Is there a role for fibreoptic bronchoscopy in patients presenting with haemoptysis and negative CT? A systematic review and meta-analysis.

INTRODUCTION: Haemoptysis can be a feature of lung cancer and patients are typically fast-tracked for evaluation with chest radiography, contrast-enhanced CT and fibreoptic bronchoscopy (FOB). OBJECTIVE: We aim to explore whether FOB should be conducted as a component of the routine evaluation of non-massive haemoptysis, especially in the context of suspected lung cancer. METHODS: MEDLINE, EMBASE and Cochrane Library were searched for studies comparing FOB with CT in the evaluation of non-massive haemoptysis while reporting at least one of the listed primary outcomes. Primary outcomes include sensitivity of diagnostic modality with respect to lung cancer. Secondary outcomes include detection of other aetiologies such as infection. Results were synthesised using a random effects meta-analysis. Sensitivity analysis was performed for patient age group and year of study. Risk of bias assessment was carried out with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: A total of 2273 citations were screened and 11 studies were included, comprising a total sample size of 2015 patients with 226 confirmed cases of lung cancer. A total of 1816 and 1734 patients received a CT scan and FOB, respectively. The pooled sensitivities for detection of lung cancer using CT scan and bronchoscopy were 98% (95% CI 93.0% to 99.0%) and 86% (95% CI 63.0% to 95.0%), respectively. The sensitivity of CT was higher than that of FOB for both primary and secondary outcomes. CONCLUSION: This study suggests that bronchoscopy does not offer significant additional diagnostic benefit in the evaluation of patients presenting with non-massive haemoptysis and a negative CT scan.

A Novel Report of Suspected Prostate Adenocarcinoma to Orbital Roof Meningioma Metastasis.

: Tumor-to-meningioma metastasis (TTMM) is an uncommon phenomenon, in which a primary malignant tumor metastasizes to a recipient preexisting meningioma. Herein, the authors report a case of a 74-year-old man with a known history of metastatic prostate adenocarcinoma who with frontal headache and right orbital apex syndrome. Initial CT studies demonstrated a right orbital roof osseous lesion. Subsequent MRI was reported as characteristic of an intraosseous meningioma with intracranial and intraorbital extensions. A biopsy of the right orbital mass was obtained and returned a diagnosis of metastatic prostate cancer. The combination of imaging and pathologic findings suggested that the clinical scenario was overall most in keeping with a skull bone-based prostate adenocarcinoma metastasis infiltrating a preexisting meningioma. This is a rare case of TTMM in an orbit-based meningioma, presenting with an orbital apex syndrome.

Outcomes of conjunctival-Müller's muscle resection surgery with and without epinephrine in local anesthetic.

PURPOSE: To determine the effect of epinephrine as an anesthetic adjunct on outcomes of conjunctival-Müller's muscle resection (CMMR) ptosis surgery. METHODS: A retrospective cohort study of patients having undergone CMMR with plain local anesthetic (LA) and local anesthetic combined with epinephrine (LA+Epi). Two measures of success were investigated: margin to reflex distance 1 (MRD1) success and overall success. MRD1 success was defined as a postoperative MRD1 between 2-4 mm. Overall success was defined as all of i) MRD1 success, ii) a ≤ 1 mm difference between the eyelid height following the preoperative phenylephrine test and post-operative MRD1 (PE-MRD1 Δ), and iii) symmetrical postoperative contour between both upper eyelids. Study inclusion criteria included blepharoptosis from levator aponeurotic dehiscence and satisfactory response to the phenylephrine test. Exclusion criteria included congenital ptosis, ptosis secondary to another cause, previous ipsilateral eyelid surgery, or a medical condition that may have impacted surgery. RESULTS: There were 26 eyelids in the LA+Epi group, and 19 eyelids in the LA group. There was no difference in the two groups in age (P =0.28), pre-operative MRD1 (P =0.37), levator function (P =0.27), intraoperative tissue resection amount (P =0.27), number of weeks postoperatively at final MRD1 measurement (P =0.99), and PE-MRD1 Δ (P =0.08). All patients achieved a symmetrical post-operative eyelid contour. The LA+Epi group had a higher attainment of MRD1 success (P =0.04) and overall success (P =0.045). CONCLUSIONS: Epinephrine as an anesthetic adjunct improves CMMR outcome. This suggests its use can be considered the standard of care.

