Louis A. Johnson VA Medical Center

BACKGROUND: The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. RESULTS: During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS: Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia.

IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.

Obesity is considered a risk factor for many cancers, including breast cancer. Our laboratory has previously shown that leptin is mitogenic in many cancer cell lines, including breast. Information regarding the effects of high leptin levels on leptin receptor expression and signaling is lacking. The purpose of this study was to characterize leptin receptor expression in response to leptin in breast cancer cells. In addition, SOCS-3 expression (a leptin inducible inhibitor of leptin signaling), plus MAPK and PI3K signaling, were examined to determine their role in leptin-induced cell proliferation. Breast cancer cell lines, ZR75-1 and HTB-26, were treated with 0, 4, 40 or 80 ng/ml of leptin. Multiplex RT-PCR was performed to determine relative mRNA expression levels of the human short (huOB-Ra) or long (huOB-Rb) leptin receptor isoforms, or SOCS-3. MAPK and PI3K signaling was analyzed by phosphorylation of ERK and Akt, respectively, via Western blotting. Cell proliferation and inhibitor studies were analyzed by MTT assay. HTB-26 and ZR75-1 both expressed huOB-Ra, huOB-Rb and SOCS-3 mRNA; however, mRNA expression levels generally remained unchanged over time with leptin treatment. MAPK and PI3K pathways were activated in the presence of leptin over time. MAPK and PI3K inhibitors significantly blocked leptin-induced proliferation. Higher levels of circulating leptin contribute to breast cancer proliferation by activation of the MAPK and PI3K signaling pathways involved in cell growth and survival. The mitogenic effects of leptin are not a consequence of altered leptin receptor or SOCS-3 mRNA expression.

Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (i.e., Ta, Tl, and carcinoma in situ) with specific objectives which include treating existing/residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival irrespective of the treatment. Presently, bacillus Calmette-Guerin (BCG) immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, Tl, CIS) and has positive outcomes on tumor recurrence rate, disease progression, and prolongation of survival. Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with BCG intravesical immunotherapy-it has demonstrated a reduction in tumor recurrence rates, but has had no positive impact on disease progression or prolongation of survival. Interferons, keyhole-limpet hemocyanin (KLH), bropirimine, and PHOTOFRIN-photodynamic therapy (PDT) are under investigation in the management of TCC and early results are encouraging. This comprehensive review highlights recent developments in intravesical therapy of bladder cancer and summarizes the mechanisms of action of BCG, and the important role of intravesical BCG immunotherapy and other immunotherapeutic agents in the therapy and prophylaxis of superficial TCC of the urinary bladder.

Transbronchial needle aspiration (TBNA) is a technique in which a cytology or histology specimen is obtained during flexible bronchoscopy from beyond the confines of the endobronchial tree. Mediastinal staging of lung cancer is the most common indication for TBNA. The procedure is also useful in diagnosis of sarcoidosis and tuberculosis as the cause of mediastinal lymph node enlargement. The procedure is performed under conscious sedation and does not need expensive guiding or tracking devices. The procedure is cost-effective, is easy to learn, and has an excellent safety record. Unfortunately, many bronchoscopists never adopted this technique in their practice due to lack of training and widespread misconceptions about the usefulness and safety issues. Endobronchial needle aspiration (EBNA) is a related technique in which the 22-gauge needle is used to obtain cytology specimen from endoscopically visible lesion. EBNA increases the diagnostic yield from submucosal and peribronchial lung tumors. Peripheral TBNA (P-TBNA) is a technique in which a ­cytology specimen is obtained from a suspected malignant peripheral lung nodule under fluoroscopic guidance. Addition of P-TBNA to conventional sampling techniques improves diagnostic yield of bronchoscopy, especially in patients with Tsuboi type III or IV tumor bronchus relationship. The role of conventional TBNA has further become a topic of hot debates with the emergence of endobronchial ultrasound (EBUS)-guided TBNA. The authors believe that even in the era of EBUS-TBNA, the standard TBNA technique maintains an important position in the diagnosis and staging of lung cancer.

