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The Great Debate session at the 2022 Melanoma Bridge congress (December 1–3) featured counterpoint views from leading experts on five contemporary topics of debate in the management of melanoma. The debates considered the choice of anti-lymphocyte-activation gene (LAG)-3 therapy or ipilimumab in combination with anti-programmed death (PD)-1 therapy, whether anti-PD-1 monotherapy is still acceptable as a comparator arm in clinical trials, whether adjuvant treatment of melanoma is still a useful treatment option, the role of adjuvant therapy in stage II melanoma, what role surgery will continue to have in the treatment of melanoma. As is customary in the Melanoma Bridge Great Debates, the speakers are invited by the meeting Chairs to express one side of the assigned debate and the opinions given may not fully reflect personal views. Audiences voted in favour of either side of the argument both before and after each debate.

The Great Debate session at the 2019 Melanoma Bridge congress (December 5-7, Naples, Italy) featured counterpoint views from experts on five topical issues in melanoma. These were whether to choose local intratumoral treatment or systemic treatment, whether patients with stage IIIA melanoma require adjuvant therapy or not, whether treatment is better changed at disease progression or during stable disease, whether adoptive cell transfer (ACT) therapy is more appropriate used before or in combination with checkpoint inhibition therapy, and whether treatment can be stopped while the patient is still on response. As was the case for previous meetings, the debates were assigned by meeting Chairs. As such, positions taken by each of the melanoma experts during the debates may not have reflected their respective personal approach.

The aim of this study was to assess the combined role of current radiographic risk indicators and patient age in predicting lower lip sensitivity disturbances after surgical removal of impacted lower third molars. The question was which combinations indicate low or high risk. A prospective study was implemented involving 247 consecutive outpatients who underwent 423 surgical extractions. The predictor variables were patient age and risk indicators observed on panoramic radiographs. The outcome variable was the incidence of self-assessed lip sensitivity alterations. The extractions were subdivided into four groups according to the predictors. Two hundred forty-five teeth were extracted in patients younger than 25 years and 178 in patients 25 years old or older; radiographic risk indicators were associated with 226 out of 423 teeth (53.43%). No permanent neurological damage was observed. Transient lip sensitivity alterations were observed in five cases (1.18%; 95% confidence interval = 0.4 to 2.7%), all in the older group with radiographic risk indicators. The data indicate a low overall incidence of transient lip sensitivity impairment that occurred only in the presence of radiographic risk indicators in patients aged ≥ 25 years. Informed consent should include the possibility of inferior alveolar nerve injury in mature patients with radiographic risk indicators. Prophylactic removal of impacted teeth with radiographic signs of risk may be indicated when the patient is not yet aged 25 years.

The purpose of this study was comparison of clinical and radiographic outcomes of immediate post-extraction implants with or without the use of pure platelet-rich plasma (P-PRP) in the short- and medium-term follow-up. A retrospective analysis was performed to assess soft tissue healing, implant and prosthesis survival, marginal bone level changes and biological complications. A total of 109 partially edentulous patients with 126 implants were included in this analysis. At 4–5 years after loading, cumulative survival rate in test group was 97.4% and in control group was 97.8%, with no significant differences. After 5 years of function, marginal bone loss (MBL) in test group was 0.8 ± 0.35 and 1.02 ± 0.27 mm for immediate and delayed loading, respectively, and in control group was 0.6 ± 0.16 and 0.8 ± 0.89 mm for immediate and delayed loading, respectively. No significant differences in MBL were observed intragroups and intergroups at any time point considered. Soft tissue healing score was significantly higher in test group compared to the control at 3 and 7 days after surgery, with significant differences. P-PRP implant group showed a better soft tissue management and wound healing in the first 7 days after surgery compared to non-P-PRP implant group. In the medium-term follow-up, comparable clinical and radiographic outcomes were noticed between two groups.

