Impact of COVID-19 pandemic on patients affected by peripheral arterial disease: an Italian single-center study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has evolved into a global pandemic, affecting a wide range of medical and surgical specialties. During COVID-19, we assisted in the reallocation of medical resources and services, as well as social distancing measures, and many patients with chronic diseases and comorbidities may have experienced difficulties in obtaining the correct medical care. The aim of the study was to investigate the impact of the COVID-19 pandemic on major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral arterial disease (PAD) and chronic limb-threatening ischemia (CLTI), compared to previous years. PATIENTS AND METHODS: We evaluated 1,335 hospital admissions of 877 patients with PAD admitted to Policlinico A. Gemelli Hospital between January 2017 and February 2020 and 368 hospital admissions of 272 patients with PAD admitted to the Policlinico A. Gemelli Hospital between March 2020 and March 2021. Data on demographic characteristics, comorbidities, symptoms, physical and radiological findings, laboratory tests, and routine visits before or after discharge were collected from electronic medical records. RESULTS: Emergency room (ER) admissions among PAD patients during COVID-19 were higher than before the pandemic [190 (51.63%) vs. 579 (43.37%), p = 0.01]. A MACE was found in 78 (5.84%) pre-pandemic hospitalizations and 126 (34.24%) pandemic hospitalizations (p < 0.01). A MALE was identified in 942 (70.56%) pre-pandemic hospitalizations and 331 (89.95%) pandemic hospitalizations (p < 0.01). Amputation rates during the pandemic were higher than before the pandemic [80 (21.74%) vs. 191 (14.31%), p < 0.01]. The number of in-hospital deaths did not differ between the pandemic and pre-pandemic periods [11 (2.99%) vs. 51 (3.82%), p = 0.55]. CONCLUSIONS: In patients with PAD and CLTI, the number of MACE, MALE, and amputations was higher during the COVID-19 period compared to the three years before the pandemic.

Identification of early predictors of clinical outcomes of COVID-19 outbreak in an Italian single center using a machine-learning approach.

OBJECTIVE: SARS-CoV-2 disease (COVID-19) has become a pandemic disease, determining a public health emergency. The use of artificial intelligence in identifying easily available biomarkers capable of predicting the risk for severe disease may be helpful in guiding clinical decisions. The aim of the study was to investigate the ability of interleukin (IL)-6, troponin I, and D-dimer to identify patients with COVID-19 at risk for intensive care unit (ICU)-admission and death by using a machine-learning predictive model. PATIENTS AND METHODS: Data on demographic characteristics, underlying comorbidities, symptoms, physical and radiological findings, and laboratory tests have been retrospectively collected from electronic medical records of patients admitted to Policlinico A. Gemelli Foundation from March 1, 2020, to September 15, 2020, by using artificial intelligence techniques. RESULTS: From an initial cohort of 425 patients, 146 met the inclusion criteria and were enrolled in the study. The in-hospital mortality rate was 15%, and the ICU admission rate was 41%. Patients who died had higher troponin I (p-value<0.01) and IL-6 values (p-value=0.04), compared to those who survived. Patients admitted to ICU had higher levels of troponin I (p-value<0.01) and IL-6 (p-value<0.01), compared to those not admitted to ICU. Threshold values to predict in-hospital mortality and ICU admission have been identified. IL-6 levels higher than 15.133 ng/L have been associated with a 22.91% risk of in-hospital mortality, and IL-6 levels higher than 25.65 ng/L have been associated with a 56.16% risk of ICU admission. Troponin I levels higher than 12 ng/L have been associated with a 26.76% risk of in-hospital mortality and troponin I levels higher than 12 ng/L have been associated with a 52.11% risk of ICU admission. CONCLUSIONS: Levels of IL-6 and troponin I are associated with poor COVID-19 outcomes. Cut-off values capable of predicting in-hospital mortality and ICU admission have been identified. Building a predictive model using a machine-learning approach may be helpful in supporting clinical decisions in a more precise and personalized way.

Could thymoglobulin increase hemorrhagic risk in the perioperative transplantation period of sensitized kidney recipients?