Human immunodeficiency virus (HIV) infection is associated with a surprisingly high frequency of myocardial dysfunction. Potential mechanisms include direct effects of HIV, indirect effects mediated by cytokines, or a combination. We have previously reported that interleukin-1beta (IL-1beta) (500 U/ml) alone induced nitric oxide (NO) production by neonatal rat cardiac myocytes (CM). Effects of the HIV-1 envelope, glycoprotein120 (gp120), on inducible NO synthase (iNOS) in CM have not been previously reported. Unlike IL-1beta, recombinant HIV-gp120 (1 microgram/ml) alone failed to enhance NO production in CM (0.5 +/- 0.4 vs. 0.4 +/- 0.5 micromol/1.25 x 10(5) cells/48 h, gp120 vs. control, respectively; n = 12, P = not significant). However, the addition of gp120 to IL-1beta significantly enhanced iNOS mRNA expression (70 +/- 1.5 vs. 26 +/- 2.4 optical units, IL-1beta + gp120 vs. IL-1beta, respectively; n = 3), iNOS protein synthesis (42 +/- 1.4 vs. 18 +/- 0.8 optical units, IL-1beta + gp120 vs. IL-1beta, respectively; n = 3), and NO production (NO(2)(-)) (6.6 +/- 0.6 vs. 4.1 +/- 0.8 micromol/1.25 x 10(5) cells/48 h, IL-1beta + gp120 vs. IL-1beta, respectively; n = 12, P </= 0.5). HIV-gp120 enhancement of IL-1beta-induced NO(2)(-) production was blocked by 10 microM of SB-203580 (SB), a selective p38 protein kinase inhibitor (3.6 +/- 0.2 vs. 6.6 +/- 0.6 micromol/1. 25 x 10(5) cells/48 h, IL-1beta + gp120 + SB vs. IL-1beta + gp120, respectively; n = 12, P </= 0.5). HIV-gp120-enhanced p38 protein kinase activity was associated with an increase in IL-1beta-stimulated NF-kappaB activity (184 +/- 12.7 vs. 92 +/- 10.7 optical units, IL-1beta + gp120 vs. IL-1beta, respectively; n = 3). None of these effects was seen with another recombinant HIV-1 protein, Tat. Thus HIV-gp120 enhancement of IL-1beta-induced NO production is associated with p38-mediated activation of NF-kappaB. Direct effects of HIV-gp120 on CM may provide a previously unrecognized mechanism contributing to HIV cardiomyopathy.

We have previously reported that interleukin-1beta (IL-1beta) alone induced nitric oxide (NO) production by neonatal rat cardiac myocytes (CM). The effects of tumor necrosis factor-alpha (TNF-alpha) on inducible NO synthase (iNOS) were not characterized. Unlike IL-1beta, TNF-alpha alone failed to enhance NO production in CM. However, the addition of TNF-alpha to IL-1beta significantly enhanced iNOS mRNA expression, iNOS protein synthesis, and NO production (NO(-)(2)). TNF-alpha enhancement of IL-1beta-induced NO(-)(2) production was blocked by PD-98059, a selective mitogen-activated protein (MAP) kinase kinase inhibitor, but not calphostin C (Cal C), a protein kinase C inhibitor. TNF-alpha-enhanced MAP kinase activity was associated with an increase in IL-1beta-stimulated NF-kappaB activity. PD-98059, but not Cal C, inhibited both TNF-alpha-enhanced MAP kinase and NF-kappaB activities. Thus TNF-alpha enhancement of IL-1beta-induced NO production is associated with MAP kinase-mediated activation of NF-kappaB.

