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BACKGROUND Women with dysmenorrhoea plus symptomatic urinary calculosis experience enhanced pain and referred muscle hyperalgesia from both conditions than women with one condition only (viscero-visceral hyperalgesia). The study aimed at verifying if enhanced dysmenorrhoea persists after urinary stone elimination in comorbid women and if local anaesthetic inactivation of myofascial trigger points (TrPs) in the lumbar area (of urinary pain referral) also relieves dysmenorrhoea. METHODS Thirty-one women with dysmenorrhoea plus previous urinary calculosis (Dys+PrCal) and lumbar TrPs, and 33 women with dysmenorrhoea without calculosis (Dys) underwent a 1-year assessment of menstrual pain and muscle hyperalgesia in the uterus-referred area (electrical pain threshold measurement in rectus abdominis, compared with thresholds of 33 healthy controls). At the end of the year, 16 comorbid patients underwent inactivation of TrPs through anaesthetic injections, whereas the remaining 12 received no TrP treatment. Both groups were monitored for another year at the end of which thresholds were re-measured. RESULTS In year1, Dys+PrCal presented significantly more painful menstrual cycles and lower abdominal thresholds than Dys, thresholds of both groups being significantly lower than normal (p

Headache is a significant reason for access to Emergency Departments (ED) worldwide. Though primary forms represent the vast majority, the life-threatening potential of secondary forms, such as subarachnoid hemorrage or meningitis, makes it imperative for the ED physician to rule out secondary headaches as first step, based on clinical history, careful physical (especially neurological) examination and, if appropriate, hematochemical analyses, neuroimaging or lumbar puncture. Once secondary forms are excluded, distinction among primary forms should be performed, based on the international headache classification criteria. Most frequent primary forms motivating ED observation are acute migraine attacks, particularly status migrainous, and cluster headache. Though universally accepted guidelines do not exist for headache management in an emergency setting, pharmacological parenteral treatment remains the principal approach worldwide, with NSAIDs, neuroleptic antinauseants, triptans and corticosteroids, tailored to the specific headache type. Opioids should be avoided, for their scarce effectiveness in the acute phase, while IV hydration should be limited in cases of ascertained dehydration. Referral of the patient to a Headache Center should subsequently be an integral part of the ED approach to the headache patients, being ascertained that lack of this referral involves a high rate of relapse and new accesses to the ED. More controlled studies are needed to establish specific protocols of management for the headache patient in the ED.

Background ATP-binding cassette A1 (ABCA1) and G1 (ABCG1) mediate cholesterol efflux from lipid-laden macrophages, thus promoting anti-atherosclerotic outcomes. The mechanism(s) linking treatment with statins and ABCA1/ABCG1 in human atherosclerosis are not fully understood and require further investigation. Therefore, we studied whether short-term treatment with low- or high-dose rosuvastatin may affect ABCA1 and ABCG1 expression in human atherosclerotic plaques. Methods Seventy patients with severe stenosis of the internal carotid artery were randomized to receive low (10 mg/day) or high (40 mg/day) dose rosuvastatin for 12 weeks before elective endarterectomy. As controls, we analyzed a reference group of 10 plaques from subjects with hypercholesterolemia but not receiving statin treatment and an additional set of 11 plaques collected from normocholesterolemic patients. On atherosclerotic plaques, ABCA1 and ABCG1 expression was evaluated at RNA level by qPCR and at protein level by immunoblotting and immunohistochemistry. Results Both rosuvastatin doses were associated with lower plaque ABCA1 mRNA levels and with a trend toward reduction for ABCG1. However, ABCA1 protein was paradoxically higher in patients treated with high-dose rosuvastatin and was associated with lower levels of miR-33b-5p, a microRNA known as a regulator of ABCA1. Multivariate analyses showed that the effect is cholesterol-independent. Finally, no effects were found for ABCG1 protein. Conclusions High-dose rosuvastatin increases macrophage ABCA1 protein levels in human atherosclerotic plaque despite mRNA reduction in a mechanism unrelated to plasma cholesterol reduction and potentially involving miR-33b-5p. This pathway may reflect an additional feature contributing to the anti-atherosclerotic effect for high-dose rosuvastatin. Trial registration: ISRCTN16590640

Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas and manifesting with clinical pictures that vary on the basis of the organs that are mainly affected. Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease. Histopathology is distinctive but not pathognomonic, since the findings can be found also in other granulomatous disorders. The knowledge of these findings is important because it could be helpful to differentiate sarcoidosis from the other granulomatous-related diseases. This review aims at illustrating the main clinical and histopathological findings that could help clinicians in their routine clinical practice.