OBJECTIVE: It has been described that thymoglobulin could increase the risk of infections and malignancies, in comparison to basiliximab. Leukopenia and thrombocytopenia are also more common within the first days after transplantation among thymoglobulin patients. Our objective was to analyze bleeding complications in this subset of patients. MATERIAL AND METHODS: Bleeding complications were evaluated among 515 renal transplants carried out at our institution between 2012 and 2018. We compared patients treated with thymoglobulin (Group 1, N=91) with those treated with basiliximab (Group 2, N=424). RESULTS: We found differences in platelet decrease: 95,142.2 (55,339.6) in Group 1 and 52,364.3 (69,116.6) in Group 2 (P=0.001), number of patients with severe thrombocytopenia (<75,000/mm3) (20.8% vs. 3.7%, P=0.001), number of blood units transfused (3.25 (0.572) vs. 2.2 (0.191, P=0.028) and percentage of patients that required surgery due to bleeding (18.2% vs. 7.7%, P=0.046). In a multiple lineal regression multivariable analysis (dependent variable was number of blood units transfused), only age [OR 0.037, 95% CI (0.003-0.070)] and type of immunosuppression [OR 1.592, 95% CI (1.38-2.84)] showed statistical significance. CONCLUSIONS: The use of thymoglobulin in the perioperative transplantation period could increase bleeding complications. In our series, in the group of patients with thymoglobulin, severe thrombocytopenia was 6 times more frequent, and active bleeding that required surgery was also 2.5 times more frequent. One way to continue with the use of this immunosuppression agent, might be to adjust the dose instead of discontinuing it. The use of thymoglobulin should be a factor to consider in the postoperative period of these patients.

Creatine supplementation exacerbates ethanol-induced hepatic damage in mice.

OBJECTIVE: The aim of this study was to investigate the effects of creatine supplementation on early stages of ethanol-induced hepatic damage. METHODS: Male Swiss mice were divided into three groups (n = 12/group): control (C), ethanol (E), and ethanol supplemented with creatine (EC). The control group received a diet containing 15.8% of total calories from proteins, 46.3% from carbohydrates, and 37.9% from lipids. The ethanol and ethanol and creatine groups received diets containing 15.8% of total calories from proteins, 16.2% from carbohydrates, and 34.5% from lipids; the remaining calories were obtained from the addition of 5% of 95% ethanol. Creatine (1%; weight/vol) was added to the diet of EC mice. After 14 and 28 d, six animals from each group were sacrificed, generating subdivisions in each group: C14 and C28, E14 and E28, EC14 and EC28. After sacrifice, the liver was removed, weighed, and prepared for histologic, biochemical, and molecular analysis, and blood was collected. RESULTS: Ethanol intake induced mild cell degeneration, liver damage, oxidative lesions, and inflammation. Surprisingly, ethanol intake combined with creatine exacerbated cell degeneration and fat accumulation, hepatic expression of genes related to ethanol metabolism, oxidative stress and inflammation, and promoted oxidative stress and elevated plasma alanine aminotransferase (P < 0.05). CONCLUSION: Creatine supplementation associated with ethanol is able to interfere in the alcohol metabolism and oxidative stress and to exacerbate ethanol-induced hepatic damage. These new findings are opposite to those observed in several studies where protective effects of creatine in a wide variety of injury models, including non-alcoholic fatty liver disease, were described.

Strategies for Disease Prevention and Health Promotion in Urban Areas: The Erice 50 Charter.

The Erice 50 Charter titled "Strategies for Diseases Prevention and Health Promotion in Urban Areas" was unanimously approved at the conclusion of the 50th Residential Course "Urban Health. Instruments for promoting health and for assessing hygienic and sanitary conditions in urban areas", held from 29th March to 2nd April 2017 in Erice, at the "Ettore Majorana" Foundation and Centre for Scientific Culture and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group "Building Hygiene" of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). At the conclusion of the intense learning experience during the Course, with more than 20 lectures, workshops and long-lasting discussions between Professors and Students, the participants identified the major points connecting urban features and Public Health, claiming the pivotal role of urban planning strategies for the management of Diseases Prevention and Health Promotion activities. The Erice 50 Charter is configured as a Decalogue for Healthy Cities and as a Think Tank for designing effective strategic actions and best practices to develop urban regeneration interventions and improve the urban quality of contemporary cities. The Decalogue is structured into the following key strategic objectives: 1. Promoting urban planning interventions that address citizens towards healthy behaviours; 2. Improving living conditions in the urban context; 3. Building an accessible and inclusive city, with a special focus on the frail population; 4. Encouraging the foundation of resilient urban areas; 5. Supporting the development of new economies and employment through urban renewal interventions; 6. Tackling social inequalities; 7. Improving stakeholders' awareness of the factors affecting Public Health in the cities; 8. Ensuring a participated urban governance; 9. Introducing qualitative and quantitative performance tools, capable of measuring the city's attitude to promote healthy lifestyles and to monitor the population's health status; 10. Encouraging sharing of knowledge and accessibility to informations. Finally, all the participants underlined that a multidisciplinary team, composed of Physicians specialized in Hygiene, Preventive Medicine, Public Health and Technicians as Architects, Urban planners and Engineers, is needed to deepen the research topic of Urban Health.

Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma.

In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide.

Difficulties in work activities and the pervasive effect over disability in patients with episodic and chronic migraine.

Migraine is associated with reduced productivity in work-related activities. The degree to which problems with work are, in turn, associated to the level of migraine-related disability as well as to headache frequency has been poorly explored. The aim of the study was to assess if migraine patients with different degrees of work difficulties showed a different level of migraine-related disability. A consecutive sample of patients with episodic migraine (EM) or with chronic migraine (CM) with medication overuse (MO) attending the Headache Centre of the Neurological Institute C. Besta of Milan was studied. All patients completed the MIDAS and the WHODAS 2.0 questionnaires. The total scores of both questionnaires, frequency of headaches, average pain intensity, and the scores of each subscale of the WHODAS 2.0 were calculated separately for EM and CM patients. The score of WHODAS 2.0 "Work difficulties" subscale was used to divide the studied patients into two groups, i.e. those above and those below the median "Work difficulties" subscale score. Independent sample t test was used to compare these two groups as far as all the other studied variables. A total of 296 patients (102 with EM and 194 with CM-MO) were enrolled. Patients with higher work difficulties score also displayed higher scores in the other WHODAS 2.0 subscales; for those with CM-MO, the differences were significant. The results of this study indicate that having more and more severe workplace problems is associated to a higher disability level in migraineurs. Further studies are needed to better understand workplace disability in different migraine forms, particularly in a qualitative way.

Persistent orthostatic headache without intracranial hypotension: which treatment?

Orthostatic headache can be the leading symptom of intracranial hypotension, however, not all orthostatic headaches are due to cerebrospinal fluid leaks and these forms can be a clinical problem, especially for treatment. Aim of this study was to review patients with persistent orthostatic headache in whom a detailed head and spinal MRI follow-up did not reveal any sign of intracranial hypotension and to evaluate which treatment can be considered the first choice. Patients admitted to our headache center for evaluation of persistent orthostatic headache and followed after first admission with clinical and neuroradiological controls were systematically reviewed. 11 patients (7 M, 4 F) followed in a period lasted from 10 months up to 2 years were studied. Six patients (54, 5 %) reported a MRI performed previously elsewhere with a suspect diagnosis of intracranial hypotension which was not confirmed at MRI at our hospital such as during the radiological follow-up. Three patients (27.2 %) had developed orthostatic headache short after a neck or head trauma with no evidence of neuroradiological pathological signs and two patients (18 %) had a previous history of psychiatric disorder. We administrated antidepressants in five patients, atypical neuroleptic in three patients, association of antidepressant and antipsychotic in one patient and muscle relaxants in two cases. All patients showed a certain improvement of headache in the weeks after introduction of the pharmacological treatment; six (54, 5 %) had pain relief during the follow-up and five (45, 5 %) were pain free at the last clinical control. We found out that patients with the best outcome were the ones treated with antidepressants. Persistent orthostatic headache without any neuroradiological sign of intracranial hypotension is a challenging problem for clinicians. Although the International Classification of Headache Disorders (ICHD-3 beta version) criteria suggests the possibility of epidural blood patch in orthostatic headache without causes, we believe that a pharmacological treatment tailored on each patient should be always considered and antidepressants can be the first choice.

Trastuzumab-based chemotherapy modulates systemic redox homeostasis in women with HER2-positive breast cancer.