Chest 2004;125:322–5. Herth F, Becker HD, Ernst A. Study Summary: In this prospective, randomized study, Herth and coworkers compared the diagnostic yield of standard transbronchial needle aspiration (TBNA) with that of endobronchial ultrasound-guided TBNA (EBUS). Two hundred patients with enlarged mediastinal lymph nodes were included in the study. The study patients were divided into 2 groups: those with subcarinal lymph node enlargement (group A, N = 100) and those with lymph node enlargement at other stations (group B, N = 100). Patients in each group were randomized into standard TBNA group and EBUS-guided TBNA group. EBUS was performed using a balloon-tipped 20-MHz transducer. After locating the lymph node, the EBUS probe was removed. The information obtained was used to guide subsequent TBNA procedure (Chest 2003;123:604–7). TBNA cytology specimens were obtained using a MW 522 needle. On-site cytology was not used, and the interpreting pathologists were not aware of the method used to retrieve the TBNA specimen. The mean lymph node size was 1.76 cm (range, 0.8–4.3 cm) in group A and 1.53 cm (range, 0.7–2.3 cm) in group B. In group A, the diagnostic yield for the specific diagnosis was 72% with conventional TBNA and 80% with EBUS-guided TBNA. This difference did not reach statistical significance. In group B, the diagnostic yield for the specific diagnosis was 54% with conventional TBNA and 74% with EBUS-guided TBNA (P < 0.001). The mean time for EBUS-guided TBNA was 6.3 minutes and for conventional TBNA it was 3.8 minutes (P < 0.05). There were no procedure-related complications. The authors concluded that US-guided TBNA improves diagnostic yield from lymph node stations other than subcarinal lymph nodes. Comments: There is a growing interest in increasing diagnostic yield of TBNA. A successful TBNA is cost-effective and avoids need for more invasive procedure such as mediastinoscopy (Chest 1996;110[suppl]:24S). In some cases, TBNA is the only source of diagnostic material during flexible bronchoscopy (Am J Respir Crit Care Med 2000;161:601–7). Rapid on-site cytology (ROSE) and computed tomography– (CT) fluoroscopy-guided TBNA have been reported to improve TBNA yield in prior studies (Chest 1990;98:59–61, Chest 2000;118:1630–8, Chest 2001;119:329–32). However, there are logistic problems with both ROSE and CT fluoroscopy. On the contrary, US guidance is simple, safe, and adds little to the overall procedure time. In addition, there are no radiation issues with EBUS. Ultrasound guidance during TBNA did not increase diagnostic yield from subcarinal lymph nodes. This is not unexpected given the easy access to this area during standard TBNA. A careful review of their data (presented in Table 2 of the original paper) also indicates that EBUS guidance during TBNA does not appear to improve yield from right or left paratracheal lymph nodes. Reanalysis of the data show that the yield of conventional TBNA from station 4r and 4l (11 of 16; 69%) is similar to yield from EBUS-guided TBNA (13 of 18; 72%). However, the diagnostic yields with EBUS-guided TBNA for other stations were higher than that with the conventional procedure. The study was not designed to look into the possible additional role of ROSE in increasing diagnostic yield when used with EBUS-guided TBNA. Cost-effectiveness and reimbursement are other important considerations. Incorporation of EBUS with TBNA will increase the overall cost of the procedure. Future studies should address this issue. Nevertheless, overall results of this study are convincing and indicate that EBUS guidance can improve diagnostic yield of TBNA in selected patients. The authors rightly point out that there is a learning curve for EBUS. Bronchoscopists should consider learning this technique and adding EBUS facilities in their bronchoscopy suites. EBUS guidance during TBNA could improve operators’ confidence and could prove to be a good learning tool for the trainees.

Research has shown that depression increases the likelihood that otherwise healthy people will develop ischemic heart disease (IHD) and worsens the prognosis of patients who already have IHD. Moreover, concerns about safety (e.g., cardiac side effects, drug-drug interactions) have caused physicians to be hesitant about using antidepressant agents in patients with IHD. This article is based on a recent roundtable of experts who met to discuss risk, diagnosis, and treatment options for depression in patients with IHD. This article reviews clinical and epidemiological studies that have described a link between depression and the subsequent development of IHD and have examined the role of depression as a predictor of cardiac events in patients with existing IHD. The article addresses the issue of whether depression can be safely and efficaciously treated both in patients with stable IHD and in those with acute coronary syndromes. The authors discuss safety issues related to the potential for interactions between antidepressants and cardiovascular medications, the use of nonpharmacologic treatment options such as psychosocial interventions, and the effect of antidepressant therapy on quality of life in patients with IHD. The article concludes with practical clinical guidance concerning the management of depression in patients who have recently experienced myocardial infarction.

