Bowel preparation for elective colorectal resection: multi-treatment machine learning analysis on 6241 cases from a prospective Italian cohort.

BACKGROUND: Current evidence concerning bowel preparation before elective colorectal surgery is still controversial. This study aimed to compare the incidence of anastomotic leakage (AL), surgical site infections (SSIs), and overall morbidity (any adverse event, OM) after elective colorectal surgery using four different types of bowel preparation. METHODS: A prospective database gathered among 78 Italian surgical centers in two prospective studies, including 6241 patients who underwent elective colorectal resection with anastomosis for malignant or benign disease, was re-analyzed through a multi-treatment machine-learning model considering no bowel preparation (NBP; No. = 3742; 60.0%) as the reference treatment arm, compared to oral antibiotics alone (oA; No. = 406; 6.5%), mechanical bowel preparation alone (MBP; No. = 1486; 23.8%), or in combination with oAB (MoABP; No. = 607; 9.7%). Twenty covariates related to biometric data, surgical procedures, perioperative management, and hospital/center data potentially affecting outcomes were included and balanced into the model. The primary endpoints were AL, SSIs, and OM. All the results were reported as odds ratio (OR) with 95% confidence intervals (95% CI). RESULTS: Compared to NBP, MBP showed significantly higher AL risk (OR 1.82; 95% CI 1.23-2.71; p = .003) and OM risk (OR 1.38; 95% CI 1.10-1.72; p = .005), no significant differences for all the endpoints were recorded in the oA group, whereas MoABP showed a significantly reduced SSI risk (OR 0.45; 95% CI 0.25-0.79; p = .008). CONCLUSIONS: MoABP significantly reduced the SSI risk after elective colorectal surgery, therefore representing a valid alternative to NBP.

Autism and intention attribution test: a non-verbal evaluation with comic strips.

BACKGROUND: Despite autism spectrum disorder (ASD) and mentalization being two words often associated in the literature, the assessment of this ability in individuals with ASD in the clinical setting is still limited. Indeed, there are no standardized Theory of Mind (ToM) tests that are adaptable to different cognitive profiles, such as individuals with language poverty, and intellectual or memory impairments. This study proposes a non-verbal test (Intentions Attribution-Comic Strip Test; IA-CST) to evaluate the ability to infer the intentions of others, a basic component of ToM, in the clinical setting. METHOD: In Study 1, the test was administered to 261 healthy individuals and we performed structural validation using Exploratory Graph Analysis. In Study 2, the final version of the test was administered to 32 individuals with ASD to assess the known group validity of the measure by comparing their scores with a sample of IQ-matched controls. Moreover, we performed logistic regression and ROC curve to preliminarily assess the diagnostic performance of the IA-CST. RESULTS: The IA-CST resulted in a 3-dimension measure with good structural stability. Group comparison indicated that the ASD group shows significantly lower performance in intention attribution but not in inferring causal consequences. The test demonstrated known group validity and that, preliminarily, it is suitable for implementation within the clinical practice. CONCLUSIONS: The results support the IA-CST as a valid non-verbal task for evaluating intentions attribution in the clinical setting. Difficulties in ToM are early and relevant in ASD, so assessing these aspects is valuable for structuring individualized and evidence-based interventions.

Short-term effect of orthodontic clear aligners on muscular activity and occlusal contacts: A cohort study.

INTRODUCTION: The simultaneous presence of maxillary and mandibular clear aligners alters the vertical dimension and the quantity and quality of occlusal contacts. Few data in the literature explain how this occurs and the effects on neuromuscular coordination. This study aimed to evaluate occlusal contacts and muscular balance during treatment with clear aligners over a short follow-up time. METHODS: Twenty-six female adult patients were enrolled in this study. The center of occlusal force (COF) was evaluated using a T-Scan II device, whereas muscular symmetry and balance were determined through surface electromyography using a standardized protocol that reduces anthropometric and electrode variations. Both evaluations were performed in centric occlusion and with aligners worn before treatment, after 3 months, and after 6 months. RESULTS: A statistically significant variation in COF position was reported in the sagittal plane but not in the transverse plane. The shift in the COF position was followed by a change in muscular balance evaluated through surface electromyography. CONCLUSIONS: Treatment with clear aligners resulted in an anterior shift of the COF when biting in centric occlusion and a posterior shift when the aligners were worn in healthy female patients after 6 months of observation. This change in occlusal contact was followed by an improvement in muscular function symmetry in the short term when aligners were worn, compared with the centric occlusion during treatment.

