Equilibrium and nonequilibrium description of negative temperature states in a one-dimensional lattice using a wave kinetic approach.

We predict negative temperature states in the discrete nonlinear Schödinger (DNLS) equation as exact solutions of the associated wave kinetic equation. Within the wave kinetic approach, we define an entropy that results monotonic in time and reaches a stationary state, that is consistent with classical equilibrium statistical mechanics. We also perform a detailed analysis of the fluctuations of the actions at fixed wave numbers around their mean values. We give evidence that such fluctuations relax to their equilibrium behavior on a shorter timescale than the one needed for the spectrum to reach the equilibrium state. Numerical simulations of the DNLS equation are shown to be in agreement with our theoretical results. The key ingredient for observing negative temperatures in lattices characterized by two invariants is the boundedness of the dispersion relation.

Interferon-gamma-release assays detect recent tuberculosis re-infection in elderly contacts.

The tuberculin skin test (TST) does not discriminate between recent and remote latent tuberculosis infection (LTBI). This study was carried out to test two interferon-gamma-based blood assays in recent contacts with high prevalence of remote LTBI. We performed a contact tracing investigation in a nursing home for the elderly, where elderly patients were exposed to a case of pulmonary tuberculosis. TST, QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (TS.TB) were performed 8 weeks after the end of potential exposure. IFN-gamma measurements were recorded and correlation with exposure was evaluated. Twenty-seven (37.5%), 32 (44.4%) and 16 (22.2%) subjects were TST, TS.TB and QFT-G positive, respectively; agreement between TS.TB and QFT-G was good among exposed subjects only (K=0.915, 0.218 in unexposed, p<0.001). When amounts of IFN-gamma were corrected for the number of producing T cells, specific IFN-gamma production was significantly different between exposed and unexposed individuals (16.75+/-5.40 vs 2.33+/-0.71 IFN-gamma IU/1000 SFC, p=0.0001). QFT-G and TS.TB provided discordant results among elderly contacts. Unlike TST, the specific IFN-gamma response might discriminate between recent and long-lasting tuberculosis infection.

Opposite activation of the Hedgehog pathway in CD138+ plasma cells and CD138-CD19+ B cells identifies two subgroups of patients with multiple myeloma and different prognosis.

Hyperactivation of the Hedgehog (Hh) pathway, which controls refueling of multiple myeloma (MM) clones, might be critical to disease recurrence. Although several studies suggest the Hh pathway is activated in CD138- immature cells, differentiated CD138+ plasma cells might also be able to self-renew by producing themselves the Hh ligands. We studied the gene expression profiles of 126 newly diagnosed MM patients analyzed in both the CD138+ plasma cell fraction and CD138-CD19+ B-cell compartment. Results demonstrated that an Hh-gene signature was able to cluster patients in two subgroups characterized by the opposite Hh pathway expression in mature plasma cells and their precursors. Strikingly, patients characterized by Hh hyperactivation in plasma cells, but not in their B cells, displayed high genomic instability and an unfavorable outcome in terms of shorter progression-free survival (hazard ratio: 1.92; 95% confidence interval: 1.19-3.07) and overall survival (hazard ratio: 2.61; 95% confidence interval: 1.26-5.38). These results suggest that the mechanisms triggered by the Hh pathway ultimately led to identify a more indolent vs a more aggressive biological and clinical subtype of MM. Therefore, patient stratification according to their molecular background might help the fine-tuning of future clinical and therapeutic studies.

18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease.

Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide (18)F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58-5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM.

Evaluating daily nursing use and needs in the intensive care unit: a method to assess the rate and appropriateness of ICU resource use.

BACKGROUND: We designed a tool to measure the rate and appropriateness of intensive care unit (ICU) nursing coverage as a proxy for the use of resources. METHODS: We tested the tool in 32 Italian ICUs during a cross-sectional study (4 days/week, October 2001 and April 2002). The level of care was classified as high or low. The appropriate patient-to-nurse ratio for both levels (2/1 and 3/1 in this ICU mix) was defined. The provided and theoretical nurse assistance was computed, the difference between the two quantifying the ICU use of personnel: a positive difference means over-utilization, a negative one under-utilization. We calculated the maximum number of high-level and low-level care days available for ICU and the relative utilization rates. These two rates quantify the appropriateness of resource use in relation to the planned use. RESULTS: Analysing 5783 treatment-days, the tool identified units using almost all available resources (five), overcrowded (14: too small units) or empty (16: too big). Units were overcrowded on account of the high-level of care required (five: utilization rate >100%) or reallocated too much of their residual high-care nursing capacity to low-level care (six). In empty units both utilization rates were lower than expected. CONCLUSIONS: The method quantifies the rate and appropriateness of resource usage and suggests the best management in units with fixed human resources or a fixed number of beds.

Importance of early absolute lymphocyte count after allogeneic stem cell transplantation: a retrospective study.

