Preoperative thrombolysis is associated with improved vein patency and functional outcomes after first rib resection in acute Paget-Schroetter syndrome.

INTRODUCTION: Most patients with acute Paget-Schroetter syndrome (PSS) present in one of two manners: (1) thrombosis managed initially with thrombolysis and anticoagulation and then referred for surgery, and (2) initial treatment with anticoagulation only and later referral for surgery. Definitive benefits of thrombolysis in the acute period (the first 2 weeks after thrombosis) over anticoagulation alone have not been well reported. Our goal was to compare patients managed with early thrombolysis and anticoagulation followed by first rib resection (FRR) and later postoperative venography with venoplasty (PTA) with those managed with anticoagulation alone followed by FRR and PTA using vein patency assessed with venography and standardized outcome measures. METHODS: We reviewed a prospectively collected database from 2000 to 2019. Two groups were compared: those managed with early thrombolysis at our institution (Lysis) and those managed with anticoagulation alone (NoLysis). All patients underwent FRR. Venography was routinely performed before and after FRR. Standardized outcome measures included Quick Disability of Arm, Shoulder, and Hand (QuickDASH) scores and Somatic Pain Scale. RESULTS: A total of 50 Lysis and 50 NoLysis patients were identified. Pre-FRR venography showed that thrombolysis resulted in patency of 98% of veins, whereas 78% of NoLysis veins were patent. After FRR, postoperative venography revealed that 46 (92%) patients in the Lysis group and 37 (74%) patients in the NoLysis group achieved vein patency. Thrombolysis was significantly associated with final vein patency (odds ratio: 17 [4-199]; P < .001). Lysis patients had a trend toward lower QuickDASH scores from pre-FRR to post-FRR compared with NoLysis patients with a mean difference of -16.4 (±19.7) vs -5.2 (±15.6) points (P = .13). The difference in reduction of Somatic Pain Scale scores was not statistically significant. CONCLUSIONS: Thrombolysis as initial management of PSS, combined with anticoagulation, followed by FFR and VenoPTA resulted in improved final vein patency and may lead to an improved functional outcome measured with QuickDASH scores. Therefore, clinical protocols using thrombolysis as initial management should be considered when planning the optimal treatment strategy for patients with acute PSS.

A new approach of immunotherapy against Crotalus snakes envenoming: ostrich (Struthio camelus) egg yolk antibodies (IgY-technology) / Un nuevo enfoque de inmunoterapia contra el envenenamiento de serpientes Crotalus: anticuerpos de yema de huevo de avestruz (Struthio camelus) (tecnología IgY)

Abstract Crotalid envenomation is a neglected collective health problem involving many countries in America, which need secure and inexpensive snake anti-venom treatments. Here, high antibody titers (IgY) were raised in the Ostrich (Struthio camelus) egg yolk by immunizing with the venom of Venezuelan venomous Crotalus snakes. Ostriches were immunized with a pool of venoms from common rattlesnake (Crotalus durissus cumanensis), Uracoan rattlesnake (Crotalus vegrandis), Guayana rattlesnake (Crotalus durissus ruruima) and black rattlesnake (Crotalus pifanorum). The anti-snake venom antibodies were prepared from egg yolk by the water dilution method, enriched by the addition of caprylic acid (CA) and precipitation with ammonium sulfate at 30% (W/V). The purity and molecular mass of the final product was satisfactory, yielding a single ∼ 175 kDa band in SDS-PAGE gels ran under non-reducing conditions. In the immunoblot analysis, specific binding of the antivenom was observed with most venom proteins. The LD50 was 16.5 g/mouse (825 μg/kg body weight). High titers of IgY against Crot/pool venom were shown by ELISA. The median effective dose (ED50) was 19.66 mg/2LD50. IgY antibodies neutralized efficiently the Crot/pool venom lethality. As far as we know, this is the first anti-snake venom produced in ostriches, which could make this technology an affordable alternative for low-income countries, since it is likely to produce manteniabout 2-4 g of IgY per ostrich egg. Hence, almost 400 g of IgY can be purified from only one ostrich during a year. In addition, there are enormous differences in the cost of investment in the maintenance of horses, from the points of view of infrastructure, feeding and veterinary care, in which the cost can reach USD 100 per animal per day, compared to a maintenance cost of USD 146 per month per producing bird. These results are encouraging and could easily be extrapolated to the manufacturing of other antivenoms and antitoxins as well, as they could be applied to the manufacturing of potential diagnostic tools.