Terminology and Etymology in Oculoplastic Surgery.

PURPOSE: To provide a collection of important terms in oculoplastic surgery, their etymology, current usage, and clarification of terms with overlapping or often misconstrued definitions. METHODS: Commonly employed terms in oculoplastic surgery were collected, and their etymologies were determined. The authors then examined how these terms are being currently used in the published literature to determine how closely their usage matched the origin of the terms, if any terms had developed multiple meanings, or if multiple terms were being used to describe the same concept. RESULTS: This article assembles in one area much of the important terms in oculoplastic surgery, highlighting how the etymology of the terms both links to their meanings as well as clarifies the appropriate usage of terms that have evolved to develop several different definitions. Special attention is placed on clarifying the correct definitions of closely related but distinct terms. CONCLUSIONS: Most terms in ophthalmology are used in a uniform manner across the literature with definitions closely matching their etymology, but some terms in oculoplastic surgery are being used in a potentially confusing overlapping manner and warrant clarification.

Genomic comparisons of Rhizobium species using in silico AFLP-PCR, endonuclease restriction, and AMPylating enzymes

Background: The whole-genome sequences of nine Rhizobium species were evaluated using different in silico molecular techniques such as AFLP-PCR, restriction digest, and AMPylating enzymes. The entire genome sequences were aligned with progressiveMauve and visualized by reconstructing phylogenetic tree using NTSYS pc 2.11X. The "insilico.ehu.es" was used to carry out in silico AFLP-PCR and in silico restriction digest of the selected genomes. Post-translational modification (PTM) and AMPylating enzyme diversity between the proteome of Rhizobium species were determined by novPTMenzy. Results: Slight variations were observed in the phylogeny based on AFLP-PCR and PFGE and the tree based on whole genome. Results clearly demonstrated the presence of PTMs, i.e., AMPylation with the GS-ATasE (GlnE), Hydroxylation, Sulfation with their domain, and Deamidation with their specific domains (AMPylating enzymes) GS-ATasE (GlnE), Fic, and Doc (Phosphorylation); Asparagine_hydroxylase and Collagen_prolyl_lysyl_hydroxylase; Sulfotransferase; and CNF (Cytotoxic Necrotizing Factors), respectively. The results pertaining to PTMs are discussed with regard to functional diversities reported in these species. Conclusions: The phylogenetic tree based on AFLP-PCR was slightly different from restriction endonuclease- and PFGE-based trees. Different PTMs were observed in the Rhizobium species, and the most prevailing type of PTM was AMPylation with the domain GS-ATasE (GlnE). Another type of PTM was also observed, i.e., Hydroxylation and Sulfation, with the domains Asparagine_hydroxylase and Collagen_prolyl_lysyl_hydroxylase and Sulfotransferase, respectively. The deamidation type of PTM was present only in Rhizobium sp. NGR234. How to cite: Qureshi MA, Pervez MT, Babar ME, et al. Genomic comparisons of Rhizobium species using in silico AFLP-PCR, endonuclease restrictions and ampylating enzymes.

Analysis and natural history of pituitary incidentalomas.

