Ancient and remote quartzite caves as a novel source of culturable microbes with biotechnological potential.

Quartzite caves located on table-top mountains (tepuis) in the Guyana Shield, are ancient, remote, and pristine subterranean environments where microbes have evolved peculiar metabolic strategies to thrive in silica-rich, slightly acidic and oligotrophic conditions. In this study, we explored the culturable fraction of the microbiota inhabiting the (ortho)quartzite cave systems in Venezuelan tepui (remote table-top mountains) and we investigated their metabolic and enzymatic activities in relation with silica solubilization and extracellular hydrolytic activities as well as the capacity to produce antimicrobial compounds. Eighty microbial strains were isolated with a range of different enzymatic capabilities. More than half of the isolated strains performed at least three enzymatic activities and four bacterial strains displayed antimicrobial activities. The antimicrobial producers Paraburkholderia bryophila CMB_CA002 and Sphingomonas sp. MEM_CA187, were further analyzed by conducting chemotaxonomy, phylogenomics, and phenomics. While the isolate MEM_CA187 represents a novel species of the genus Sphingomonas, for which the name Sphingomonas imawarii sp. nov. is proposed, P. bryophila CMB_CA002 is affiliated with a few strains of the same species that are antimicrobial producers. Chemical analyses demonstrated that CMB_CA002 produces ditropolonyl sulfide that has a broad range of activity and a possibly novel siderophore. Although the antimicrobial compounds produced by MEM_CA187 could not be identified through HPLC-MS analysis due to the absence of reference compounds, it represents the first soil-associated Sphingomonas strain with the capacity to produce antimicrobials. This work provides first insights into the metabolic potential present in quartzite cave systems pointing out that these environments are a novel and still understudied source of microbial strains with biotechnological potential.

Successful Open Chest Epicardial Ablation for Refractory Ventricular Tachycardia in an LVAD Recipient.

A patient with history of dilated cardiomyopathy, a cardiac resynchronization therapy defibrillator, and endocardial ablation presented for refractory ventricular tachycardia 3 years after implantation of a Jarvik 2000 left ventricular assist device (Jarvik Heart, Inc., New York, New York). Open-chest epicardial ablation safely and effectively terminated the arrhythmia, without ventricular tachycardia recurrence at 9-month follow-up and in the absence of complications during the hospital stay. (Level of Difficulty: Advanced.).

Vasopressor Therapy in Cardiac Surgery-An Experts' Consensus Statement.

Hemodynamic conditions with reduced systemic vascular resistance commonly are observed in patients undergoing cardiac surgery and may range from moderate reductions in vascular tone, as a side effect of general anesthetics, to a profound vasodilatory syndrome, often referred to as vasoplegic shock. Therapy with vasopressors is an important pillar in the treatment of these conditions. There is limited guidance on the appropriate choice of vasopressors to restore and optimize systemic vascular tone in patients undergoing cardiac surgery. A panel of experts in the field convened to develop statements and evidence-based recommendations on clinically relevant questions on the use of vasopressors in cardiac surgical patients, using a critical appraisal of the literature following the GRADE system and a modified Delphi process. The authors unanimously and strongly recommend the use of norepinephrine and/or vasopressin for restoration and maintenance of systemic perfusion pressure in cardiac surgical patients; despite that, the authors cannot recommend either of these drugs with respect to the risk of ischemic complications. The authors unanimously and strongly recommend against using dopamine for treating post-cardiac surgery vasoplegic shock and against using methylene blue for purposes other than a rescue therapy. The authors unanimously and weakly recommend that clinicians consider early addition of a second vasopressor (norepinephrine or vasopressin) if adequate vascular tone cannot be restored by a monotherapy with either norepinephrine or vasopressin and to consider using vasopressin as a first-line vasopressor or to add vasopressin to norepinephrine in cardiac surgical patients with pulmonary hypertension or right-sided heart dysfunction.

Veno-Arterial Extracorporeal Membrane Oxygenation in the Adult: A Bridge to the State of the Art.

Despite the technological advancements in the last 40 years, conditions such as refractory cardiogenic shock and cardiac arrest still present a very high mortality rate in real-world clinical practice. In this light, we have reviewed the techniques, indications, contraindications, and results of the socalled Veno-Arterial Extracorporeal Circulatory Membrane Oxygenation (VA-ECMO) in the adult population to evaluate the current results of this temporary cardio-pulmonary support as salvage and/or bridge therapy in the patient suffering from refractory cardiogenic shock or cardio-circulatory arrest. The results are encouraging, especially in the setting of refractory cardiogenic shock and in-hospital cardiac arrest. Among a selected population, the prompt institution of a VA-ECMO may radically change the prognosis by sustaining vital functions while looking for the leading cause or waiting for the reversal of the temporary cardio-respiratory negative condition. The future directions aim to standardized and shared protocols, miniaturization of the machines, and possibly the institution of specialized "ECMO teams" for in and the out-of-hospital institution of the tool.

