De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Epidemiologic and clinical profiles of bacterial myocarditis. Report of two cases and data from a pooled analysis.

We aimed to characterize the epidemiology, diagnostic peculiarities and outcome determinants of bacterial myocarditis. Two cases from our institution and literature reports were collected ending up with a total of 66 cases. In 37 (56%) patients, the diagnosis was confirmed by magnetic resonance and histopathological criteria. The other patients were classified as having possible myocarditis. Only occurrence of rhythm disturbances was associated with the specific diagnosis of myocarditis (p = 0.04). Thirty-two (48%) patients presented with severe sepsis that was associated with a worse prognosis. At multivariate analysis, left ventricular ejection fraction (LVEF) at admission and heart rhythm disturbances were associated with incomplete recovery (odds ratio (OR) 1.1, 95% (CI) 1.03-1.2, p = 0.004 and OR 6.6, 95% CI 1.35-32.5, p = 0.02, respectively). In summary, bacterial myocarditis is uncommon. Most commonly, it is secondary to septic dissemination of bacteria or to transient secondary myocardial toxicity.

Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters. MATERIAL AND METHODS: Pre-, Intra- and Post-operative data were collected. Tumor necrosis factor (TNF), interleukine 6, procalcitonine (PCT), cancer antigen 125 (CA-125) in blood and in peritoneal fluids were evaluated. RESULTS: Thirty-eight patients included, 29 (76.3%) female. Mean/median PCI: 9.2/5. Primary malignancy: 5 colo-rectal (13.2%), 5 gastric (13.2%), 23 ovarian (60.5%) and 5 others (13.2%). CCR 0-1 reached in all patients. Cardiac Index, Heart rate and Central Venous Pressure, increased during the procedure while Stroke Volume Variation showed a decrease. Mean Arterial Pressure and Superior Vena Cava Oxygenation were stable through the whole procedure. TNF and CA-125 were steady during the whole procedure; IL-6 had a relevant increase from baseline to start of perfusion (p<0.01); PCT had a steady increase at every time point. Peritoneal sampling showed a statistically significant increase (p<0.01) between start and end of the perfusion phase for all markers but TNF. Serum and peritoneal marker concentration were similar for TNF, PCT and CA-125. IL-6 showed a sharp difference. CONCLUSION: The most significant variations are those of IL-6 and PCT. The cytokines level parallel the hemodynamic derangements. Treatment during HIPEC should mimic the established treatment during sepsis and septic shock.

Twenty-four hour hyperinsulinemic-euglycemic clamp improves postoperative nitrogen balance only in low insulin sensitivity patients following cardiac surgery.

BACKGROUND: Critically ill patients often suffer from a protein catabolic state. The aim of this study was to demonstrate that nitrogen balance (NB) in cardiac patients admitted to the intensive care unit (ICU) is related to their insulin sensitivity level and that supraphysiologic doses of insulin can restore anabolism. MATERIALS AND METHODS: Twenty-eight patients that were admitted to ICU in enteral and/or parenteral nutrition have been enrolled in this study. All patients received a standard nutrition protocol for at least 3 days before starting the study. These patients received either enteral or parenteral nutrition based on 1.4 kcal/kg/h and 1.1 g/kg/24 h of proteins. Participants were studied for three 24 h periods (P1 , P2 , and P3 ). Twenty-four hour NB was calculated from urinary urea nitrogen excretion, fixed protein and energy intake during each of the three periods (P1 , P2 , and P3 ). Simultaneous to P2, a 24 h hyperinsulinemic-euglycemic clamp (HEC) was performed to determine patients' insulin sensitivity (IS) or insulin resistance (IR), as well as the impact of high doses of insulin on NB. RESULTS: Nitrogen balance remained consistently positive in the IS group regardless of the clamp. In IR patients, NB was negative before the clamp and became positive during P2 and P3 . Insulin sensitivity improved during the HEC in IR patients (P < 0.001). CONCLUSIONS: A negative NB was found only in insulin resistant patients admitted to the ICU for more than 7 days. A 24-h period HEC improved NB in these patients.

Experimental realization of an optical second with strontium lattice clocks.

Progress in realizing the SI second had multiple technological impacts and enabled further constraint of theoretical models in fundamental physics. Caesium microwave fountains, realizing best the second according to its current definition with a relative uncertainty of 2-4 × 10(-16), have already been overtaken by atomic clocks referenced to an optical transition, which are both more stable and more accurate. Here we present an important step in the direction of a possible new definition of the second. Our system of five clocks connects with an unprecedented consistency the optical and the microwave worlds. For the first time, two state-of-the-art strontium optical lattice clocks are proven to agree within their accuracy budget, with a total uncertainty of 1.5 × 10(-16). Their comparison with three independent caesium fountains shows a degree of accuracy now only limited by the best realizations of the microwave-defined second, at the level of 3.1 × 10(-16).

Lattice-induced frequency shifts in Sr optical lattice clocks at the 10(-17) level.