OBJECTIVES: Pituitary incidentalomas (PI) are frequently found on brain imaging. Despite their high prevalence, little is known about their long-term natural history and there are limited guidelines on how to monitor them. METHODS: We conducted a retrospective study to compare epidemiological characteristics at presentation and the natural history of PI in population-based vs referral-based registries from two tertiary-care referral centers in Canada. RESULTS: A total of 328 patients with PI were included, of whom 73% had pituitary adenomas (PA) and 27% had non-pituitary sellar masses. The commonest indications for imaging were headache (28%), dizziness (12%) and stroke/transient ischemic attack (TIA) (9%). There was a slight female preponderance (52%) with a median age of 55 years at diagnosis; 71% presented as macroadenomas (>10mm). Of PA, 25% were functioning tumors and at presentation 36% of patients had evidence of secondary hormonal deficiency (SHD). Of the total cohort, 68% were treated medically or conservatively whereas 32% required surgery. Most tumors (87% in non-surgery and 68% in post-surgery group) remained stable during follow-up. Similarly, 84% of patients in the non-surgery and 73% in the surgery group did not develop additional SHD during follow-up. The diagnosis of non-functioning adenoma was a risk factor for tumor enlargement and a change in SHD status was associated with a change in tumor size. CONCLUSIONS: Our data suggest that most PI seen in tertiary-care referral centers present as macroadenomas and may frequently be functional, often requiring medical or surgical intervention.

Sellar Masses: An Epidemiological Study.

BACKGROUND: Sellar masses (SM) are mostly benign growths of pituitary or nonpituitary origin that are increasingly encountered in clinical practice. To date, no comprehensive population-based study has reported the epidemiology of SM from North America. AIM: To determine the epidemiology of SM in the province of Nova Scotia, Canada. METHODS: Data from all pituitary-related referrals within the province were prospectively collected in interlinked computerized registries starting in November 2005. We conducted a retrospective analysis on all patients with SM seen within the province between November 2005 and December 2013. RESULTS: A total of 1107 patients were identified, of which 1005 were alive and residing within the province. The mean age at presentation was 44.6±18 years, with an overall female preponderance (62%) and a population prevalence rate of 0.1%. Of patients with SM, 837 (83%) had pituitary adenomas and 168 (17%) had nonpituitary lesions. The relative prevalence and standardized incidence ratio, respectively, of various SM were: nonfunctioning adenomas (38.4%; 2.34), prolactinomas (34.3%; 2.22), Rathke's cyst (6.5%; 0.5), growth hormone-secreting adenomas (6.5%; 0.3), craniopharyngiomas (4.5%; 0.2), adrenocorticotropic hormone-secreting adenomas (3.8%; 0.2), meningiomas (1.9%), and others (3.9%; 0.21). At presentation, 526 (52.3%) had masses ≥1 cm, 318 (31.6%) at <1 cm, and 11 (1.1%) had functioning pituitary adenomas without discernible tumor, whereas tumor size data were unavailable in 150 (14.9%) patients. The specific pathologies and their most common presenting features were: nonfunctioning adenoma (incidental, headaches, and vision loss), prolactinomas (galactorrhea, menstrual irregularity, and headache), growth hormone-secreting adenomas (enlarging extremities and sweating), adrenocorticotropic hormone-secreting adenoma (easy bruising, muscle wasting, and weight gain) and nonpituitary lesions (incidental, headaches, and vision problems). Secondary hormonal deficiencies were common, ranging from 19.6% to 65.7%; secondary hypogonadism, hypothyroidism, and growth hormone deficiencies constituted the majority of these abnormalities. CONCLUSIONS: This is the largest North American study to date to assess the epidemiology of SM in a large stable population. Given their significant prevalence in the general population, more studies are needed to evaluate the natural history of these masses and to help allocate appropriate resources for their management.

Different responses by cultured aortic and venous smooth muscle cells to gamma radiation.