Resumen El envenenamiento por crotálidos es un problema de salud colectiva desatendido, que involucra a muchos países del continente americano, los cuales necesitan tratamientos seguros y económicos. En este trabajo, se obtuvieron títulos altos de anticuerpos (IgY) producidos en yema de huevo de avestruz (Struthio camelus) mediante la inmunización con el veneno de serpientes venezolanas del genero Crotalus. Se inmunizaron avestruces con una colección de veneno de serpientes de cascabel común (Crotalus durissus cumanensis), cascabel de Uracoa (Crotalus vegrandis), cascabel de Guayana (Crotalus durissus ruruima) y cascabel negra (Crotalus pifanorum). Los anticuerpos anti-veneno de serpiente se prepararon a partir de yema de huevo por el método de dilución en agua, enriquecidos mediante la adición de ácido caprílico (CA), seguido de una precipitación con sulfato de amonio al 30% (P/V). La pureza y masa molecular de los anticuerpos (IgY) se definieron mediante ensayos de SDS-PAGE nativos y las masas moleculares se establecieron electroforéticamente, obteniéndose una única banda de IgY de ∼ 175 kDa. El análisis de inmunotransferencia mostró la unión específica del antiveneno con la mayoría de las proteínas del veneno. La DL50 fue de 16,5 μg/ratón (825 μg / kg de peso corporal); Se mostraron títulos altos de IgY contra el veneno de Crot / pool mediante ELISA. La dosis mediana efectiva (DE50) fue de 19,66 mg/2 LD50. Los anticuerpos IgY neutralizaron eficazmente la letalidad del veneno de Crot / pool. Hasta donde sabemos, se trata del primer antídoto de serpiente producido en avestruces, lo que podría abaratar la producción de este tratamiento en países del tercer mundo. Ya que es probable que se obtengan alrededor de 2-4 g de IgY por huevo de avestruz. Por lo tanto, se podrían purificar casi 400 g de IgY de un solo avestruz durante un año. Asimismo, debido a las enormes diferencias en el costo de inversión en el mantenimiento de los caballos desde el punto de vista de infraestructura, alimentación y atención veterinaria, en los que el costo puede llegar a los 100 USD por día, frente a los 146 USD por mes de mantenimiento de la producción de aves. Estos resultados abren un campo terapéutico, para la fabricación de otros antivenenos contra un amplio espectro de toxinas y también como probables herramientas de diagnóstico.

Evaluation of health outcomes after the implementation of rotational thromboelastometry in patients undergoing cardiac surgery.

BACKGROUND: Viscoelastic tests (rotational thromboelastometry, ROTEM®), together with the implementation of a specific algorithm for coagulation management in cardiac surgery, enable perioperative coagulopathy to be better controlled. METHODS: Retrospective cohort study including 675 patients who underwent cardiac surgery with cardiopulmonary bypass. The incidence of allogeneic blood transfusions and clinical postoperative complications were analyzed before and after ROTEM® implementation. RESULTS: Following viscoelastic testing and the implementation of a specific algorithm for coagulation management, the incidence of any allogeneic blood transfusion decreased (41.4% vs 31.9%, p = .026) during the perioperative period. In the group monitored with ROTEM®, decreased incidence of transfusion was observed for packed red blood cells (31.3% vs 19.8%, p = .002), fresh frozen plasma (9.8% vs 3.8%, p = .008), prothrombin complex concentrate administration (0.9% vs 0.3%, p = .599) and activated recombinant factor VII (0.3% vs 0.0%, p = .603). Increased incidence was observed for platelet transfusion (4.8% vs 6.8%, p = .530) and fibrinogen concentrate (0.9% vs 3.5%, p = .066), tranexamic acid (0.0% vs 0.6%, p = .370) and protamine administration (0.6% vs 0.9%, p = .908). Similar results were observed in the postoperative period, but with a decreased incidence of platelet transfusion (4.8% vs 3.8%, p = .813). In addition, statistically significant reductions were detected in the incidence of postoperative bleeding (9.5% vs 5.3%, p = .037), surgical reexploration (6.0% vs 2.9%, p = .035), and length of Intensive Care Unit (ICU) stay (6.0 days vs 5.3 days, p = .026). CONCLUSIONS: The monitoring of hemostasis by ROTEM® in cardiac surgery, was associated with decreased incidence of allogeneic blood transfusion, clinical hematologic postoperative complications and lengths of ICU stay.

Elective Resection of Symptomatic Arteriovenous Fistulae and Grafts in Patients with Functioning Renal Allografts at A High Volume Transplant Hospital.