Fast magic-angle spinning and partial sample deuteration allows direct detection of 1H in solid-state NMR, yielding significant gains in mass sensitivity. In order to further analyze the spectra, 1H detection requires assignment of the 1H resonances. In this work, resonance assignments of backbone HN and Hα are presented for HET-s(218–289) fibrils, based on the existing assignment of Cα, Cβ, C’, and N resonances. The samples used are partially deuterated for higher spectral resolution, and the shifts in resonance frequencies of Cα and Cβ due to the deuterium isotope effect are investigated. It is shown that the deuterium isotope effect can be estimated and used for assigning resonances of deuterated samples in solid-state NMR, based on known resonances of the protonated protein.

Virus-based vaccines and appropriate costimulation potently enhance antigen-specific T cell immunity against cancer. Here we report the use of recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against solid tumors. Therapeutic treatment with rMVA-CD40L-expressing tumor-associated antigens results in the control of established tumors. The expansion of tumor-specific cytotoxic CD8+ T cells is essential for the therapeutic antitumor effects. Strikingly, rMVA-CD40L also induces strong natural killer (NK) cell activation and expansion. Moreover, the combination of rMVA-CD40L and tumor-targeting antibodies results in increased therapeutic antitumor efficacy relying on the presence of Fc receptor and NK cells. We describe a translationally relevant therapeutic synergy between systemic viral vaccination and CD40L costimulation. We show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combination with tumor-targeting antibodies. This immunotherapeutic approach could translate into clinical cancer therapies where tumor-targeting antibodies are employed., CD40 agonists have been investigated as a strategy to awaken the immune system against cancers. Here, the authors use a virus encoding CD40L and tumour-associated antigens to enhance innate and adaptive immunity that together with tumour targeting antibodies controls the growth of tumours in mice.

Postmastectomy radiotherapy (PMRT) following immediate breast reconstruction is increasingly adopted in the management of breast cancer patients. We retrospectively evaluate the complication rates of PMRT using VMAT technique to immediate tissue expander-based reconstructions and the possible impact of tissue expander volume on radiotherapy planning. We reviewed the data of patients who underwent immediate expander breast reconstruction and received PMRT with VMAT (50 Gy in 25 fractions) on the reconstructed breast and axillary levels III–IV. Neoadjuvant or adjuvant systemic therapy was administered in most of the patients. Autologous fat grafting was routinely performed at the time of second-stage reconstruction. Between 2015 and 2017, PMRT was delivered to 46 consecutive patients (median age 50 years) with expander reconstruction. Median follow-up was 27 months (range 10–41). Two patients (4.3%) had a reconstruction failure, as expander rupture and infection, following the first- and the second-stage reconstruction, respectively. In most cases expanders were completely inflated before PMRT (65.2%). Median expander volume before PMRT was 425 cm3 (range 150–700 cm3). The amount of expander inflation did not significantly affect dosimetry, except for skin dose, with a surface receiving more than 30 Gy of 36.6 ± 0.9 cm2 and 47.0 ± 2.5 cm2 for a volume expander below or above the median, respectively. However, this variable was not predictor for complications. Disease progression was recorded in 15.2% of patients. PMRT using VMAT technique for breast cancer patients with expander reconstruction is associated with a very low complication rate. The expander volume before PMRT does not significantly compromise radiotherapy dose distribution.

As decision-making research becomes more popular, the inclusion of personality traits has emerged as a focal point for an exhaustive analysis of human behaviour. In this study, we investigate the impact of psychopathic traits on cooperation in an iterated Prisoner’s Dilemma game with emotional facial feedback. Firstly, we observed how receiving a facial feedback after each decision affected players with different psychopathic trait scores, and how being informed about the opponent’s identity influenced cooperative behaviour. Secondly, we analysed the strategies adopted by each player, and how these choices were correlated with their psychopathic traits. Although our results showed no effect of different emotional content in the feedback on cooperation, we observed more cooperative behaviours in those players who were told their opponent was another fellow human, compared to those who were told it was a computer. Moreover, fearless dominance had a very small but consistent negative effect on overall cooperation and on the tendency to maintain cooperative behaviours. We also found that players’ personality scores affected the strategies they chose to play throughout the game. Hence, our experiment adds complexity to the body of work investigating psychopathic traits and social interactions, considering not only the environment of facial feedback but also the role of deception in experimental games.

