Visual lung ultrasound protocol (VLUP) in acute respiratory failure: description and application in clinical cases.

Lung ultrasound (LUS) is widely used as a diagnostic and monitoring tool in critically ill patients. Lung ultrasound score (LUSS) based on the examination of twelve thoracic regions has been extensively validated for pulmonary assessment. However, it has revealed significant limitations: when applied to heterogeneous lung diseases with intermediate LUSS pattern (LUSS 1 and 2), for instance, intra-observer consistency is relatively low. In addition, LUSS is time-consuming and a more rapid overview of the extent of lung pathology and residual lung aeration is often required, especially in emergency setting. We propose a Visual Lung Ultrasound Protocol (VLUP) as a rapid monitoring tool for patients with acute respiratory failure. It consists of a probe sliding along the mid-clavicular, mid-axillary and scapular lines in transversal scan. VLUP allows a visualization of a large portion of the antero-lateral and/or posterior pleural surface. Serial assessments of two clinical cases are recorded and visually compared, enabling rapid understanding of lung damage and its evolution over time. VLUP allows a semi-quantitative and qualitative point-of-care assessment of lung injury. Through this standardized approach it is possible to accurately compare subsequent scans and to monitor the evolution of regional parenchymal damage. VLUP enables a quick estimation of the quantitative-LUSS (qLUSS) as the percentage of pleura occupied by artifacts, more suitable than LUSS in inhomogeneous diseases. VLUP is designed as a standardized, point-of-care lung aeration assessment and monitoring tool. The purpose of the paper is to illustrate this new technique and to describe its applications.

Daratumumab in multiple myeloma: experience of the multiple myeloma GIMEMA Lazio group.

Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.

Previous infection and the risk of ischaemic stroke in Italy: the IN2 study.

BACKGROUND AND PURPOSE: There is an increasing interest in new risk factors for ischaemic stroke. Acute and chronic infections could contribute to different aetiological mechanisms of atherosclerosis that lead to cerebrovascular disease. The aim of this study was to investigate the hypothesis that previous infections and Chlamydia pneumoniae in particular increase the risk of ischaemic stroke in the population. METHODS: This was a prospective case-control study involving 11 Italian stroke units. Controls were age- and sex-matched with cases, represented by patients admitted to hospital for acute ischaemic stroke. For each participant classical vascular risk factors and previous inflammatory and infectious events up to 1 month before were registered. Blood samples were collected to analyse inflammatory markers and titres of antibodies against C. pneumoniae. RESULTS: A total of 1002 participants were included (mean age 69 years) with 749 ischaemic stroke patients. Infections occurred within 1 month previously in 12% of the entire sample with a higher prevalence in the case group (14.4% vs. 3.9%). At multivariate analysis of the seropositivity of IgA antibodies against C. pneumoniae increased the risk of stroke significantly (relative risk 2.121; 95% confidence interval 1.255-3.584) and an early previous infection (up to 7 days before the event) contributed to a rise in probability of acute cerebral ischaemia (relative risk 3.692; 95% confidence interval 1.134-6.875). CONCLUSIONS: Early previous infections and persistent chronic infection of C. pneumoniae could contribute to increase the risk of ischaemic stroke significantly, in the elderly especially.

Induction therapy in adult intestinal transplantation: reduced incidence of rejection with "2-dose" alemtuzumab protocol.

The incidence of early rejection after intestinal transplantation correlates with heightened risk of graft loss and mortality. Many different induction or pre-conditioning protocols have been reported in the last 10 yr to improve outcomes; however, sepsis remains prevalent and diminishes long-term results. We recently began a "2-dose" alemtuzumab trial protocol - 15 mg at day 0 and 15 mg repeated on day 7 - with the hope of reducing our infection rate. We compared three different protocols used at our institution (daclizumab, conventional "4-dose" alemtuzumab, and "2-dose" alemtuzumab). There was a significantly lower rate of early rejection with the "2-dose" alemtuzumab protocol in our study group of mainly (88%) intestinal grafts without accompanying liver engraftment with its protective immunologic effect. Sepsis remained low. Longer follow-up will be required to evaluate the effects of this new protocol on longer-term outcomes.

