No stone unturned: Nodule Net, an intervention to reduce loss to follow-up of lung nodules.

OBJECTIVE: Inadequate lung nodule surveillance leads to diagnostic delays. We implemented a retrospective intervention program, Nodule Net, to improve surveillance in our hospital. METHODS: 9,224 Chest computed tomography (CT) scans between January 1, 2015 and December 31, 2016 were manually reviewed for lung nodules. For patients without follow-up, charts were reviewed to assess follow-up. If follow-up appeared indicated, the clinician or patient was contacted, and follow-up was tracked. RESULTS: Lung nodules were identified on 5,101 (55%) of 9,224 scans. Follow-up was potentially indicated and not completed in 1,385 (27%). 183 (13%) were excluded after imaging review. 1,202 received outreach. Of the 801 (66%) with a provider in our system, 225 (27%) returned for follow-up. Nodules were stable in 199 (88%), new or growing in 23 (11%), resolved in 3 (1%), and stage 1 lung cancer in 2 (1%). 90 (11%) had follow-up outside our system and 431 (51%) had no follow-up due to a clinical contraindication. 55 (7%) have imaging pending and 14 (2%) are awaiting pulmonary evaluation. Of the 302 (25%) patients with providers outside our system, 121 (40%) had followed-up elsewhere. 146 (48%) had no follow-up due to a clinical reason. 35 (12%) providers did not respond to outreach. CONCLUSIONS: We identified 1,202 patients with lung nodules who needed follow-up over a two-year period. Compliance was more successful with providers within our hospital system. We recommend robust surveillance for patients to ensure follow-up is completed and clinical contraindications are well documented.

Autofluorescence imaging captures heterogeneous drug response differences between 2D and 3D breast cancer cultures.

Two-photon microscopy of cellular autofluorescence intensity and lifetime (optical metabolic imaging, or OMI) is a promising tool for preclinical drug development. OMI, which exploits the endogenous fluorescence from the metabolic coenzymes NAD(P)H and FAD, is sensitive to changes in cell metabolism produced by drug treatment. Previous studies have shown that drug response, genetic expression, cell-cell communication, and cell signaling in 3D culture match those of the original in vivo tumor, but not those of 2D culture. The goal of this study is to use OMI to quantify dynamic cell-level metabolic differences in drug response in 2D cell lines vs. 3D organoids generated from xenograft tumors of the same cell origin. BT474 cells and Herceptin-resistant BT474 (HR6) cells were tested. Cells were treated with vehicle control, Herceptin, XL147 (PI3K inhibitor), and the combination. The OMI index was used to quantify response, and is a linear combination of the redox ratio (intensity of NAD(P)H divided by FAD), mean NADH lifetime, and mean FAD lifetime. The results confirm that the OMI index resolves significant differences (p<0.05) in drug response for 2D vs. 3D cultures, specifically for BT474 cells 24 hours after Herceptin treatment, for HR6 cells 24 and 72 hours after combination treatment, and for HR6 cells 72 hours after XL147 treatment. Cell-level analysis of the OMI index also reveals differences in the number of cell sub-populations in 2D vs. 3D culture at 24, 48, and 72 hours post-treatment in control and treated groups. Finally, significant increases (p<0.05) in the mean lifetime of NADH and FAD were measured in 2D vs. 3D for both cell lines at 72 hours post-treatment in control and all treatment groups. These whole-population differences in the mean NADH and FAD lifetimes are supported by differences in the number of cell sub-populations in 2D vs. 3D. Overall, these studies confirm that OMI is sensitive to differences in drug response in 2D vs. 3D, and provides further information on dynamic changes in the relative abundance of metabolic cell sub-populations that contribute to this difference.

Association of angiotensin converting enzyme (ACE) gene polymorphism with hypertension in a Bangladeshi population.

The association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with hypertension has not been confirmed. Inconsistencies may be due to the differences of background population characteristics. Till date, there has been no report in Bangladeshi population. This study was to examine the association of ACE (I/D) polymorphism with hypertension. Fifty-one primary hypertensives and fifty-two normotensives were recruited from a hospital in Dhaka city. Height, weight and blood pressure were measured. ACE (I/D) genotypes was established using polymerase chain reaction protocol. The genotype and allele frequencies did not differ significantly (P > 0.05) between the groups. In logistic regression analysis, adjusted for age, sex and body mass index, the genotypes were not associated with hypertension (DD vs II: Adds ratio = 2.6, P = 0.34; ID vs II: 0.4, 0.23; ID + DD vs II: 0.8, 0.69). In this hospital-based sample of Bangladeshi people, significant association of ACE I/D genotype with hypertension was not observed.

Myocardial abscess due to Klebsiella pneumoniae complicating acute infarction.

A case is described in which Klebsiella pneumoniae urosepsis associated with acute myocardial infarction resulted in myocardial abscess and papillary muscle rupture. The diagnosis was made during surgery for mitral valve replacement. The patient improved after therapy with cefotaxime; however, cardiac rupture occurred on the sixth postoperative day. The pathogenesis of myocardial abscess and the use of non-invasive techniques for diagnosis are discussed.