Comparing efficacy of lumen-apposing stents to plastic stents in the endoscopic management of mature peripancreatic fluid collections: a single-center experience

Introduction: Mature peripancreatic fluid collection (MPFC) is a known and often challenging consequence of acute pancreatitis and often requires intervention. The most common method accepted is the step-up approach, which consists of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. Our paper aims to distinguish between plastic stents and lumen-apposing stents in the endoscopic management of MPFC in terms of morbidity, mortality, and haste of fluid collection resolution. Methods: A retrospective analysis was performed at UMass Memorial Medical Center in patients with a diagnosis of MPFC. Utilizing medical records, clinical data, radiology, as well as endoscopic evidence, patients were differentiated by stent type used (plastic versus lumen-apposing) for the management of the MPFC. The primary outcome of the study was to assess the time to MPFC resolution following the placement of either plastic or lumen-apposing stents (on endoscopic ultrasound or computerized tomography scan) using a multivariate analysis with a logistic regression model. Results: A total of 54 patients were included in this study from UMass Memorial Medical Center between 2012 and 2015. Twelve (22%) of these patients received lumen-apposing stents and 42 (78%) of these patients received plastic pigtail stents. For the lumen-apposing stent group, the mean interval between stent placement and resolution of MPFC was 57 days as compared to 102 days for plastic pigtail stents (p=0.02). The mean interval for placement/removal of lumen-apposing stents was 48 days as compared to 81 days for plastic pigtail stents (p=0.01). Stent migration was seen in 5 patients (11%) who received a plastic pigtail stent compared to 0 (0%) patients who received a lumen-apposing stent. Discussion: Our study demonstrates that lumen-apposing stents result in a significant reduction in the interval between stent placement and MPFC resolution as well as the time from stent placement to removal, when compared to plastic pigtail stents, the prior standard-of-care. Our study reached similar conclusions regarding the number of stents placed. However, we did not find a significant difference between the complication rates, specifically peri- and postprocedural bleeding or perforation, between the 2 study groups, as demonstrated in prior papers

Senile Systemic Amyloidosis: Clinical Features at Presentation and Outcome

Background Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac‐isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors. Methods and Results All patients with biopsy‐proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N‐terminal pro‐B‐type natriuretic peptide (NT pro‐BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro‐BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro‐BNP <1420 pmol/L. Conclusions Factors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro‐BNP level can aid in distinguishing ATTRwt from AL amyloidosis

Antiphospholipid Antibodies Bind ATP: A putative Mechanism for the Pathogenesis of Neuronal Dysfunction

Antiphospholipid antibodies (aPL) generated in experimental animals cross-react with ATP. We therefore examined the possibility that aPL IgG from human subjects bind to ATP by affinity column and an enzyme linked immunosorbent assay (ELISA). Sera with high levels of aPL IgG were collected from 12 patients with the antiphospholipid syndrome (APS). IgG fractions from 10 of 12 APS patients contained aPL that could be affinity-bound to an ATP column and completely eluted with NaCl 0.5 M. A significant (>50%) inhibition of aPL IgG binding by ATP 5 mM was found in the majority. Similar inhibition was obtained with ADP but not with AMP or cAMP. All the affinity purified anti-ATP antibodies also bound β2-glycoprotein-I (β2-GPI, also known as apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding depends on this serum cofactor. We further investigated this possibility and found that the binding of β2-GPI to the ATP column was similar to that of aPL IgG in that most was reversed by NaCl 0.5 M. Furthermore, addition of β2-GPI to aPL IgG significantly increased the amount of aPL binding to an ATP column. We conclude that aPL IgG bind ATP, probably through β2-GPI. This binding could interfere with the normal extracellular function of ATP and similar neurotransmitters

