Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry).

BACKGROUND AND AIMS: Ischemic or bleeding events might occur after transcatheter aortic valve replacement (TAVR), with the potential to hamper clinical outcomes. This study aimed to characterize the average daily ischemic risks (ADIRs) and the average daily bleeding risks (ADBRs) over 1-year in all consecutive patients undergoing TAVR. METHODS: ADBR included all bleeding events according to VARC-2 definition, and ADIR included cardiovascular deaths, myocardial infarction and ischemic stroke. ADIRs and ADBRs were assessed within different timeframes post TAVR: acute (0-30 days), late (31-180 days), and very late (>181 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparison of ADIRs and ADBRs. Our analysis was performed in the overall cohort and according to antithrombotic strategy (LT-OAC vs No LT-OAC). RESULTS: Ischemic burden was higher than bleeding burden, independently from the indication to LT-OAC, and in all timeframes examined. In the overall population, ADIRs were three-fold ADBRs (0.0467 [95% CI, 0.0431-0.0506] vs 0.0179 [95% CI, 0.0174-0.0185]; p < 0.001*). While ADIR was significantly higher in the acute phase, ADBR was relatively stable in all timeframes analysed. Of note, in LT-OAC population, OAC + SAPT group showed lower ischemic risk and higher bleeding events compared with OAC alone (ADIR: 0.0447 [95% CI: 0.0417-0.0477] vs 0.0642 [95% CI: 0.0557-0.0728]; p < 0.001*, ADBR 0.0395 [95% CI: 0.0381-0.0409] vs 0.0147 [95% CI: 0.0138-0.0156]; p < 0.001*). CONCLUSIONS: In patients undergoing TAVR Average daily risk fluctuates over time. However, ADIRs overcome ADBRs in all timeframes, especially in the acute phase and regardless of antithrombotic strategy adopted.

Collateral presence and extent do not predict myocardial viability and ischemia in chronic total occlusions: A stress-CMR study.

BACKGROUND: Well-developed collaterals are assumed as a marker of viability and ischemia in chronic total occlusions (CTO). We aim to correlate viability and ischemia with collateral presence and extent in CTO patients by cardiac magnetic resonance (CMR). METHODS: Multicentre study of 150 CTO patients undergoing stress-CMR, including adenosine if normal systolic function, high-dose-dobutamine for patients with akinetic/>2 hypokinetic segments and EF ≥35%, otherwise low-dose-dobutamine (LDD); all patients underwent late gadolinium enhancement (LGE) imaging. Viability was defined as mean LGE transmurality ≤50% for adenosine, as functional improvement for dobutamine-stress-test, ischemia as ≥1.5 segments with perfusion defects outside the scar zone. RESULTS: Rentrop 3/CC 2 defined well-developed (WD, n = 74) vs poorly-developed collaterals (PD, n = 76). Viability was equally prevalent in WD vs PD: normo-functional myocardium with ≤50% LGE in 52% vs 58% segments, p = 0.76, functional improvement by LDD in 48% vs 52%, p = 0.12. Segments with none, 1-25%,26-50%,51-75% LGE showed viability by LDD in 90%,84%,81%,61% of cases, whilst in 12% if 76-100% LGE (p < 0.01). There was no difference in WD vs PD for ischemia presence (74% vs 75%, p = 0.99) and extent (2.7 vs 2.8 segments, p = 0.77). CONCLUSIONS: In a large cohort of CTO patients, presence and extent of collaterals did not predict viability and ischemia by stress-CMR. Scar extent up to 75% LGE was still associated with viability, whereas ischemia was undetectable in 25% of patients, suggesting that the assessment of CTO patients with CMR would lead to a more comprehensive evaluation of viability and ischemia to guide revascularization.

Iatrogenic atrial septal defect does not affect acute hemodynamic modifications after transcatheter edge-to-edge repair in patients with functional mitral regurgitation.

OBJECTIVE: The correction of functional mitral regurgitation (FMR) with transcatheter edge-to-edge repair (TEER) can favorably affect patients' hemodynamic profile. However, the procedure requires inter-atrial trans-septal access and the hemodynamic relevance of the residual iatrogenic atrium septal defect (iASD) is still debated. This study aimed at investigating the hemodynamic modifications during TEER with MitraClip, before and after the iASD creation, in patients with heart failure with reduced ejection fraction (HFrEF) and severe FMR. METHODS: Thirty-nine HFrEF patients with 3+ or 4+/4+ FMR were included. Right heart catheterization was performed at baseline after general anesthesia induction and at the end of TEER, both before and after removing the device guiding catheter. RESULTS: Compared with baseline, MitraClip positioning was followed by a significant immediate improvement in cardiac output (respectively: 3.36 vs 5.05 ml/min), pulmonary artery wedge pressure (23.7 vs 18.2 mmHg), mean pulmonary artery pressure (34.4 vs 27.7 mmHg) and pulmonary vascular resistance (3.6 vs 2.2 Wood Units) (all p < 0.001). No further significant modifications occurred after removing the device guiding catheter. CONCLUSIONS: Our data suggest that the acute hemodynamic modifications after TEER are not influenced by the induction of iASD in patients with FMR.