Trastuzumab is an immunotargeting therapeutic against breast tumors with amplification of the human epithelial growth factor receptor 2 (HER2). HER2 patients naturally exhibit disruption in the pro-oxidant inflammatory profiling; however, the impact of trastuzumab-based chemotherapy in modulating this process is still unknown. Here we determined the systemic pro-inflammatory profile of women diagnosed with HER2-amplified tumors, undergoing trastuzumab-based chemotherapy (TZ), and compared the results with that of healthy controls (CTR) and untreated patients with HER2-amplified breast cancer (CA). The plasmatic inflammatory profile was assessed by evaluating pro-oxidant parameters such as lipid peroxidation, total antioxidant capacity (TRAP), levels of advanced oxidation protein products (AOPPs), nitric oxide (NO), C-reactive protein (CRP), and total thiol content. Markers of cardiac damage were also assessed. Our findings showed increased NO levels in TZ than that in either CA or CTR groups. Furthermore, TZ augmented TRAP and reduced total thiol than that of the CA group. Our data also revealed that AOPP levels were significantly higher in the TZ than the CA group. AOPP and the MB fraction of creatine-kinase (CKMB) levels were positively correlated in TZ patients. These findings suggest that trastuzumab-associated chemotherapy can modulate the pro-inflammatory markers of HER2-positive breast cancer patients to the levels found in healthy controls.

Genistein prevents ultraviolet B radiation-induced nitrosative skin injury and promotes cell proliferation.

Nitric oxide (NO) levels increase considerably after 24h of exposure of skin to ultraviolet B (UVB) radiation, which leads to nitrosative skin injury. In addition, increased NO levels after exposure to UVB radiation are associated with inhibition of cell proliferation. Compared to the UV-control group, UV-genistein at 10 mg/kg (UV-GEN10) group showed tissue protection, decreased lipid peroxide and nitrotyrosine formation, and low CAT activity. Furthermore, NO levels and iNOS labeling remained high. In this group, the reduction in lipid peroxides and nitrotyrosine was accompanied by upregulation of cell proliferation factors (Ki67 and PCNA), which indicated that prevention of nitrosative skin injury promoted cell proliferation and DNA repair. Genistein also prevented nitrosative events, inhibited ONOO(-) formation, which leads to tissue protection and cell proliferation. The UV-GEN15 group did not result in a greater protective effect compared to that with UV-GEN10 group. In the UV-GEN15 group, histological examination of the epidermis showed morphological alterations without efficient protection against lipid peroxide formation, as well as inhibition of Ki67 and PCNA, and VEGF labeling, which suggested inhibition of cell proliferation. These results help to elucidate the mechanisms underlying the photoprotective effect of genistein and reveal the importance of UVB radiation-induced nitrosative damage.

Oxidative and proteolytic profiles of the right and left heart in a model of cancer-induced cardiac cachexia.

Cardiac cachexia is a syndrome that has received increased attention in recent years. Although an association between proteolysis and cardiac cachexia has been proposed, the direct influence of oxidative stress on the process has not been demonstrated. In the present study, the right (RH) and left (LH) hearts (atrium and ventricle of each side of the heart) were collected from rats at the 5th and 10th days after phosphate buffer (control) orWalker-256 solid tumour implantation. Immediately after sacrifice, cachexia was determined in tumour-bearing animals by the formula: [(inicial body weight-final body weight+tumour weight+weight gain of control group)/(initial body weight+body mass gain of control group)]×100%; RH and LH were stored until use. Oxidative stress and proteolysis were determined in each collected sample. In addition, heart samples were collected from a separate set of animals to determine the thickness of the left and right ventricles. Cachexia values increased over time after tumour implantation from 6.85% at the 5th day to 17.76% at the 10th day. There was no significant difference in LH wet weight and ventricle thickness compared with the control, where as RH wet weight (0.109±0.09g at the 5th day and 0.093±0.09g at the 10th day) and thickness (420±16µm at the 5th day and 279±08µm at the 10th day) were significantly decreased at both time points when compared with control values (0.153±0.06g and 607±21µm, respectively). tert-Butyl-stimulated chemiluminescence analysis revealed a significant increase in the LH and decrease in the RH oxidative stress profiles. Carbonylated proteins increased in the LH (140%, p<0.05) and RH (100%, p<0.05) at the 5th day, and significantly decreased in both sides on the 10th day compared to controls. Chemotrypsin-like, caspase-like, and calpain-like activities were evaluated by chemiluminescence, and only calpain-like activity was found to increase at the 5th day in the RH. In the LH, all proteolytic activities systems were decreased when compared with controls. Together, these results demonstrate that oxidative stress appears to play a different role in mass modulation on the LH and RH. The proteolytic systems evaluated herein also appear to have different effects on the responses developed during cardiac cachexia in the two sides of the heart.

