Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. The burden of disease on individuals and societies is ...significant due to high costs and comorbidities. In the Third Edition of the International Classification of Headache Disorders, medication-overuse headache is recognized as a separate secondary entity next to mostly primary headache disorders, although many clinicians see the disease as a sole complication of primary headache disorders. In this review, we explore the historical background of medication-overuse headache, its epidemiology, phenomenology, pathophysiology and treatment options. The review explores relevant unanswered questions and summarizes the current debates in medication-overuse headache.
The Role of β-Blockers in Melanoma De Giorgi, Vincenzo; Geppetti, Pierangelo; Lupi, Chiara ...
Journal of neuroimmune pharmacology,
03/2020, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Melanoma is one of the most aggressive and less chemotherapy-responsive human cancers, representing a major public health issue worldwide. The early diagnosis still represents the best approach in ...order to reduce mortality, especially in advanced stages. Preclinical evidence, collected through several in vitro and in vivo models, has been accumulating about the pathophysiological involvement of β-adrenoceptors in melanoma progression. This involvement has been paralleled by the evidence that drugs blocking β-adrenoceptors (β-blockers) may have a relevant role in the treatment of melanoma and in the prevention of its progression. β-blockers are a class of drugs extensively used in clinical practice, not limited to cardiovascular therapeutics. Evidence collected through retrospective and prospective observational studies suggests that treatment with β-blockers, mainly propranolol, is able to delay melanoma progression. Although conclusive evidence is still lacking, current knowledge proposes β-blockers as an opportunity for antitumor treatment in melanoma. Clinical trials are needed in order to prove their claimed efficacy.
Graphical Abstract
Decades of quality control efforts have raised the standards of immunohistochemistry (IHC), the principle method used for biomarker testing in breast cancer; however, computational pathology and ...reverse transcription quantitative PCR (RT-qPCR) may also hold promise for additional substantial improvements.
Herein, we investigated discrepancies in the assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki67 comparing routinely obtained IHC (and FISH) data (ORI) with the results of manual (REV) and semi-automated (DIA) re-evaluation of the original IHC slides and then with RNA expression data from the same tissue block using the MammaTyper® (MT) gene expression assay.
Correlation for ER and PR was high between ORI IHC and the other three study methods (REV, DIA and RT-qPCR). For HER2, 10 out of 96 discrepant cases can be detected between ORI and REV that involved at least one call in the equivocal category (except for one case). For Ki67, 22 (29.1%) cases were categorized differently by either REV alone (n = 17), DIA alone (n = 15) or both (n = 10) and 28 cases (29.2%) for RT-qPCR. Most of the discrepant Ki67 cases changed from low to high between the original and following assessment and belonged to the intermediate Ki67 expression range (between 9 and 30%).
Determination of the breast cancer biomarkers ER, PR, HER2 and Ki67 at the mRNA level shows high degree of correlation with IHC and compares well with correlations between original with subsequent independent manual or semi-automated IHC assessments. The use of methods with wider dynamic range and higher reproducibility such as RT-qPCR may offer more precise assessment of endocrine responsiveness, improve Ki67 standardization and help resolve HER2 cases that remain equivocal or ambiguous by IHC/FISH. In summary, our findings seem to configure RT-qPCR as a complementary method to be used in cases of either equivocal results or presenting, at the traditional determination assays, biomarkers expressions close to the cut-off values.
