) receptor antagonists in several animal models of Parkinson's disease is described. Compound 1 was previously reported as a potential treatment for Parkinson's disease. Further characterization of 1 revealed that it was metabolized to reactive intermediates that caused the genotoxicity of 1 in the Ames and mouse lymphoma L51784 assays. The identification of the metabolites enabled the preparation of two optimized compounds 13 and 14 that were devoid of the metabolic liabilities associated with 1. Compounds 13 and 14 are potent dual A(2A)/A(1) receptor antagonists that have excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse and rat models of reserpine-induced akinesia, and the rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation.

Portable ultrasound: the next generation arrives.

PURPOSE: A new category of handheld devices has recently emerged that are even smaller than current portable models, with their main advantages being increased portability and affordability relative to their counterparts. However, these new devices have not yet been thoroughly evaluated in the clinical setting. METHODS: A prospective, non-blinded, three-phase study was designed to evaluate a handheld ultrasound device as compared to a common compact ultrasound machine for the performance of paracenteses and thoracenteses on human patients. RESULTS: For the vast majority of straight-forward evaluations, the handheld device was sufficient to safely complete the procedure without further imaging. For difficult cases with smaller fluid collections or anatomic aberrations, further localization with the common compact machine continued to be useful to improve the operator's confidence in the findings. CONCLUSION: This novice handheld device represents only one of what appears to be a growing number of new ultra-portable ultrasound devices on the market. These devices represent a new and exciting form of ultrasound technology that may benefit patients and physicians in multiple venues. While they are unlikely to replace standard ultrasound devices for many of the more complex applications, their extreme portability allows for ultrasound imaging in more diverse situations that has previously been practical. Based on our limited experience, the image quality is adequate and the learning curve is reasonable. Future integration of PDA technology could further the utility of these devices and additional study will be important to further define their appropriate niche and clinical utility.

Optimization of arylindenopyrimidines as potent adenosine A(2A)/A(1) antagonists.

Two reactive metabolites were identified in vivo for the dual A(2A)/A(1) receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro and in vivo activity.