Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain. An observational analysis

INTRODUCTION: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. METHODS: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0-10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. RESULTS: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. CONCLUSION: OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function

B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial

INTRODUCTION: An over-expression of CD19 has been shown in B cells of systemic sclerosis (SSc) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model. The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry. METHODS: Nine patients with SSc with mean age 40.9 +/- 11.1 years were treated with anti-CD20, 1 g at time 0 and after 14 days. Skin biopsy was performed at baseline and during the follow-up. B-cell activating factor (BAFF) and IL-6 levels were also determined at the follow-up times. RESULTS: After 6 months patients presented a median decrease of the skin score of 43.3% (range 21.1-64.0%), and a decrease in disease activity index and disease severity index. IL-6 levels decreased permanently during the follow up. After treatment, a complete depletion of peripheral blood B cells was observed in all but 2 patients. Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline. CONCLUSIONS: Anti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms. The clear fall in IL-6 levels could contribute to the skin fibrosis improvement, while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion

Pliocene Diatom Biomarkers in Sabrina Coast. EAIS Continental Marginal Dynamics

PNRA Tytan project, supported by the National Institute of Oceanography and Applied Geophysics (OGS), focused on the advances and retreats dynamics of the ice sheet and on variations in the glacial regime. Unit 2 focused on Diatom biomarkers and assemblages analysis on sediments of core PC03, collected during the IN2017-V01 cruise on the eastern flank of the Minang-a (or Whale) submarine Canyon. The project aims at reconstructing the depositional environment of the continental margin off the Totten Glacier and diatom data remained a key tools to constrain past ice-sheet dynamics and to forecasting future behaviour in a warming world. Preliminary dataset from diatom biostratigraphic tools allows to refer the base of the core to Pliocene while the upper part of the core records more modern EAIS dynamics, indicative of minor sedimentary evolution steps of the continental margin. Diatom assemblage analyses highlight Eocene-Oligocene reworked material and freshwater diatom inputs in Pliocene sequence, strengthening the debate about ice-sheet and paleoceanographic models, WAIS cyclic collapse and suspected Pliocene EAIS retreat into major subglacial Antarctic basins

Primary, secondary and compensated male biochemical hypogonadism in people living with HIV (PLWH): relevance of sex hormone-binding globulin (SHBG) measurement and comparison between liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay for sex steroids assay

Background: Data about classification of hypogonadism and estrogen deficiency in male people living with HIV (PLWH) are scanty. Aim: To investigate the prevalence and characterization of biochemical hypogonadism and relative estrogen deficiency in male PLWH aged &lt; 50 comparing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with chemiluminescent immunoassay (CI), and combining gonadotropin, sex hormone-binding globulin (SHBG) and serum estradiol (E2) measurements. Methods: Prospective, cross-sectional, observational study. Serum total testosterone (TT), E2, gonadotropins, SHBG were measured by CI. TT and E2 were also assessed by LC-MS/MS. Free testosterone (cFT) was calculated by Vermeulen equation. Results: A total of 316 PLWH (45.3 ± 5.3 years) were enrolled. TT and cFT by LC-MS/MS were lower compared to CI (p &lt; 0.0001). The prevalence of biochemical hypogonadism was higher with LC-MS/MS than CI, both for TT (5.1% vs 3.2%, p &lt; 0.0001) or cFT (9.5% vs 7%, p &lt; 0.0001). The prevalence of hypogonadism (overt + compensated) was 17.1% for cFT using LC-MS/MS. Secondary form of hypogonadism was more prevalent than primary. The prevalence of relative estrogen deficiency was of 30.0% among hypogonadal patients and 15.5% among eugonadal. Conclusions: The prevalence of male hypogonadism results underestimated by CI compared to LC-MS/MS in PLWH, both for TT and cFT. SHBG and gonadotropins are essential for detecting T deficiency.Background: Data about classification of hypogonadism and estrogen deficiency in male people living with HIV (PLWH) are scanty. Aim: To investigate the prevalence and characterization of biochemical hypogonadism and relative estrogen deficiency in male PLWH aged &lt; 50 comparing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with chemiluminescent immunoassay (CI), and combining gonadotropin, sex hormone-binding globulin (SHBG) and serum estradiol (E2) measurements. Methods: Prospective, cross-sectional, observational study. Serum total testosterone (TT), E2, gonadotropins, SHBG were measured by CI. TT and E2 were also assessed by LC-MS/MS. Free testosterone (cFT) was calculated by Vermeulen equation. Results: A total of 316 PLWH (45.3 ± 5.3 years) were enrolled. TT and cFT by LC-MS/MS were lower compared to CI (p &lt; 0.0001). The prevalence of biochemical hypogonadism was higher with LC-MS/MS than CI, both for TT (5.1% vs 3.2%, p &lt; 0.0001) or cFT (9.5% vs 7%, p &lt; 0.0001). The prevalence of hypogonadism (overt + compensated) was 17.1% for cFT using LC-MS/MS. Secondary form of hypogonadism was more prevalent than primary. The prevalence of relative estrogen deficiency was of 30.0% among hypogonadal patients and 15.5% among eugonadal. Conclusions: The prevalence of male hypogonadism results underestimated by CI compared to LC-MS/MS in PLWH, both for TT and cFT. SHBG and gonadotropins are essential for detecting T deficiency