CPAP Effects on Oxygen Delivery in One-Lung Ventilation During Minimally Invasive Surgical Ablation for Atrial Fibrillation in The Supine Position.

OBJECTIVE: In minimally invasive surgical ablation for atrial fibrillation during video-assisted thoracoscopy surgery, one-lung ventilation (OLV) with a double- lumen tube is commonly employed. In contrast with the majority of thoracic procedures, the patient lies supine; thus, the protective effect of gravity is lost and intrapulmonary shunt remains high. To decrease intrapulmonary shunt and to increase oxygenation, many strategies are utilized: high inspiratory fraction of oxygen (FIO2), positive end-expiratory pressure on the ventilated lung, and continuous positive airway pressure (CPAP) on the deflated lung. DESIGN: The authors performed a prospective, single- center, randomized study to evaluate the effect of additional CPAP in the nonventilated lung on oxygen delivery during surgical ablation for atrial fibrillation via video-assisted thoracoscopy in the supine position. SETTING: University hospital Centro Cardiologico Monzino IRCCS, Milano, Italy. PARTICIPANTS: Twenty-two patients scheduled for minimally invasive surgical ablation for atrial fibrillation. INTERVENTIONS: The patients underwent pressure-controlled ventilation, adjusting inspiratory pressure to obtain a tidal volume of 7 mL/kg while keeping FIO2 constantly 1.0, a respiratory rate to maintain arterial partial pressure of carbon dioxide (PaCO2) between 35 and 40 mmHg, and positive end-expiratory pressure of 5 cmH2O. During OLV, inspiratory pressure was reduced to obtain a tidal volume of 5 mL/kg, maintaining FIO2 of 1.0, a respiratory rate to maintain PaCO2 between 35 and 40 mmHg with capnothorax of 10 cmH2O. The patients were then randomized into the CPAP group (CPAP 10 cmH20 on deflated lung) and NO CPAP group. Inotropic agents (dopamine or dobutamine) were used if cardiac index fell below 1.5 L/min/m2. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients were enrolled, randomized, and completed the study. Median age was 62 years. The difference in arterial partial pressure of oxygen between the 2 groups was shy of significance, p = 0.16. Cardiac index progressively increased during OLV until the end of the procedure in both groups (p < 0.01) and was maintained above 1.5 mL/min/m2 during the whole study time. Arterial oxygen content remained stable during the entire procedure in both groups (p = 0.27). Oxygen delivery index (DO2I) increased significantly during the procedure (p < 0.01); nevertheless, the difference in DO2I between the CPAP and NO CPAP group was nonsignificant (p = 0.61). Intrapulmonary shunt (Qs/Qt) increased during OLV (p < 0.01 for the time effect) and remained high until total lung ventilation was reintroduced. No difference in Qs/Qt was observed between the CPAP and NO CPAP groups (p = 0.98). Similarly, mean pulmonary artery pressure increased significantly during OLV and remained high at the end of the procedure in both groups (time effect p < 0.01). CONCLUSIONS: During OLV for atrial fibrillation surgical ablation in the supine position, CPAP on the deflated lung seemed to be ineffective to reduce Qs/Qt or to increase arterial partial pressure of oxygen and DO2I, provided cardiac output was maintained above 1.5 L/min/m2.

EEG to Identify Attempted Movement in Unresponsive Wakefulness Syndrome.

Assessment of consciousness following severe brain-injury is challenging. Our hypothesis is that electroencephalography (EEG) can provide information on awareness, in terms of oscillatory activity and network task-related modifications, in people with disorders of consciousness. Similar results were obtained with neuroimaging techniques; we aim at demonstrating the use of EEG, which is low cost and routinely implemented, to the same goal. Nineteen-channel EEG was recorded in 7 persons with unresponsive wakefulness syndrome (UWS) and in 10 healthy subjects during the execution of active (attempted movement) and passive motor tasks as well as 2 mental imagery tasks. Event-related synchronization/desynchronization (ERS/ERD), coherence and network parameters were calculated in delta (1-4 Hz), theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-12 Hz), and beta (13-30 Hz) ranges. In UWS subjects, passive movement induced a weak alpha2 ERD over contralateral sensorimotor area. During motor imagery, ERD was detected over the frontal and motor contralateral brain areas; during spatial imagery, ERS in lower alpha band over the right temporo-parietal regions was missing. In UWS, functional connectivity provided evidence of network disruption and isolation of the motor areas, which cannot dialog with adjacent network nodes, likely suggesting a diffuse structural alteration. Our findings suggest that people with a clinical diagnosis of UWS were able to modulate their brain activity when prompted to perform movement tasks and thus suggest EEG as a potential tool to support diagnosis of disorders of consciousness.