Antiepileptic drugs for central post-stroke pain management.

Antiepileptic drugs (AEDs) are commonly prescribed for a wide range of disorders other than epilepsy, including both neurological and psychiatric disorders. AEDs play also a role in pharmacological management of neuropathic pain. Central post-stroke pain (CPSP) is a disabling morbidity occurring in 35% of patients with stroke. The pathophysiology of CPSP is not well known but central disinhibition with increased neuronal excitability has been suggested. AEDs include many different drugs acting on pain through several mechanisms, such as reduction of neuronal hyperexcitability. To our knowledge conclusive evidence has not been published yet. The aim of this review is to delineate efficacy and safety of AEDs in CPSP.

Alkaline phosphatase (alp) levels in multiple myeloma and solid cancers with bone lesions: Is there any difference?

INTRODUCTION: Bone involvement in Multiple Myeloma results from increased osteoclast formation and activity that occurs in proximity to myeloma cells. The role of Alkaline Phosphatse (ALP) in this process and the diagnostic significance of plasma levels in patients with MM are unclear. AIM: To compare plasma ALP levels in patients with MM and solid cancers and metastatic lesions to the bone. RESULTS: In this observational retrospective study we enrolled 901 patients were enrolled: 440 patients (49%) with Multiple Myeloma, 461 (51%) with solid cancers. All 901 patients had bone lesions. Among patients with Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. This difference is independent of stage, number and type of bone lesions. CONCLUSION: This study suggests that plasma ALP has a different clinical significance in MM than in other neoplasms and could be used as a discriminating marker in presence of bone lesions. In particular, lower or normal values, should suggest further investigations such as urinary and serum electrophoresis, associated with bone marrow aspirate in case of the presence of a monoclonal component, in order to confirm or exclude a MM diagnosis.

A geo-chemo-mechanical study of a highly polluted marine system (Taranto, Italy) for the enhancement of the conceptual site model.

The paper presents the results of the analysis of the geo-chemo-mechanical data gathered through an innovative multidisciplinary investigation campaign in the Mar Piccolo basin, a heavily polluted marine bay aside the town of Taranto (Southern Italy). The basin is part of an area declared at high environmental risk by the Italian government. The cutting-edge approach to the environmental characterization of the site was promoted by the Special Commissioner for urgent measures of reclamation, environmental improvements and redevelopment of Taranto and involved experts from several research fields, who cooperated to gather a new insight into the origin, distribution, mobility and fate of the contaminants within the basin. The investigation campaign was designed to implement advanced research methodologies and testing strategies. Differently from traditional investigation campaigns, aimed solely at the assessment of the contamination state within sediments lying in the top layers, the new campaign provided an interpretation of the geo-chemo-mechanical properties and state of the sediments forming the deposit at the seafloor. The integrated, multidisciplinary and holistic approach, that considered geotechnical engineering, electrical and electronical engineering, geological, sedimentological, mineralogical, hydraulic engineering, hydrological, chemical, geochemical, biological fields, supported a comprehensive understanding of the influence of the contamination on the hydro-mechanical properties of the sediments, which need to be accounted for in the selection and design of the risk mitigation measures. The findings of the research represent the input ingredients of the conceptual model of the site, premise to model the evolutionary contamination scenarios within the basin, of guidance for the environmental risk management. The study testifies the importance of the cooperative approach among researchers of different fields to fulfil the interpretation of complex polluted eco-systems.

Anesthesia for liver transplantation: the experience of the University of Bologna in the MELD era.