A variety of seemingly unrelated clinical conditions manifest the same effects on the heart. These effects include: (1) reversible myocardial dysfunction, (2) beta-adrenergic desensitization, and (3) activation of inflammatory mediators. We provide evidence supporting a role for cytokines, mitogen activated protein kinases (MAP kinases), and nitric oxide (NO) as common mediators of reversible myocardial dysfunction and beta-adrenergic desensitization. Data from animal models and human studies support a pathogenic role for these inflammatory mediators in ischemic as well as non-ischemic myocardial dysfunction. It is suggested that compensatory cellular programs are activated to provide short-term protection from brief periods of ischemia and infection. Continuous activation of these compensatory pathways leads to cardiomyopathy and chronic (congestive) heart failure. Elucidating the signaling pathways involved has the potential to provide the opportunity to exploit the cardioprotective advantages of these agents without bearing the burden of excessive stimulation.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Chest 2003;124:1073–80. Snell GI, Holsworth L, Borrill ZL, et al. Comments: In this study, the authors examine the feasibility and safety of the bronchoscopic lung volume reduction (BLVR) procedure using an endobronchial prosthesis. The purpose of placing the prosthesis was to promote the absorption atelectasis of the distal lung to achieve physiological changes similar to those seen after lung volume reduction surgery (LVRS). The investigators used the Emphasys Medical endobronchial prosthesis, which are silicone-based, one-way valves mounted in a Nitinol bronchial stent. The design of this prosthesis is purported to be such that it allows venting of air and passage of secretions from the distal parts of the lung to the proximal airways, but blocks the movement of air from proximal airways to the distal parts of the lung. Free movement of air from distal to proximal airways across the prosthesis is thought to reduce the chances pressure build-up distal to the prosthesis that could cause valve expulsion. The procedure was performed under general anesthesia. To select a prosthesis of matching size, the investigators estimated the caliber of the target airway using an Olympus M2/1C measuring device and a Swan-Ganz catheter balloon. The valve was placed using an introducer delivery system advanced over the guidewire. The goal was to place multiple prostheses in both upper lobes to produce complete bilateral upper lobe obstruction. The primary end point was 30-day major complications. Secondary end points were radiologic changes, lung functions, 6-minute walk distance, and distribution of nuclear ventilation and perfusion. Ten patients with severe, predominantly upper-lobe emphysema were included in the study. The mean baseline FEV1 was 0.73 L (30%), TLC was 6.81 L (128%), RV was 4.2 L (209%), DLCO was 7.47 (31%), PaO2 on room air was 73.9 mm Hg, and 6-minute walk distance was 340.4 m. The average total anesthesia time was 2 hours 24 minutes. A mean of 6.7 ± 2.2 valves were placed in different segments of both upper lobes. There was no immediate or 30-day life-threatening complication. The mean length of hospital stay was 3.4 ± 2.1 days. One patient had postprocedure pneumothorax needing simple aspiration. During follow up, 3 patients developed acute exacerbation of chronic obstructive pulmonary disease, and 1 patient developed pneumonia. Perivalvular leak was suspected in 2 patients on follow-up bronchoscopy. Prosthesis migration, hyperinflation, or excessive coughing was not seen. No statistically significant difference in FEV1, forced vital capacity (FVC), RV, TLC, arterial blood gas, Medical Research Council dyspnea scale, and 6-minute walk distance were observed at 30 days as compared with baseline values. Diffusion capacity showed minor improvement from 7.47 ± 2.0 to 8.26 ± 2.6 (P = 0.04). Similarly, perfusion of upper lobes on 99mTc perfusion scan showed minor decline (P = 0.02). The atelectasis on chest computed tomography examination was minimal. Overall, the results appear to indicate that although it was safe to place the endobronchial prosthesis, there was no improvement in most clinically relevant end points. The main problems with LVRS are high early surgical mortality and high perioperative complication rates. For instance, in the National Emphysema Treatment Trial, the overall 90-day mortality after surgery was 7.9% as compared with 1.3% among medically treated patients (N Engl J Med 2003;348:2059–73). Patients with more advanced disease have higher surgical mortality, and the LVRS is not suitable for them (N Engl J Med 2001;345:1075–83). Nonfatal complications, especially prolonged air leak, are seen in nearly one half of all patients after LVRS (J Thorac Cardiovasc Surg 2003;125:513–25). The primary reason to develop the BLVR procedure is to avoid surgical complications and early surgical mortality associated with LVRS. In this context, the patients enrolled by Snell and coworkers experienced no serious complications as a result of the procedure. Unfortunately, there were no clinical benefits either. The main setback was a failure to achieve atelectasis in the areas of the lung supplied by the segmental bronchi in which the prostheses were placed. The authors offer several explanations for this failure. The leading hypothesis was that collateral ventilation from the surrounding lobes into the target area prevented the development of atelectasis. However, it is more likely that desired results were not achieved as a result of the inability of the prosthesis to fully block the passage of air into the lung during inspiration. A recent study seems to support this argument (Lancet 2003;361:931–3). In this study, unilateral BLVR was attempted in 8 patients with severe emphysema using a modified version of the same endobronchial valve. The outcome data were more encouraging. After valve insertion, median FEV1, as well as diffusion capacity, improved significantly. However, the computed tomography scan showed the intended lobar collapse only in 4 of 8 patients. The results, nonetheless, were better than those of Snell and coworkers. In conclusion, while the BLVR procedure appears safe; the initial clinical results are mixed and somewhat disappointing. Much work is needed before this technique can be put into clinical use.