OBJECTIVE: Patients with functioning renal allografts may need ligation of pre-existing hemodialysis conduits. Chronic immunosuppression for renal allografts may adversely affect wound healing and perioperative complications following these procedures. We sought to analyze outcomes following elective ligation and resection of symptomatic arteriovenous (AV) access in immunosuppressed patients with renal allografts no longer requiring dialysis at a high-volume renal transplant hospital. METHODS: We retrospectively reviewed procedure codes for hemodialysis access resection and revision from 2014-2020 at a single academic tertiary care hospital. Patients who underwent complete or subtotal dialysis access resection with a functioning renal allograft were included for analysis of preoperative, operative, and postoperative outcomes. We performed descriptive statistics, and student's t-test using Microsoft Excel. RESULTS: Thirty-four patients met inclusion criteria. The majority were male, 56%, and the most common causes of renal failure were hypertension and diabetes, respectively. Ligation and resection of proximal upper extremity access was performed in 68%. The mean operative time was 126 minutes with pain being the most common indication for intervention. Four patients required arterial reconstruction. Mean postoperative follow-up was 13 months. Arm pain and swelling resolved in 100% and 88% of patients following AV access resection, respectively. No impairment in mean postoperative glomerular filtration rates were noted. One patient required hemodialysis and died three months after fistula resection following complications from treatment of a newly diagnosed neuroendocrine tumor and subsequent fungemia, CONCLUSION: Elective operative resection of symptomatic AV access may be performed safely in immunosuppressed patients with functioning renal transplants. The risk of allograft impairment and/or failure as a result of AV access resection in our series was low. Elective ligation and resection can be achieved with low mortality, excellent symptomatic relief, and few wound complications despite chronic immunosuppression.

Short- and intermediate-term clinical outcome comparison between laparoscopic and robotic-assisted median arcuate ligament release.

While laparoscopic median arcuate ligament (MAL) release remains the most common approach, robotic-assisted MAL release has been increasingly performed by several institutions. This study aims to compare surgical outcomes between laparoscopic and robotic-assisted MAL release. This is a retrospective study of patients undergoing laparoscopic and robotic-assisted MAL release in a teaching hospital from January 1999 to December 2018. Intraoperative and postoperative outcomes as well as short- and intermediate-term clinical outcomes were compared between the two groups. A total of 16 laparoscopic and 18 robotic cases were included. Demographics and baseline characteristics were similar between the two comparison groups. Median operative time was shorter in the robotic group [179.5 (IQR 127.3-225) vs. 106 (IQR 80.8-122.8) minutes; p < 0.001]. The rates of conversion to open operation were similar in both groups (6.3% vs. 5.6%, p = 0.99). Conversions to laparotomy were performed due to bleeding and extensive adhesions in one laparoscopic case and due to technical difficulties in a patient with narrow body habitus in the robotic group. Postoperative complication rates were similar (12.5% vs. 16.7%, p = 0.99), all in grade I and II. Complete pain resolution rates (37.5% vs. 44.4%, p = 0.93), symptom recurrence rates (37.5% vs. 27.8%, p = 0.93), and overall clinical improvement at last follow-up (87.5% vs. 77.8%, p = 0.66) were not statistically different. Both laparoscopic and robotic-assisted MAL release offer similar short- and intermediate-term clinical outcomes. A shortened operative time may be achieved by incorporating the robot platform.

Factors Associated with Symptomology of Celiac Artery Compression and Outcomes following Median Arcuate Ligament Release.

BACKGROUND: This study aims to identify potential risk factors for becoming symptomatic in patients with radiographic celiac artery compression (CAC) as well as prognostic factors for patients with median arcuate ligament syndrome (MALS) who underwent surgical ligament release. METHODS: This is a retrospective cohort study of patients with findings of CAC on computed tomography or magnetic resonance angiography (CT/MRA) who were asymptomatic and who were diagnosed with MALS at a single university hospital between January 2001 and 2018. RESULTS: Following a review of 1,330 CT/MRA reports, a total of 109 patients were identified as having radiographically apparent CAC. Among these, 48 (44.0%) patients were symptomatic. Univariate comparison between those with and without symptoms showed that symptomatic patients were more commonly younger than 30 years old [17/48 (35.4%) vs. 8/61 (13.1%), P = 0.006], had a history of prior abdominal surgery [25/48 (52.1%) vs. 18/61 (29.5%), P = 0.017], and had high-grade stenosis [32/43 (74.4%) vs. 25/61 (41.0%), P = 0.001]. Among 41 included patients who underwent surgical release of the median arcuate ligament including open, laparoscopic, and robotic approaches, 82.9% reported overall clinical improvement, 5/41 (12.2%) reported persistent pain, and 13/36 (36.0%) experienced pain recurrence. The only identified risk factor associated with symptom recurrence was American Society of Anesthesiologists class III [7/13 (53.8%) vs. 4/23 (17.4%), P = 0.029]. CONCLUSIONS: The severity of stenosis and prior abdominal surgery both contributed to symptom development in patients with radiographically apparent CAC from the median arcuate ligament.

