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This analysis from the GARIBALDI study was aimed to address the role of center self-declared expertise, type and commitment on the overall survival (OS) of patients with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC). Treatment-naïve patients ≥18-year with pathological diagnosis of mPDAC were enrolled. OS was defined as the time from chemotherapy start to death from any cause. The impact of clinical-demographic and centers characteristics on OS was evaluated using Cox models. Between July 2017 and October 2019, 473 patients enrolled in 43 centers were eligible for this analysis. Median age was 69.3 (first-third quartile 61.2-74.5); 46.1 % females; 90.8 % ECOG PS 0-1; 67.4 % had liver metastases; median CA19.9700.5 UI/mL (first-third quartile 77.5-6629.5). For 37.1 % of patients chemotherapy started <4 weeks from diagnosis; 69.9 % of patients received nab-paclitaxel + gemcitabine; 16.9 % gemcitabine alone; 7.6 % FOLFIRINOX. The median follow-up was 51.8 months and 428 patients died. No statistically significant role of the type of institution was observed. Additionally, no statistically significant role of neither the self-declared expertise nor the accrual rate was observed. The GARIBALDI study suggests that the self-declared center expertise and the academic brand are not associated to OS in patients with mPDAC, while center commitment warrants further exploration.
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Central pain sensitivity (CS) is defined as an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold inputs. The main aim of this paper is to investigate if and how specific psychological constructs are related with CS burden in patients with chronic headache (CH). Specifically, research question 1 explores the association of temperament, personality, childhood adversities, defense mechanisms and mental pain with CS burden. Research question 2 aims to test the role of the best predictors of CS burden in affecting the quality of life (QoL) using path analysis. A total of 508 women with CH completed a psycho-diagnostic survey. Results showed that higher levels of low sensory threshold (ß = 0.200), bodily threat traumatic experiences (ß = 0.156), neurotic defenses (ß = 0.109) and mental pain (ß = 0.343) emerged as the best predictors of higher CS burden. The model presented demonstrated a satisfactory fit (GFI = 0.984; NFI = 0.966; CFI = 0.979; RMSEA = 0.056 [95% CI 0.028-0.085]) with large and medium effect sizes on physical (-0.654) and psychological QoL (-0.246). The study showed a key role of psychological dimensions in CS burden levels and their relationships with QoL in CH patients. From a clinical perspective, these results suggest the importance of evaluating the level of CS burden during the clinical assessment for chronic pain conditions such as CH, since it may contribute to guide patients to tailored psychological and medical treatments, thereby saving time and costs on diagnostic procedures for chronic pain.
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BACKGROUND: The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM). OBJECTIVES: To investigate whether the extent of ulceration (EoU) predicts relapse-free survival (RFS) and overall survival (OS) in PCM. MATERIALS AND METHODS: We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU. RESULTS: A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS [hazard ratio (HR) (1-mm increase) 1·26, 95% confidence interval (CI) 1·08-1·48, P = 0·0047] and OS [HR (1-mm increase) 1·25, 95% CI 1·05-1·48, P = 0·0120] was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour-infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01-4 mm and > 4 mm BT. CONCLUSIONS: This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports.
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Melanoma , Neoplasias Cutáneas , Humanos , Italia/epidemiología , Melanoma/patología , Estadificación de Neoplasias , Pronóstico , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patologíaRESUMEN
INTRODUCTION: Opioid switching is a possible strategy for inadequate analgesia or unmanageable side effects. Its effectiveness ranges from 50 to 90% and is still debated. PURPOSE: We analyzed the impact of opioid switching in a cancer pain population treated with strong opioids for pain. METHODS: This is a post hoc analysis from a multicenter, randomized, four-arm, controlled, phase IV clinical trial. Outcome variables included the percentages of switches, the reasons for the switch, the dose changes before and after the switch, depending on the starting opioid, the response in case of inadequate analgesia, and unmanageable toxicity, and the variability of response among and within patients. RESULTS: We analyzed 498 patients. The opioid was switched in 79 patients (15.9%) 87 times, mainly for uncontrolled pain (52.3%), adverse opioid reactions (22.1%), both of these (4.8%), and dysphagia (20.8%). The reasons for switching varied depending on the starting opioid. Pain reduction was good after 51.45% of switches and control of opioid side effects was good after 43.5%. The relief of opioid-induced toxicity varied among adverse events and within each patient. The daily doses were higher after switching oral opioids and lower after transdermal drugs. CONCLUSIONS: Half of the patients who underwent switching experienced improved relief of pain or amelioration of opioid toxicity. The switch can help in the management of some cases but with many limits and uncertainties.