Mitral valve regurgitation in patients undergoing TAVI: Impact of severity and etiology on clinical outcome.

BACKGROUND: Mitral regurgitation (MR) is frequently associated with severe aortic stenosis, but its influence on outcomes after transcatheter aortic valve implantation (TAVI) remains controversial. This study sought to assess the baseline etiology and degree of MR in TAVI population, identify the predictors of MR changes and investigate the clinical and prognostic impact of baseline MR at mid and long-term follow-up. METHODS: We enrolled 572 consecutive patients who underwent TAVI. MR degree and etiology were evaluated by echocardiography at baseline and 1-year follow-up. Clinical outcomes were obtained up to 3-year follow-up. RESULTS: At baseline, 168 patients (29%) had moderate-to-severe MR (MR ≥ 2). Organic MR was more frequently associated with MR ≥ 2 (MR < 2: 20%, MR ≥ 2: 43%, p < 0.001). Relevant MR had improved more in functional MR (79%) compared to organic MR (50%, p = 0.001). At the multivariate analysis, the coexistence of coronary artery disease (p = 0.026), absence of atrial fibrillation (p = 0.038) and functional etiology (p = 0.025) were predictors of MR improvement after TAVI. Patients with baseline MR ≥ 2 had a higher mortality rate than those with MR < 2 at 1-year and 3-year follow-up. Moreover, a landmark analysis starting from 1-year to 3-year follow-up, demonstrated that organic MR was associated with an increased risk of mortality throughout 3-year follow-up compared with functional MR, irrespective of MR severity. CONCLUSIONS: Baseline MR ≥ 2 in TAVI patients was associated with early and late mortality rate. At 1-year, significant improvement in MR severity was observed mainly in patients with functional MR ≥ 2. Organic MR ≥ 2 had a negative impact on 3-year, but not 1-year, mortality rate.

Trans-Iliac Aortic Valve Replacement: Feasibility, Safety, and Medium-Term Follow-up.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is nowadays generally accepted as the treatment of choice for high- to intermediate-risk patients with severe aortic stenosis not suitable for the standard surgical replacement. Many vascular accesses have been described for the valve delivery, comprising the common iliac artery as the arterial site of access. METHODS: From September 2008 to June 2014, 440 patients underwent TAVR at our institution. We report a series of 12 patients that have undergone TAVR via a trans-iliac (TI) retroperitoneal surgical approach and also discuss its feasibility, security, and medium-term follow-up. RESULTS: The 30-day survival rate was 92%. Only 1 local vascular access major complication occurred requiring an iliac-femoral bypass grafting with a vascular graft. Two patients experienced transient neurological ischemic attack. At 3-year follow-up, all the 11 patients were alive and well and the echocardiographic evaluation revealed good function of the prosthesis. CONCLUSIONS: The TI route seems to be feasible with a low profile of local complications. It may be a reasonable access alternative to the femoral artery and to the trans-apical approach. A broader, prospective study is advisable to gain general consensus on this approach.

Nephrocheck after cardiac surgery: Does it play a role in daily practice? A sequel of "Nephrocheck results should be corrected for dilution".

Acute kidney injury is a well-recognized complication after cardiac surgery and significantly affects morbidity and mortality. Although the mechanisms of acute kidney injury are not fully understood, Nephrocheck (Astute Medical, San Diego, CA, USA) is a meter for early detection of acute kidney injury based on bedside urinalysis of two cell-cycle arrest biomarkers. However, considerable overlap in the AKIRiskTM score of different RIFLE groups makes interpretation of the score uncertain. A possible reason for the overlap in the AKIRisk score between different RIFLE groups could be that the score is not corrected for dilution. We performed a pilot study to explore the applicability of the test in our daily practice. A total of 68 patients electively scheduled for cardiac surgery with at least two of the following inclusion criteria: age > 70 years, glomerular filtration rate <60 mL/min, left ventricular ejection fraction <41%, redo procedure and combined procedures have been enrolled in the study, and 25 of them developed acute kidney injury. We described the correlation between urine creatinine and Nephrocheck, all the samples with low Nephrocheck (<0.2) also have low urine creatinine, less than 50 mg/dL, detecting a potential diluted sample. In conclusion, in our daily practice AKIRisk score, together with an assessment of whether urine is diluted or concentrated can better discriminate between various degrees of acute kidney injury.