Background and case presentation We report a case of septic shock syndrome caused by Streptococcus pneumoniae in a patient who had undergone splenectomy due to an autoimmune lymphoproliferative syndrome (ALPS), which is characterized as a dysfunction of immunoregulation. Although the patient was vaccinated with a conjugated polysaccharide vaccine after the splenectomy, he was still susceptible to S. pneumoniae infection, because the isolated serovar (24F), a serovar long thought to be apathogenic, is not covered by any vaccine currently approved, neither a conjugated nor an unconjugated polysaccharide one. Conclusions This case demonstrates that, due to presence of different serovars, also infections with bacteria against which patients are vaccinated have to be considered as differential diagnosis. Although vaccine development has extended the coverage of S. pneumoniae from 7 to 23 serovars within recent years, there is still demand for novel vaccines which can provide broader protection also against so-thought “apathogenic” strains, especially for groups at high risk.

Data about acute renal function in hypertensive crises are scarce. We hypothesised that acute kidney damage could result from hypertensive emergency (HE), as indicated by the earliest biomarker of kidney injury, neutrophil gelatinase-associated lipocalin (NGAL). Thus, we compared renal function between patients with HE, patients with urgencies and normotensive controls. Sixty emergency department patients were enroled in a prospective, cross-sectional study. Creatinine, blood urea nitrogen (BUN), NGAL and cystatin C were measured and estimated glomerular filtration rate was calculated (eGFR). Creatinine and BUN were significantly higher and eGFR was significantly lower in HE as compared with urgencies or controls (P < 0.01). Similarly, cystatin C and NGAL levels were significantly higher in emergencies compared with the other groups (P < 0.001). All renal function parameters were similar between urgencies and controls. Among HE, NGAL was significantly higher (61%) in patients with pulmonary oedema than in those with cerebral events (P = 0.008), whereas the other parameters were not significantly different. In conclusion, this cross-sectional investigation showed that markers of acute and chronic kidney injury were higher in patients with HE than in urgencies or controls. These results should encourage further studies to better characterise the role of acute kidney damage in hypertensive pulmonary oedema, and HE in general.

To investigate whether whole-body diffusion-weighted imaging (WB-DWI) alone is adequate for detecting metastases in melanoma patients, or if standard WB contrast-enhanced magnetic resonance imaging (WB-ceMRI) is required. Seventy-one WB-DWI studies were performed quarterly along with whole-body MRI including contrast-enhanced sequences (WB-ceMRI) in 19 patients with advanced melanoma. The reference standard was biopsy, other imaging investigations, or changes observed on follow-up. Findings of metastasis in separate WB-DWI and WB-DWI + WB-ceMRI readings were compared using κ statistics. Additionally, the distribution of findings was examined and calculated per body region (brain, neck, chest, abdomen, liver, pelvis, subcutaneous tissues, bones) and diagnostic accuracy (DA), sensitivity, specificity, negative predictive value, and positive predictive value were calculated per patient. The eight examinations that were positive by the reference standard contained a total of 14 metastatic findings. With almost perfect agreement between techniques (κ = 85 %, 95 % CI 70–100 %) for detection of examinations with metastatic findings, and complete agreement in extracranial metastasis detection, 10 metastases were detected using WB-DWI and 13 using WB-DWI + WB-ceMRI. WB-DWI and WB-DWI + WB-MRI had equivalent per patient DA (79 %). WB-DWI without additional WB-ceMRI sequences is promising for the detection of extracranial metastases in melanoma patients, but contrast-enhanced MRI is required for evaluating the brain. • Whole-body (WB) magnetic resonance imaging (MRI) is increasingly used for oncological disease assessment. • WB diffusion-weighted MRI detects extracranial metastases in melanoma patients. • Contrast-enhanced MRI is only required for detecting brain metastases. • WB-DWI is inferior to low-dose CT for detecting lung metastases.