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Analgésicos Opioides/uso terapéutico , Dolor en Cáncer/tratamiento farmacológico , Anciano , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/farmacología , Femenino , Humanos , Estudios Longitudinales , MasculinoRESUMEN
The role of spirituality on the psychological health was mostly investigated through studies conducted in terminally ill patients. However, there are not studies investigating the role of religious and spiritual beliefs on psychological state and on burden dimensions in caregivers. The purpose of this study was to investigate the association between spirituality, burden, and psychological state in caregivers of terminally ill cancer patients. Two hundred caregivers of terminally ill patients with cancer were interviewed using Prolonged Grief Disorder 12 (PG-12), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Caregiver Burden Inventory (CBI) and System of Belief Inventory (SBI-15R). The caregiver burden was positively correlated with anxiety, depression and PG-12 scores. The intrinsic spirituality was a significant predictor of the time-dependence burden (positively associated); and of the emotional burden (negatively associated). In caregivers of terminally ill cancer patients, higher levels of intrinsic spirituality predicted a higher amount of time devote to caregiving, and also protected against the emotional distress linked to providing assistance.
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Cuidadores/psicología , Costo de Enfermedad , Neoplasias/psicología , Espiritualidad , Cuidado Terminal/psicología , Adaptación Psicológica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermo TerminalRESUMEN
Oxygen enriched air intensifies oxidation processes since smaller reactors reach the same conversion of typical unit operations that employ simple air as reactant. However, the cost to produce pure oxygen or oxygen enriched air with traditional methods, i.e. cryogenic separation or membrane technologies, may be unaffordable. Here, we propose a new continuous technology for gas mixture separation, focusing on the production of oxygen enriched air as a case study. This operation is an absorption-desorption process that takes advantage of the higher oxygen solubility in water compared to nitrogen. In a pressurized solubilisation tank, water absorbs air. Subsequently, reducing pressure desorbs oxygen enriched air. PRO/II 9.3 (Simsci-Scheider Electrics) simulated, optimized, and calculated the capital and operative expenses of this technology. Moreover, we tested for the first time salt water instead of distilled water as appealing possibility for chemical plant near sea and ocean. We varied the inlet water flowrate between 5 and 15â¯m3/h. The optimum operative absortion unit pressure is 15-35 barg. After degassing, water may be recycled. With salt water, the extracted quantity of enriched air decreases compared with the desorption from fresh water (20% less), while the concentration of oxygen is independent from the salt concentration. The cost of enriched air at the optimum condition is 2-3.35 EUR/Nm3.
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Oxígeno , Agua de Mar , Aire , Gases , Nitrógeno , Solubilidad , AguaRESUMEN
BACKGROUND: Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. PATIENT AND METHODS: In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106). RESULTS: Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine. CONCLUSION: The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders. CLINICAL TRIAL REGISTRATION: NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).
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Analgésicos Opioides/administración & dosificación , Dolor en Cáncer/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Analgésicos Opioides/efectos adversos , Dolor en Cáncer/complicaciones , Dolor en Cáncer/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Morfina/efectos adversos , Neoplasias/complicaciones , Neoplasias/patología , Oxicodona/administración & dosificación , Oxicodona/efectos adversosRESUMEN
AIM: The aim of this study was to evaluate the psychological factors associated with a negative outcome following detoxification in a 2-month follow-up in medication-overuse headache. METHODS: All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion. Psychiatric conditions and personality characteristics were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I) and the Minnesota Multiphasic Personality Inventory (MMPI)-2. χ2 tests, one-way analyses of variance, and odds ratios (ORs) were used. RESULTS: A total of 248 patients completed the follow-up: 156 stopped overuse and their headaches reverted to an episodic pattern (Group A); 23 kept overusing without any benefit on headache frequency (Group B); and 51 stopped overuse without any benefit on headache frequency (Group C). The prognostic factors for the outcome of Group B were higher scores on the correction (OR 1.128; p = 0.036), depression (OR 1.071; p = 0.05), hysteria (OR 1.106; p = 0.023), and overcontrolled hostility (OR 1.182; p = 0.04) MMPI-2 scales, whereas those for Group C were psychiatric comorbidities (OR 1.502; p = 0.021) and higher scores on the hysteria scale (OR 1.125; p = 0.004). CONCLUSIONS: The outcome of detoxification is influenced by psychological factors that should be considered when considering treatment strategies.