Cytokine profile, ferritin and multi-visceral involvement characterize macrophage activation syndrome during adult-onset Still's disease.

OBJECTIVES: To multidimensionally characterize macrophage activation syndrome (MAS) complicating adult-onset Still's disease (AOSD) considering cytokine profile, inflammatory markers and multi-visceral involvement of the disease. To perform a high-dimensional phenotypic analysis of circulating immune cells in AOSD patients with and without MAS. To assess interferon (IFN)-related pathways in AOSD synovial tissues by a bulky RNA sequencing. METHODS: Clinical and biologic data were collected and compared in AOSD patients with and without MAS. Sera biomolecules were analysed by Luminex multiplexing technology. Mass cytometry (CyTOF) was used to characterize circulating immune cells. A bulky RNA sequencing was performed in AOSD synovial tissues. RESULTS: Forty consecutive AOSD patients were assessed, 14 complicated with MAS. Paralleling with increases of systemic score and ferritin, MAS patients showed higher levels of IL-1α, IL-1ß, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-17A, IFN-γ, G-CSF, MCP-1, MIP-1α and SCF. Combining the discriminatory ability of these data in identifying MAS, the best model was composed by systemic score, ferritin, IFN-γ and IL-10. By CyTOF analysis, MAS patients showed an increase of circulating 'classical monocytes' and a reduction of total NK cells. Our assessment showed 3477 IFN-related genes (IRGs) were differently expressed in AOSD synovial tissues. CONCLUSIONS: A multidimensional characterization of AOSD patients suggested that IFN-γ, IL-10, ferritin and systemic score discriminated the occurrence of cytokine storm syndrome associated with MAS. The inflammatory milieu of AOSD and MAS may be related to a signature of circulating immune cells. Finally, our results about IRGs reinforced the role of IFN-γ in these patients.

Circulating tumour cell gene expression and chemosensitivity analyses: predictive accuracy for response to multidisciplinary treatment of patients with unresectable refractory recurrent rectal cancer or unresectable refractory colorectal cancer liver metastases.

BACKGROUND: Patients with unresectable recurrent rectal cancer (RRC) or colorectal cancer (CRC) with liver metastases, refractory to at least two lines of traditional systemic therapy, may receive third line intraarterial chemotherapy (IC) and targeted therapy (TT) using drugs selected by chemosensitivity and tumor gene expression analyses of liquid biopsy-derived circulating tumor cells (CTCs). METHODS: In this retrospective study, 36 patients with refractory unresectable RRC or refractory unresectable CRC liver metastases were submitted for IC and TT with agents selected by precision oncotherapy chemosensitivity assays performed on liquid biopsy-derived CTCs, transiently cultured in vitro, and by tumor gene expression in the same CTC population, as a ratio to tumor gene expression in peripheral mononuclear blood cells (PMBCs) from the same individual. The endpoint was to evaluate the predictive accuracy of a specific liquid biopsy precision oncotherapy CTC purification and in vitro culture methodology for a positive RECIST 1.1 response to the therapy selected. RESULTS: Our analyses resulted in evaluations of 94.12% (95% CI 0.71-0.99) for sensitivity, 5.26% (95% CI 0.01-0.26) for specificity, a predictive value of 47.06% (95% CI 0.29-0.65) for a positive response, a predictive value of 50% (95% CI 0.01-0.98) for a negative response, with an overall calculated predictive accuracy of 47.22% (95% CI 0.30-0.64). CONCLUSIONS: This is the first reported estimation of predictive accuracy derived from combining chemosensitivity and tumor gene expression analyses on liquid biopsy-derived CTCs, transiently cultured in vitro which, despite limitations, represents a baseline and benchmark which we envisage will be improve upon by methodological and technological advances and future clinical trials.