Phosphoinositide Conversion Inactivates R-RAS and Drives Metastases in Breast Cancer

Breast cancer is the most prevalent cancer and a major cause of death in women worldwide. Although early diagnosis and therapeutic intervention significantly improve patient survival rate, metastasis still accounts for most deaths. Here it is reported that, in a cohort of more than 2000 patients with breast cancer, overexpression of PI3KC2α occurs in 52% of cases and correlates with high tumor grade as well as increased probability of distant metastatic events, irrespective of the subtype. Mechanistically, it is demonstrated that PI3KC2α synthetizes a pool of PI(3,4)P2 at focal adhesions that lowers their stability and directs breast cancer cell migration, invasion, and metastasis. PI(3,4)P2 locally produced by PI3KC2α at focal adhesions recruits the Ras GTPase activating protein 3 (RASA3), which inactivates R-RAS, leading to increased focal adhesion turnover, migration, and invasion both in vitro and in vivo. Proof-of-concept is eventually provided that inhibiting PI3KC2α or lowering RASA3 activity at focal adhesions significantly reduces the metastatic burden in PI3KC2α-overexpressing breast cancer, thereby suggesting a novel strategy for anti-breast cancer therapy

Intrahepatic Cholestasis in Sickle Cell Disease: A Case Report

Intrahepatic cholestasis (SCIC) is an uncommon but potentially fatal complication of sickle cell disease (SCD), with a high death rate, observed mainly in patients with homozygous sickle cell anemia. Herein, we describe a case of severe SCIC treated successfully with aggressive manual exchange transfusion (ET). The patient was admitted with enlarged liver and signs of hepatic failure, such as hyperbilirubinemia and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. We performed several sessions of ET in order to reduce the percentage of HbS to levels inferior to 30%, which was successfully accomplished. The patient had a complete recovery of hepatic function. This case has shown that ET is an effective treatment of SCIC and should be introduced early on the onset of this severe complication

The Italian version of the Depressive Experiences Questionnaire: psychometric properties and validation in students, community, and clinical groups

The current study evaluated the psychometric properties of the Italian validation of the Depressive Experiences Questionnaire (DEQ), conceived as a measure of self-criticism and dependency, i.e. two personality factors acting, according to Blatt (2004), as risk factors for depression in particular and psychopathology in general. A series of standardized measures [Beck Depression Inventory-II (BDI-II), DEQ, Symptom Checklist-90-R (SCL-90-R), Millon Clinical Multiaxial Inventory, 3rd edition (MCMI-III)] was administered to three samples (i.e., students, community and clinical). Factorial validity was evaluated along with convergent and predictive validity. In order to evaluate the reliability and internal consistency, a specific subgroup of participants was retested on the DEQ and BDI-II. Results showed correlations between DEQ dimensions and some personality traits of the MCMI-III. The traditional three-factor model of the DEQ structure as identified by principal component analysis appears to be as stable factors as typically found in American samples, although some items showed elevated cross-loading or low loadings on any factor. Clinical and diagnostic implications of the findings will be discussed

Phthalates and Bisphenol A: presence in blood serum and follicular fluid of italian women undergoing assisted reproduction techniques

Background: folliculogenesis is a strictly regulated process that may be affected by endocrine disrupting chemicals (EDCs) through sometimes not so clear molecular mechanisms. Methods: we conducted a multicentric observational study involving six fertility centers across Italy, prospectively recruiting 122 women attending a fertility treatment. Recruited women had age ≤42 years, and normal ovarian reserve. Blood and follicular fluid samples were taken for EDCs measurement using liquid chromatography tandem mass spectrometry and each woman completed an epidemiological questionnaire. Results: The main EDCs found were monobutyl phthalate (MBP) (median blood: 8.96 ng/mL, follicular fluid 6.43 ng/mL), monoethylhexyl phthalate (MEHP) (median blood: 9.16 ng/mL, follicular fluid 7.68 ng/mL) and bisphenol A (BPA) (median blood: 1.89 ng/mL, follicular fluid 1.86 ng/mL). We found that serum MBP concentration was significantly associated with the considered area (p &lt; 0.001, adj. mean: 7.61 ng/mL, 14.40 ng/mL, 13.56 ng/mL; Area 1: Milan–Turin, Area 2: Rome–Naples; Area 3: Catania–Bari, respectively) but negatively with home plastic food packaging (p = 0.004). Follicular MBP was associated with irregular cycles (p = 0.019). No association was detected between EDCs and eating habits and other clinical and epidemiological features. Conclusions: This study represents the first Italian biomonitoring of plastic EDCs in follicular fluid, laying the basis for future prospective evaluation on oocyte quality before assisted reproduction techniques (ART

European Association of Nuclear Medicine Focus 5:Consensus on Molecular Imaging and Theranostics in Prostate Cancer

BACKGROUND: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.OBJECTIVE: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.DESIGN, SETTING, AND PARTICIPANTS: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.RESULTS AND LIMITATIONS: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy.CONCLUSIONS: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.PATIENT SUMMARY: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.</p