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Cefaleas Secundarias/psicología , Cefaleas Secundarias/terapia , Trastornos de Cefalalgia/psicología , Trastornos de Cefalalgia/terapia , Uso Excesivo de Medicamentos Recetados/psicología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Background: The development of personalized interventions aimed at coping with multiple sclerosis is enriched by the understanding of patients' representations of the illness. Objective: The aim of this study was to investigate the association between patients' illness representations versus contextual factors (i.e. presence/absence and type of caregiver, engagement, frequency and type of rehabilitation), fatigue, pain, and neurological impairment. Methods: Interviews of 28 patients were analysed through an automated text analysis procedure. After a systematic labelling procedure four illness representations were identified: daily life, search for meaning of the disease, relationship to people and the diagnosis, coping and physical growth. Results: Findings showed that the representation of the relational aspects of the illness was associated with the caregiver's presence, while the representation related to coping and growth tended to be associated with participation in rehabilitation programs. Moreover, the representation related to daily life was associated with lower levels of fatigue compared to the representation related to coping and growth, and with higher levels of neurological impairment compared to the representations related to coping and growth and the relational aspects of the illness. Conclusion: Exploring illness representations is a key step that can help health professionals to get an integrated perspective that could be useful in designing and calibrating interventions according to specific patient needs.
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To describe theoretically the creation and evolution of the quark-gluon plasma, one typically employs three ingredients: a model for the initial state, nonhydrodynamic early time evolution, and hydrodynamics. In this Letter we study the nonhydrodynamic early time evolution using the AdS/CFT correspondence in the presence of inhomogeneities. We find that the AdS description of the early time evolution is well matched by free streaming. Near the end of the early time interval where our analytic computations are reliable, the stress tensor agrees with the second order hydrodynamic stress tensor computed from the local energy density and fluid velocity. Our techniques may also be useful for the study of far-from-equilibrium strongly coupled systems in other areas of physics.
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BACKGROUND: In the American Joint Committee on Cancer (AJCC) classification, acral lentiginous melanoma (ALM) histotype ALM is not included as an independent prognostic factor; in small series its negative prognostic impact on disease-free survival (DFS) and overall survival (OS) has been linked to the greater Breslow thickness (BT). PATIENTS AND METHODS: The study was carried out at four referral melanoma centers (three Italian and one Polish). Clinical consecutive patients with stage I-II melanoma, who were diagnosed, treated, and followed up between January 1998 and March 2018 in annotated specific databases were included. RESULTS: Overall, 6734 were evaluable, 4349 with superficial spreading melanoma (SSM), 2132 with nodular melanoma (NM), and 253 with ALM. At univariable analysis, a statistically significant worse DFS [hazard ratio (HR) 2.72, 95% confidence interval (CI) 2.24-3.30; P < 0.001] and OS (HR 2.67, 95% CI 2.15-3.32; P < 0.001) were found in patients with ALM compared with SSM. Similarly, the NM histotype was associated with a worse prognosis compared with the SSM histotype (DFS: HR 2.29, 95% CI 2.08-2.52; P < 0.001 and OS: HR 2.21, 95% CI 1.99-2.46; P < 0.001). At multivariable analysis, after adjusting for age, sex, BT, ulceration, and the sentinel lymph node status, a statistically significant worse DFS [adjusted HR (aHR; ALM versus SSM) 1.25, 95% CI 1.02-1.52; P = 0.028] was confirmed for patients with ALM. For patients with NM, instead, no impact of histology was found in terms of DFS [aHR (NM versus SSM) 1.04, 95% CI 0.93-1.15; P = 0.513] and OS [aHR (NM versus SSM) 0.96, 95% CI 0.86-1.08; P = 0.548]. CONCLUSIONS: ALM is associated with a worse long-term DFS. Our results could have important clinical implications for patients' stratification in future clinical trials and the incorporation of ALM histotype in the new AJCC classification as an independent prognostic factor.