Are Autism Spectrum Disorder and Asexuality Connected?

Asexuality is a lack of sexual attraction to any gender. There is some evidence to suggest that many self-identified asexuals have a formal diagnosis of autism spectrum disorder which is characterized by deficits in social interaction and communication, as well as by restricted and repetitive interests and behaviors. Additionally, the literature shows that asexuality and lack of sexual attraction or low sexual interest is overrepresented in people with autism spectrum disorder compared with neurotypical samples. Nevertheless, no studies have been conducted to investigate the relationship between autism and asexuality in depth. We conducted a systematic review of the literature to examine whether asexuality and autism spectrum disorder are connected. We conclude that asexuality and autism share various aspects, such as a possible role of prenatal factors, reference to romantic dimensions of sexual attraction and sexual orientation, and non-partner-oriented sexual desire, but future research should explore and clarify this link.

A Prospective Study of Intraarterial Infusion Chemotherapy in Advanced Wild-Type BRAF Melanoma Patients.

BACKGROUND: Treatment strategies for advanced cutaneous melanoma (CM) patients, resistant or not treatable with novel target and immunotherapeutic drugs, remain a significant challenge, particularly for patients with unresectable stage IIIC/D disease localized to inferior limbs and pelvis, for whom specific outcomes are rarely considered. MATERIALS AND METHODS: This is a prospective study of multidisciplinary treatments, including locoregional melphalan chemotherapy, in 62 BRAF wild-type CM patients with locoregional metastases in the inferior limbs and pelvis, including inguinal regions. Patients were either in progression following or ineligible for, or not treatable with novel immunotherapy. For exclusively inferior limb-localised disease, patients received locoregional melphalan chemotherapy performed by hyperthermic isolated limb perfusion (n = 19) or isolated limb infusion (n = 19), and for synchronous lesions localised to inferior limbs and pelvis, received hypoxic pelvic and limb perfusion (n = 24). Additional multidisciplinary therapy included local, locoregional and systemic treatments and the primary endpoint was tumour response. RESULTS: The objective response rate following first cycle of locoregional chemotherapy was 37.1% at 3 mo and median progression-free survival was 4-mo, with 12.9% procedure-related complications, 30.6% low-grade haematological toxicity and 11.3% severe limb toxic tissue reactions. Multivariate logistic regression showed that the odds of response were significantly higher for patients ≤ 75 y of age and for patients with locoregional metastases exclusively located in the inferior limbs. CONCLUSION: In this subgroup of CM patients with BRAF wild-type status, locoregional metastases localized to inferior limbs and pelvis, in progression following or ineligible for immunotherapy, melphalan locoregional chemotherapy demonstrated a safe and effective profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01920516; date of trial registration: August 6, 2013.

Real-world clinical validity of cardiac magnetic resonance tissue tracking in primitive hypertrophic cardiomyopathy.

OBJECTIVE: Cardiac magnetic resonance (CMR) is an uncontested diagnostic tool for identifying and assessing hypertrophic cardiomyopathy (HCM) patients. Concerning the necessity to identify valid prognosticators for predicting the individual risk of clinical evolution, this study aimed to evaluate the clinical validity of CMR tissue tracking (TT) analysis in patients affected by primitive HCM in a real-world setting. METHODS: This historical prospective study included 33 patients. Diagnostic validity and clinical validation were assessed for strain values. CMR-TT diagnostic validity was studied comparing HCM patients with healthy control groups and phenotypic presentation of HCM. The impact of strain values and all phenotypic disease characteristics were assessed in a long-term follow-up study. RESULTS: The inter-reading agreement was good for all strain parameters. Significant differences were observed between the control group and HCM patients. Similarly, hypertrophic and LGE + segments showed lower deformability than healthy segments. The AUC of predictive model, including conventional risk factors for MACE occurrence and all strain values, reached 98% of diagnostic concordance (95% CI .94-1; standard error: .02; p value .0001), compared to conventional risk factors only (86%; 95% CI .73-99; standard error: .07; p value .002). CONCLUSION: In patients with primitive HCM, CMR-TT strain proves high clinical validity providing independent and non-negligible prognostic advantages over clinical features and traditional CMR markers.

Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain.

BACKGROUND: This study aimed to assess the characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain in comparison with patients receiving at least 60 mg of oral morphine equivalents (OME). MATERIALS AND METHODS: Patients with advanced cancer receiving less than 60 mg/day of OME with episodes of BTcP were included in the analysis (group L). Data were compared with patients receiving doses of opioids ≥60 mg of OME (group H). Pain intensity, current analgesic therapy, number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, and time to meaningful pain relief were collected. Adverse effects imputable to a BTcP medication were recorded. RESULTS: A total of 1,418 and 2,474 patients were included in groups L and H, respectively. A lower number of BTcP episodes (p = .005), a lower BTcP intensity (p = .0001), a faster BTcP onset (p = .024), and a longer time to meaningful pain relief after taking a BTcP medication (p = .009) were found in group L as compared with group H. In group L, BTcP interference on daily activity was less than in group H (p = .009). Patients in group L were less likely to be prescribed an opioid as BTcP medication in comparison with patients in group H (p = .0001). Opioid doses used for BTcP were significantly higher in group H. Patients in group L were more likely to be less satisfied (p = .003) than patients in group H. No adverse effects of severe intensity were reported in both groups. CONCLUSION: Patients receiving lower doses of opioids exhibit some differences in BTcP presentation: fewer episodes with lower intensity and a faster onset, a longer time to meaningful pain relief, and less satisfaction with BTcP medication. A relevant percentage of patients was receiving fentanyl preparations normally reserved for patients receiving higher doses of opioids. IMPLICATIONS FOR PRACTICE: Breakthrough pain is present in patients receiving low doses of opioids. It has its own peculiarities: less frequent, lower intensity, faster onset, longer time to meaningful pain relief, and less satisfaction with medication. Many patients were prescribed fentanyl preparations, which are normally reserved for patients receiving higher doses of opioids.

A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer.

Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic EOC CTCs, from 10 patients, nine with stage IIIC and one with stage IV disease, in progression after systemic chemotherapy, submitted for hypoxic isolated abdominal perfusion (HAP), are both feasible and useful in predicting response to therapy. Viable metastatic EOC CTCs (>5 cells/mL for all 10 blood samples), enriched by transient culture and identified by reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence (IF), were subjected to flow cytometry-based Annexin V-PE assays for chemosensitivity to several chemotherapeutic agents and by RT-PCR for tumour gene expression profiling. Using a cut-off value of >80% cell death, CTC chemosensitivity tests were predictive of patient RECIST 1.1 responses to HAP therapy associated with 100% sensitivity, 50% specificity, 33% positive predictive, 100% negative predictive and 60% accuracy values. We propose that the methodology employed in this study is feasible and has the potential to predict response to therapy, setting the stage for a larger study.

Anti-interleukin-1 treatment in patients with rheumatoid arthritis and type 2 diabetes (TRACK): A multicentre, open-label, randomised controlled trial.

BACKGROUND: The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis). METHODS AND FINDINGS: This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (ß: -0.85, p < 0.001, 95% CI -1.28 to -0.42) and 6 months (ß: -1.05, p < 0.001, 95% CI -1.50 to -0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (ß: -1.04, p < 0.001, 95% CI -1.52 to -0.55) and 6 months (ß: -1.24, p < 0.001, 95% CI -1.75 to -0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs. CONCLUSIONS: In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D. TRIAL REGISTRATION: The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481.

Notch2 pathway mediates breast cancer cellular dormancy and mobilisation in bone and contributes to haematopoietic stem cell mimicry.