BACKGROUND: Stenosis of hemodialysis arteriovenous grafts is usually focal and caused by the proliferation of vascular smooth muscle cells (SMCs). External radiation of the graft is a potential strategy to prevent stenosis; however, the relative responsiveness of arterial and venous SMCs to radiation is unknown. METHODS: Human aortic and saphenous vein SMCs were cultured in a medium containing growth factors and serum and treated with 0 to 50 Gy in a gamma irradiator. At 2 to 20 days post-irradiation, cell counting, methylthiazoletetrazolium dye reduction, [(3)H]-thymidine uptake, and bromodeoxyuridine (BrdU) incorporation assays were performed. RESULTS: All assays showed that 1 to 50 Gy inhibited the proliferation of both aortic and venous SMCs in a dose-dependent manner. Importantly, venous cells were less susceptible to radiation in all assays, compared to aortic cells. At day 10, 1 to 50 Gy of radiation inhibited the increase in the number of aortic cells by 24% to 66% and venous cells by 8% to 25% (P < 0.01) (aortic vs. venous). The differences between aortic and venous cells varied among different assays and were most pronounced in the BrdU assay. CONCLUSION: Inasmuch as myointimal hyperplasia occurs at both arterial and venous anastomoses, future strategies using radiation to prevent hemodialysis vascular access stenosis should take these differences into consideration.

Inhibition of neointimal hyperplasia in vascular grafts by sustained perivascular delivery of paclitaxel.

BACKGROUND: Neointimal hyperplasia occurs commonly at the anastomoses of arteriovenous grafts for chronic hemodialysis, causing stenosis and occlusion. Antiproliferative drugs may be effective in inhibiting hyperplasia, but local drug delivery would be required to minimize systemic side effects. We examined the feasibility of local drug delivery to inhibit neointimal hyperplasia at dialysis grafts in a canine model. METHODS: Bilateral polytetrafluoroethylene loop grafts (10-cm length and 6-mm internal diameter) were placed between the femoral artery and ipsilateral femoral vein of five mongrel dogs. At the time of surgery or 1 to 5 weeks later, 2 mL of a thermosensitive biodegradable copolymer (ReGel) mixed with 0.26 mg or 0.65 mg paclitaxel were applied to the external surface of one graft around the anastomoses to provide a depot for sustained release of the drug. ReGel alone without paclitaxel was applied to the contralateral graft as a control. The grafts and the connecting vessels were explanted at eight or nine weeks, and the cross-sections were examined histologically. The degree of hyperplasia at the anastomoses was graded by five blinded independent reviewers, with scores ranging from 0 to 5. RESULTS: The median (25th-75th percentile) hyperplasia score of both arterial and venous anastomoses was 1.80 (0.90-3.05) in the grafts treated with ReGel alone, and 0.95 (0.70-1.50) in the grafts treated with ReGel/paclitaxel (N= 8; P < 0.05 by Wilcoxon signed rank test). There were no noticeable localized or systemic complications attributed to the treatments in these animals. Paclitaxel levels in the plasma obtained from forelimb veins were undetectable (<10 ng/mL). CONCLUSION: These results suggest that the local delivery of antiproliferative agents using a thermosensitive, injectable biodegradable copolymer (ReGel) for sustained delivery is a promising strategy to inhibit neointimal hyperplasia of arteriovenous hemodialysis grafts.

In vitro pharmacological inhibition of human vascular smooth muscle cell proliferation for the prevention of hemodialysis vascular access stenosis.

BACKGROUND: Vascular access for chronic hemodialysis often fails as a result of stenosis caused primarily by the proliferation of vascular smooth muscle cells (VSMC). Various drugs have been shown to inhibit the proliferation of VSMC under different conditions. METHODS: In this study, we compared the inhibitory effect of ten drugs on the proliferation of human aortic smooth muscle cells (SMC) in culture. Quiescent cells were cultured in the presence of growth factors, fetal bovine serum and incremental concentrations of the test drug. Cell proliferation was assessed by the MTT reduction assay. RESULTS: Aspirin, enalaprilat, heparin, hydroxyurea, indomethacin and tirofiban were ineffective. While dipyridamole, paclitaxel, tranilast and verapamil inhibited cell proliferation, the concentrations required were significantly higher than the clinical plasma levels achieved after systemic administration. CONCLUSION: Local delivery of these drugs to the target site may therefore be a more effective and appropriate strategy for the prevention of hemodialysis vascular access stenosis.