Prevalence and profile of obsessive-compulsive trait in patients with chronic migraine and medication overuse.

Patients with chronic migraine (CM) and medication overuse headache (MOH) have high frequency of psychiatric comorbidity or psychopathological traits, the presence of which can influence the clinical course. The presence of subclinical obsessive compulsive disorder (OCD) is underestimated in migraine patients. The aim of this study was to estimate the prevalence and profile of obsessive-compulsive (OBS) trait in a sample of CM patients with MOH using the OBS questionnaire of Spectrum Collaborative Project. According to the new international classification of headache disorders (ICHD-III beta) criteria, 106 patients (15 M, 91 F, mean age 47.3 years) were selected in a consecutive clinical series. Our results showed that 36 % of patients with CM and MOH were positive at OBS-questionnaire. As far as the profile of OBS trait, we performed an evaluation of prevalence of items separating the first part of the questionnaire (childhood/adolescence and doubts in lifetime) from the other five domains: 21 % of the patients showed prevalence of items in childhood/adolescence domain; 79 % in doubts in lifetime domain; as for other five domains, 10.5 % of patients had prevalence of pathological answers among hypercontrol, 5.2 % in spending time, 23.7 % in perfectionism, 29 % in repetition and automation, and 31.5 % in specific themes (obsessive thoughts). The presence of subclinical OCD in migraine patients, and the link between progression to CM, particularly through MO, and OBS trait is still not well defined. The use of specific tools to assess this possible comorbidity should be encouraged in clinical and research settings.

Clinical insights from adiponectin analysis in breast cancer patients reveal its anti-inflammatory properties in non-obese women.

Adiponectin is a cytokine reported as a determinant of poor prognosis in women with breast cancer. However, because data regarding its role in breast cancer have been obtained primarily from studies employing overweight or obese women, the adiponectin profile in non-obese women is poorly understood. In this study, we determined adiponectin levels in plasma from non-obese women with breast cancer and investigated a possible correlation with systemic inflammatory status. We determined the plasma adiponectin levels as well as biochemical and oxidative stress parameters in 80 women. Our results revealed that plasma adiponectin levels were affected by chemotherapy, estrogen receptor status, and disease progression. Adiponectin was positively correlated with antioxidant levels, without affecting either the metastatic behavior of disease or patient outcome. These findings highlight adiponectin as a novel player in the endocrine signaling that modulates the oxidative inflammatory response in human breast cancer, and contribute to the understanding of the role of adiponectin in pathological conditions in non-obese women.

Occipital neurostimulation in primary headaches: update.

A subset of headache patients are chronic and results refractory to standard medical treatments, they are unsatisfied or unable to tolerate the side effects of medications. In the lack of more effective prophylactic treatment, there is need of alternative approach. Migraine is conceptualized as a chronic and potentially progressive disorder. It is conceivable that more aggressive therapeutic efforts could be warranted in drug-refractory chronic migraine. In this prospective, the new, device-based therapies that allow to affect brain function in less invasive ways may represent a therapeutic opportunity. Peripheral occipital neurostimulation resulted in several trials and case reports to be beneficial in a large variety of headache and craniofacial pain disorders, with chronic primary headache the most studied. We comment on our experience in the application of ONS in drug-refractory chronic cluster headache and chronic migraine patients.

Positive outcome of occlusal freeway space reestablishment in patients with medication overuse due to chronic migraine.