Background: Previous studies during SARS and Ebola pandemics have shown that quarantine is associated with several negative psychological effects, such as post-traumatic stress symptoms, confusion, ...and anger. These conditions may affect the course of many diseases, including migraine. Although it is possible that the quarantine measures for the current COVID-19 pandemic affect migraine burden, no information is currently available on this issue. Aim: In this study, we aimed to: (1) explore the possible changes in migraine frequency, severity, and days with acute medication intake during quarantine period; (2) evaluate possible differences in migraine outcomes in consideration of lifestyle changes, emotions, pandemic diffusion, and COVID-19 infection. Methods: We interviewed patients who were included in the observational Italian Headache Registry (Registro Italiano Cefalee, RICE), retrospectively collecting information on main headache features, lifestyle factors, emotions, individual infection status, and perception of COVID-19 for 2 months before (pre-quarantine) and after the beginning of the quarantine (quarantine). Inclusion criteria were: age > 18, diagnosis of migraine without aura, migraine with aura and chronic migraine, last in-person visit more than 3 months preceding the beginning of quarantine. Results: A total of 433 migraine subjects agreed to be interviewed. We found an overall reduction in headache frequency (9.42 ± 0.43 days with headache vs. 8.28 ± 0.41) and intensity (6.57 ± 0.19 vs. 6.59 ± 0.21) during the quarantine, compared to pre-quarantine. There was a correlation between improvement and number of days of stay-at-home. When results were stratified for geographic area, we found a tendency toward worsening of headache frequency in northern Italy. Disgust regarding viral infection corresponded to a minor improvement in migraine. Conclusions: Migraine patients showed a mild improvement of migraine features, probably attributable to resilient behavior toward pandemic distress. Disgust regarding the contagion whereas potentially favoring defensive behavior, could potentially worsen migraine. The spontaneous limitation of migraine burden during quarantine could favor patient follow-up via the use of telemedicine visits, reliable diaries, and frequent remote contacts.
Objective
To investigate headache treatment before and during pregnancy.
Background
Most headaches in pregnancy are primary disorders. Headaches are likely to ameliorate during pregnancy, although ...they may also begin or worsen. Most headache medications should be avoided during pregnancy because of potential fetal risks. However, only scarce evidence on headache drug consumption during pregnancy is available.
Design
ATENA was a retrospective, self-administered questionnaire-based, cohort study on women in either pregnancy or who have just delivered and reporting headache before and/or during pregnancy.
Results
Out of 271 women in either pregnancy or who have just delivered, 100 (37%) reported headache before and/or during pregnancy and constituted our study sample. Before pregnancy, the attitude toward the use of symptomatic drugs was characterized by both a strong focus on their safety and the willingness to avoid possible dependence from them. Compared to the year before, pregnancy led to changes in behavior and therapeutic habits as shown by a higher proportion of patients looking for information about drugs (44/100 44% vs. 36/100 36%) and a lower proportion of those treating headache attacks (88/100 88% vs. 52/100 52%) and by a lower use of nonsteroidal anti-inflammatory drugs (68/100 68% vs. 5/100 5%) and a much higher use of paracetamol (33/100 33% vs. 95/100 95%).
Conclusions
Pregnancy changes how women self-treat their headache, and leads to search for information regarding drug safety, mostly due to the perception of fetal risk of drugs. Healthcare providers have to be ready to face particular needs of pregnant women with headache.
Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the ...function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage between IDO2 expression and cancer progression is still unclear, in particular in non-small cell lung cancer (NSCLC). Immunohistochemical expression and cellular localization of IDO2 was evaluated on 191 formalin-fixed and paraffin-embedded resected NSCLC. Correlations between IDO2 expression, clinical-pathological data, tumor-infiltrating lymphocytes (TILs), immunosuppressive tumor molecules (IDO1 and programmed cell death ligand-1 - PD-L1 -) and patients' prognosis were evaluated. IDO2 high expression is strictly related to high PD-L1 level among squamous cell carcinomas group (
= 0.012), to either intratumoral or mixed localization of TILs (
< 0.001) and to adenocarcinoma histotype (
< 0.001). Furthermore, a significant correlation between IDO2 high expression and poor non-small cell lung cancer prognosis was detected (
= 0.011). The current study reaches interesting knowledge about IDO2 in non-small cell lung cancer. The close relationship between IDO2 expression, PD-L1 increased levels, TILs localization and NSCLC poor prognosis, assumed IDO2 as a potential prognostic biomarker to be exploited for optimizing innovative combined therapies with immune checkpoint inhibitors.
Cluster headache (CH) shows a more severe clinical picture than migraine (Mig). We tested whether brain changes can explain such difference. Multimodal MRI was acquired in attack-free patients with ...CH (
n
= 12), Mig (
n
= 13) and in normal controls (NC, n = 13). We used FSL for MRI data analysis and nonparametric permutation testing for voxelwise analyses (
p
< 0.01, corrected). CH showed lower grey matter (GM) volume, compared to Mig and NC, in frontal cortex regions (inferior frontal gyrus and frontal pole FP, respectively) and, only compared to Mig, in lateral occipital cortex (LOC). Functional connectivity (FC) of CH was higher than Mig and NC within working memory and executive control networks and, only compared to Mig, between cerebellar and auditory language comprehension networks. In the attack-free state, the CH brain seems to be characterized by: (i) GM volume decrease, compared to both Mig and NC, in pain modulation regions (FP) and, only with respect to Mig, in a region of visual processing modulation during pain and working memory (LOC); (ii) increased FC at short range compared to both Mig and NC and at long range only with respect to Mig, in key cognitive networks, likely due to maladaptation towards more severe pain experience.