Although sentinel node biopsy (SNB) has become standard of care in patients with melanoma, its use in patients with thin or thick melanomas remains a matter of debate.This was a retrospective analysis of patients with thin (≤1 mm) or thick (≥4 mm) melanomas who underwent SNB at two Italian centers between 1998 and 2011. The associations of clinicopathologic features with sentinel lymph node positive status and overall survival (OS) were analyzed.In 492 patients with thin melanoma, sentinel node was positive for metastatic melanoma in 24 (4.9 %) patients. No sentinel node positivity was detected in patients with primary tumor thickness0.3 mm. Mitotic rate was the only factor significantly associated with sentinel node positivity (p = 0.0001). Five-year OS was 81 % for patients with positive sentinel node and 93 % for negative sentinel node (p = 0.001). In 298 patients with thick melanoma, 39 % of patients had positive sentinel lymph nodes (median Breslow thickness 5 mm). In patients with positive sentinel node, 93 % had mitotic rate1/mm(2). Five-year OS was 49 % for patients with positive sentinel lymph nodes and 56 % for patients with negative sentinel nodes (p = 0.005).The rate of sentinel node positivity in patients with thin melanoma was 4.9 %. The only clinicopathologic factor related to node positivity was mitotic rate. Given its prognostic importance, SNB should be considered in such patients. SNB should also be the standard method for melanoma ≥4 mm, not only for staging, but also for guiding therapeutic decisions.

To further promote the health of European consumers, their right not to be misled and to make informed choices when purchasing foods and beverages, as well as the fairness of commercial practices and competition, the European Union regulatory system on information to consumers on food and beverages is rapidly evolving. This evolution goes in the direction of a system in which more mandatory regulated information will be provided to consumers, more modern and simpler rules will apply to operators and it will be easier and faster to adapt these rules to technological and societal developments. In this context, voluntary information is being more strictly regulated in order to better ensure its scientific validity and usefulness for consumers. This paper highlights some of the main current trends and priority issues of this substantial and important evolution likely to continue for some years.

In our recent publication (Smith et al., J Biomol NMR 65:171–191, 2016) on the dynamics of HET-s(218–289), we reported on page 176, that calculation of solid-state NMR R1ρ rate constants using analytical equations based on Redfield theory (Kurbanov et al., J Chem Phys 135:184104:184101–184109, 2011) failed when the correlation time of motion becomes too long.

The EORTC 18991 trial assessed the effect of long-term adjuvant pegylated interferon (Peg-IFN) alpha-2b administered weekly in patients with lymph node-positive melanoma. Serum concentrations were analyzed to determine exposure to Peg-IFN alpha-2b.After surgery, patients were randomized to receive Peg-IFN alpha-2b or to observation only. The treatment group received 6 microg/kg/week Peg-IFN alpha-2b subcutaneously for 8 weeks, followed by a maintenance dose of 3 microg/kg/week for up to 5 years. Blood samples were collected between months 3 and 60.A total of 208 Peg-IFN alpha-2b concentrations from 48 patients were available. Serum trough concentrations increased in a dose-related manner. Mean dose-normalized serum concentrations and intersubject variability over the 5-year study period in patients with melanoma were similar to those observed in patients with chronic hepatitis.Data suggest that the exposure to Peg-IFN alpha-2b was sustained during long-term adjuvant treatment with Peg-IFN alpha-2b in patients with melanoma, consistent with the EORTC 18991 trial's conclusion of a significant, sustained, and relapse-free survival benefit.

Demographische Daten belegen, dass die Zahl der uber 80-Jahrigen in den kommenden Jahren weiter ansteigen wird. Aufgrund dieser Tatsache haben wir Grunde fur Rettungseinlieferungen an die Notfallaufnahme und das weitere Management dieser Patienten analysiert und mit den Jungeren verglichen. Es wurde eine retrospektive Analyse von Daten eines prospektiven Registers durchgefuhrt in der konsekutiv alle, von Rettungsorganisationen an die Notfallaufnahme des AKH Wien eingelieferten Patienten, erfasst werden. In dieser Datenbank werden die Diagnosen (im ICD-10-Code), Alter und Geschlecht jener Patienten registriert sowie der unmittelbare Ausgang der Erkrankung, das weitere Management und die unmittelbar applizierten intensivtherapeutischen Interventionen erfasst. Die Patienten wurden nach Alter in eine Gruppe