A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis.

The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman's reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive vaginal health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 31 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 3 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, reference ranges were determined in a group of 50 self-reported healthy women. The HPV sequencing portion of the test was evaluated against the digene High-Risk HPV HC2 DNA test. For hrHPV genotyping, agreement was 95.3% with a kappa of 0.804 (601 samples); after removal of samples in which the digene hrHPV probe showed cross-reactivity with lrHPV types, the sensitivity and specificity of the hrHPV genotyping assay were 94.5% and 96.6%, respectively, with a kappa of 0.841. For lrHPV genotyping, agreement was 93.9% with a kappa of 0.788 (148 samples), while sensitivity and specificity were 100% and 92.9%, respectively. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.

Robotic-assisted laparoscopic median arcuate ligament release: 7-year experience from a single tertiary care center.

BACKGROUND: Despite previous reports of robotic-assisted laparoscopic release for median arcuate ligament syndrome (MALS), the safety and efficacy profile of this approach has been difficult to establish due to the rarity of this diagnostic entity. We aim to present our experience from a tertiary minimally invasive surgery referral center. METHODS: A case series was performed whereby all patients who underwent robotic-assisted MAL release from July 2010 to July 2017 at our institution were included. Diagnosis of MALS was made based on consideration of symptom presentation, celiac artery duplex ultrasound, and corresponding findings on Computed Tomography (CT) or Magnetic Resonance Angiography (MRA). Outcomes up until the most recent clinic follow-up were reviewed. RESULTS: A total of 13 patients underwent robotic-assisted MAL release. Patients' age ranged from 16 to 71 years (mean 38 years) and consisted primarily of females (76.9%). Most common presenting symptoms included postprandial pain (76.9%), weight loss (76.9%), nausea and vomiting (76.9%). Mean symptom duration was 3 years (range 1-10 years). No intraoperative complications. None required conversion to open surgery. One case required a conversion back to laparoscopy due to anatomical complexity. The mean operative time for successfully completed robotic cases was 94.6 min (range 52-120 min), and for all cases including converted case was 103.5 min (52-210 min). Mean follow-up duration was 19.7 months (range 1-77 months). During subsequent follow-up, a 30-day readmission rate of 23.1% was observed. All but one of the patients experienced prompt symptom improvement. Four patients had symptom recurrence during follow-up. CONCLUSIONS: Our experience demonstrates that the robotic-assisted approach to MAL release may be safe and efficacious in selected patients. Prospective comparative studies are required to further evaluate its outcomes against conventional laparoscopic approach, the current gold standard.

El agonista del receptor de serotonina-2C Ro 60-0175 decrementa la expresión de la sensibilización locomotora inducida por etanol / Serotonin-2C receptor agonist Ro 60-0175 decreases the expression of ethanol-induced locomotor sensitization

Resumen: El objetivo principal de la presente investigación fue evaluar los efectos del agonista 5-HT2C Ro 60-0175 en la expresión de la sensibilización locomotora inducida por la administración de etanol. Además, también se evaluaron los efectos del antagonista 5-HT2C SB 242084 sobre los efectos del Ro 60-0175 en la sensibilización locomotora producida por etanol para determinar si los efectos del Ro 60-0175 resultan de una acción específica sobre los receptores 5-HT2C. Diferentes grupos de ratas se sometieron al desarrollo de sensibilización locomotora producida por etanol. En las pruebas de expresión de la sensibilización locomotora se evaluaron los efectos del Ro 60-0175 y del SB 242084 sobre la sensibilización locomotora producida por etanol. Adicionalmente se evaluó el pretratamiento con SB 242084 sobre los efectos del Ro 60-0175 en la sensibilización locomotora producida por etanol. Los resultados mostraron que el Ro 60-0175 disminuyó la sensibilización locomotora producida por etanol y que este efecto fue prevenido por el pretratamiento con SB 242084. Estos resultados sugieren que los receptores 5-HT2C juegan un papel modulatorio en la sensibilización locomotora producida por etanol.