[Reduction of the incidence of nosocomial infections after assessing and revising the quality of assistance in a thoracic surgery unit]. / Riduzione del tasso d'incidenza delle infezioni ospedaliere in una U.O. di Chirurgia Toracica mediante verifica e revisione della qualità assistenziale.

An active surveillance for nosocomial infections has been lead in a Thoracic Surgery with the intention, first to point out their frequency and characteristics, and then to outline all the measures to remove the main risk factors checking the results obtained. A prospective incidence study has been promoted in a Thoracic Surgery in the years 2000, 2001, 2002. The analysis has been lead weekly gathering all necessary data from the health records and making laboratory tests to look for microbes growth in the air of Thoracic Surgery Operating Rooms. A nosocomial infections incidence of 13.3% among surgically treated patients has been registered in 2000. Deep surgical site infections were the most frequent localizations, and microbes isolated were Staphylococcus aureus and coagulase negative Staphylococcus with an high oxacillin resistance (70.6%-76.5%). From the observation of the risk factors the sterilization system has been modified and the assistance and environmental protocols have been improved. In the further evaluation period, a global reduction of nosocomial infections incidence (7.1%), of surgical site infections (from 10.1% to 4.5%) (p = 0.007), of Staphylococcus aureus and coagulase negative Staphylococcus isolations have been obtained even if short results in antibiotic resistances have been registered. Thoracic Surgery has to be considered an area at medium-high risk of nosocomial infections. The quite high incidence of nosocomial infections recorded at the beginning of the study in presence of prevalent deep surgical site infections from staphylococci with an high oxacillin resistance compelled to promote corrections. These lead to a remarkable decrease in incidence of nosocomial infections even if the same results can not be reached in antibiotic resistances.

Age-related effects on atherogenesis and scavenger enzymes of intracranial and extracranial arteries in men without classic risk factors for atherosclerosis.

BACKGROUND AND PURPOSE: Atherosclerosis occurs later and is less extensive in intracranial arteries than in extracranial arteries. However, the mechanisms responsible are poorly understood. A previous study has suggested a better antioxidant protection of intracranial arteries. METHODS: To assess the influence of age on arterial activity of antioxidant enzymes and atherogenesis, we compared intracranial and extracranial arteries of humans of different ages who retrospectively lacked confounding classic risk factors (48 premature fetuses aged 6.4+/-0.8 months [mean+/-SD], 58 children aged 7.9+/-3.8 years, 42 adults aged 42.5+/-5.1 years, and 40 elderly subjects aged 71.8+/-3.4 years; all males). Lesions were quantified by computer-assisted imaging analysis of sections of the middle cerebral and basilar arteries, the left anterior descending coronary artery, the common carotid artery, and the abdominal aorta. Macrophages, apolipoprotein B, oxidized LDL, and matrix metalloproteinase-9 in lesions were determined by immunocytochemistry. The effect of aging on atherogenesis was then compared with that on the activity of 4 antioxidant enzymes in the arterial wall. RESULTS: Atherosclerosis was 6- to 19-fold greater (P<0.01) in extracranial arteries than in intracranial arteries, and it increased linearly with age. Intracranial arteries showed significantly greater antioxidant enzyme activities than did extracranial arteries. However, the antioxidant protection of intracranial arteries decreased significantly in older age, coinciding with a marked acceleration of atherogenesis. An increase in matrix metalloproteinase-9 protein expression and in gelatinolytic activity consistent with the degree of intracranial atherosclerosis was also observed. CONCLUSIONS: These results suggest that a greater activity of antioxidant enzymes in intracranial arteries may contribute to their greater resistance to atherogenesis and that with increasing age intracranial arteries respond with accelerated atherogenesis when their antioxidant protection decreases relatively more than that of extracranial arteries.

Clinical applications of independent lung ventilation with unilateral high-frequency jet ventilation (ILV-UHFJV).

