Recruitment maneuvers in acute respiratory distress syndrome: The safe way is the best way

Acute respiratory distress syndrome(ARDS) represents a serious problem in critically ill patients and is associated with in-hospital mortality rates of 33%-52%. Recruitment maneuvers(RMs) are a simple, low-cost, feasible intervention that can be performed at the bedside in patients with ARDS. RMs are characterized by the application of airway pressure to increase transpulmonary pressure transiently. Once non-aerated lung units are reopened, improvements are observed in respiratory system mechanics, alveolar reaeration on computed tomography, and improvements in gas exchange(functional recruitment). However, the reopening process could lead to vascular compression, which can be associated with overinflation, and gas exchange may not improve as expected(anatomical recruitment). The purpose of this review was to discuss the effects of different RM strategies- sustained inflation, intermittent sighs, and stepwise increases of positive end-expiratory pressure(PEEP) and/or airway inspiratory pressure- on the following parameters: hemodynamics, oxygenation, barotrauma episodes, and lung recruitability through physiological variables and imaging techniques. RMs and PEEP titration are interdependent events for the success of ventilatory management. PEEP should be adjusted on the basis of respiratory system mechanics and oxygenation. Recent systematic reviews and meta-analyses suggest that RMs are associated with lower mortality in patients with ARDS. However, the optimal RM method(i.e., that providing the best balance of benefit and harm) and the effects of RMs on clinical outcome are still under discussion, and further evidence is needed.

Amyloid positron emission tomography and cognitive reserve

Alzheimer's disease(AD) is characterized by a nonlinear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve(CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis(Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography(PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD.

Comparisons between glucose analogue 2-deoxy-2-(^(18)F)fluoro-D-glucose and ^(18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM: To compare 2-deoxy-2-(^(18)F)fluoro-D-glucose(^(18)FFDG) and ^(18)F-sodium(^(18)F-NaF) positron emission tomography/computed tomography(PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent ^(18)F-FDG and ^(18)F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity(Se), specificity(Sp), overall accuracy, positive and negative predictive values, error rate, and Youden's index. Mc Nemar's χ~2 test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the coregistered CT(sclerotic, lytic, mixed, no-lesions) and the divergent site of disease(skull, spine, ribs, extremities, pelvis). The impact of adding ^(18)F-Na F PET/CT to the work-up of patients was also measured in terms of change in their management due to ^(18)F-Na F PET/CT findings. RESULTS: The two imaging methods of ^(18)F-FDG and ^(18)F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively(Mc Nemar's χ~2 = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis(Mc Nemar's χ~2 = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, ^(18)F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis(P < 0.002) and vertebral localizations(P < 0.002); ^(18)F-Na F PET/CT was more accurate in detecting sclerotic(P < 0.005) and rib lesions(P < 0.04). ^(18)F-Na F PET/CT led to a change of management in 3 of the 45 patients(6.6%) by revealing findings that were not detected at ^(18)F-FDG PET/CT. CONCLUSION: ^(18)F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of ^(18)F-Na F PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of ^(18)F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings(i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative ^(18)F-FDG PET and conventional imaging).

Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis,fibrosis,and cirrhosis to hepatocellular carcinoma.Forty-four per cent of all deaths from cirrhosis are attributed to alcohol.Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation(LT).The vast majority of transplant programmes(85%)require 6 mo of abstinence prior to transplantation;commonly referred to as the"6-mo rule".Both in the case of progressive end-stage liver disease(ESLD)and in the case of severe acute alcoholic hepatitis(AAH),not responding to medical therapy,there is a lack of evidence to support a 6-mo sobriety period.It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking.The"Group of Italian Regions"suggests that:in a case of ESLD with model for end-stage liver disease<19 a 6-mo abstinence period is required;in a case of ESLD,a 3-mo sober period before LT may be more ideal than a 6-mo period,in selected patients;and in a case of severe AAH,not respond-ing to medical therapies(up to 70%of patients die within 6 mo),LT is mandatory,even without achieving abstinence.The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist.Patients have to participate in self-help groups.

Is current clinical practice modified about intraoperative breast irradiation?

After the results obtained in the two randomized clinical trial, the ELIOT trial and the TARGIT-A trial, a heated debate is going on concerning the question of applying intraoperative radiotherapy （IORT） instead of postoperative whole breast irradiation （WBI） after breast conservative treatment. Currently, many centers are applying the IORT following the strict selection criteria dictated by the working groups American Society for Radiation Ontology （ASTRO） and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology （GEC-ESTRO） and monitoring the oncological outcome together with radiation toxicity on breast tissue. The clinical experience of the Geneva University Hospital regarding the use of the Intrabeam system is evaluated and compared with current evidences.

Immunomodulatory effects of anesthetics in obese patients

Anesthesia and surgery have an impact on inflammatory responses, which influences perioperative homeostasis. Inhalational and intravenous anesthesia can alter immune-system homeostasis through multiple processes that include activation of immune cells(such as monocytes, neutrophils, and specific tissue macrophages) with release of pro-or anti-inflammatory interleukins, upregulation of cell adhesion molecules, and overproduction of oxidative radicals. The response depends on the timing of anesthesia, anesthetic agents used, and mechanisms involved in the development of inflammation or immunosuppression. Obese patients are at increased risk for chronic diseases and may have the metabolic syndrome, which features insulin resistance and chronic low-grade inflammation. Evidence has shown that obesity has adverse impacts on surgical outcome, and that immune cells play an important role in this process. Understanding the effects of anesthetics on immune-system cells in obese patients is important to support proper selection of anesthetic agents, which may affect postoperative outcomes. This review article aims to integrate current knowledge regarding the effects of commonly used anesthetic agents on the lungs and immune response with the underlying immunology of obesity. Additionally, it identifies knowledge gaps for future research to guide optimal selection of anesthetic agents for obese patients from an immunomodulatory standpoint.

Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor

Mycosis fungoides(MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokinechemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10.

Metformin and cancer: Technical and clinical implications for FDG-PET imaging

Metformin is the most widely used hypoglycemic agent. Besides its conventional indications, increasing evidence demonstrate a potential efficacy of this biguanide as an anticancer drug. Possible mechanisms of actions seem to be independent from its hypoglycemic effect and seemto involve the interference with key pathways in cellular proliferation and glycolysis. To date, many clinical trials implying the use of metformin in cancer treatment are on-going. The increasing use of 18F-2-fluoro-2-deoxyd-glucose positron emission tomography(FDG-PET) in cancer evaluation raises a number of questions about the possible interference of the biguanide on FDG distribution. In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway(the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution. A better comprehension of the impact of metformin on FDG uptake is needed in order to optimize the use of PET in this setting. This evaluation would be useful to ameliorate scans interpretation in diabetic patients under chronic metformin treatment and to critically interpret images in the context of clinical trials. Furthermore, collecting prospective data in this setting would help to verify whether FDG-PET could be a valid tool to appreciate the anticancer effect of this new therapeutic approach.