Development of an ultraprecision metal mirror on additively manufactured Ti-6Al-4V.

Metal mirrors for precise optical applications are commonly fabricated by coating of a metal base substrate with a nickel-phosphorus alloy (NiP). The NiP layer is then processed by precision diamond turning and polishing to obtain a high-quality mirror surface. In this work, Ti-6Al-4V samples that were made by additive manufacturing, also called 3D printing, were used as a base for the development of metal mirrors. The additively manufactured samples were electroplated with a NiP coating and machined using single-point diamond turning (SPDT) to obtain a flat mirror with optical quality and low form error surface. The periodic structure of the SPDT toolmark was then removed by polishing postprocessing. Polishing optimization was first performed on NiP-coated aluminum test samples to find an optimal polishing setup. Based on this optimization, postprocessing of titanium samples was carried out by pitch polishing in combination with 1, 0.25, and 0.1µm diamond slurries. Using this polishing processing, a scratch-free surface was attained with surface microroughness below 0.5 nm.

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant.

PURPOSE: To apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation. MATERIAL AND METHODS: The study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy. RESULTS: The median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1-7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12-40Gy). At a median follow-up of 35 months (range, 1-132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis. CONCLUSION: The adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.

Interstitial Pregnancy: From Medical to Surgical Approach-Report of Three Cases.

BACKGROUND: Interstitial pregnancy is a rare form of ectopic pregnancy that usually leads to uterine rupture resulting in sudden life-threatening haemorrhage, need for blood transfusion, and admission to intensive care unit. Mortality rate is 6-7 times higher than that in classical ectopic pregnancy. Uterine rupture has been typically reported to occur at more advanced gestational ages compared to tubal pregnancy although several recent reports have shown a high risk of rupture before 12 weeks of gestation. CASES PRESENTATION: We report three cases of women affected by interstitial pregnancy, with different clinical symptoms, and managed to be treated with surgery or medical therapy. An emergency laparotomy was performed in the first case by the general surgeon, while in the second case laparoscopy was made by a gynecologist; last case shows the success of systemic administration of methotrexate. CONCLUSION: Interstitial pregnancy is still a challenging condition to diagnose and treat; early diagnosis may help to choose the proper management.

Lenalidomide plus R-CHOP21 in newly diagnosed diffuse large B-cell lymphoma (DLBCL): long-term follow-up results from a combined analysis from two phase 2 trials.

Lenalidomide-RCHOP (R2-CHOP21) has been shown to be safe and effective in patients with untreated diffuse large B-cell lymphoma (DLBCL). The aim of this analysis is to report long-term outcome and toxicities in newly diagnosed DLBCL patients who received R2-CHOP21 in two independent phase 2 trials, conducted by Mayo Clinic (MC) and Fondazione Italiana Linfomi (FIL). All patients received R-CHOP21 plus lenalidomide. Long-term progression-free survival (PFS), time to progression (TTP), overall survival (OS) and late toxicities and second tumors were analyzed. Hundred and twelve patients (63 MC, 49 FIL) were included. Median age was 69 years, 88% were stage III-IV. At a median follow-up of 5.1 years, 5y-PFS was 63.5%, 5y-TTP 70.1% and 5y-OS 75.4%; according to cell of origin (COO): 5y-PFS 52.8% vs 64.5%, 5y-TTP 61.6% vs 69.6% and 5y-OS 68.6% vs 74.1% in germinal center (GCB) vs non-GCB respectively. Four patients experienced grade 4-5 late toxicities. Grade ≤ 3 toxicities were infections (N = 4), thrombosis (N = 1) and neuropathy (N = 3). Seven seconds tumors were observed. Long-term follow-up demonstrates that R2-CHOP21 efficacy was maintained with high rates of PFS, TTP, and OS. Lenalidomide appears to mitigate the negative prognosis of non-GCB phenotype. Incidence of therapy-related secondary malignancies and late toxicities were low.

ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma.