Background
Nummular headache (NH) is a rare headache disorder characterized by a small, circumscribed painful area of the scalp. The description of many cases in the last years has supported its ...re-classification as a primary headache from the International Headache Society, moving it from its previous placement in the Appendix of the International Criteria of Headache Disorders.
Methods
Data were collected from a retro-prospective observational study about rare headaches promoted by the RegistRare Network, a collaborative group of seven Italian Headache Centres. According to the gender-biased profile of certain primary headaches, we have looked further NH patients from a gender perspective.
Results
Nineteen NH patients (11 men, 8 women) have been enrolled in the study. Headache onset was at 39 years and preceded approximately 8 years the diagnosis. No clinically evident differences between men and women have been found, including treatment prescriptions and headache resolution. Of note, the mean time from the onset of NH to the first visit in a Headache Centre was longer in men, compared with women (13.5 vs. 0.9 years). NH attacks were efficaciously treated with nonsteroidal anti-inflammatory drugs in 60% of patients receiving treatment. Headache prophylaxis with pregabalin and amitriptyline has been reported as effective in 40% and 67% of the treated patients, respectively.
Conclusions
NH is a primary headache clinically heterogeneous in terms of temporal patterns and pain characteristics. Further research is needed to investigate the existence of male and female phenotypes, by clarifying whether it may be relevant for therapeutic purposes.
Objectives
A refractory chronic migraine (RCM) accompanied by medication-overuse headache (MOH) is an extremely disabling disease. Evidence suggests that in selected patients, chronic opioids may be ...a valuable therapeutic option for RCM. The aim of the present study was to evaluate the effectiveness and safety of prophylaxis with low-dose methadone (LDM) in patients affected by RCM with continuous headache and MOH.
Methods
A prospective cohort study was performed between May 2012 and November 2015 at the Headache Center and Toxicology Unit of the Careggi University Hospital. Eligible patients were treated with prophylactic LDM and followed up for 12 months. Headache exacerbations, pain intensity, use of rescue medications, and occurrence of adverse drug reactions (ADRs) were recorded.
Results
Thirty patients (24 females, median age 48 years) were enrolled. Nineteen (63%) patients dropped out, mainly because of early ADRs (
n
= 10), including nausea, vomiting, and constipation. At last available follow-up, LDM was associated with a significant decrease in the number of headache attacks/month (from a median of 45 (interquartile range 30–150) to 16 (5–30),
p
< 0.001), in pain intensity (from 8.5 (8–9) to 5 (3–6),
p
< 0.001), and in the number of rescue medications consumed per month (from 95 (34–240) to 15 (3–28),
p
< 0.001). No misuse or diversion cases were observed.
Conclusion
LDM could represent a valuable and effective option in selected patients affected by RCM with continuous headache and MOH, although the frequency of early ADRs poses major safety concerns. Randomized controlled trials are needed to confirm the efficacy and safety of LDM prophylaxis.
COVID-19 is a major global health threat, with millions of confirmed cases and deaths worldwide. Containment and mitigation strategies, including vaccination, have been implemented to reduce ...transmission and protect the population. We conducted two systematic reviews to collect nonrandomized studies investigating the effects of vaccination on COVID-19-related complications and deaths in the Italian population. We considered studies conducted in Italian settings and written in English that contained data on the effects of vaccination on COVID-19-related mortality and complications. We excluded studies that pertained to the pediatric population. In total, we included 10 unique studies in our two systematic reviews. The results showed that fully vaccinated individuals had a lower risk of death, severe symptoms, and hospitalization compared to unvaccinated individuals. The review also looked at the impact of vaccination on post-COVID-19 syndrome, the effectiveness of booster doses in older individuals, and nationwide adverse events. Our work highlights the crucial role that vaccination campaigns have played in reducing the burden of COVID-19 disease in the Italian adult population, positively impacting the pandemic trajectory in Italy.