Abstract: The main goal of the present research was to evaluate the effects of 5-HT2C receptor agonist Ro 60-0175 on the expression of ethanol-induced locomotor sensitization. In order to determine if these effects result from a specific action of Ro 60-0175 on 5-HT2C receptors, we also examined the effects of the selective 5-HT2C receptor antagonist SB 242084 on Ro 60-0175's effects on the ethanol-induced locomotor sensitization. Different groups of rats were subjected to development of ethanol-induced locomotor sensitization. On the expression tests of the locomotor sensitization the effects of the Ro 60-0175 and SB 242084 on the ethanol-induced locomotor sensitization were evaluated. In addition, the pretreatment with SB 242084 on the effects of Ro 60-0175 on the ethanol-induced locomotor sensitization was also evaluated. The results showed that Ro 60-0175 produced a dose-dependent prevention of the expression of ethanol-induced locomotor sensitization. This effect was reversed by administration of SB 242084. These data suggest that 5-HT2C receptors play a regulatory role on ethanol-induced locomotor sensitization.

Pericarditis postraumática como manifestación del síndrome de lesión postcardiaca: Post-traumatic pericarditis as a manifestation of post cardiac injury syndrome / Post-traumatic pericarditis as a manifestation of post cardiac injury syndrome

La pericarditis constrictiva ocurre cuando el pericardio engrosado y calcificado impide el llenado ventricular adecuado y en consecuencia ocasiona una limitación del volumen cardiaco total. En la actualidad, una de las causas más comunes es el trauma cardiaco. Los cuadros de pericarditis secundarios a daño del pericardio constituyen el síndrome de lesión postcardiaca, el cual incluye pericarditis postinfarto o síndrome de Dressler, síndrome postpericardiotomía y pericarditis postraumática. Se ha decidido utilizar este nuevo término en la medida en que es más incluyente puesto que la lesión inicial también puede estar en el miocardio y no sólo en el pericardio. Su fisiopatología no se conoce por completo, pero cree que puede tener un componente tanto inflamatorio como autoinmune. Usualmente es un diagnóstico de exclusión que requiere tratamiento definitivo con pericardiectomía. A continuación se reporta el caso de una paciente con pericarditis constrictiva posterior a un trauma cerrado de tórax.

Constrictive pericarditis occurs when thickened and calcified pericardium prevents adequate ventricular filling and consequently causes a limitation of the total cardiac output. Currently, one of its most common causes is cardiac trauma. Clinical conditions of pericarditis secondary to pericardial injury constitute the post cardiac injury syndrome which includes post-infarction pericarditis or Dressler syndrome, post-pericardiotomy syndrome and post-traumatic pericarditis. It was decided to use this new term to the extent that is more inclusive, since the initial injury may also be in the myocardium and not only in the pericardium. Its pathophysiology is not completely understood, but is believed to have both an inflammatory and an autoimmune component. Usually it is a diagnosis of exclusion that requires definitive treatment with pericardiectomy. The case of a patient with constrictive pericarditis subsequent to a closed chest trauma is reported.

La administración del antagonista GABA A bicuculina previene los efectos de la administración del agonista 5-HT 1A 8-OH-DPAT en las propiedades discriminativas de la anfetamina / Administration of GABA A receptor antagonist bicuculline prevents the effects of administration of 5-HT 1A receptor agonist on the discriminative properties of amphetamine

Resumen En esta investigación se evaluaron los efectos de la administración sistémica del antagonista GABAA bicuculina sobre los efectos del agonista 5-HT1A 8-OH-DPAT en las propiedades discriminativas de la anfetamina (ANF) utilizando el condicionamiento de aversión a los sabores. Los resultados mostraron que ni el 8-OH-DPAT, ni la bicuculina, sustituyeron la señal discriminativa de la ANF. Sin embargo, la administración del 8-OH-DPAT disminuyó la señal discriminativa de la ANF, y la administración de la bicuculina, previa a la administración del 8-OH-DPAT más una dosis de ANF, previno el efecto del 8-OH-DPAT sobre la señal discriminativa de la ANF. Estos datos apoyan la hipótesis de que las conductas relacionadas con la adicción a las drogas, como la ANF, involucran diferentes sistemas de neurotransmisión como la DA, la 5-HT y el GABA.