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Melanoma , Neoplasias Cutáneas , Humanos , Pronóstico , Supervivencia sin Progresión , Neoplasias Cutáneas/terapia , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab. MATERIALS AND METHODS: DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab. Patients with locally advanced/metastatic MPM who progressed after platinum-pemetrexed chemotherapy were enrolled to receive durvalumab (1500 mg, intravenously Q4W) for 12 months or until evidence of disease progression or unacceptable toxicity. The primary endpoint was the proportion of patients alive and free from progression at 16 weeks (PFS16wks) calculated from treatment initiation. Secondary endpoints were progression-free survival, overall survival, overall response rate, and safety. RESULTS: Sixty-nine patients with a median age of 69 years (range 44-82 years) were enrolled; 62 patients (89.9%) had epithelioid histotype. As first-line treatment, all patients received platinum derivatives-pemetrexed combination (60.9% with carboplatin and 39.1% with cisplatin). As of March 2021, the median follow-up was 9.2 months (interquartile range 5.2-11.1 months). Six patients (8.7%) completed the 12-month treatment; 60 patients discontinued, of whom 42 for progressive disease, and 4 died. Seventeen patients (28.3%; 95% confidence interval 17.5% to 41.4%) were alive or free from progression at 16 weeks. Eleven patients (18.6%) had a grade 3 or 4 treatment-related adverse event (AE), and one (1.4%) had a grade ≥3 immune-related, treatment-related AE. There was one drug-related death. CONCLUSION: Durvalumab alone in pretreated non-selected MPM did not reach a meaningful clinical activity, showing any new major safety issue signals.
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Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma Maligno/etiología , Pemetrexed/farmacología , Pemetrexed/uso terapéutico , Mesotelioma/patología , Platino (Metal)/uso terapéutico , Neoplasias Pleurales/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: The PEOPLE trial aimed to identify new immune biomarkers in negative and low programmed death-ligand 1 (PD-L1) (0%-49%) advanced non-small-cell lung cancer (aNSCLC) patients treated with first-line pembrolizumab. Here we report the main outcomes and the circulating immune biomarkers analysis. PATIENTS AND METHODS: The primary endpoint of this phase II trial was the identification of immune biomarkers associated with progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety were secondary endpoints. Absolute cell counts for 36 subsets belonging to innate and adaptive immunity were determined by multiparametric flow cytometry in peripheral blood at baseline and at first radiologic evaluation. An orthoblique principal components-based clustering approach and multivariable Cox regression model adjusted for clinical variables were used to analyze immune variables and their correlation with clinical endpoints. RESULTS: From May 2018 to October 2020, 65 patients were enrolled. After a median follow-up of 26.4 months, the median PFS was 2.9 months [95% confidence interval (CI) 1.8-5.6 months] and median OS was 12.1 months (95% CI 8.7-17.1 months). The ORR was 21.5%, DCR was 47.7% and median DoR was 14.5 months (95% CI 6.4-24.9 months). Drug-related grade 3-4 adverse events were 9.2%. Higher T cell and natural killer (NK) cell count at baseline and at the first radiologic evaluation were associated with improved PFS, DCR and OS. On the contrary, higher myeloid cell count at baseline or at the first radiologic evaluation was significantly associated with worse OS and DCR. CONCLUSIONS: Circulating immune biomarkers can contribute to predict outcomes in negative and low PD-L1 aNSCLC patients treated with first-line single-agent pembrolizumab.
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Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Antígeno B7-H1 , Neoplasias Pulmonares/terapia , Antineoplásicos Inmunológicos/efectos adversos , BiomarcadoresRESUMEN
Vitamin K denotes a group of lipophilic vitamins determining post-translational modification of proteins. There are 2 main forms of vitamin K: vitamin K1 (phylloquinone, found in vegetables); vitamin K2 (menaquinone, produced by bacteria in the intestine and in fermented foods). Vitamin K stores are limited in humans, but it can be recycled. Vitamin K1 is principally transported to the liver, regulating the production of coagulation factors. Vitamin K2, instead, is also transported to extra-hepatic tissues, such as bone and arteries, regulating the activity of matrix Gla-protein (MGP) and osteocalcin [bone Gla-protein (BGP)]. In patients with chronic kidney disease (CKD), cardiovascular mortality is the first cause of death. Some pathogenetic mechanisms of vascular calcification (such as hyperparathyroidism, hyperphosphatemia, hypercalcemia, role of vitamin D) have been widely investigated, but the potential role of vitamin K is still uncertain. Vitamin K could play a key role, as it transforms glutamic acid residues into γ-carboxyglutamic acid, through a carboxylation process, makings both MGP (cMGP) and BGP (cBGP) biologically active. cMGP inhibits vascular calcifications (VC), while cBGP has an important role for a proper mineralization process. Uncarboxylated MGP and BGP (ucMGP and ucBGP) concentrations are indirect markers of vitamin K2 deficiency. The purpose of this review is to analyze the current literature to understand the relationship between vitamin K2 status, fragility fractures and VC in CKD patients. This analysis could be of help in planning investigations of Vitamin K status and its possible supplementation in CKD patients to avert fragility fractures and VC.