The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (1) the elderly patient, (2) prognostic factors suitable for clinical use, and (3) the 'ultra-high-risk' group. Before the conference, the expert panel was divided into three working groups; each group focused on one of these areas in order to address clinically-relevant questions relating to that topic. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, each working group developed recommendations to address each of the four questions assigned to their group. These recommendations were presented to the entire panel and a consensus was reached. This consensus, which was further developed in continuous post-meeting discussions, formed the basis of three manuscripts, each covering one of the three key areas identified. This manuscript presents the consensus recommendations regarding the clinical management of elderly patients diagnosed with malignant lymphoma. Four clinically-relevant topics identified by the panel were: 1) how to define patient fitness, 2) assessing quality of life, 3) diagnostic work-up and 4) clinical management of elderly patients with lymphoma. Each of these key topics is addressed in the context of five different lymphoma entities, namely: CLL, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma and diffuse large B-cell lymphoma. Results, including a summary of evidence supporting each recommendation, are detailed in this manuscript.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

Optically switched magnetism in photovoltaic perovskite CH3NH3(Mn:Pb)I3.

The demand for ever-increasing density of information storage and speed of manipulation boosts an intense search for new magnetic materials and novel ways of controlling the magnetic bit. Here, we report the synthesis of a ferromagnetic photovoltaic CH3NH3(Mn:Pb)I3 material in which the photo-excited electrons rapidly melt the local magnetic order through the Ruderman-Kittel-Kasuya-Yosida interactions without heating up the spin system. Our finding offers an alternative, very simple and efficient way of optical spin control, and opens an avenue for applications in low-power, light controlling magnetic devices.

Lorenzo Gotte (1926-1991): a pioneer of elastin.

Lorenzo Gotte (1926-1991) was an outstanding histologist at the School of Medicine of Padua. This year marks the 25th anniversary of his passing away - commemorated during the recent congress of the Italian Society for the Connective Tissue (SISC), held in Padua (September 30 - October 1, 2016). This brief note recalls this outstanding figure: indeed, forthose who knew him, Lorenzo Gotte was an exceptional scientist and at the same time, an unparalleled teacher - and, for many, a great friend. It is still difficult to separate these aspects of his personality, so intertwined in his life: studying elastin and elastic tissue was a passion central to Gotte's life.

PO-03 - Khorana score and histotype predict the incidence of early venous thromboembolism (VTE) in Non Hodgkin Lymphoma (NHL). A pooled data analysis of twelve clinical trials of Fondazione Italiana Linfomi (FIL).