BACKGROUND: Recurrence after >5-year disease-free survival affects one-fifth of breast cancer patients and is the clinical manifestation of cancer cell reactivation after persistent dormancy. METHODS: We investigated cellular dormancy in vitro and in vivo using breast cancer cell lines and cell and molecular biology techniques. RESULTS: We demonstrated cellular dormancy in breast cancer bone metastasis, associated with haematopoietic stem cell (HSC) mimicry, in vivo competition for HSC engraftment and non-random distribution of dormant cells at the endosteal niche. Notch2 signal implication was demonstrated by immunophenotyping the endosteal niche-associated cancer cells and upon co-culture with sorted endosteal niche cells, which inhibited breast cancer cell proliferation in a Notch2-dependent manner. Blocking this signal by in vivo acute administration of the γ-secretase inhibitor, dibenzazepine, induced dormant cell mobilisation from the endosteal niche and colonisation of visceral organs. Sorted Notch2HIGH breast cancer cells exhibited a unique stem phenotype similar to HSCs and in vitro tumour-initiating ability in mammosphere assay. Human samples confirmed the existence of a small Notch2HIGH cell population in primary and bone metastatic breast cancers, with a survival advantage for Notch2HIGH vs Notch2LOW patients. CONCLUSIONS: Notch2 represents a key determinant of breast cancer cellular dormancy and mobilisation in the bone microenvironment.

Personalized Symptom Goals and Patient Global Impression on Clinical Changes in Advanced Cancer Patients.

BACKGROUND: The aim of this study was to assess the patients' global impression (PGI) after symptom management, as well as the achievement of personalized symptom goals (PSG). The secondary outcome was to assess related factors. SUBJECTS, MATERIALS, AND METHODS: Advanced cancer patients admitted to palliative care units rated symptom intensity by using the Edmonton Symptom Assessment Score (ESAS) at admission and then after 1 week. For each symptom, patient-reported PGI and PSG, as well as the rate of PSG response, were evaluated. RESULTS: Eight hundred seventy-six patients were taken into consideration for this study. A mean of 1.71-2.16 points was necessary to perceive a bit better improvement of symptom intensity. Most patients had a PSG of ≤3. A statistically significant number of patients achieved their PSG after starting palliative care. Patients with high intensity of ESAS items at admission achieved a more favorable PGI response. In the multivariate analysis, symptom intensity and PSG were the most frequent factors independently associated to a best PGI, whereas high levels of Karnofsky had a lower odd ratio. CONCLUSION: PSG and PGI seem to be relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response. IMPLICATIONS FOR PRACTICE: Personalized symptom goals and global impression of change are relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response.

Pancreatic enzyme supplementation after gastrectomy for gastric cancer: a randomized controlled trial.

BACKGROUND: Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional status and quality of life after gastrectomy, but the pertinent clinical research to date remains controversial. A randomized controlled trial to test this hypothesis was carried out. METHODS: After gastrectomy, 43 patients with gastric cancer were randomly assigned to a normal diet (Normal-d; n = 21) or to a pancreatic enzyme supplementation diet (PES-d; n = 22) and were followed up during a 12-month period, assessing nutritional status and quality of life through body mass index (BMI), instant nutritional assessment (INA) class status, serum pre-albumin (SPA) values, and GastroiIntestinal Quality of Life Index (GIQLI). RESULTS: BMI was not significantly influenced by the type of diet; INA class status was significantly improved in the PES-d arm, particularly during the first 3 months after gastrectomy; SPA levels increased in both arms at 6 months after gastrectomy, reaching significantly higher values in the PES-d arm at 12 months. GIQLI was not significantly influenced by the type of diet throughout the follow-up period; however, this index significantly improved in the PES-d arm between the first and third month after gastrectomy. CONCLUSIONS: PES-d improves nutritional status and quality of life after gastrectomy for gastric cancer, particularly within 3 months from the operation. A larger, multicenter trial is necessary to address the potential influence of several confounding variables such as disease stage and adjuvant treatments.

Prevalence of delirium in advanced cancer patients in home care and hospice and outcomes after 1 week of palliative care.