INTRODUCTION: Early lymphocyte recovery after allogeneic hematopoietic stem cell transplantation (HSCT) is related to the prevention of serious infections and the clearing of residual tumor cells. METHODS: We analyzed the absolute lymphocyte count at 20 (D+20) and 30 (D+30) days after HSCT in 100 patients with malignant hematologic diseases and correlated with the risk of transplant-related mortality, overall survival (OS), disease-free survival (DFS), nonrelapsed mortality (NRM), and risk of infection. RESULTS: Patients presenting with lymphocyte counts of <300 × 103/µL on D+30 have a 3.76 times greater risk of death in <100 days. Over a medium follow-up of 20 months OS, DFS, and NRM were similar between the groups. CONCLUSION: In our group of patients delayed lymphocyte recovery after HSCT was a predictor of early death post-HSCT.

Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation.

Incorporation of novel agents into auto-SCT for patients with multiple myeloma has led to improvement in their outcomes. However, the effects of new drugs, either single or combined, on PBSC mobilization have not been fully evaluated, particularly in phase 3 clinical studies. We analyzed the impact of two novel agent-based induction treatments in patients enrolled in the GIMEMA MMY-3006 study comparing bortezomib, thalidomide and dexamethasone (VTD) versus thalidomide and dexamethasone (TD) in preparation for double auto-SCT. Results showed that a short-term induction therapy with VTD did not adversely affect CD34(+) cell yields as compared with TD (9.75 vs 10.76 × 10(6) CD34(+) cells/kg, P=0.220). For poor mobilizers (<4 × 10(6) CD34(+) cells/kg), 5-year rates of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were significantly shorter than for successful mobilizers (TTP:17 vs 48%, P<0.0001; PFS: 16 vs 46%, P<0.0001; OS: 50 vs 80%, P<0.0001). These differences were retained across patients randomized to the TD arm; conversely, no differences in outcomes were seen in patients treated with VTD, irrespective of the number of harvested CD34(+) cells. The number of collected PBSCs predicted better outcomes after auto-SCT and VTD overcame the negative impact of a poor stem cell mobilization.

Description of trends in the course of illness of critically ill patients. Markers of intensive care organization and performance.

OBJECTIVE: To identify objective trends of the course of illness that might be used as benchmarks in the auditing of the organization/performance of Intensive Care Units (ICU). DESIGN: Retrospective analysis. PATIENTS AND SETTING: A group of 12,615 patients and 55,464 patient-days prospectively collected in 89 ICUs of 12 European countries. METHODS: The complexity of daily care in the ICU was classified as high (HT) or low (LT), according to six activities registered in NEMS,a daily therapeutic index for ICUs. RESULTS: Six trends of clinical course were identified: LT during the whole ICU stay (5,424 patients, mortality 1.8%); HT (3,480 patients, mortality 30.4%); HT followed by LT (2,781 patients, mortality 2.8%); LT followed by HT (197 patients, mortality 39.1%); finally, LT/HT/LT in 298 patients (mortality 10.5%); and HT/LT/HT (mortality 20.1%) in 438 patients. A group of 930 patients had the complexity of treatment increased (mortality 21.1%) and 3,711 patients received both treatments. Low-care before high-care periods had a mean duration of 2.2 +/- 3.5 days, low-care after high-care 2.7 +/- 3.1 days, and between two high-care periods 2.1 +/- 2.2 days. A group of 1,538 'surgical scheduled' patients only received LT, whereas 2,231 received HT (whether or not exclusively). Overall ICU mortality rate was low (3%) and the length of stay short, regardless of diagnosis and complexity of care received. CONCLUSIONS: The use of therapeutic indexes help to classify the daily complexity of ICU care. The classification can be used as an indicator of clinical performance and resource utilization.

Daily classification of the level of care. A method to describe clinical course of illness, use of resources and quality of intensive care assistance.

OBJECTIVE: To develop a simple and comparable clinical method able to distinguish between higher and lower complexities of care in the ICU. DESIGN: Retrospective analysis. SETTING: Database of European ICUs Study I (Euricus-I: including 12,615 patients and 55,464 patient/days), prospectively collected in 89 ICUs of 12 European countries. METHODS AND RESULTS: A panel of experts developed the classification of the complexity of care. Six (in addition to monitoring, two levels of respiratory support--R and r--two levels of circulatory support--C and c--and dialysis) out of the nine items of Nine Equivalents of Nursing Manpower use Score (NEMS), a therapeutic index, were utilised. Two levels of care (LOCs) were defined according to a more (HT) and a less complex (LT) combination of common activities of care. The two LOCs were significantly related to mortality: higher in HT and they rose with increasing cumulative number of HT days. HT accounted for 31,976 NEMS days (57.7%) while 23,488 (42.3 %) were LT. Major respiratory and cardiovascular support accounted for about 80 % of the HT days. Respiratory assistance and monitoring were responsible for an equivalent percentage of LT days. The distribution of the clinical classification of LOCs coincided with that of the managerial scores of LOCs in the literature. CONCLUSIONS: The managerial instrument described uses simple and reliable clinical data. It is able to distinguish between patients with different severity and outcome, and shows that every additional consecutive day spent in ICU as HT increases the probability of death. Moreover, (1) it suggests the possibility of describing the clinical course of illness by relating the complexity/level of medical care to the available technology and staff; (2) using relevant markers of clinical activity, it might be useful to include in quality control programmes.