BACKGROUND: Malignant melanoma is an uncommon metastatic tumor found in the gastrointestinal tract but most commonly involves the small bowel. Less than 5% of patients with metastases to the gastrointestinal tract are diagnosed antemortem. Clinical presentation could be an acute abdominal emergency such as a bowel obstruction, intussusception, bleeding and perforation or chronic symptoms with weight loss, abdominal pain and anemia. METHODS: We report two unusual cases with acute gastrointestinal complications related to metastatic melanoma. Case 1 developed acute upper gastrointestinal bleeding and was diagnosed with gastric mass. Biopsy revealed metastatic melanoma. The patient died of his advanced disease. Case 2 with unknown primary melanoma presented with acute abdomen secondary to small bowel perforation. He underwent laparotomy and small bowel resection with palliative intent. The patient remains alive and free of symptoms at 4 year follow up. CONCLUSIONS: Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with history of cutaneous melanoma and new gastrointestinal symptoms. Surgical interventions for symptomatic patients with melanoma of the gastrointestinal tract significantly relieve pain and improve quality of life and may confer a survival advantage.

BACKGROUND: We tested the capacity of the 60-site VA Women's Health Practice-Based Research Network (WH-PBRN), embedded within VA, to employ a multisite card study to collect women Veterans' perspectives about Complementary and Integrative Health (CIH) and to rapidly return findings to participating sites and partnered national policy-makers in support of a Learning Health System (LHS) wherein evidence generation informs ongoing improvement. METHODS: VA primary care clinic clerks and nurses distributed anonymous surveys (patient feedback forms) at clinics for up to two weeks in fiscal year 2017, asking about CIH behavior and preferred delivery methods. We examined the project's feasibility, representativeness, acceptability, and impact via a tracking system, national administrative data, debriefing notes, and three surveys of WH-PBRN Site Leads. RESULTS: Twenty geographically diverse and largely representative VA Medical Centers and 11 Community-Based Outpatient Clinics volunteered to participate. Over six months, N = 1191 women Veterans responded (median 57; range 8-151 per site). In under three months, we returned local findings benchmarked against multisite findings to all participating sites and summary findings to national VA partners. Sites and partners disseminated results to clinical and leadership stakeholders, who then applied results as warranted. CONCLUSIONS: VA effectively mobilized an embedded PBRN to implement a timely, representative, acceptable and impactful operations project. IMPLICATIONS: Card studies by PBRNs within large, national healthcare systems can provide rapid feedback to participating sites and national leaders to guide policies, programs, and practices. LEVEL OF EVIDENCE: Self-selected respondents could have biased results.