AIM: The aim of this study was to assess the prevalence of delirium in advanced cancer patients admitted to different palliative care services in Italy and possible related factors. The secondary outcome was to assess the changes of delirium after 1 week of palliative care. METHODS: A consecutive sample of patients was screened for delirium in period of 1 year in seven palliative care services. General data, including primary tumor, age, gender, concomitant disease, palliative prognostic score (PaP), and Karnofsky status, were collected. Possible causes or factors associated with delirium were looked for. The Edmonton Symptom Assessment Scale was used to assess physical and psychological symptoms and the Memorial Delirium Assessment Scale (MDAS) to assess the cognitive status of patients, at admission (T0) and 1 week after palliative care (T7). RESULTS: Of 848 patients screened, 263 patients were evaluated. Sixty-six patients had only the initial evaluation. The mean Karnofsky status was 34.1 (SD = 6.69); the mean PaP score at admission was 6.9 (SD = 3.97). The mean duration of palliative care assistance, equivalent to survival, was 38.4 days (SD = 48, range 2-220). The mean MDAS values at admission and after 1 week of palliative care were 6.9 (SD = 6.71) and 8.8 (SD = 8.26), respectively. One hundred ten patients (41.8%) and 167 patients (67.3%) had MDAS values ≥ 7 at admission and after 1 week of palliative care, respectively. Age, dehydration, cachexia, chemotherapy in the last three months, and intensity of drowsiness and dyspnea were independently associated with a MDAS > 7. A worsening of drowsiness, the use of opioids, and the use of corticosteroids were independently associated with changes of MDAS from T0 to T7. CONCLUSION: Although the prevalence of delirium seems to be similar to that reported in other acute settings, delirium tended to worsen or poorly responded to a palliative care treatment. Some clinical factors were independently associated with delirium. This information is relevant for decision-making when delirium does not change despite a traditional intervention. Continuous assessment of delirium should be performed in these settings to detect deterioration of cognitive function. Further studies should elucidate whether an earlier approach to palliative care would decrease the prevalence of delirium at a late stage of disease.

Predictable method to deliver physiologic force for extrusion of palatally impacted maxillary canines.

INTRODUCTION: Orthodontic treatment of palatally impacted maxillary canines raises many difficulties; to minimize complications, careful planning of orthodontic extrusion and the use of physiologic force are crucial. The aim of this study was to quantitatively evaluate a simple and reproducible system for orthodontic extrusion of impacted canines that can provide the correct amount of force. METHODS: Ten specimens were constructed, consisting of a cantilever made with a 0.6-mm or 0.7-mm stainless steel wire modeled around a transpalatal bar with 3, 5, or 7 loops in the shape of a helical torsion spring. A mechanical testing machine was used to measure the force produced by the cantilever at 3, 6, 9, 12, and 15 mm of activation. RESULTS: The force values ranged from 1.24 ± 0.13 N for the 0.7-mm wire with 3 loops to 0.48 ± 0.04 N for the 0.6-mm wire with 7 loops. The forces measured for the 0.6-mm wire with 3 loops and the 0.7-mm wire with 7 loops were similar at 15 mm of deflection. CONCLUSIONS: The proposed system has a simple and robust design, is easy to construct and manage, and can provide the desired amount of force by changing the wire diameter and number of loops.

Melphalan hypoxic perfusion with hemofiltration for melanoma locoregional metastases in the pelvis.

BACKGROUND: For patients with melanoma metastases in the pelvic and groin regions, the median survival time (MST) was 8 mo with old treatments, whereas today is approximately 20 mo with new target therapy and novel immunotherapy. Unfortunately, approximately 30% of patients are nonresponsive to these new drugs. MATERIALS AND METHODS: Thirty-six patients, previously progressing after standard treatments, collectively received 146 melphalan (30 mg/m2) hypoxic pelvic perfusions with hemofiltration, in association with palliative excision in most cases. RESULTS: The median follow-up time was 15 mo. Among 36 patients, three patients were alive without evidence of disease after 62, 95, and 118 mo, respectively. Thirty-three patients died of melanoma. The overall MST was 15 mo. The 5-y survival rate was 8%. The MST was 37 mo for stage IIIB; 19 mo for stage IIIC; and 6 mo for stage IV. The MST was 11 mo for patients with ≥1 mitosis per mm2 and 20 mo for patients with <1 mitosis per mm2; 17 mo for patients who received excision and 7 mo for patients who did not receive excision; and 19.5 mo for patients who received >2 treatments and 7.5 mo for patients who received ≤2 treatments. CONCLUSIONS: Pelvic/inguinal perfusion is a safe and feasible treatment for patients with advanced melanoma. Further studies are necessary to establish if it may play a role in patients who fail current systemic therapies.