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

Fibroma ossificante dei seni paranasali: diagnosi e management

Le lesioni fibro-ossee benigne raramente colpiscono i seni paranasali e sono suddivise in 3 entità: osteoma, displasia fibrosa e fibroma ossificante. Questi presentano simili caratteristiche cliniche, radiologiche e istologiche ma hanno un comportamento diverso. Il fibroma ossificante, in particolare la variante istologica giovanile, può presentare un comportamento aggressivo con un alto rischio di recidiva se rimosso in modo incompleto. Lo scopo dello studio è quello di paragonare il comportamento clinico del fibroma ossificante con quello delle altre lesioni fibro-ossee; di evidenziare un eventuale comportamento differente tra i vari sottotipi istologici; di descrivere i vantaggi, i limiti e i risultati della chirurgia endoscopica endonasale rispetto ai dati presenti in letteratura. Abbiamo analizzato retrospettivamente 11 pazienti affetti da fibroma ossificante naso-sinusale e trattati in un centro ospedaliero di terzo livello. Tutti i pazienti sono stati sottoposti a TC. La RM è stata eseguita in caso di coinvolgimento del basicranio o in caso di recidiva. Una biopsia pre-operatoria è stata effettuata nei casi in cui la massa era raggiungibile per via endoscopica. Un paziente è stato sottoposto a embolizzazione pre-operatoria ed ha riportato una cecità monolaterale al termine della procedure. In base alla localizzazione, l’exeresi del tumore è stata eseguita con un approccio endoscopico (7 pazienti), esterno (3), combinato (1). Istologicamente 5 pazienti hanno riportato un sottotipo convenzionale, 5 la variante giovanile psammomatoide associata in un caso a cisti aneurismatica ossea, e un paziente la variante giovanile trabecolare. Tre pazienti affetti dalla variante istologica giovanile psammomatoide hanno presentato un’invasione del basicranio e sono stati sottoposti ad exeresi subtotale per via endoscopica che ha richiesto in seguito, a causa di un aumento di volume del residuo, un secondo intervento per via transbasale. I reperti clinici, radiologici e istologici dovrebbero essere considerati insieme per una accurata diagnosi differenziale tra le lesioni fibro-ossee. Ulteriori studi sono necessari per concludere se la localizzazione e l’estensione del fibroma ossificante al momento della diagnosi sono più importanti della variante istologica. L’approccio endoscopico è la prima opzione nella maggior parte dei casi anche se in alcuni selezionati pazienti l’approccio esterno risulta ancora necessario

Sex-Chromosome Homomorphy in Palearctic Tree Frogs Results from Both Turnovers and X-Y Recombination.

Contrasting with birds and mammals, poikilothermic vertebrates often have homomorphic sex chromosomes, possibly resulting from high rates of sex-chromosome turnovers and/or occasional X-Y recombination. Strong support for the latter mechanism was provided by four species of European tree frogs, which inherited from a common ancestor (∼ 5 Ma) the same pair of homomorphic sex chromosomes (linkage group 1, LG1), harboring the candidate sex-determining gene Dmrt1. Here, we test sex linkage of LG1 across six additional species of the Eurasian Hyla radiation with divergence times ranging from 6 to 40 Ma. LG1 turns out to be sex linked in six of nine resolved cases. Mapping the patterns of sex linkage to the Hyla phylogeny reveals several transitions in sex-determination systems within the last 10 My, including one switch in heterogamety. Phylogenetic trees of DNA sequences along LG1 are consistent with occasional X-Y recombination in all species where LG1 is sex linked. These patterns argue against one of the main potential causes for turnovers, namely the accumulation of deleterious mutations on nonrecombining chromosomes. Sibship analyses show that LG1 recombination is strongly reduced in males from most species investigated, including some in which it is autosomal. Intrinsically low male recombination might facilitate the evolution of male heterogamety, and the presence of important genes from the sex-determination cascade might predispose LG1 to become a sex chromosome

The Efficacy of Pharmacotherapy for Decreasing the Expansion Rate of Abdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis

BACKGROUND: Pharmacotherapy may represent a potential means to limit the expansion rate of abdominal aortic aneurysms (AAAs). Studies evaluating the efficacy of different pharmacological agents to slow down human AAA-expansion rates have been performed, but they have never been systematically reviewed or summarized. METHODS AND FINDINGS: Two independent reviewers identified studies and selected randomized trials and prospective cohort studies comparing the growth rate of AAA in patients with pharmacotherapy vs. no pharmacotherapy. We extracted information on study interventions, baseline characteristics, methodological quality, and AAA growth rate differences (in mm/year). Fourteen prospective studies met eligibility criteria. Five cohort studies raised the possibility of benefit of beta-blockers [pooled growth rate difference: -0.62 mm/year, (95%CI, -1.00 to -0.24)], but this was not confirmed in three beta-blocker RCTs [pooled RCT growth rate difference: -0.05 mm/year (-0.16 to 0.05)]. Statins have been evaluated in two cohort studies that yield a pooled growth rate difference of -2.97 (-5.83 to -0.11). Doxycycline and roxithromycin have been evaluated in two RCTs that suggest possible benefit [pooled RCT growth rate difference: -1.32 mm/year (-2.89 to 0.25)]. Studies assessing NSAIDs, diuretics, calcium channel blockers and ACE inhibitors, meanwhile, did not find statistically significant differences. CONCLUSIONS: Beta-blockers do not appear to significantly reduce the growth rate of AAAs. Statins and other anti-inflammatory agents appear to hold promise for decreasing the expansion rate of AAA, but need further evaluation before definitive recommendations can be made