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Calcinosis/etiología , Calcinosis/metabolismo , Fracturas Óseas/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/metabolismo , Vitamina K 1/metabolismo , Vitamina K 2/metabolismo , Animales , Calcinosis/patología , Fracturas Óseas/metabolismo , Humanos , Fallo Renal Crónico/terapia , Estructura Molecular , Osteocalcina/metabolismo , Diálisis Renal/efectos adversos , Vitamina K 1/química , Vitamina K 2/químicaRESUMEN
To investigate factors influencing prognosis in medication-overuse headache (MOH), we conducted a 12-month follow-up of patients with probable MOH. We recruited 215 patients consecutively admitted to our headache centre for an inpatient detoxification treatment. We analysed likely predictor factors for headache resolution (sex, age, primary headache, psychiatric comorbidity, type and timing of overuse). Mann-Whitney U-test and chi-squared test were used. One year after withdrawal, we had complete data on 172 patients (80%): 38 of these patients (22%) had relapsed into overuse and 134 (78%) had not. The negative prognostic factors for relapse were: intake of more than 30 doses/month (P = 0.004), smoking (P = 0.012), alcohol consumption (P = 0.037), non-confirmation of MOH diagnosis 2 months after detoxification (P = 0.000), and return to overused drug(s) (P = 0.000). The 1-year relapse rate was 22%. The existence of sub-groups of MOH patients with such risk factors could influence treatment strategies.
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Analgésicos/efectos adversos , Analgésicos/farmacocinética , Cefaleas Secundarias/epidemiología , Cefaleas Secundarias/terapia , Inactivación Metabólica , Anciano , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Factores de RiesgoRESUMEN
Intracellular pathogens are a critical challenge for antimicrobial therapies. Staphylococcus aureus (S. aureus) causes approximately 85% of all skin and soft tissue infections in humans worldwide and more than 30% of patients develop chronic or recurrent infections within three months, even after appropriate antibacterial therapies. S. aureus is also one of the most common bacteria found in chronic wounds. Recent evidences suggest that S. aureus is able to persist within phagolysosomes of skin cells (i.e. keratinocytes, phagocytic cells), being protected from both the immune system and a number of antimicrobials. To overcome these limits, nano-formulations that enable targeted therapies against intracellular S. aureus might be developed. Herein, the biodistribution and intracellular localisation of hyaluronan (HA) and HA-based nanoparticles (nanogels, NHs) are investigated, both after intravenous (i.v.) injections (in mice) and topical administrations (in ex vivo human skin). Results indicate HA and NHs accumulate especially in skin and liver of mice after i.v. injection. After topical application on human skin explants, no penetration of both HA and NHs was detected in skin with intact stratum corneum. By contrast, in barrier-disrupted human skin (with partial removal and loosening of stratum corneum), HA and NHs penetrate to the viable epidermis and are taken up by keratinocytes. In mechanically produced wounds (skin without epidermis) they accumulate in wound tissue and are taken up by dermis cells, e.g. fibroblasts and phagocytic cells. Interestingly, in all cases, the cellular uptake is CD44-mediated. In vitro studies confirmed that after CD44-mediated uptake, both HA and NHs accumulate in lysosomes of dermal fibroblasts and macrophages, as previously reported for keratinocytes. Finally, the colocalisation between intracellular S. aureus and HA or NHs is demonstrated, in macrophages. Altogether, for the first time, these results strongly suggest that HA and HA-based NHs can provide a targeted therapy to intracellular S. aureus, in persistent skin or wound infections.