Attitudes of palliative home care physicians towards palliative sedation at home in Italy.

BACKGROUND: Information about the attitudes towards palliative sedation (PS) at home is limited. AIM: The aim of this survey was to assess the attitudes of palliative care physicians in Italy regarding PS at home. DESIGN: A questionnaire was submitted to a sample of palliative care physicians, asking information about their activity and attitudes towards PS at home. SETTING: This is a survey of home care physicians in Italy who were involved in end-of-life care decisions at home. RESULTS: One hundred and fifty participants responded. A large heterogeneity of home care organizations that generate some problems was found. Indications, intention and monitoring of PS seem to be appropriate, although some cultural and logistic conditions were limiting the use of PS. Specialized home care physicians are almost involved to start PS at home. Midazolam was seldom available at home and opioids were more frequently used. CONCLUSION: These data should prompt health care agencies to make a minimal set of drugs easily available for home care. Further research is necessary to compare attitudes in countries with different sociocultural profiles.

Sleep disturbances in advanced cancer patients admitted to a supportive/palliative care unit.

The aim of this study was to assess the prevalence of sleep disturbances and possible correlations with associated factors in a sample of patients admitted to an acute palliative/supportive care unit.A consecutive sample of patients with advanced cancer was prospectively assessed for a period of 6 months. Epidemiological and clinical data, treatments received in the last month, Karnofsky status, Edmonton Symptom Assessment System (ESAS), and concomitant medical treatment were also recorded. Patients were administered the Athens Insomnia Scale (AIS) and the Hospital Anxiety and depression scale (HADS).Two hundred nineteen patients met the inclusion criteria. The mean age was 65.4 years (SD 12.4), and 111 patients were males. The mean Karnofsky status was 46.6 (SD = 12). All patients had consistent sleep disturbances (AIS ≥6), with a large number of patients having intense-maximum sleep disturbances. No relationships of AIS with gender, age, primary diagnosis, socio-educational factors, and anticancer treatments were found. AIS score was significantly associated with Karnofsky; intensities of pain, asthenia, anorexia, anxiety, depression, drowsiness, and well-being; and the use of corticosteroids and benzodiazepines. There was a positive correlation of HADS anxiety and HADS depression with sleep disturbances (p = 0.000). In the multivariate analysis, AIS increased only with the level of anxiety and depression assessed by HADS.Sleep disturbances were ubiquitous in advanced cancer patients admitted to a supportive/palliative care unit and were strongly correlated with psychological distress. Assessment of sleep disorders is mandatory in this population for the obvious interference with quality of life.

Does Locoregional Chemotherapy Still Matter in the Treatment of Advanced Pelvic Melanoma?

Pelvic Melanoma relapse occurs in 15% of patients with loco regional metastases, and 25% of cases do not respond to new target-therapy and/or immunotherapy. Melphalan hypoxic pelvic perfusion may, therefore, be an option for these non-responsive patients. Overall median survival time (MST), stratified for variables, including BRAF V600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases. They had received a total of 175 treatments with Melphalan hypoxic perfusion and cytoreductive excision. Among the 41 patients, 22 (53.7%) patients exhibited a wild-type BRAF genotype, 11 of which were not eligible for immunotherapy. The first treatment resulted in a 97.5% response-rate in the full cohort and a 100% response-rate in the 22 wild-type BRAF patients. MST was 18 months in the full sample, 20 months for the 22 wild-type BRAF patients and 21 months for the 11 wild-type BRAF patients not eligible for immunotherapy. Melphalan hypoxic perfusion is a potentially effective treatment for patients with pelvic melanoma loco regional metastases that requires confirmation in a larger multicenter study.