Six patients with unilateral acute lung injury (ALI) were treated with a new form of ventilatory support: independent lung ventilation with unilateral high-frequency jet ventilation (ILV-UHFJV). The first three patients suffered from unilateral ALI complicated by a bronchopleural fistula (BPF); they were at first ventilated with HFJV, but remained unresponsive to treatment, showing a progressive impairment of the ventilation/perfusion ratio with a deterioration in clinical condition. After selective bronchial intubation, ILV-UHFJV was started, ventilating the healthy lung with CPPV and the contralateral with HFJV. ILV-UHFJV caused a significant improvement in alveolar gas exchange leading to a rapid fall in Qs/Qt; it was also associated with a stable haemodynamic condition throughout the duration of the treatment. Subsequently, three more patients were treated; their respiratory failure was due to a unilateral ALI without BPF, unresponsive to either HFJV or CPPV. Once again, ILV-UHFJV was followed by a dramatic improvement in respiratory function; the haemodynamics remained unchanged and it was also possible to demonstrate a rapid improvement in individual and overall lung function.

Clinical use of differential continuous positive airway pressure in the treatment of unilateral acute lung injury.

In some instances of unilateral acute lung injury (ALI) refractory to conventional ventilatory support, the intact lung is still able to ensure an efficient CO2 washout, the concomitant hypoxaemia being due to the loss of volume of the injured parenchyma. In these cases, the administration of a sufficient selective continuous distending pressure by means of differential continuous positive airway pressure may restore to normal the resting volume and thus the ventilatory performance of the affected lung, contemporarily avoiding the occurrence of pulmonary and systemic barotrauma.

High frequency jet ventilation (HFJV) has no better haemodynamic tolerance than controlled mechanical ventilation (CMV) in cardiogenic shock.

Six patients with acute myocardial infarction (AMI) complicated by cardiogenic shock were studied in order to compare the haemodynamic tolerance of controlled mechanical ventilation (CMV) and high frequency jet ventilation (HFJV). The comparative analysis of the two techniques was performed with the same levels of PaO2 (CMV: 101 +/- 13 mmHg; HFJV: 104.2 +/- 14 p = ns); and PaCO2 (CMV: 37 +/- 1.7; HFJV: 35.7 +/- 1.4 p = ns). In this situation the values of mean airway pressure (Paw) did not differ significantly (CMV: 13 +/- 3 cm H2O; HFJV: 12.6 +/- 3.8 cm H2O) and no statistically significant difference in haemodynamic values was observed. These results demonstrate that in patients with cardiogenic shock, there is no difference between HFJV and CMV in terms of haemodynamic tolerance. Because of the more difficult clinical management of HFJV, this technique does not seem indicated as ventilatory support in patients with cardiogenic shock states.

Detection of leukotrienes B4, C4 and of their isomers in arterial, mixed venous blood and bronchoalveolar lavage fluid from ARDS patients.

Seven patients with the adult respiratory distress syndrome (ARDS) were studied. As a control group we used 6 surgical patients who underwent minor surgical operation (inguinal hernia). For both groups the same sample collection and analysis was used. The presence of leuktorienes (LTs) B4 and C4 and of their isomers 11-trans LTC4 and delta 6-trans-12-epi LTB4 was determined in arterial, mixed venous blood and in bronchoalveolar lavage (BAL) fluid. The samples, analysed by reverse phase high performance liquid chromatography (RP-HPLC), showed a similar chromatographic picture among ARDS patients, while the control group showed no detectable amounts of LTs in BAL or blood. The distribution of these arachidonic acid metabolites in mixed venous blood, arterial blood and BAL seems to suggest pulmonary metabolism and/or inactivation. It is suggested that these mediators act as humoral factors in pathogenesis of the ARDS.

Effects of L-carnitine administration on mitochondrial electron transport activity present in human muscle during circulatory shock.

Carnitine was administered to a group of patients in shock, and the activities of cytochrome oxidase and succinate cytochrome c reductase in muscle needle biopsies from these patients were compared to those activities present in a non-carnitine treated control group of patients. Carnitine seemingly exerted a significant protective action on cytochrome oxidase activity during the initial phases of shock, but not to such an extent on succinate cytochrome c reductase activities.

Chlorpromazine plus thiorazidine poisoning and treatment with extracorporeal dialysis.

One case of self-poisoning by 3075 mg of Chlorpromazine and 250 mg Thiorazidine is referred. In this case coma and uremia rose 3 days after the intoxication. Treated with extracorporeal circulation through Travenol Coil kidney, this patient recovered from coma and uremia and survived. Chlorpromazine and Thiorazidine intoxications are reviewed with particular attention to the possible kidney damage.

[Problems of alimentation in massive intestinal resections]. / Problemi di alimentazione nelle resezioni intestinali massive.

Before reviewing the consequences of extensive exeresis of the small intestine, the physiology of the entero-hepatic circulation of bile salts, the absorption of triglycerides and the varying sites of absorption of foodstuffs at intestinal level are discussed. It has been found that massive (i.e. at least 2/3) removal of the small intestine is incompatible with life owing to the onset of serious metabolic disturbances due to the increase in the speed of transit of foodstuffs from stomach to colon. Malabsorption of lipides causes steatorrhoea and is often associated with choleriform diarrhoea owing to the massive losses of water and electrolytes (Na, Cl, Ca, Mg). Some surgical techniques are illustrated and the local compensation mechanisms (anatomical adaptation of the intestinal mucosa, functional adaptation) designed to prolong transit time are described. Feeding must be parenteral for the first 2--3 months and oral during the alimentary adaptation phase.

