Less-invasive off-pump ventricular assist device implantation in regional paravertebral analgesia

We describe the clinical course and treatment of a 58-year-old male with a primary cardiogenic shock, who underwent a minimally invasive off-pump ventricular-assist-device (VAD) implantation with the aid of paravertebral regional analgesia. He was extubated soon after the procedure, in the operating room, with the aim to reduce the right ventricle impairment. We illustrate how a minimally invasive implant may improve the clinical outcomes of VAD patients shortening their return time to active life.     

Control of type III secretion activity and substrate specificity by the cytoplasmic regulator PcrG

Pathogenic Gram-negative bacteria use syringe-like type III secretion systems (T3SS) to inject effector proteins directly into targeted host cells. Effector secretion is triggered by host cell contact, and before contact is prevented by a set of conserved regulators. How these regulators interface with the T3SS apparatus to control secretion is unclear. We present evidence that the proton motive force (pmf) drives T3SS secretion in Pseudomonas aeruginosa, and that the cytoplasmic regulator PcrG interacts with distinct components of the T3SS apparatus to control two important aspects of effector secretion: (i) It coassembles with a second regulator (Pcr1) on the inner membrane T3SS component PcrD to prevent effectors from accessing the T3SS, and (ii) In conjunction with PscO, it controls protein secretion activity by modulating the ability of T3SS to convert pmf.Many Gram-negative bacterial pathogens rely on a type III secretion system (T3SS) to promote disease by directly injecting effector proteins into the cytoplasm of host cells. This apparatus consists of a base that spans the bacterial envelope and a needle that projects from the base and ends in a specialized tip structure. The bacterium secretes two translocator proteins via the T3SS, which insert into the host cell membrane to form a pore, through which effector proteins are then transferred (1, 2).One of the hallmarks of type III secretion is that export of effector proteins is triggered by host cell contact (3–5). The secretion apparatus is fully assembled before cell contact, but effector secretion is prevented through the concerted action of needle tip-associated proteins and regulators that control secretion from the bacterial cytoplasm.In most systems, the needle tip protein prevents premature effector secretion, most likely by allosterically constraining the T3SS in an effector secretion “off” conformation (6–10). PcrG, the needle tip protein chaperone, as well as PopN, a member of the YopN/MxiC family of proteins, control effector secretion from the bacterial cytoplasm in Pseudomonas aeruginosa. PcrG’s regulatory function is independent of its function in promoting the export of needle tip protein PcrV. Deletion of pcrG or pcrV results in partial deregulation of effector secretion, whereas removal of both genes results in high-level secretion of effectors (8). In some bacteria, the needle tip protein promotes its own export with the aid of a self-chaperoning domain, rather than with a separate export chaperone (11). Recent evidence suggests that in these systems, the needle tip protein itself also regulates effector secretion from the cytoplasm, in addition to its regulatory role at the T3SS needle tip (12). The mechanism of this regulation is unclear.YopN/MxiC family proteins, PopN in P. aeruginosa, are T3SS regulators that are exported once effector secretion is triggered (13–17). These proteins control effector secretion from the bacterial cytoplasm (18–20). P. aeruginosa PopN and the closely related YopN associate with three other proteins that are required to prevent premature effector secretion (21–23). For PopN, these three proteins are Pcr1, Pcr2, and PscB. Pcr2 and PscB form a heterodimeric export chaperone, and Pcr1 is thought to tether the PopN complex to the apparatus (23). The prevailing model for explaining how PopN and related regulators control effector secretion is that they partially insert and plug the secretion channel while being tethered to the T3SS, either directly via a C-terminal interaction or indirectly via a C-terminal–associated protein, i.e., Pcr1 in P. aeruginosa (19, 20). The apparatus component with which these regulators interact is unknown, however.Triggering of effector secretion results in the rapid injection of effector proteins into the host cell (4, 5). How this rapid burst of secretion is energized is a matter of some controversy. The flagellum, which also uses a type III secretion mechanism, uses the proton motive force (pmf) to catalyze the rapid export of flagellar subunits. In fact, secretion is possible in mutants lacking the flagellum-associated ATPase, FliI, if the associated regulatory protein, FliH, is eliminated as well (24–26). The pmf’s contribution to the rate of secretion relative to the ATPase has been questioned in the case of virulence-associated T3SS (27), where removal of the ATPase results in a complete block of secretion (28, 29) that is not alleviated by deletion of the associated FliH homolog (30).Here we present evidence that export via the P. aeruginosa T3SS is energized primarily by the pmf, thereby offering a unified model for how protein secretion is energized in all T3SSs. The cytoplasmic T3SS regulator PcrG controls both the access of effectors to the T3SS and, surprisingly, the secretion activity of the apparatus. These two functions are controlled by separate regions of PcrG. Control of secretion activity involves the central portion of PcrG as well as PscO, which regulate the pmf-dependent export of secretion substrates. Mutants that up-regulate translocator secretion without turning on effector export confirm that effector secretion is not blocked by physical obstruction of the secretion channel. Instead, access of effectors to the T3SS is controlled by the C terminus of PcrG in conjunction with the PopN complex through an interaction with the inner membrane T3SS component PcrD. This protein complex likely blocks an acceptor site for effectors. Thus, PcrG is a multifaceted protein that, along with its export chaperone function, serves as a brake and a switch to control effector secretion.     