Considering the great chapter of migraines, it is important to note the signs and symptoms caused by an alteration of the relationship of the facial musculature and the occlusal freeway space (FWS) that is the distance from maximal intercuspation to the habitual rest position (measurable in 1.4-2.5 mm). To any mandible position changing (detected by periodontal, muscle and joint proprioceptors), there is an influence on the neuromuscular system and then an alteration of the FWS. A group of 60 patients with chronic migraine (CM) underwent a withdrawal of overused medication and were subjected to electromyographic and kinesiographic evaluation. All those who presented an alteration of the FWS at rest position have been subjected to treatment with orthosis device for about 12 months. The aim of our work is to obtain and define a correct mandibular position, physiological, in agreement with the neuromuscular structures of the patient. Clinical results obtained on this pool of patients, in terms of reduction of the VAS, let us understand the importance of the inviolability of the FWS and to eliminate any type of mandibular deviation with respect to the closure trajectory induced by TENS in patients suffering from CM.

Outcome of patients with chronic migraine with medication overuse and depression after duloxetine: influence of coexisting obsessive compulsive disorder.

Patients with chronic migraine (CM) and medication overuse (MO) have high frequency of psychiatric comorbidity. Aims of this open label, prospective, independent study were: to evaluate the efficacy of duloxetine in a sample of patients with MO due to CM and with concomitant depression; to investigate, if the presence of OCD influences the outcome in this subgroup of patients. A total of 50 consecutive patients (40 F,10 M, aged 20-65 years, mean 39.4 years) from those attending our Headache Center to undergo an inpatient withdrawal programme followed by anti-migraine prophylaxis was enrolled. After a 1-month baseline period, all patients were prescribed duloxetine 30 mg in the morning for the first week, and 60 mg for the following 12 weeks. They filled a daily headache diary during the whole study period. They also completed Hamilton depression rating scale (HDRS) and migraine disability assessment scale (MIDAS) at baseline and at the 12-week follow-up. The primary outcome measure was the percentage of responders, i.e. of patients with a reduction ≥50 % in headache frequency as well as in symptomatic drug consumption. Comparison between patients with and without OCD was performed. Our results showed a rather high responder rate in the total sample (64 %), while none of the patients with OCD fell among responders. MIDAS and HDRS scores had a more evident decrease in patients without OSD. These findings suggest that duloxetine may be effective in patients with MO due to CM and with comorbid depression. They also confirm the importance of a systematic assessment of the psychopathological profile in these patients, and indicate that clinicians should be aware of the relevant prognostic role of OCD in favoring a poor outcome and persistent disability in headache patients with MO.

Decreased oxidant profile and increased antioxidant capacity in naturally postmenopausal women.

Recent works have shown a dual side of estrogens, and research on the relationship between oxidative stress and menopausal status remains unclear and has produced controversial results. In this work, we aimed to evaluate by sensitive methods the oxidant and antioxidant changes that develop after natural menopause. Thirty premenopausal and 28 naturally postmenopausal women volunteered for this study. Blood was collected and plasma used. 17-OH estradiol levels in plasma were estimated. Plasma levels of advanced oxidation protein products (AOPP), lipid peroxidation products (such as hydroperoxides and malondialdehyde (MDA)), and nitrites were measured, and total radical antioxidant parameter testing was performed to determine the oxidant and antioxidant profiles, respectively. Estrogen levels were significantly increased (p < 0.02) in premenopausal women (54.28 ± 9.34 pg/mL) as compared with postmenopausal women (18.10 ± 1.49 pg/mL). Postmenopausal women had lower levels of lipid hydroperoxide oxidation (p < 0.0001), lipid hydroperoxide levels evaluated by the area under the curve (AUC; 1,366,000 ± 179,400 AUC; p < 0.01), and hydroperoxides as measured by the ferrous oxidation-xylenol orange method (31.48 ± 2.7 µM; p < 0.0001). The MDA levels did not differ between pre- and postmenopausal women whether measured by thiobarbituric acid-reactive substances or high-performance liquid chromatography assays. No differences in AOPP and nitrite levels were observed between pre- and postmenopausal women. Postmenopausal women also exhibited a higher total radical antioxidant level (0.89 ± 0.08 µM Trolox; p < 0.0001). Postmenopausal women demonstrated lower levels of oxidative damage and a higher antioxidant capacity than premenopausal women.

Drug-resistant chronic migraine: the Italian GON project.