Since it has been recognized that sarcoidosis (SA) is not an exclusive disorder of the lungs but can also affect other organs such as the liver and spleen, efforts have been made to define specific imaging criteria for the diagnosis of the single organ involvement, and the concept has been reinforced that the exclusion of alternative causes is important to achieve the correct diagnosis. Ultrasound (US) is a useful tool to evaluate patients with suspected abdominal SA, such as of the liver, spleen, kidney, pancreas and other organs, showing findings such as organomegaly, focal lesions and lymphadenopathy. While the diagnosis of abdominal SA is more predictable in the case of involvement of other organs (e.g., lungs), the problem is more complex in the case of isolated abdominal SA. The recent use of contrast-enhanced ultrasound and endoscopic ultrasound elastography has provided additional information about the enhancement patterns and tissue rigidity in abdominal SA. Here we critically review the role of US in abdominal SA, reporting typical findings and limitations of current evidence and by discussing future perspectives of study.

Background: Point-of-care lung ultrasound (LUS) score is a semiquantitative score of lung damage severity. High-resolution computed tomography (HRCT) is the gold standard method to evaluate the severity of lung involvement from the novel coronavirus disease (COVID-19). Few studies have investigated the clinical significance of LUS and HRCT scores in patients with COVID-19. Therefore, the aim of this study was to evaluate the prognostic yield of LUS and of HRCT in COVID-19 patients. Methods: We carried out a multicenter, retrospective study aimed at evaluating the prognostic yield of LUS and HRCT by exploring the survival curve of COVID-19 inpatients. LUS and chest CT scores were calculated retrospectively by 2 radiologists with >10 years of experience in chest imaging, and the decisions were reached in consensus. LUS score was calculated on the basis of the presence or not of pleural line abnormalities, B-lines, and lung consolidations. The total score (range 0–36) was obtained from the sum of the highest scores obtained in each region. CT score was calculated for each of the 5 lobes considering the anatomical extension according to the percentage parenchymal involvement. The resulting overall global semiquantitative CT score was the sum of each single lobar score and ranged from 0 (no involvement) to 25 (maximum involvement). Results: One hundred fifty-three COVID-19 inpatients (mean age 65 ± 15 years; 65% M), including 23 (15%) in-hospital deaths for any cause over a mean follow-up of 14 days were included. Mean LUS and CT scores were 19 ± 12 and 10 ± 7, respectively. A strong positive linear correlation between LUS and CT scores (Pearson correlation r = 0.754; R2 = 0.568; p < 0.001) was observed. By ROC curve analysis, the optimal cut-point for mortality prediction was 20 for LUS score and 4.5 for chest CT score. According to Kaplan-Meier survival analysis, in-hospital mortality significantly increased among COVID-19 patients presenting with an LUS score ≥20 (log-rank 0.003; HR 9.87, 95% CI: 2.22–43.83) or a chest CT score ≥4.5 (HR 4.34, 95% CI: 0.97–19.41). At multivariate Cox regression analysis, LUS score was the sole independent predictor of in-hospital mortality yielding an adjusted HR of 7.42 (95% CI: 1.59–34.5). Conclusion: LUS score is useful to stratify the risk in COVID-19 patients, predicting those that are at high risk of mortality.

Background Triptans and erenumab are both migraine-specific agents acting on the calcitonin gene-related peptide pathway. Therefore, response to triptans might be associated with response to erenumab. Main body In our study, consecutive patients referring to the Headache Centers of the Abruzzo region from January 2019 to March 2020 and treated with erenumab were interviewed about past use and efficacy of triptans. Triptan users were classified as ‘triptan responders’ if they were headache-free 2 h after treating ≥3 migraine attacks with ≥1 triptan. We considered patients as ‘erenumab responders’, if they had a ≥ 50% mean reduction in monthly migraine days between the 4th and the 6th month from treatment start compared with baseline. Of 91 triptan users, 73 (80.2%) were triptan responders and 58 (63.7%) were erenumab responders. The odds ratio of being erenumab responder was 3.64 (95% CI, 1.25–10.64) for triptan users as compared to non-users. (P = 0.014). Besides, starting erenumab improved triptan response in both erenumab responders and non-responders. Conclusions Our data of an association between response to triptans and response to erenumab can be useful for patient advice and to improve the understanding of migraine pathophysiology and treatment.

The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses. ispartof: Pain vol:162 issue:7 pages:2087-2096 ispartof: location:United States status: published

Sarcoidosis is a granulomatous disorder of unknown etiology characterized by noncaseating granulomas virtually in every organ and tissue. This finding represents the most important diagnostic clue to reach a correct definition of sarcoidosis, although the biopsy is invasive and has several risk procedures. Several efforts are made to suspect the diagnosis of sarcoidosis by combining noninvasive elements, in particular from imaging, though these findings are often nonspecific and reflect the wide multifactorial pathogenesis. Every effort should be made to obtain a detailed radiological picture that, if associated with a suggestive clinical picture, could avoid the need of biopsy in some specific cases. In this narrative review, we aim to describe main computed tomography (CT) features of pulmonary and abdominal sarcoidosis, by reporting strengths and limits of this technique, in particular for the identification of extrapulmonary, isolated disease.