[Does the preoperative administration of ketorolac improve postoperative analgesia]. / La somministrazione preoperatoria di ketorolac migliora l'analgesia postoperatoria?

AIM OF THE STUDY: 1) To verify the usefulness of ketorolac administration (30 mg i.v.) before a surgical operation in terms of postoperative analgesia improvement; 2) To evaluate the impact of preoperative ketorolac administration on perioperative renal function and on intraoperative water balance; 3) to evaluate the presence of adverse effect due to preoperative NSAID use. DESIGN: Prospective randomized trial. SETTING: University surgical department. PATIENTS AND METHODS: Forty adult patients undergoing major abdominal surgery, randomized in 2 groups: in group 1 ketorolac (30 mg i.v.) was administered immediately after the induction and, for postoperative analgesia, ketorolac (30 mg i.v.) was administered beginning at the time of skin closure; in group 2 no ketorolac was administered before the operation and postoperative treatment was the same. Buprenorphine (0.3 mg i.m.) was administered in case of unsatisfactory analgesia. Fluids infused and diuresis were measured intraoperatively. One, 6 and 24 hours after the end of operation pain was evaluated using pain intensity score and VAS. The day after the operation serum creatinine and urea were measured. RESULTS: No statistically significant differences were found between groups regarding fluids infused, intraoperative diuresis, postoperative pain, adverse effects and number of bleeding episodes. More than 50% of patients, in either groups, required opioids administration. CONCLUSIONS: Ketorolac (30 mg i.v.) administration before a major abdominal operation does not improve postoperative analgesia nor determines significant alterations in renal function or increase in the frequency of abnormal bleedings. Opiate administration is necessary in more than 50% of the patients to achieve adequate analgesia.

[Comparison of ketorolac/buprenorphine in the treatment of post-cholecystectomy pain]. / Confronto ketorolac/buprenorfina nel trattamento del dolore post-colecistectomia.

The authors compared the efficacy of ketorolac trometamin (30 mg i.m. every 6 hours) and buprenorphine (0.3 mg i.m. every 12 hours) in the treatment of pain following cholecystectomy. Ketorolac was found to be equally efficacious in comparison to buprenorphine and caused fewer side effects.

Micrometástasis y células tumorales aisladas en ganglio centinela: nuestra experiencia y revisión de la literatura / Micrometastases and isolated tumor cells in sentinel lymph node: our experience and literature review

El estado de los ganglios axilares es el factor de predicción de sobrevida más importante en pacientes con cáncer de mama, siendo además considerado para la decisión de indicación de tratamientos adyuvantes.La biopsia del ganglio centinela (GC) es actualmente el procedimiento estándar para la estadificación axilar en cáncer de mama con axila clínicamente negativa. Esto redujo el número de ganglios axilares a ser estudiados por el patólogo; de un promedio de 15 a 20 ganglios en una pieza de linfadenectomía axilar a 1 a 3 ganglios en los casos de biopsia de GC. Asimismo, permitió un estudio más exhaustivo del GC y con ello aumentó la detección de metástasis de menor tamaño, sean estas micrometástasis (MMT) o células tumorales aisladas (CTA). Las primeras presentan un tamaño entre 0,2 mm y no mayor a 2,0 mm, y las segundas un tamaño que no supera los 0,2 mm. En la actualidad existen controversias respecto al impacto clínico y manejo de las MMT y CTA. El siguiente trabajo muestra la experiencia en el manejo de estos casos en el Hospital Universitario CEMIC y realiza una revisión de la literatura.

Shock-induced damage to mitochondrial function and some cellular antioxidant mechanisms in humans.

The effects of circulatory shock on skeletal muscle mitochondrial oxidative activity in various substrates and cytochrome oxidase activity have been investigated using samples of muscle obtained by the needle biopsy technique from human subjects. The effect of shock on superoxide dismutase activity and glutathione content of skeletal muscle was also examined. The results show that there is a large decrease in cytochrome oxidase activity during shock and also in the capacity of the mitochondria to oxidize either succinate, or pyruvate, or palmitoyl carnitine. There is a fall in the tissue content of superoxide dismutase and in the total glutathione present. Furthermore, an increased oxidized glutathione content causes a decrease in the molar ratio of reduced to oxidized glutathione present in the muscle. These findings suggest that mitochondrial electron transport chain (ETC) oxidative damage can play a relevant role in the pathogenesis of circulatory shock and support the hypothesis of oxygen-free radical involvement in the cellular injury.