Cancer of the appendix in long-standing ulcerative colitis: a case report.

Cancer of the appendix was found in a 69-year-old female patient affected by long-standing ulcerative colitis (UC). On histological examination the cancer was a typical cystadenocarcinoma of the appendix. The appendiceal mucosa not invaded by the neoplastic process was normal. Histological examination of the colorectal mucosa did not show dysplasia or cancer. These findings suggest that appendiceal cancer and UC may be unrelated diseases. A surveillance program for early detection of cancer of the appendix in patients with long-standing UC does not seem mandatory.

Emergency medical services in mass gatherings: the experience of the Formula 1 Grand Prix 'San Marino' in Imola.

Mass gatherings are special situations for which mass medical care must be preplanned. Acute emergencies occur at public gatherings and medical coverage on site has proven benefit. Responsibility of general plan, management of specific problems, transport planning, communications system, guidelines and protocols, special situations management, ancillary supports, sources of extra help for unforeseen needs are the most important items to consider. In mass gatherings the whole emergency medical service (EMS) planning and management has to depend on the emergency department direction, with its authority on all aspects of patient care in the EMS system. This report concerns the planning of EMS and of medical care in a situation at risk for mass casualties at the Formula I Grand Prix-Championship Racing 'San Marino' of Imola.

[Prepyloric annular diaphragm in the adult]. / Diaframma anulare prepilorioco nell'adulto.

A case of prepyloric myo-mucosal annular diaphragm in a 47-yr-old woman with a 4-month history of subocclusion is presented. A "distal hourglass" gastric deformity was present, along with gastritis and marked spasm. The case is included in a survey of the recent literature and classed as a transitional form lying between ring diaphragm and annular hypoplasic stenosis of the antrum.

Intensive care of patients requiring open abdomen treatment: a case-series analysis.

BACKGROUND: This retrospective overview examines the management of patients with temporary open abdomen (OA). METHODS: The clinical characteristics and intensive care treatment of 34 consecutive patients with OA (1996-2012) were reviewed. RESULTS: Average age was 61 years, SAPS II score 43, SOFA 8. Two patients had non-contaminated abdomen; 12 had intact gut (only 8 later during stay); 7 repaired gut (only later 4); 13 cutaneous stoma (later 14), and 2 entero-atmospheric fistula (later 8+1 entero-enteral). The median ICU stay was 48 [36-94] days. One quarter of the 2376 ICU-days were classified as severe sepsis/septic shock (antibiotics were given for two thirds of the stay); three quarters were with ventilation; in 95% of days sedatives were given (mainly enterally). Continuous cavity lavage was done in three quarters of days; in 3% of days patients were fasted whereas >20 kcal/kg was given for 74% of days; we fed the gut in 95% of fed-days, in half of them combined with parenteral nutrition. Complications are discussed; mortality was 32.4%, limited to the ICU stay. CONCLUSION: The intensive care of patients with OA is challenging but can achieve better outcomes than expected. Continuous abdominal lavage improves the evacuation of contaminated fluid or debris and, coupled with antiseptics and low antibiotic pressure, reinforces the control of infection. The gut can be used for nutrition (even without gastrointestinal continuity), and long-term light sedation (mainly enteral) with minimal impact on perfusion, ventilation and gut motility.

The Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) Italian collaborative: national results from the Picker survey.

BACKGROUND: The aim of the Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) project is to create an internationally acceptable competency-based training program for specialists in intensive care medicine. The CoBaTrICE Project has performed a survey, in collaboration with the Picker institute, United Kingdom, to identify desirable characteristics of Intensive Care Unit (ICU) specialists, as expressed by patients and their relatives. METHODS: A questionnaire was developed to assess 21 elements of professional competence. Each element was assigned to one of four categories of a Likert scale: 1=essential; 2=very important; 3=not too important; 4=does not matter. The results were dichotomized into essential (score: 1) and not essential (scores: 2-4) categories. Further, the documents were related to three key concepts: "medical skills and competencies", "communication with patients", and "communication with relatives". Questionnaire statements grouped by theme were also ranked for each item using a number: 1=highest rank; 21=lowest rank. Free text responses were also invited. RESULTS: Ten Italian ICUS were enrolled in the study. There were 249 questionnaires completed (18% total return rate). CONCLUSION: Priority in Italy was given to medical skills and competence. Involvement of patients and relatives in decision-making processes were among the items considered least important. Italian families preferred a paternalist approach to the end of life decision-making process.