Cardiac surgeon and electrophysiologist shoulder-to-shoulder approach: Hybrid room, a kingdom for two. A zero mortality transvenous lead extraction single center experience.

BACKGROUND: Nowadays, transvenous lead extraction (TLE) is considered an essential technique in lead management strategy. Since 2011, a multidisciplinary approach was undertaken in our centre involving electrophysiologists, cardiac surgeons and anaesthesiologists to improve cross- unit cooperation and minimize complications and mortality. The present paper reports procedural outcomes and complications of our lead extraction experience. METHODS: We retrospectively collected and analysed data from all consecutive patients undergoing cardiac implantable electronic device leads TLE at the IRCCS Centro Cardiologico Monzino between January 2011 and November 2017. RESULTS: One-hundred fifty patients (111 males, 68 ±â€¯13 years) underwent extraction procedures. The most common extraction indication were infections (86.7%) and TLE was carried out by laser-based approach in 88 (58.6%) patients, by mechanical dilating sheaths in 58 (38.7%) patients and by a combined approach (TLE + open surgical intervention) in 4 (2.7%) patients. Procedural success was obtained in 146 (97.3%) cases with only 3 (2.0%) major complications with 2 cases of structural injury with tamponade requiring emergent median sternotomy. Open surgery extraction was required in 4 patients, after an attempt to TLE, due to leads strict adhesion to cardiac or vascular structures, whereas in 5 (3.3%) cases, the treatment of choice was a combined approach consisting in transvenous leads extraction followed by planned surgery. CONCLUSIONS: TLE is a complex procedure that sometimes leads to fatal complications. In our single center experience, a multidisciplinary approach involving electrophysiologist, cardiac surgeon, anaesthesiologist in an operating room allows a safer approach and major complications treatment.

Improvement of neutrophil gelatinase-associated lipocalin sensitivity and specificity by two plasma measurements in predicting acute kidney injury after cardiac surgery.

INTRODUCTION: Acute kidney injury (AKI) remains among the most severe complication after cardiac surgery. The aim of this study was to evaluate the neutrophil gelatinase-associated lipocalin (NGAL) as possible biomarker for the prediction of AKI in an adult cardiac population. MATERIALS AND METHODS: Sixty-nine consecutive patients who underwent cardiac surgeries in our hospital were prospectively evaluated. In the intensive care unit (ICU) NGAL was measured as a new biomarker of AKI besides serum creatinine (sCrea). Patients with at least two factors of AKI risk were selected and samples collected before the intervention and soon after the patient's arrival in ICU. As reference standard, sCrea measurements and urine outputs were evaluated to define the clinical AKI. A Triage Meter for plasma NGAL fluorescence immunoassay was used. RESULTS: Acute kidney injury occurred in 24 of the 69 patients (35%). Analysis of post-operative NGAL values demonstrated an AUC of 0.71, 95% CI (0.60 - 0.82) with a cut-off = 154 ng/mL (sensitivity = 76%, specificity = 59%). Moreover, NGAL after surgery had a good correlation with the AKI stage severity (P ≤ 0.001). Better diagnostic results were obtained with two consecutive tests: sensitivity 86% with a negative predictive value (NPV) of 87%. At 10-18 h after surgery sCrea measurement, as confirmatory test, allowed to reach a more sensitivity and specificity with a NPV of 96%. CONCLUSIONS: The assay results showed an improvement of NGAL diagnostic accuracy evaluating two tests. Consequently, NGAL may be useful for a timely treatment or for the AKI rule out in ICU patients.

Comprehensive effects of left ventricular assist device speed changes on alveolar gas exchange, sleep ventilatory pattern, and exercise performance.