We present a comprehensive study of the frequency shifts associated with the lattice potential in a Sr lattice clock by comparing two such clocks with a frequency stability reaching 5×10(-17) after a 1 h integration time. We put the first experimental upper bound on the multipolar M1 and E2 interactions, significantly smaller than the recently predicted theoretical upper limit, and give a 30-fold improved upper limit on the effect of hyperpolarizability. Finally, we report on the first observation of the vector and tensor shifts in a Sr lattice clock. Combining these measurements, we show that all known lattice related perturbations will not affect the clock accuracy down to the 10(-17) level, even for lattices as deep as 150 recoil energies.

Fenoldopam to prevent renal replacement therapy after cardiac surgery. Design of the FENO-HSR study.

INTRODUCTION: Acute kidney injury requiring renal replacement therapy is a serious complication following cardiac surgery associated with poor clinical outcomes. Until now no drug showed nephroprotective effects. Fenoldopam is a dopamine-1 receptor agonist which seems to be effective in improving postoperative renal function. The aim of this paper is to describe the design of the FENO-HSR study, planned to assess the effect of a continuous infusion of fenoldopam in reducing the need for renal replacement therapy in patients with acute kidney injury after cardiac surgery. METHODS: We're performing a double blind, placebo-controlled multicentre randomized trial in over 20 Italian hospitals. Patients who develop acute renal failure defined as R of RIFLE score following cardiac surgery are randomized to receive a 96-hours continuous infusion of either fenoldopam (0.025-0.3 µg/kg/min) or placebo. RESULTS: The primary endpoint will be the rate of renal replacement therapy. Secondary endpoints will be: mortality, time on mechanical ventilation, length of intensive care unit and hospital stay, peak serum creatinine and the rate of acute renal failure (following the RIFLE score). CONCLUSIONS: This trial is planned to assess if fenoldopam could improve relevant outcomes in patients undergoing cardiac surgery who develop acute renal dysfunction. Results of this double-blind randomized trial could provide important insights to improve the management strategy of patients at high risk for postoperative acute kidney injury.

Correlation between pre-operative metabolic syndrome and persistent blood glucose elevation during cardiac surgery in non-diabetic patients.

BACKGROUND: Cardiopulmonary-bypass (CPB) induces hyperglycemia. There is growing evidence that perioperative maintenance of blood glucose within the physiological range improves patients' outcome. Nevertheless, perioperative normoglycemia is often difficult to achieve during surgery with CPB and the response to insulin infusion is characterized by a considerable variability. The aim of this study was to determine to what extent the presence of pre-operative metabolic syndrome (MS) influences the blood glucose and insulin response during cardiac surgery. METHODS: Forty-five patients scheduled for elective cardiac surgery were screened for the presence of MS according to the International Diabetes Federation definition. Patients were then assigned to two groups: those with metabolic syndrome (MSP) and those without (control). During surgery, blood glucose levels were measured in all patients and hyperglycemia was treated with a standard protocol of continuous insulin infusion. RESULTS: The mean blood glucose levels during CPB increased only in the MSP group (P<0.001). Mean blood glucose in control patients did not increase during CPB (P=0.4). Patients with MS received 13.3+/-8.4 IU of insulin during CPB, while the control group did not require insulin treatment (P<0.001). Forty percent of patients in the control group and 100% of those in the MSP group developed post-operative insulin resistance. C-reactive protein was higher in the MSP group before, during and at 48 h after surgery. CONCLUSIONS: The mean blood glucose levels during CPB increased only in patients with MS, while they remained unchanged in patients in the control group.

Frequency ratio of Al+ and Hg+ single-ion optical clocks; metrology at the 17th decimal place.

Time has always had a special status in physics because of its fundamental role in specifying the regularities of nature and because of the extraordinary precision with which it can be measured. This precision enables tests of fundamental physics and cosmology, as well as practical applications such as satellite navigation. Recently, a regime of operation for atomic clocks based on optical transitions has become possible, promising even higher performance. We report the frequency ratio of two optical atomic clocks with a fractional uncertainty of 5.2 x 10(-17). The ratio of aluminum and mercury single-ion optical clock frequencies nuAl+/nuHg+ is 1.052871833148990438(55), where the uncertainty comprises a statistical measurement uncertainty of 4.3 x 10(-17), and systematic uncertainties of 1.9 x 10(-17) and 2.3 x 10(-17) in the mercury and aluminum frequency standards, respectively. Repeated measurements during the past year yield a preliminary constraint on the temporal variation of the fine-structure constant alpha of alpha/alpha = (-1.6+/-2.3) x 10(-17)/year.

Randomized controlled trial of duration of analgesia following intravenous or rectal acetaminophen after adenotonsillectomy in children.