Background Patients with primary multiple malignancies are progressively increasing due to prolonged survival of cancer patients and to the advances in diagnostic techniques and therapeutic options. Case presentation Here we present a 66 year-old caucasian patient with four synchronous primary malignant tumors affecting the lung, oropharynx, large bowel and prostate gland, respectively, treated with multidisciplinary approach. Conclusions The increased incidence of multiple malignant tumors is a real challenge to the clinician and clinical attention should be made to avoid a misdiagnosis. In addition an early diagnosis is essential to achieve a radical treatment. We believe that the treatment modality should be carefully made and tailored on the individual patient suffering from this disease.

Die Notfallaufnahme der Universitatsklinik fur Notfallmedizin stellt eine Drehscheibe in der Versorgung von Vergiftungspatienten am AKH Wien dar. In der folgenden Analyse wurden die Haufigkeit exogener Vergiftungen, ihre Ursachen und das weitere Management ausgewertet um allgemeine Ruckschlusse fur die Errichtung von Notfallaufnahmen zu erhalten. Die Dateneingabe erfolgte in eine Microsoft-Access Datenbank in der neben Vergiftungsdiagnosen nach ICD-10 auch Alter, Geschlecht, ambulante/stationare Betreuung, maschinelle Beatmung, Reanimation und weitere intensivmedizinische Betreuung bzw. Tod an der Notfallaufnahme erfasst wurden. Im Jahr 2003 wurden 550 Personen mit Vergiftungen—das sind 0,7% der Gesamtpatientenanzahl von 74 117—in der Notfallaufnahme behandelt. Von diesem Kollektiv konnten 161 Patienten (29,3%) bereits nach ambulanter Versorgung wieder aus dem Spital entlassen werden. 345 Patienten (62,7%) wurden auf die Notfallstation zur weiteren Versorgung aufgenommen. Zur weiteren stationaren Behandlung wurden 171 Patienten (31,1%) auf eine Normalstation uberwiesen und 18 (3,3%) benotigten eine Transferierung auf eine Intensivstation. In 35 Fallen (6,4%) war es notwendig den Patienten zu intubieren und maschinell zu beatmen. Davon erlitten 8 Personen einen Herz-Kreislauf- Stillstand von denen 6 (75%) nach kardio-pulmonaler Reanimation verstarben. In einem Fall kam der cardio-pulmonale Bypass—leider frustran—zum Einsatz. Obwohl die Zahl der Vergiftungen gemessen an der Gesamtzahl der Patienten der Notfallaufnahme relativ gering ist, zeigt unsere Analyse doch, dass es sich um eine relevante Diagnosegruppe mit potentieller Beatmungs- und Reanimationspflichtigkeit handelt. Diese Tatsachen sind bei der Errichtung von Notfallaufnahmen zu berucksichtigen.

This study evaluated the role of pulsed dose-rate (PDR) brachytherapy (BRT), delivered alone or as a boost to external beam radiotherapy, as adjuvant therapy for the local control of soft tissue sarcomas of the extremities and skeletal muscles of the trunk that have undergone surgical treatment.Between July 1998 and January 2002, 42 patients were treated with a combination of surgery and BRT alone (18 patients) or BRT/external beam radiotherapy (24 patients) for the treatment of primary (n = 32) and recurrent (n = 10) soft tissue sarcomas located in the proximal extremity (n = 17), distal extremity (n = 17), and trunk (n = 8). Tumor size was5 cm in 20 cases and5 cm in 22 cases, with histological grading of 1 (n = 7), 2 (n = 18), or 3 (n = 17). The median BRT dose delivered was 15 Gy, and the median external beam irradiation dose was 50 Gy.With a median follow-up of 34 months, the 36-month survival was 83.9% (SE, 6.1%), and the local control was 89%.PDR interstitial BRT for soft tissue sarcoma is an effective, well-tolerated adjuvant radiation treatment that offers several practical advantages, among which are low acute and late toxicity with maximum normal tissue and critical structure sparing and overall shorter radiotherapy and hospital stay.