BACKGROUND: Increasing left ventricular assist device (LVAD) pump speed according to the patient's activity is a fascinating hypothesis. This study analyzed the short-term effects of LVAD speed increase on cardiopulmonary exercise test (CPET) performance, muscle oxygenation (near-infrared spectroscopy), diffusion capacity of the lung for carbon monoxide (Dlco) and nitric oxide (Dlno), and sleep quality. METHODS: We analyzed CPET, Dlco and Dlno, and sleep in 33 patients supported with the Jarvik 2000 (Jarvik Heart Inc., New York, NY). After a maximal CPET (n = 28), patients underwent 2 maximal CPETs with LVAD speed randomly set at 3 or increased from 3 to 5 during effort (n = 15). Then, at LVAD speed randomly set at 2 or 4, we performed (1) constant workload CPETs assessing O2 kinetics, cardiac output (CO), and muscle oxygenation (n = 15); (2) resting Dlco and Dlno (n = 18); and (3) nocturnal cardiorespiratory monitoring (n = 29). RESULTS: The progressive pump speed increase raised peak volume of oxygen consumption (12.5 ± 2.5 ml/min/kg vs 11.7 ± 2.8 ml/min/kg at speed 3; p = 0.001). During constant workload, from speed 2 to 4, CO increased (at rest: 3.18 ± 0.76 liters/min vs 3.69 ± 0.75 liters/min, p = 0.015; during exercise: 5.91 ± 1.31 liters/min vs 6.69 ± 0.99 liters/min, p = 0.014), and system efficiency (τ = 65.8 ± 15.1 seconds vs 49.9 ± 14.8 seconds, p = 0.002) and muscle oxygenation improved. At speed 4, Dlco decreased, and obstructive apneas increased despite a significant apnea/hypopnea index and a reduction of central apneas. CONCLUSIONS: Short-term LVAD speed increase improves exercise performance, CO, O2 kinetics, and muscle oxygenation. However, it deteriorates lung diffusion and increases obstructive apneas, likely due to an increase of intrathoracic fluids. Self-adjusting LVAD speed is a fascinating but possibly unsafe option, probably requiring a monitoring of intrathoracic fluids.

A myosin II nanomachine mimicking the striated muscle.

The contraction of striated muscle (skeletal and cardiac muscle) is generated by ATP-dependent interactions between the molecular motor myosin II and the actin filament. The myosin motors are mechanically coupled along the thick filament in a geometry not achievable by single-molecule experiments. Here we show that a synthetic one-dimensional nanomachine, comprising fewer than ten myosin II dimers purified from rabbit psoas, performs isometric and isotonic contractions at 2 mM ATP, delivering a maximum power of 5 aW. The results are explained with a kinetic model fitted to the performance of mammalian skeletal muscle, showing that the condition for the motor coordination that maximises the efficiency in striated muscle is a minimum of 32 myosin heads sharing a common mechanical ground. The nanomachine offers a powerful tool for investigating muscle contractile-protein physiology, pathology and pharmacology without the potentially disturbing effects of the cytoskeletal-and regulatory-protein environment.

Care pathways models and clinical outcomes in Disorders of consciousness.

OBJECTIVE: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care pathway for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients' clinical outcomes. MATERIALS AND METHODS: A multicenter observational pilot study was realized. Clinicians collected data on the care pathways of patients with Disorder of consciousness by asking 90 patients' caregivers to complete an ad hoc questionnaire through a structured phone interview. Questionnaire consisted of three sections: sociodemographic data, description of the care pathway done by the patient, and caregiver evaluation of health services and information received. RESULTS: Seventy-three patients were analyzed. Length of hospital stay was different across the health care models and it was associated with improvement in clinical diagnosis. In long-term care units, the diagnosis at admission and the number of caregivers available for each patient (median value = 3) showed an indirect relationship with worsening probability in clinical outcome. Caregivers reported that communication with professionals (42%) and the answer to the need of information were the most critical points in the acute phase, whereas presence of Non-Governmental Organizations (25%) and availability of psychologists for caregivers (21%) were often missing during long-term care. The 65% of caregivers reported they did not know the UN Convention on the Rights of Persons with Disabilities. CONCLUSION: This study highlights relevant differences in analyzed models, despite a recommended national pathway of care. Future public health considerations and actions are needed to guarantee equity and standardization of the care process in all European countries.

Accumulation of RNA on chromatin disrupts heterochromatic silencing.

Long noncoding RNAs (lncRNAs) play a conserved role in regulating gene expression, chromatin dynamics, and cell differentiation. They serve as a platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA methylation in many eukaryotic organisms. We found in Schizosaccharomyces pombe that heterochromatin is lost at transcribed regions in the absence of RNA degradation. We show that heterochromatic RNAs are retained on chromatin, form DNA:RNA hybrids, and need to be degraded by the Ccr4-Not complex or RNAi to maintain heterochromatic silencing. The Ccr4-Not complex is localized to chromatin independently of H3K9me and degrades chromatin-associated transcripts, which is required for transcriptional silencing. Overexpression of heterochromatic RNA, but not euchromatic RNA, leads to chromatin localization and loss of silencing of a distant ade6 reporter in wild-type cells. Our results demonstrate that chromatin-bound RNAs disrupt heterochromatin organization and need to be degraded in a process of heterochromatin formation.