Abstract In this research, the effects of systemic administration of the GABAA receptor antagonist bicuculline on the effects of 5-HT1A receptor agonist 8-OH-DPAT on the discriminative properties of the AMPH using the conditioned taste aversion procedure were evaluated. The results showed that neither 8-OH-DPAT nor bicuculline administration did not substitute for AMPH. However, the 8-OH-DPAT administration decreased the discriminative signal of AMPH and the bicuculline administration, prior to the 8-OH-DPAT administration plus a dose of AMPH prevented the effect of the 8-OH-DPAT on discriminative signal of AMPH. These data support the hypothesis that addiction-related behaviors of drugs such as AMPH involve several neurotransmitter systems such as DA, 5-HT and GABA.

Antibody and cytokine responses to Giardia excretory/secretory proteins in Giardia intestinalis-infected BALB/c mice.

The humoral and cellular responses against excretory/secretory proteins and soluble extracts of Giardia intestinalis were evaluated in the course of experimental G. intestinalis infection in BALB/c mice. Production of IgG1, IgG2a, IgA, and IgE antibodies against excreted/secreted proteins and soluble extract was detected after infection by G. intestinalis. Specific IgA antibody against E/S proteins and soluble extract form intestinal fluids in infected mice was detected by ELISA. The Western blotting identified proteins of 30, 58, 63, and 83 kDa for IgA and IgG, respectively. High proliferation rate in vitro of spleen cell and secretion of interleukin-4 (IL-4) at 21 days p.i. after stimulation with excreted/secreted proteins and low proliferative response in the presence of soluble extract in infected BALB/c mice was observed. High production of interferon gamma (IFN-γ) and interleukin-5 (IL-5) at the time of decreasing cyst output (14-21 days p.i.) in infected mice was recorded, suggesting the important role of these cytokines in the control of the infection. Interestingly, progressive and gradual increase of the interleukin-10 after stimulation with both preparations was recorded from 7 days until 28 days after infection, indicating the possible regulatory effect of these antigens on the immune response during Giardia infection. Therefore, the infection by Giardia duodenalis stimulates a mixed response Th1 and Th2, mainly stimulated by excretory/secretory antigens. The immunogenicity of these antigens may be a suitable for identification of the proteins related with the effective immune response in the course of infection by G. duodenalsis.

The type VI secretion system encoded in Salmonella pathogenicity island 19 is required for Salmonella enterica serotype Gallinarum survival within infected macrophages.

Salmonella enterica serotype Gallinarum is the causative agent of fowl typhoid, a disease characterized by high morbidity and mortality that causes major economic losses in poultry production. We have reported that S. Gallinarum harbors a type VI secretion system (T6SS) encoded in Salmonella pathogenicity island 19 (SPI-19) that is required for efficient colonization of chicks. In the present study, we aimed to characterize the SPI-19 T6SS functionality and to investigate the mechanisms behind the phenotypes previously observed in vivo. Expression analyses revealed that SPI-19 T6SS core components are expressed and produced under in vitro bacterial growth conditions. However, secretion of the structural/secreted components Hcp1, Hcp2, and VgrG to the culture medium could not be determined, suggesting that additional signals are required for T6SS-dependent secretion of these proteins. In vitro bacterial competition assays failed to demonstrate a role for SPI-19 T6SS in interbacterial killing. In contrast, cell culture experiments with murine and avian macrophages (RAW264.7 and HD11, respectively) revealed production of a green fluorescent protein-tagged version of VgrG soon after Salmonella uptake. Furthermore, infection of RAW264.7 and HD11 macrophages with deletion mutants of SPI-19 or strains with genes encoding specific T6SS core components (clpV and vgrG) revealed that SPI-19 T6SS contributes to S. Gallinarum survival within macrophages at 20 h postuptake. SPI-19 T6SS function was not linked to Salmonella-induced cytotoxicity or cell death of infected macrophages, as has been described for other T6SS. Our data indicate that SPI-19 T6SS corresponds to a novel tool used by Salmonella to survive within host cells.

Results of a double-barrel technique with commercially available devices for hypogastric preservation during aortoilac endovascular abdominal aortic aneurysm repair.