AIM: The hepatic cirrhosis is associated with an important cardiovascular alterations. In this report, we review our transplant center experience with liver transplantation in the Model for End-Stage Liver Disease (MELD) era, in particular this study investigate the relationship between severity of liver disease assessed by MELD score and postoperative events. METHODS: Our retrospective review was performed on 242 cirrhotic patients underwent liver transplanation at the Department of Surgery and Transplantation of the University of Bologna. Biochemical and hemodynamic variables were evaluated by Swan-Ganz catherization. Dindo's classification of postoperative complications was used for the evaluation of postoperative course. RESULTS: Morbidity occurred in 158 patients (65.2%) and 13 patients died during the hospital stay. Considering the highest grade of complication occurred, non life-threatening complications occurred in the 47.9% of cases (116 patients) and life-threatening complications, excluding patient death, in 17.3% (42 patients). Patients with MELD >30 showed a longer ICU stay, tracheal intubation and in-hospital stay. CONCLUSION: In conclusion MELD score is tightly related to postoperative complications.

The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study.

OBJECTIVE: To investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). METHODS: Prospective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010-2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. RESULTS: We analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05-1.39) and 1.17 (95% CI 1.07-1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11-115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98-1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76-50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95-41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20-5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00-1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48-4.67), re-intervention (HR 2.16, 95% CI 1.21-3.84) and rejection (HR 2.81, 95% CI 1.52-5.21). CONCLUSIONS: CPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.

Serum prolactin levels in repetitive temporal epileptic seizures.

The primary aim of this work was: to evaluate the time course of serum prolactin (PRL) increase following repetitive seizures in epileptic patients with (Group II) and without (Group I) temporal ischemia. Epileptic patients were examined after 2 or 3 epileptic seizures in wakefulness with seizure-free intervals of 4 hours. Serum PRL levels was assessed within 3 hours of the last epileptic seizure and up to 48 hours after. The increase of serum PRL attained within baseline levels after 6 h in Group I and after 12 h in Group II. A longer increase of serum PRL levels were observed in Group II patients respect to Group I (P < 0.01). In conclusion, this different long time attenuation of serum PRL following repetitive temporal seizures with and without damage of temporal structure, may be useful in order to better analyse the synaptic transmission involved in the pathways interconnect limbic areas.

Fluid management of patients undergoing intestinal and multivisceral transplantation.

Small bowel transplantation can be associated with large fluid shifts due to massive blood loss, dehydration, vascular clamping, long ischemia times, intraoperative visceral exposure, intestinal denervation, ischemic damage, and lymphatic interruption. Fluid management is the major intra- and postoperative problem after small bowel and multiple organ transplantation, because of the highly variable fluid and electrolyte needs of the transplant recipient. Third-space fluid requirements can be massive; inadequate replacement leads to end-organ dysfunction, particularly renal failure. Several liters of fluid may be required in the initial 24 to 48 hours postoperatively to simply maintain an adequate central pressure to provide a satisfactory urine output. During this time patients may develop extensive peripheral edema, which dissipates over the next few days as the fluids are mobilized and requirements stabilize. Based on our experience in 29 cases of intestinal transplantation and 4 cases of multivisceral transplantation, we have herein described the intraoperative fluid management and hemodynamic changes. Our study confirmed a large quantity of fluid administration during and after small bowel transplantation that required adequate volume monitoring.

Serotonin modulation of cell excitability and of [3H]GABA and [3H]D-aspartate efflux in primary cultures of rat cortical neurons.