Background To report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. Methods Between September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy respectively, delivered in 15 fractions over 3 weeks. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8–16). Cosmetic outcomes were assessed as excellent/good or fair/poor. Results The median age of the population was 68 years (range 36–88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up. Conclusions The 3-week course of postoperative radiation using VMAT with SIB showed to be feasible and was associated with acceptable acute skin toxicity profile. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

In stage I cutaneous melanoma, biopsy of the first tumour-draining lymph node (sentinel node, SN) may replace routine elective lymph node dissection (ELND). The patent blue dye (PBD) technique has been shown to be an original method for the localization of the SN, but its sensitivity is sometimes unsatisfactory, depending on the basin where the SN is located. We compared three methods to locate the SN: intraoperative PBD mapping, lymphoscintigraphy (LS) with an aspecific tracer (colloid) and LS with a specific tracer (monoclonal antibody, MoAb). Fifty patients with cutaneous melanoma were enrolled in this study. The day before surgery LS was performed following an intradermal injection of 55 MBq technetium-99m-labelled HSA colloidal particles (25 patients: group A) or 220 MBq of 99mTc-F(ab')2 MoAb 225.28 S (25 patients: group B) around the site of the primary lesion. In group B an equal amount of tracer was injected, as a control, in the contralateral site. Early and delayed images were acquired with a gamma camera and SN(s) marked on the skin. In all 50 patients the PBD technique was also performed immediately before surgery. When a blue node was identified intraoperatively, its radioactivity level was measured with a gamma probe. In the absence of blue coloration, the probe alone was used to detect the SN. Lymphoscintigraphic visualization of SNs was possible in 50/50 patients (100%), a total of 73 SNs (38 in group A and 35 in group B) were found, distributed in 55 basins. Gamma probe detection (GPD) allowed the identification of SNs in 49/50 patients (98%), and 72 SNs in 54 basins were localized. By contrast, using PBD, SNs were stained only in 40/50 patients (50 SNs in 40 basins). A tumour-positive SN was histologically proven in 13 patients (26%). In group B, no increase uptake was observed in the seven positive SNs (6/25 patients) compared with the contralateral uninvolved nodes. In conclusion this study demonstrates that LS combined with GPD is a safe method for detecting SNs and is more sensitive than the PBD technique. The use of MoAb fragments did not show any advantage over the non-specific tracer.

The effects of amlodipine 5 to 10 mg/day on hypertension and metabolic indices was assessed in 113 patients with recently diagnosed untreated mild hypertension, and non-insulin-dependent diabetes mellitus (NIDDM). Comparisons were made with normotensive patients matched with similar demographic and clinical characteristics.

Background Patients with advanced melanoma are faced with a poor prognosis and, until recently, limited treatment options. Ipilimumab, a novel immunotherapy that blocks cytotoxic T-lymphocyte-associated antigen-4, was the first agent to improve survival of patients with advanced melanoma in a randomised, controlled phase 3 trial. We used data from an expanded access programme (EAP) at Italian centres to evaluate the clinical activity and safety profile of ipilimumab 10 mg/kg in patients with advanced melanoma in a setting more similar to that of daily practice. Methods Data were collected from patients enrolled in an ipilimumab EAP across eight participating Italian centres. As per the EAP protocol, patients had life-threatening, unresectable stage III/IV melanoma, had failed or did not tolerate previous treatments and had no other therapeutic option available. Treatment comprised ipilimumab 10 mg/kg every 3 weeks for a total of four doses. If physicians believed patients would continue to derive benefit from ipilimumab treatment, maintenance therapy with ipilimumab 10 mg/kg was provided every 12 weeks. Tumour responses were assessed every 12 weeks using modified World Health Organization criteria and safety continuously monitored. Results Seventy-four pretreated patients with advanced melanoma were treated with ipilimumab 10 mg/kg. Of these, 9 (13.0%) had an objective response, comprising 3 patients with a complete response and 6 with a partial response. Median overall survival was 7.0 months (95% confidence interval, 5.3–8.7) and 16.6% of patients were alive after 3 years. Forty-five patients (60.8%) reported treatment-related adverse events of any grade, which were most commonly low-grade pruritus, pain, fever and diarrhoea. Grade 3 or 4 treatment-related AEs were reported in 8 patients (10.8%). Conclusions The clinical activity and safety profile of ipilimumab 10 mg/kg in the EAP was similar to that seen in previous clinical trials of ipilimumab in pretreated patient populations.