Placement of peripheral intravenous (PIV) lines in difficult-to-access patients can be daunting. Multiple unsuccessful peripheral sticks, numerous PIV restarts, and potentially excess use of peripherally inserted central catheters can result. The goals of this project were to decrease the number of peripherally inserted central catheter referrals and lower the number of PIV restarts by having clinical nurses employ ultrasound guidance when initiating deep PIVs. After 10 months of nurses using the ultrasound as needed to insert a PIV line, the number of total peripherally inserted central catheter referrals decreased by 20%.

A solitary pulmonary nodule (SPN) on a chest radiograph represents a major diagnostic dilemma. The goals of management are to resect malignant tumors without delay and to avoid unnecessary thoracotomy if the nodule is benign. But because of the difficulty distinguishing benign from malignant nodules, even with advances in imaging techniques, these goals cannot be met in all cases.

Background: A vancomycin target of area under the curve to minimum inhibitory concentration (AUC:MIC) ratio ≥400 is recommended for treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Objective: To evaluate vancomycin total daily dose (TDD) achieving trough targets versus a calculated strategy achieving AUC targets based on body mass index (BMI). Methods: A retrospective cohort study was performed within a large hospital network. Patients with MRSA bacteremia were eligible if they received vancomycin with a steady-state trough (15-20 mg/L). Cockcroft-Gault was used to estimate creatinine clearance, calculating vancomycin clearance and AUC. Patients were stratified by BMI (less than/greater than 30 kg/m 2 ). The primary outcome was vancomycin TDD for the trough-based strategy compared with an AUC-dosing strategy. Results: A total of 119 patients were included, including 51 (42.9%) and 68 (57.1%) patients with high- and low-BMI, respectively. The TDD for trough-based dosing (2390.76 ± 1224.59 mg) differed significantly from AUC-based dosing (1985.07 ± 616.18 mg) across the cohort ( P = 0.0014). For patients with high BMI, there was a significant difference ( P &lt; 0.0001) in TDD between trough (2637.25 ± 1327.89 mg) versus AUC (1918.71 ± 625.89 mg) strategies. No difference in TDD between dosing strategies was observed among low-BMI patients. Across all patients, 46 (38.7%) experienced acute kidney injury (AKI); high-BMI patients experienced higher rates of AKI compared with low-BMI patients (54.9 vs 26.5%; P = 0.002). Conclusions and Relevance: An AUC-based dosing strategy may reduce vancomycin TDD required for MRSA bacteremia compared with trough-based dosing, particularly for patients with higher BMI.

The field of interventional bronchoscopy is rapidly expanding and has emerged as a new and exciting subspecialty in pulmonary medicine. To date, the impact of interventional bronchoscopy procedures ha

Despite the advent of newer broad-spectrum antibiotics, infection in critically ill patients still is associated with significant morbidity and mortality. For these patients, who frequently receive inappropriate and excessive empiric antibiotic therapy, it is important to develop rational drug usage criteria. Current economic forces, including personnel shortages and the effects of diagnosis-related groups, are also a critical factor in this patient population. Criteria for rational antibiotic selection are based on patterns of infection and knowledge of the pharmacokinetic and pharmacodynamic properties of individual antibiotics. The development and use of treatment protocols, or algorithms, will provide quality patient care for the lowest overall cost.