Chronic daily headache is a major problem due to severe disability and high socio-economic costs. In the last years, some trials have shown potential benefit from new therapeutic approach by occipital neurostimulation techniques, already applied with some success for the treatment of chronic cluster headache. Due to the extremely heterogeneous population suffering from refractory chronic daily headaches, we propose a national multicenter experimental study involving Italian ANIRCEF Headache Centres with the aim to evaluate the efficacy of occipital neurostimulation in a selected group representative for the drug-resistant chronic migraine. Patients with chronic migraine according to Manzoni's modified IHS criteria-2011, with or without medication overuse headache, will be selected. Duration of illness should be at least 2 years and pharmacological refractoriness defined strictly for experimental-surgical purposes as those patients who have properly tried without success almost all available classes of prophylactic medications. Those presenting with medication overuse should have tried at least two previous detoxification treatments. A full psychopathological assessment will be performed by a psychiatrist, to exclude mainly psychotic disorder, ongoing severe status of an affective disorder, severe post traumatic stress disorder. Headache characteristics and abortive treatments used will be reported daily on a predisposed diary during 3-month baseline and continuously through the post implant follow up, while disability and QoL scale (MIDAS, SF-12) will be completed baseline, 6 and 12 months after implant.

Molecular subtype is determinant on inflammatory status and immunological profile from invasive breast cancer patients.

Breast cancer consists in a chronic inflammatory disease with multiple biological and clinical behaviors. Based on high throughput technologies data, this disease is currently classified according to the molecular expression of estrogen (ER), progesterone (PR) and human epidermal growth factor (HER-2) receptors. In this study, we defined the inflammatory profile of the main molecular subtypes of breast cancer patients: luminal (ER and PR positive, HER-2 negative), HER-2 enriched (HER-2 positive) and triple negative (ER, PR and HER-2 negative). Cytokines panel was assessed by measurement of TNF-α, TGF-ß, IL-1, IL-10 and IL-12 plasmatic levels. Oxidative profile was assessed by determination of lipid peroxidation, total antioxidant capacity of plasma, malondialdehyde levels, carbonyl content and nitric oxide (NO). Clinical data were correlated with inflammatory findings. Our findings demonstrated that patients bearing the luminal subtype displayed high TNF-α, TGF-ß and enhanced oxidative stress levels associated with reduced IL-12. HER-2-enriched group exhibited higher levels of TNF-α, IL-12 and TGF-ß associated with enhanced oxidative stress. Triple-negative subtype exhibited the most aggressive profile of disease behavior, with reduction in both TNF-α and TGF-ß, with high levels of lipid peroxidation and NO. The clinical importance of our findings lies in the fact that the inflammatory status varies in distinct ways due to molecular subtype of breast cancer, opening potential therapeutic targets to future therapies.

Time-dependent reactive species formation and oxidative stress damage in the skin after UVB irradiation.

This study provides evidence that skin oxidative stress injury caused by UVB irradiation is mediated predominantly by reactive oxygen species immediately after irradiation and by reactive nitrogen species at later time points. Animals were pre-treated with free radical scavengers (deferrioxamine, histidine), α-tocopherol, or inhibitors of nitric oxide synthase (NOS) (L-NAME or aminoguanidine) or left untreated and subjected to UVB irradiation. α-Tocopherol inhibited the increase in lipid peroxidation, as evaluated by chemiluminescence at 0 h and 24 h after UVB irradiation. Immediately after UVB irradiation, lipid peroxidation increased moderately and was abolished by free radical scavengers but not by NOS inhibitors. Likewise, the reduction of antioxidant capacity was not reversed by NOS inhibitors. Nitric oxide augmentation was not observed at this time point. Twenty-four hours after irradiation, increased lipid peroxidation levels and nitric oxide elevation were observed and were prevented by NOS inhibitors. Low concentrations of GSH and reduced catalase activity were also observed. Altogether, these data indicate that reactive oxygen species (singlet oxygen and hydroxyl radicals) are the principal mediators of immediate damage and that reactive nitrogen species (*NO and possibly ONOO(-)) seem to be involved later in skin oxidative injury induced by UVB radiation. The reduced catalase activity and low level of GSH suggest that *NO and H(2)O(2) may react to generate ONOO(-), a very strong lipid peroxidant species.