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Ácido Hialurónico , Staphylococcus aureus Resistente a Meticilina , Animales , Humanos , Queratinocitos , Ratones , Nanogeles , Staphylococcus aureus , Distribución TisularRESUMEN
Medication overuse headache (MOH) is a growing problem worldwide and a challenge for clinicians and investigators. This study aims to contribute to the ongoing debate surrounding the classification of MOH. Applying the revised diagnostic criteria for MOH contained in the updated International Classification of Headache Disorders (ICHD-II), we enrolled 140 probable MOH (p-MOH) patients. They were submitted to an in-patient detoxification protocol and re-examined 2, 6 and 12 months later to confirm, or otherwise, the diagnosis of MOH and to observe the evolution of their headache. MOH diagnosis was confirmed 2 months after detoxification in 71% of patients, who reverted to an episodic headache pattern and stopped their drug overuse The overall clinical situation at 2 months closely reflected the 1-year trend. The 2-month period after drug withdrawal should be retained as a diagnostic criterion in the ICHD-II because it is useful not only as a diagnostic parameter, but also as predictor of a good outcome of 1-year drug withdrawal. In addition, the present findings point to the need for a more objective criterion to quantify headache frequency after drug withdrawal.
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Cefaleas Secundarias/diagnóstico , Cefaleas Secundarias/terapia , Adulto , Anciano , Analgésicos/efectos adversos , Ergotamina/efectos adversos , Femenino , Estudios de Seguimiento , Cefaleas Secundarias/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Triptaminas/efectos adversos , Adulto JovenRESUMEN
We investigated a possible correlation between brain excitability in children with migraine and tension-type headache (TTH) and their behavioural symptomatology, assessed by using the Child Behaviour Checklist (CBCL). The mismatch negativity (MMN) and P300 response were recorded in three successive blocks to test the amplitude reduction of each response from the first to the third block (habituation). MMN and P300 habituation was significantly lower in migraineurs and TTH children than in control subjects (two-way ANOVA: P < 0.05). In migraineurs, but not in TTH patients, significant positive correlations between the P300 habituation deficit and the CBCL scores were found (P < 0.05), meaning that the migraineurs with the most reduced habituation showed also the worst behavioural symptomatology. To the best of our knowledge, this is the first study showing a correlation between neurophysiological abnormality and emotional symptomatology in migraine, suggesting a role of the latter in producing the migrainous phenotype.
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Conducta del Adolescente , Encéfalo/fisiopatología , Conducta Infantil , Emociones , Migraña sin Aura/fisiopatología , Cefalea de Tipo Tensional/fisiopatología , Adolescente , Análisis de Varianza , Ansiedad , Niño , Electroencefalografía , Potenciales Evocados , Femenino , Humanos , Masculino , Migraña sin Aura/psicología , Pruebas Neuropsicológicas , Cefalea de Tipo Tensional/psicologíaRESUMEN
The authors present a case of prosthetic-implant intraforaminal mandibular reconstruction surgery to correct severe atrophy using the application of autologous bone transplants with submental endermic access. The prosthetic-implant method applied in this case study with the close collaboration between the surgeon and prosthodontist, represents, if scrupulously executed in selected cases only, a valid alternative to the implant protocols used on a daily basis in the intraforaminal mandibular sector.
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Mandíbula/patología , Mandíbula/cirugía , Prótesis e Implantes , Atrofia , Femenino , Humanos , Persona de Mediana Edad , Procedimientos Ortopédicos/métodos , Implantación de Prótesis/métodos , Índice de Severidad de la EnfermedadRESUMEN
In Italy, the logistics for the creation of a vascular access are not well arranged. Numerous specialists are involved, mostly on a voluntary basis: they are those who ''know how to make the vascular access'', and have earned the title on the battlefield. When a native arteriovenous fistula, the gold standard, cannot be created, different solutions may prevail, depending on the local availability of specific skills. The use of vascular grafts for vascular access is not common in Italy. Grafts are mainly performed by vascular surgeons or, less frequently, by nephrologists with specific expertise in centers of excellence. By contrast, venous catheterization as an emergency access for dialysis is very common in Italian nephrology and dialysis centers. In optimal operating conditions, when both options are available and fistula creation and management are feasible, the choice of a graft fistula would be almost obligatory, although there are exceptions. Usually, the need urges the renal physician to favor compromise solutions: a compromise between physician and patient, between who performs the vascular access and who manages dialysis, between the patient's right to express a choice and acute disease that requires a quick solution and positive outcome. We need a revision (or revolution?) of vascular access creation and management that will lead to a choice between venous catheter or vascular graft that is balanced and useful for the patient.