BACKGROUND: Recent studies show that the risk of VTE in NHL pts is similar to that observed in high risk solid tumors (i.e. pancreatic, ovarian cancer). VTE in NHL occurs in most cases within three months from diagnosis and can have substantial impact on treatment delivery and outcome as well as on quality of life. However few data are available on potential predictors. AIMS: To better clarify the epidemiology of early (within six months from treatment start) VTE in NHL we conducted a pooled data analysis of 12 clinical trials from FIL. Our analysis included basic demographic features, lymphoma-related characteristics as well the Khorana score (based on histology, BMI, platelets WBC and HB counts) which is extensively used in solid tumors to predict VTE risk. PATIENTS AND METHODS: From Jan. 2010 to Dec. 2014, all pts with B-cell NHL enrolled in prospective clinical trials from FIL for frontline treatment were included. For 9 studies study period included the entire trial population was included. The analyses were conducted based on CRFs as well as pharmacovigilance reports. VTE definition and grading was stated according to standard criteria of toxicity (CTCAE V4.0). Cumulative incidence of VTE from the study enrollment was estimated using the method described by Gooley et al. accounting for death from any causes as a competing risk. The Fine & Gray survival model was used to identify predictors of VTE among NHL pts. Factors predicting the grade of VTE were investigated using an ordinal logistic regression model. This pooled data analysis was approved by local IRB. RESULTS: Overall, 1,717 patients belonging to 12 studies were evaluated. Eight were phase I/II or II (25% of pts) and 4 phase III (75% of pts). M/F ratio was 1.41, Median age was 57, (IQ range (IQR) 49-66). Histologies were: DLCL-B 34%, FL 41%, MCL 18%, other 6%. Median BMI was 25 (IQR 22-28). Median Hb, WBC and platelets counts were 13g/dl) (IQR 11.5-14.2), 7.1*10^(9)/l (IQR 5.6-10.3), 224*10^(9)/l (IQR 169-298), respectively. 1189 pts were evaluable Khorana score: 58% low risk, 30% intermediate risk, 12% were high risk. Human erythropoetin support was given to 9% of patients. All pts received Rituximab. Planned therapeutic programs included ASCT in 27% of pts, conventional chemotherapy in 67% a conventional chemotherapy plus lenalidomide in 6%. Overall 59 any grade VTE episodes occurred in 51 pts (2.9%), including 21 grade III-IV VTE (18 pts). None was fatal. Median time from study enrolment to VTE was 63 days (IQR: 35-110). Considering death as a competitive event the 6 months cumulative incidence of VTE was 2,2% in low risk Khorana score, 4.5% (95%IC: 2.3-6.7) in intermediate and 6.6% (95%IC: 2.4-10.8) in high risk (p=0.012) (figure 1). Khorana score was predictive also for grade III-IV events as they were 0,7% (95% CI:0.1-1.4) in low risk and 2.0% (95% CI:0.8-3.3) in intermediate-high risk (p=0.048). The results were similar also after excluding lenalidomide containing studies. The Fine and Gray multivariate analyses, adjusted for age and stage, showed that Khorana score (intermediate risk adjHR=1.96; 95%IC: 0.84-4.56 and high risk adjHR=3.81; 95%IC: 1.51-9.58) and DLCL-B histotype (adjHR=2.58; 95% CI: 1.01-6.55) were independently associated to an increased risk of VTE. Moreover an ordinal logistical regression model indicated that the increase of one point in the Khorana score resulted in an increased risk of VTE (OR=1.85; 95% CI: 1.23-2.79). CONCLUSIONS: Our results suggest that DLCL-B histotype and Khorana score are predictors of VTE in NHL. The latter might become a simple and effective tool to assess the risk of VTE in NHL. Prospective validation including also patients not eligible for clinical trials is needed.

Ultrasensitive 1D field-effect phototransistors: CH3NH3PbI3 nanowire sensitized individual carbon nanotubes.

Field-effect phototransistors were fabricated based on individual carbon nanotubes (CNTs) sensitized by CH3NH3PbI3 nanowires (MAPbI3NWs). These devices represent light responsivities of R = 7.7 × 10(5) A W(-1) under low-lighting conditions in the nW mm(-2) range, unprecedented among CNT-based photodetectors. At high incident power (∼1 mW mm(-2)), light soaking results in a negative photocurrent, turning the device insulating. We interpret the phenomenon as a result of efficient free photoexcited charge generation and charge transfer of photoexcited holes from the perovskite to the carbon nanotube. The charge transfer improves conductance by increasing the number of carriers, but leaves electrons behind. At high illumination intensity their random electrostatic potential quenches mobility in the nanotube.

Clinical presentation and outcome of non-AIDS defining cancers, in HIV-infected patients in the ART-era: the Italian Cooperative Group on AIDS and tumors activity.

The advent of antiretroviral therapy (ART) has markedly extended the survival rates of patients with human immunodeficiency virus (HIV), leading to suppression even though not eradication of HIV. In HIV infected patients, cancer has become a growing problem, representing the first cause of death. A large number of worldwide studies have shown that HIV infection raises the risk of many non-AIDS defining cancers (NADCs), including squamous cell carcinoma of the anus (SCCA), testis cancer, lung cancer, cancer of the colon and rectum (CRC), skin (basal cell skin carcinoma and melanoma), Hodgkin disease (HD) and hepatocellular carcinoma (HCC). Generally in HIV positive patients NADCs are more aggressive and in advanced stage disease than in the general population. In the ART era, however, the outcome of HIV positive patients is more similar as in the general population. Only about lung cancer the outcome seems different between HIV positive and HIV negative patients. The aim of this article is to provide an up-date on NADCs within the activity of the Italian Cooperative Group on AIDS and Tumors (GICAT) to identify clinical prognostic and predicting factors in patients with HIV infection included in the GICAT.

FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.

Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma.

BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.

Anterior Combined Endopelvic (ACE) approach for the treatment of acetabular and pelvic ring fractures: A new proposal.

PURPOSE: We present our experience of using the Anterior Combined Endopelvic (ACE) approach, which consists of a combination of a newly modified Stoppa approach with the lateral approach to the iliac crest. This approach is discussed in terms of fracture reduction and fixation, technical aspects, and the incidence of complications, and as an alternative to the ilioinguinal approach for the treatment of acetabular fractures. METHODS: A consecutive group of 34 adult patients with acetabular fractures treated surgically with the ACE approach was compared with a group of 42 adult patients treated with the ilioinguinal approach between 2010 and 2013. Both approaches were performed by a single surgeon to fix the acetabular fractures with main anterior displacement and the anterior and lateral parts of the pelvis. All the patients were analysed with typical X-ray projections for acetabular fractures and CT-scan. Charts and radiographs were reviewed for fracture pattern. Operative time, blood loss, quality of reduction, functional outcomes and perioperative complications were compared between the two groups of patients. RESULTS: The mean follow-up of patients was 26 months (range 6-49 months), with a median of 24.5 months. The types of acetabular fraction in the study were as follows: 32 anterior and posterior columns, 18 anterior columns, 10 anterior columns with posterior hemitransverse, 10 transverse associated with posterior walls, two transverse; two T-Type transverse and two anterior walls. Average blood loss was 1090 mL in the ACE group and 1200 mL in the ilioinguinal group. Anatomic or satisfactory reduction was achieved in 94% of the acetabular fractures. Two patients (one in each group) had mild symptoms of the lateral femoral cutaneous nerve and improved within 4-6 months; one patient in the ilioinguinal group developed ossification Brooks grade III. CONCLUSION: The ACE approach for the treatment of acetabular fractures is highly recommended when the fracture involves the quadrilateral surface and anterior column. This approach provides a direct good-to-excellent visualisation and access to the entire fracture, which makes reduction and fixation easier. The clinical outcomes were slightly better with ACE compared with the ilioinguinal approach. Complication rate was similar in the two groups. The ACE technique is a viable alternative to the ilioinguinal approach when exposure of the anterior acetabulum is required.

Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi.

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.

Lung cancer in HIV positive patients: the GICAT experience.

PURPOSE: AIDS incidence and mortality have decreased since the introduction of highly active antiretroviral therapy (HAART) into clinical practice. HIV-related malignancies, namely Kaposi's sarcoma and Non-Hodgkin's lymphoma, have decreased, whereas non-AIDS defining tumors have been increasing. Our aim was to study the impact of HAART on natural history of lung cancer in HIV-positive patients, comparing patients with HIV-lung cancer treated in the pre-HAART era versus the HAART era. PATIENTS AND METHODS: We collected 68 patients with HIV-lung cancer diagnosed from 1986 to 2003. Pre-HAART era included 34 patients who did not receive HAART, whereas the HAART era included 34 patients diagnosed after January 1997 who received HAART. RESULTS: At diagnosis Performance Status (PS) was significantly different, patients with PS ≥ 2 were 44% in the pre-HAART era, versus 29% in the post-HAART era, p = 0.02. The 79.4% of patients in the post-HAART era received chemotherapy alone or with radiotherapy versus 47% in the pre-HAART era, p = 0.04. Cancer was the leading cause of death for both groups, with 29 (85.3%) and 21 (61.8%) patients in the pre- and post-HAART settings, respectively. The median overall survival (OS) was 3.8 months for the pre-HAART population vs. 7 months for the post-HAART patients, p = 0.01. CONCLUSIONS: HIV-lung cancer patients have a longer overall survival in the post-HAART era versus the pre-HAART era, due to a not detrimental effect of chemotherapy and positive effect of HAART. Lung cancer is the leading cause of death, showing that treatment of the cancer is the most important target now to improve their outcome.