The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarization-induced firing rate, and on amino acid release, measured as electrically-evoked [(3)H]GABA and [(3)H]d-aspartate efflux, were investigated in rat primary cortical neuronal cultures. 5-HT displayed a concentration-dependent, bimodal effect on neuronal excitability: at 3-10microM it increased excitability through 5-HT(2A) receptors, and was blocked by the selective 5-HT(2A) antagonist MDL 100907, whereas at 30-100microM it reduced excitability through 5-HT(1A) receptors, and was, in turn, blocked by the selective 5-HT(1A) antagonist WAY 100135. The electrically-evoked [(3)H]GABA efflux was concentration-dependently inhibited by 5-HT (pEC(50)=4.74) and such inhibition was prevented by WAY 100135, but not by GR 55562, a selective 5-HT(1D/B) receptor antagonist. Conversely, 5-HT concentration-dependently increased stimulus-evoked [(3)H]d-aspartate efflux (pEC(50)=4.71). The increase was facilitated by methiothepin and was reversed into inhibition by ICS 205930, a selective 5-HT(3) receptor antagonist. In the presence of ICS 205930, the inhibition induced by 5-HT was prevented by the selective 5-HT(1D/B) receptor antagonist GR 55562, but not by WAY 100135. These findings suggest that 5-HT inhibits GABA release through 5-HT(1A) receptors and exerts a dual modulation on glutamate release, mostly facilitatory (through 5-HT(3) receptors) but also inhibitory (through 5-HT(1D/B) receptors), leading to a prevalently positive modulation of the excitatory signal by amino acid neurotransmitter containing neurons.

Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceral transplantation: A comparison of two different regimens on 29 recipients during the early post-operative period.

INTRODUCTION: Induction therapy has been recently adopted for intestinal transplant. PATIENTS AND METHODS: We compared during first 30 days post-transplantation 29 recipients, allocated in two groups, treated with Daclizumab (Zenapax) or Alemtuzumab (Campath-1H). RESULTS: During first month, 45% of Daclizumab recipients experienced six acute cellular rejections (ACRs) of mild degree, while 63% of them developed an infection requiring treatment. We found three acute cellular rejections in 17.6% of Alemtuzumab recipients, two with moderate degree; 64.7% of them required treatment for infection. DISCUSSION AND CONCLUSIONS: Graft and patient 3-years cumulative survival rate were not significantly different between groups. Alemtuzumab seems to offer a better immunosuppression during first month.

Adult-to-adult living donor liver transplantation using left lobes: the importance of surgical modulations on portal graft inflow.

BACKGROUND: Due to the shortage of available cadaveric organs, living donor liver transplantation (LDLT) has been recently applied extensively in adults. The use of the left lobe should be encouraged because of donor safety, but frequently the metabolic requirements of severely cirrhotic patients are great and subsequent graft dysfunction is encountered after transplantation. The importance of increased portal inflow to the graft in previously severely cirrhotic patients and other hemodynamic changes in LDLT using left lobes are still under debate, as are the surgical modulations to correct them. In this study, we have reported an initial series of adult-to-adult LDLT using left lobes, underlining the hemodynamic changes encountered during the transplant and the surgical modulations we applied to correct them. METHODS: Eight adult recipients underwent left lobe liver transplantation from living donors. Portal vein pressure and central venous pressure were measured before and after surgical modulation. RESULTS: We encountered four cases of small-for-size syndrome. Two patients were retransplanted; the other two died. Seventy-five percent of our recipients survived and 50% did not require further surgery. CONCLUSION: Surgical portal inflow modulation should be considered in cases of left lobe liver transplantation between adults.

Combined liver transplants: main characteristics from the standpoint of anesthesia and support in intensive care.

Combined transplants with the liver represent a small number of associated pathologies with little chance of resolving with a single transplant. The small case number prevents us from establishing homogeneous criteria for the procedure. The insertion of the Model for End-Stage Liver Disease in the preoperative evaluation of the patients awaiting liver transplant has definitely increased the number of combined liver-kidney transplants, which have reached more significant numbers. The number of heart-liver transplants is still too low to establish the efficacy of the measure. The multiorgan transplant with the liver represents a rare event entrusted to a series of case reports, each one of which has a history unto itself. Our experience in this field includes 14 combined liver-kidney, six combined heart-liver, and two multiorgan transplants with liver among 36 intestine transplants. We have examined the main pre-, intra-, and postsurgical problems for each one of these transplants, particularly relating to the anesthetic and intensive-care aspects.

Acute renal failure requiring renal replacement therapy after orthotopic liver transplantation.