Conventional risk factors and acute coronary syndrome during a period of socioeconomic transition: population-based case-control study in Tirana, Albania

Aim

To assess the association between conventional risk factors and acute coronary syndrome in Albania, a transitional country in Southeast Europe.

Methods

A population-based case-control study was conducted in Tirana in 2003-2006. A total of 467 consecutive patients with nonfatal acute coronary syndrome were recruited. There were 370 men with mean ± standard deviation (SD) age of 59.1 ± 8.7 years and 97 women with mean±SD age of 63.3 ± 7.1 years. The control group comprised a population-representative sample of Tirana residents. In the control group, there were 469 men with mean±SD age of 53.1 ± 10.4 years and 268 women aged 54.0 ± 10.9 years. A structured questionnaire on demographic, socioeconomic, psychosocial factors, and health behaviors was administered. Physical measurements included anthropometrics and blood pressure. Venous blood and adipose tissue aspirations from the gluteal region were frozen-stored for future analysis. Multivariable-adjusted logistic regression was used to assess the independent associations of conventional risk factors with acute coronary syndrome.

Results

Upon adjustment for covariates, family history of coronary heart disease was found to be a strong predictor of acute coronary syndrome in both men (odds ratio [OR], 3.70; 95% confidence interval [CI], 2.58-5.30) and women (OR, 4.53; 2.40-8.57). Waist-to-hip ratio in men (OR, 4.03; 2.83-5.73) and obesity in women (OR, 3.31; 1.54-7.14) were strongly associated with acute coronary syndrome. In men, but not in women, there was a significant association with hypertension and current smoking (P = 0.011 and P<0.001, respectively). Diabetes was not significantly independently associated in either sex.

Conclusion

Classical risk factors predicted coronary heart disease in Albania, similarly as in the rest of the world, although associations with family history and anthropometric indices were stronger. These findings are resulting largely from the heterogeneous adoption of lifestyles conducive to increased coronary risk in transitional countries, and they point to the urgent need for targeted public health interventions.The relationship between coronary heart disease and risk factors such as smoking, high blood pressure, diabetes, obesity, and distribution of body fat is well established in developed countries (1-4). However, data on conventional risk factors, their patterns, determinants, and associations with coronary heart disease are scarce for the transitional countries of South East Europe. Unique among former communist countries in Southeast Europe, Albania was under Stalinist communist regime, and following the breakdown of this rigid government in 1990, it experienced a major social, cultural, and economic upheaval (5). Over the past 15 years changes in life-style (diet, tobacco, alcohol consumption, and physical exercise) have taken place, particularly in urban settings (6-8). The available evidence suggests an increase in alcohol intake, particularly among men (6). Smoking appears to have increased too, although smuggling makes it very difficult to validly estimate cigarette consumption in Albania (7). In 2001, the lifetime prevalence of smoking in Tirana was 61% in men and 24% in women (8). Furthermore, in 2001, 49% of men and 58% of women in Tirana reported largely sedentary leisure time activities such as reading and watching television (9). Although there is little information about cardiovascular disease occurrence in Albania, available data suggest that cardiovascular disease mortality may have increased over the past few years (10,11), and that cardiovascular disease morbidity (based on hospital admission counts) in both Tirana and the whole country has been increasing continually in the last decade (10).In this context, we undertook a population-based case-control study of coronary heart disease in Tirana between June 2003 and January 2006. Here, we report on the association of selected conventional risk factors such as smoking, anthropometric indices, hypertension, diabetes, and family history of coronary heart disease with acute coronary syndrome.     