Dendritic cell tumors are extremely rare neoplasms and occur both in nodal and extranodal sites. We report a case of an intra-abdominal follicular dendritic cell sarcoma (FDCS). The aim of this study is to describe histological, immunohistochemical, and ultrastructural features of FDCS in order to better define an abdominal mass with unusual immunophenotype and atypical clinical and radiological presentation.

Introduction Animal and human studies suggest beneficial outcome effects of mild hypothermia for stroke, for acute myocardial infarction, and for cardiogenic shock. The aim of this study was to investigate the feasibility and safety of non-invasive surface cooling for induction and maintenance of mild hypothermia (32 to 34°C) in healthy, conscious volunteers. Methods The trial was set at a clinical research ward in a tertiary care center, and included 16 healthy male volunteers 18 to 70 years old. Surface cooling was established by a novel non-invasive cooling pad with an esophageal target temperature of 32 to 34°C and maintenance for six hours. Shivering-control was achieved with meperidine and buspirone and additional administration of magnesium in eight subjects. Results The primary endpoint to reach a target temperature of 32 to 34°C was only reached in 6 of the 16 participating subjects. Temperatures below 35°C were reached after a median cooling time of 53 minutes (38 to 102 minutes). Cooling rate was 1.1°C/h (0.7 to 1.8°C). Additional administration of magnesium had no influence on cooling rate. At no time during the cooling procedure did the participants report uncomfortable conditions for which termination of cooling had to be considered. No severe skin damage was reported. Conclusions Cooling to body temperature below 35°C by the use of non-invasive surface cooling is feasible and safe in conscious healthy volunteers. Further studies are needed to investigate an altered cooling protocol to achieve temperatures below 35°C. Trial Registration ISRCTN: ISRCTN50530495

Introduction: Our purpose was to study whether the time to target temperature correlates with neurologic outcome in patients after cardiac arrest with restoration of spontaneous circulation treated with therapeutic mild hypothermia in an academic emergency department. Methods: Temperature data between April 1995 and June 2008 were collected from 588 patients and analyzed in a retrospective cohort study by observers blinded to outcome. The time needed to achieve an esophageal temperature of less than 34°C was recorded. Survival and neurological outcomes were determined within six months after cardiac arrest. Results: The median time from restoration of spontaneous circulation to reaching a temperature of less than 34°C was 209 minutes (interquartile range [IQR]: 130-302) in patients with favorable neurological outcomes compared to 158 min (IQR: 101-230) (P < 0.01) in patients with unfavorable neurological outcomes. The adjusted odds ratio for a favorable neurological outcome with a longer time to target temperature was 1.86 (95% CI 1.03 to 3.38, P = 0.04). Conclusions: In comatose cardiac arrest patients treated with therapeutic hypothermia after return of spontaneous circulation, a faster decline in body temperature to the 34°C target appears to predict an unfavorable neurologic outcome.

Acute clonidine administration is known to induce a significant rise in plasma glucose in man. In order to evaluate the possible effect of prolonged drug treatment on glucose metabolism, paired OGTTs were performed in 12 hypertensive patients (6 with normal and 6 with abnormal glucose tolerance) in basal conditions and following 1-week's administration of clonidine (0.15 mg every 8 h). Basal plasma glucose and serum insulin concentration as well as glucose tolerance and insulin response to oral glucose did not change in either group after treatment. Although the mechanism(s) mediating the transient hyperglycemic action of clonidine are not fully understood, the present findings indicate that this drug does not exert diabetogenic effects during chronic treatment, and suggest that homeostatic mechanisms may counteract the acute effect of clonidine on glucose metabolism.