OBJECTIVE: To assess technical feasibility and short-term outcome of a novel hypogastric preservation technique in patients with aortoiliac aneurysms using commercially available endografts without device modification. METHODS: Multi-institution review of prospectively acquired database of patients undergoing double-barrel endograft repair of aortoiliac aneurysms. RESULTS: Twenty-two patients underwent endovascular aneurysm repair for aortoiliac aneurysms from 2010 to 2011, with 23 double-barrel hypogastric preservation procedures successfully completed in 21 patients. The technique involved bifurcated main body placement followed by simultaneous deployment of parallel endograft limbs into the external iliac (ipsilateral approach) and hypogastric (contralateral femoral or brachial approach) arteries. Bilateral hypogastric branches were performed in two patients, and unilateral branches with and without contralateral coil embolization were performed in nine and ten patients, respectively. Procedural success rate was 96%, technical success rate (successful implantation with immediate aneurysm exclusion and no observed endoleak) was 88%, and access was fully-percutaneous in 86%. Two type III endoleaks between branch components were noted on completion angiograms, but both resolved spontaneously on follow-up imaging. One type Ib endoleak was noted on postoperative imaging (contralateral to hypogastric branch, repaired with limb extension), as were three type II endoleaks (14%) without sac expansion. Early (<2 weeks) limb occlusion (one external iliac, two hypogastric) occurred in two patients, though no subsequent occlusions have occurred (mean follow-up, 7.2 months; range, 1-20 months). Primary patency for external iliac and hypogastric limbs at 6 months was 95% and 88%, respectively. There were no deaths; complications included groin hematoma in 10% and acute renal insufficiency in 5%. Buttock claudication (n = 4) only occurred in patients who had ipsilateral coil embolization of hypogastric arteries (n = 9) for bilateral iliac aneurysms in which only unilateral hypogastric preservation was performed, resulting in rate of 44% in these patients. CONCLUSIONS: The double-barrel technique for hypogastric preservation is technically feasible across multiple interventionalists using commercially available endografts without device modification. These procedures are associated with minimal morbidity, acceptable short-term limb-patency rates, and reduced buttock claudication compared with those involving contralateral hypogastric embolization.

Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development.

Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3) have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG), and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp) and a metalloprotease (eep), supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1). These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide receptors across the Firmicute phylum.

Early postoperative hemorrhage after first rib resection for vascular thoracic outlet syndrome.

BACKGROUND: Thrombosis and embolization are the most frequent complications associated with the vascular presentation of thoracic outlet syndrome (VTOS). Therefore, surgery for these conditions requires careful balancing of anticoagulation and hemostasis. Our goal is to identify the optimal postoperative anticoagulation management of these patients. METHODS: A prospective database of consecutive patients who have presented to our institution with the diagnosis of thoracic outlet syndrome was reviewed from 1996 through 2010 for instances of postoperative hemorrhage. All venous cases were managed with transaxillary first rib resection followed by postoperative venography and percutaneous angioplasty when required. All arterial cases first underwent thrombolysis, then decompression with transaxillary first and cervical rib resection with concomitant arterial repair when indicated. RESULTS: Over the study period, 423 patients diagnosed with thoracic outlet syndrome underwent 551 procedures. Of these, 108 presented with VTOS (12 arterial and 96 venous). Mean age of the patients in the cohort was 33.7 ± 11.5 years, with 53 women and 55 men. Postoperative hemorrhage occurred in four patients (4%): three venous cases and one arterial case. Three patients required tube thoracostomy (average blood return: 800 mL) and two required video-assisted thoracoscopic surgery for decortication. Age, gender, preoperative anticoagulation, interval from thrombolysis to surgery, operative duration, and operative blood loss had no effect on the risk of bleeding. No hemorrhage occurred in patients treated with postoperative coumadin alone (82 patients) or with no anticoagulant (24 patients). The four cases of hemorrhage occurred only in patients treated with postoperative low-molecular-weight heparin (LMWH; 14 patients; p < 0.01). CONCLUSION: Postoperative hemorrhage was not a common complication of first rib resection for VTOS. In our experience, it occurred exclusively in patients receiving LMWH postoperatively. Postoperative LMWH should be used with caution in patients with VTOS.

Technical modifications for endovascular infrarenal AAA repair for the angulated and dumbbell-shaped neck: the precuff Kilt technique.

BACKGROUND: High risk surgical patients with abdominal aortic aneurysms and difficult infrarenal necks continue to be challenged when performing endovascular repair. Although fenestrated and branched endografts may ultimately be the main method of repair for these patients, their current limited availability has prompted the use of alternative endovascular techniques to enhance success of endovascular aortic aneurysm repair in patients with "dumbbell" shaped and angulated necks. METHODS: A retrospective review of all patients who underwent endovascular abdominal aneurysm repair with a predeployed aortic cuff (Kilt) at University of California, Los Angeles between January 2009 and April 2010 was performed. RESULTS: Four patients underwent initial Kilt placement before endovascular abdominal aortic aneurysm (AAA) repair. The mean age of these patients was 78.0 + 7.0 years. All were American Society of Anesthesiologists class 3 patients with multiple medical comorbidities. All of them had angulated and dumbbell-shaped necks. Median follow-up period was 11 months (8-18 months). All patients had postoperative computed tomography at 1 and 6 months because of their high-risk neck anatomy. One patient was found to have a large type I endoleak on computed tomography 1 month postoperatively. He required placement of an additional aortic cuff and Palmaz stent, after which the endoleak was found to have resolved. There were no open conversions, aneurysm sac enlargement, or perioperative deaths. CONCLUSION: Short-term follow-up suggests that the Kilt technique may be useful in certain high-risk patients with traditionally unfavorable anatomy for endovascular abdominal aortic aneurysm repair. It can be performed with minimal patient morbidity, even in high-risk patients. Anatomic features most amenable to this technique include dumbbell-shaped and angulated infrarenal necks.