How to evaluate the outflow tract of LVAD after minimally invasive implantation by 3D CT-scan

During a minimally invasive implantation technique, the outflow graft of left ventricular assist device (LVAD) is tunnelled blindly through the pericardium or left pleura, with an inability to assess for twisting or malposition. Three-dimensional computed tomography scan (CT-scan) has a role in qualitative evaluation of the different outflow tract configurations. The different surgical minimally invasive approaches include: (a) mini-sternotomy and left mini-thoracotomy, (b) right mini-thoracotomy and left mini-thoracotomy, (c) subclavian artery access and left mini-thoracotomy. The outflow graft could be anastomosed to the left axillary artery or the ascending aorta. CT-scan reconstruction using syngo InSpace4D (Siemens, Muenchen, Germany) was used to provide fast segmentation and high-resolution images. The 3D reconstructions permit an evaluation of different anastomosis configurations and to assess the route of outflow graft.     

Low vitamin D level is not associated with increased incidence of rheumatoid arthritis

To evaluate the association of vitamin D level with incident rheumatoid arthritis (RA) in a patient population using electronic health records (EHR). Case–control study with data extracted from EHR from 1/1/2001 to 12/31/2012 in the Geisinger Health System (GHS). Incident RA was defined as International Classification of Disease-9 code 714.0 twice by a GHS rheumatologist. Patients were identified at time of RA diagnoses and were matched 1:5 for age and gender with non-RA controls. Vitamin D levels were identified and extracted prior to RA diagnosis. The subjects were followed retrospectively with regard to their vitamin D levels; the most recent value of vitamin D prior to the RA diagnosis was used in the analysis. Vitamin D levels were treated both as continuous and categorical with two different cutoff values, 30 and 20 ng/ml. The association between vitamin D and RA was presented as the odds ratios with 95 % confidence intervals (OR, 95 % CI) from a conditional logistic regression model adjusting for obesity and smoking status. A total of 270 patients with incident RA and 1,341 matched controls were identified. The RA patients were 83.3 % female with median age at RA diagnosis of 62 years. The adjusted OR (95 % CI) for the association of vitamin D levels with incident RA compared with controls was 1.00 (0.99, 1.01), 0.98 (0.75, 1.29) and 1.12 (0.80, 1.57) for continuous, <30 and <20 ng/ml vitamin D levels, respectively. Subgroup analysis according to gender or rheumatoid factor positivity yielded similar results. In this patient population, vitamin D levels were not associated with the development of RA.     

Coronary Artery Bypass Grafting in Elderly Patients: Insights from a Comparative Analysis of Total Arterial and Conventional Revascularization

The benefits of total arterial (TAR) versus conventional (CR) revascularization are controversial in the higher-risk cohort of elderly patients. Taking for granted its benefit on long-term survival, we evaluated the effect of TAR on safety (death, myocardial infarction, and stroke) of patients undergoing CABG. Between 2000 and 2009, 487 patients >75 years underwent isolated CABG at our institution (150 TAR and 337 CR). Patients with arterial free-grafts were excluded. After propensity matching, the outcomes of 131 TAR and 127 CR patients were compared. TAR patients had lower incidence of post-operative myocardial infarction (p?=?0.025) and stroke (p?=?0.005). They also experienced shorter intensive care unit (p?=?0.046) and ward stay (p?=?0.028), lower output of TnI (p?=?0.035), and less wound complications (leg included) (p?=?0.0001), while mortality was comparable (p?=?0.57). In our cohort of elderly patients with multivessel disease, TAR was associated with lower rates of myocardial infarction, stroke, and shorter hospital stay.     

How to implant the Jarvik 2000 post-auricular driveline: evolution to a novel technique

Journal of Artificial Organs - The post-auricular (PA) driveline positioning for percutaneous power delivery is a specific feature of the Jarvik 2000 FlowMaker LVAD. We applied several technical...     

Bilateral mini‐thoracotomy approach for minimally invasive implantation of HeartMate 3

Left ventricular assist devices (LVADs) are an established option for the treatment of end‐stage heart failure. Last‐generation devices are characterized by a miniaturized pump size, allowing for intra‐pericardial placement. This feature enabled the introduction of less‐invasive implantation techniques, which have been linked to many favorable effects. The HeartMate 3 LVAD is a continuous‐flow centrifugal pump, recently introduced for clinical use. Here, we describe the minimally invasive implantation of the HeartMate 3 through a bilateral mini‐thoracotomy.