BACKGROUND: Doses of acetaminophen 40 mg kg(-1) rectally and 15 mg kg(-1) i.v. produce similar effect-site concentrations. However, the clinical effectiveness of these routes has not been compared. The aim of this study was to compare duration and efficacy of analgesia in children following adenotonsillectomy after acetaminophen either 40 mg kg(-1) rectally or 15 mg kg(-1) i.v. METHODS: Fifty children aged between 2 and 5 yr were recruited. They received a standardized anaesthetic, including 2 microg kg(-1) of fentanyl. Children were randomized to receive either rectal or i.v. acetaminophen. Postoperative pain was assessed regularly with the Children and Infants Postoperative Pain Scale score and rescue analgesia provided if scores were 4 or greater. The primary outcome measure was time to first analgesia. Results were plotted with a Kaplan-Meier analysis and median time to rescue analgesia compared between the groups. RESULTS: The protocol was successfully completed in 46 children. Forty-five children required rescue medication. The time to first rescue analgesia was longer in children receiving rectal acetaminophen (median 10 h, inter-quartile range 9-11 h) compared with those receiving i.v. acetaminophen (7, 6-10 h) with a P-value of 0.01 by log-rank test for equality in survivor function. Few children in either group required rescue analgesia within the first 6 h with differences between the groups being most prominent in the period from 6 to 10 h. CONCLUSIONS: Rectal acetaminophen 40 mg kg(-1) provides longer analgesia for moderately painful procedures when compared with 15 mg kg(-1) acetaminophen i.v.

Precision atomic spectroscopy for improved limits on variation of the fine structure constant and local position invariance.

We report tests of local position invariance and the variation of fundamental constants from measurements of the frequency ratio of the 282-nm 199Hg+ optical clock transition to the ground state hyperfine splitting in 133Cs. Analysis of the frequency ratio of the two clocks, extending over 6 yr at NIST, is used to place a limit on its fractional variation of <5.8x10(-6) per change in normalized solar gravitational potential. The same frequency ratio is also used to obtain 20-fold improvement over previous limits on the fractional variation of the fine structure constant of |alpha/alpha|<1.3x10(-16) yr-1, assuming invariance of other fundamental constants. Comparisons of our results with those previously reported for the absolute optical frequency measurements in H and 171Yb+ vs other 133Cs standards yield a coupled constraint of -1.5x10(-15)

Reduction of the cold collisions frequency shift in a multiple velocity fountain: a new proposal.

In this paper, we propose a new scheme for operating an atomic fountain frequency standard. A sequence of time-spaced balls of atoms, launched over non-overlapping trajectories, makes possible a reduction of the atomic density and consequently the cold collision frequency shift by one order of magnitude without significant reduction of the useful signal and of the overall stability of the clock. The ultimate accuracy of a Cs fountain could be improved below the 10(-15) level currently achieved in operating clocks.

Improved sensitivity of tunable far-infrared spectroscopy: application to the detection of HBr in the ? = 1 state.

We report the first detection of the pure rotational spectra of H79 Br and H81 Br in the first excited vibrational state at room temperature. We recorded the spectra with a tunable far-infrared spectrometer equipped with an optimized Ge:Ga photodetector and an improved multiple-pass gas cell to enhance the overall sensitivity. In particular, a minimum detectable absorption of better than 10-7 cm-1 was achieved. We measured a total of 60 frequencies for the two isotopomers with an accuracy of a few parts in 108 . The hyperfine structure was observed at the lower J values. The derived spectroscopic parameters, which include nuclear and quadrupole hyperfine constants, reproduce the assigned transitions within their experimental errors.

Accurate frequency measurements for H(2)O and (16)O(3) in the 119-cm(-1)OH atmospheric window.

We report frequency measurements for relatively weak H(2)O and (16)O(3) rotational transitions in the ground state and in the nu(2) = 1 vibrationally excited state. We obtained the frequency measurements by using the laboratory technique of tunable far-infrared spectroscopy with the objective of improving H(2)O and O(3) line parameters required for modeling the important atmospheric spectral window near 119 cm(-1). New sets of molecular constants are calculated from the (16)O(3) data, and improved values are reported for the frequencies of the H(2)O lines. The improvement in atmospheric simulations obtained with the new results is illustrated by comparison with recent high-resolution balloon-based atmospheric measurements. These new data significantly improve simulations of high-resolution atmospheric emission spectra.

[Plasmapheresis and intraoperative hemodilution. Comparison of 2 methods]. / Plasmaferesi ed emodiluizione intraoperatoria. Due metodiche a confronto.

Fifty patients undergoing cardiac surgery suffering from coronary artery disease and valvular incompetence or stenosis, were randomly divided into two groups of 25 patients to compare the plasmapheresis effects on bleeding, transfusion requirements, economicity and paramedical staff compliance versus intraoperative autotransfusion. Standardized anesthetics, perfusion, and surgical techniques were used. We used plasmapheresis with cell saver and haemodilution with bypass ultrafiltration. Platelet counts, haemoglobin concentration, haematocrit, fibrinogen, bleeding times were evaluated at fixed times for the patients on plasmapheresis and after surgical homologous transfusion. It was that these parameters did not change significantly in the two groups. Intraoperative plasmapheresis is more expensive and less accepted into an operating room than autotransfusion. Intraoperative plasmapheresis will be a good alternative to haemodilution for selected patients.