Postoperative thrombotic thrombocytopenic purpura after open heart operations.

BACKGROUND: Postoperative thrombotic thrombocytopenic purpura (pTTP) after cardiovascular operations has an alarmingly high mortality rate if untreated. Five patients after coronary artery bypass graft (CABG) procedure were diagnosed with pTTP when they were observed to have a persistent thrombocytopenia associated with symptoms of fever, renal insufficiency, thromboembolic events, or altered mental status in conjunction with a microangiopathic hemolytic anemia (MAHA). A guideline for early diagnosis, followed by timely treatment in these cases, is reviewed. METHODS: A retrospective record review of postoperative patients with thrombocytopenia identified 5 patients that met the criteria for pTTP from 2004 to 2008. We examined these 5 cardiovascular surgical patients in terms of clinical presentation, laboratory data, and outcomes. RESULTS: All patients had the combination of an unexplained thrombocytopenia (platelets < 50,000 mm(3)) in conjunction with a MAHA as determined by the presence of schistocytes. Symptoms of neurologic dysfunction and renal insufficiency developed in all patients. Thromboembolic events were noted in 1 patient. All patients underwent plasmapheresis. In 3 patients, response time to clinical recovery and normalization of hematologic laboratory values after plasmapheresis was 3, 4, and 8 days. Two patients did not recover and died. One patient had a clinical and laboratory recovery after 19 days of plasmapheresis; however, after 11 days, thrombocytopenia with MAHA developed and he died on day 53 from complications related to the operation. CONCLUSIONS: Postoperative TTP should be recognized as a possible pathophysiologic mechanism for unexplained postoperative thrombocytopenia and treatment should be initiated once the diagnosis is established.

Aneurysmectomy with arterial reconstruction of renal artery aneurysms in the endovascular era: a safe, effective treatment for both aneurysm and associated hypertension.

BACKGROUND: Renal artery aneurysms (RAAs) represent a rare vascular pathology with an estimated incidence of <1%. Although an endovascular approach is being increasingly used to treat RAAs, we hypothesized that open surgical repair of RAA, specifically via aneurysmectomy with arterial reconstruction (AAR), is a safe, effective treatment, particularly for those with complex aneurysm anatomy. METHODS: A review was performed of all patients with RAA, identified by ICD-9 codes, from January 2003 to December 2008 seen at a tertiary care medical center. Data were collected regarding patient demographics, aneurysm characteristics, surgical repair, and outcomes, as well as follow-up care. RESULTS: A total of 14 patients (10 women and 4 men; mean age, 48+/-19 years) were included, representing 15 aneurysms. Ten aneurysms underwent open repair via AAR and five were followed nonoperatively. Mean RAA size was larger for those undergoing repair (2.12 cm vs. 1.62 cm, p=0.037). Seven RAAs were repaired in situ with either patch angioplasty or primary repair; three required ex vivo reconstruction; and none underwent bypass. Average operative time was similar for repair type, with a higher blood loss with ex vivo repair. Median length of stay was 5 days (range, 4 to 14 days). Operative repair had no effect on mean systolic blood pressure or GFR. This repair, however, resulted in lower medication requirement for those with concurrent hypertension (2.7 pre vs. 1.6 post, p=0.03). There was a trend toward shorter time until oral intake for retroperitoneal approach compared with transperitoneal. Mean follow-up time was 11.6 months (range, 3 to 30 months). No incidences of rupture, death, nephrectomy, or renal failure occurred in the operative group. CONCLUSION: In the era of endovascular repairs for RAAs, open repair, specifically via AAR, of RAAs remains a safe treatment with low associated morbidity. RAA repair resulted in a reduction in medications for those with associated hypertension. Open repair of RAAs should be the primary treatment modality for complex RAA, with specific consideration given to those with associated hypertension.