OBJECTIVES: Acute renal failure (ARF) is a severe complication in patients undergoing orthotopic liver transplantation (OLT), which predicts a poor outcome. The aim of this study was to analyze risk factors for the development of ARF, including severity of illness, onset time of ARF prognostic factors of outcome, and mortality in a group of critically patients requiring renal replacement therapy (RRT). METHODS: Retrospective analysis of 240 consecutive liver transplant cases from 1999 to 2001 admitted to the intensive care unit (ICU) was performed to identify risk factors for ARF development after OLT. The analyzed factors were: age, sex, CrS, BUN, diuresis, sepsis, hypovolemia, cardiac failure, nephrotoxic drugs (cyclosporine or FK506, antibiotics), hyperbilirubinemia, associated diseases (DM, CRF), onset time of renal failure and progressiveness, timing of RRT, number of days of RRT, and mortality. We examined variables upon admission to the ICU, before the first RRT, and on the last ICU day before resignation or death. We used Students' t test. Quantitative parameters were expressed as mean values +/- SD. RESULTS: Of the 240 patients, 20 (8.3%) experienced ARF needing renal replacement therapy during the postoperative period. The results of our study suggested that ARF among patients undergoing RRT conferred an excessive risk of in-hospital death: eight patients died (40%). This increased risk cannot be explained solely by a more pronounced severity of illness. CONCLUSION: Our results provide strong evidence that ARF presents a specific, independent risk factor for a poor prognosis.

Intraoperative coagulation monitoring and small bowel transplantation: a way to explore.

BACKGROUND: The existence of coagulation disorders during intestinal transplantation is getting more important for a correct anesthetic management. Both a condition of hypocoagulation and hypercoagulation can happen during the intraoperative course. Thromboelastography (TEG), a test on whole blood coagulation, allows measurement of different phases of coagulation function. The aims of our study were to evaluate coagulation derangements during bowel transplantation using TEG. MATERIALS AND METHODS: We measured cold ischemia time in 19 patients who underwent general anesthesia for intestinal transplantation. We measured five TEG indicators (R, K, angle, MA, CL50) at defined intervals: dissection phase (T1), vascular anastomosis phase (T2), 30' (T3) and 120' (T4) after reperfusion during the intestinal reconstruction. RESULTS: We found a statistically significant difference between MA measured at T1 versus T3 and T4. There was no significant relation between MA derangements and ischemia time. CONCLUSIONS: Patients showed hypocoagulation pattern during all periods. MA indicator variation between the initial value and the value after reperfusion may relate to release of hypocoagulation factors. We observed important coagulation derangements during small bowel transplantation, particularly on platelet function after graft reperfusion. The derangements did not depend on ischemia time.

Analysis of cardiovascular, acid-base status, electrolyte, and coagulation changes during small bowel transplantation.

The analysis of intraoperative hemodynamic, metabolic, and coagulation disorders of the recipients in relation to the newly reperfused organ during intestinal transplantation is necessary for an optimal patient management during small bowel transplantation (SBT). The interaction may be minor or may lead to postreperfusion syndrome, producing intense hemodynamic instability, important metabolic changes, and coagulation disorders. This research is based upon experience with 27 patients who underwent SBT. We observed significant decreases in PAM and IRVS after reperfusion in accordance with minor changes of mean pulmonary artery pressure, central venous pressure, and pulmonary capillary wedge pressure. The fall in pH upon revascularization was associated with a concomitant rise in partial carbon dioxide pressure probably due to the increased metabolic activity of the new organ. We found a significant increase in K levels, a rise that may be due to the output of metabolic products by the donor intestine. Patients displayed an hypocoagulative pattern, a derangement that did not seem to depend on ischemia time. It is possible that the same factors supporting the initial TEG pattern endure throughout the surgical procedure. The important and significant maximum amplitude indicator variation between the initial value and that after reperfusion may relate to the release of hypocoagulative factors superimposed on background abnormalities. These interesting metabolic disorders presumably reflected graft function and may provide predictive indices for a good outcome.