BackgroundMost patients treated with erenumab in clinical practice have chronic migraine (CM). We assessed the rate and possible predictors of conversion from CM to episodic migraine (EM) in a real-life study.Main bodyWe performed a subgroup analysis of patients treated with erenumab from January 2019 to February 2020 in the Abruzzo region, central Italy. Treatment was provided according to current clinical practice. For the purpose of the present study, we included patients fulfilling the definition of CM for the three months preceding erenumab treatment and with at least 6 months of follow-up after treatment. We assessed the rate of conversion to EM from baseline to Months 4–6 of treatment and during each month of treatment. To test the clinical validity of conversion to EM, we also assessed the decrease in monthly headache days (MHDs), acute medication days, and median headache intensity on a Numerical Rating Scale (NRS). We included in our study 91 patients with CM. At Months 4–6, 62 patients (68.1%) converted from CM to EM; the proportion of converters increased from Month 1 to Month 5. In the overall group of patients, median MHDs decreased from 26.5 (IQR 20–30) to 7.5 (IQR 5–16;P P P ConclusionsIn our study, two thirds of patients with CM converted to EM during 6 months of treatment with erenumab. MHDs, acute medication use, and headache intensity decreased regardless of conversion from CM to EM.

Background We aimed to assess the efficacy and safety of erenumab, a fully human monoclonal antibody inhibiting the calcitonin gene-related peptide receptor (CGRPr), for the prevention of migraine in a real-life setting. Main body We included in our observational study all patients with episodic or chronic migraine treated with erenumab during the year 2019 in the Abruzzo region, central Italy, and with a 6-month follow-up. We included 89 patients; 76 (85.4%) received 6 doses of erenumab, 11 (12.4%) autonomously withdrew the drug due to perceived inefficacy, and 2 (2.2%) due to adverse events. Seventy-eight patients (87.6%) were female, with a mean age of 46.8 ± 11.2 years; 84 (94.4%) had chronic migraine, and 64 (71.9%) medication overuse. All patients had ≥2 prior preventive treatment failures. Fifty-three patients (69.7%) had a 50% decrease in monthly migraine days (MMDs) within the first three doses; 46 (71.9%) of 64 patients withdrew medication overuse. In the 76 patients who completed a 6-dose treatment, erenumab decreased median MMDs from 19 (interquartile range [IQR] 12–27.5) to 4 (IQR 2–9.5; P Conclusions Our real-life data confirm the efficacy and tolerability of erenumab for the prevention of migraine in a difficult-to-treat population of patients with a high prevalence of chronic migraine and medication overuse.

Hyperuricemia and gout represent important issues in the obese patients. Considering the epidemic trend of overweight and obesity in developed countries, the impact of these conditions is likely to increase. At present, bariatric surgery represents the most effective treatment for the management of severe obesity for reducing weight and the impact of associated comorbidities, but its effects on hyperuricemia and gout have not been fully elucidated.In this narrative review, we discuss the current knowledge about hyperuricemia and gout in obese patients undergoing bariatric surgery. We also suggest a useful approach to prevent gouty attacks in the perioperative period.Weight loss seems to reduce hyperuricemia in the long-term follow-up, but there is evidence also of a high frequency of acute attacks early after surgery in patients with a diagnosis of gout.Bariatric surgery has a high impact on hyperuricemia and gout. A perioperative approach is suggested, based on appropriate hydration, early physical resumption, urate lowering drugs and nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine and corticosteroids if NSAIDs are ineffective or not tolerated.

Background and aims: Individuals with non-acute pain are challenged with variable pain responses following surgery as well as psychological challenges, particularly depression and catastrophizing. The purpose of this study was to compare pre- and postoperative psychosocial tests and the associated presence of sensitization on a cohort of women undergoing elective laparoscopic surgery for non-acute pain defined as pain sufficient for surgical investigation without persistent of chronic pain. Methods: The study was a secondary analysis of a previous report (Am J Obstet Gynecol 2014 Oct;211(4):360–8.). The study was a prospective cohort trial of 77 women; 61 with non-acute pain and 16 women for a tubal ligation. The women had the following tests: Pain Disability Index, Pain Catastrophizing Scale, CES-D (Center for Epidemiologic Studies Depression Scale) depression scale and the McGill Pain Scale (short form) as well as their average pain score and the presence of pain sensitization. All test scores were correlated together and comparisons were done using paired t-test. Results: There were reductions in pain and psychosocial test scores that were significantly correlated. Pre-operative sensitization indicated greater changes in psychosocial tests. Conclusions: There was a close association of tests of psychosocial status with average pain among women having surgery on visceral tissues. Incorporation of these tests in the pre- and postoperative evaluation of women having laparoscopic surgery appears to provide a means to a broader understanding of the woman’s pain experience.

Altered iron status may be relevant to the pathophysiology of aging. We have assessed redox-active catalytic low molecular weight iron (LMWI), non-heme iron (NHI), heme iron (HI), and total iron (TI) in the aerobically perfused hearts of aged rabbits (AR, about 4.5years old) and young adult control rabbits (YACR, 3-4months old); myocardial lipid and protein oxidations were also assessed as oxidative stress biomarkers. The levels of LMWI and NHI, as well as of lipid and protein oxidation, were higher, while HI content was lower, in the hearts of AR than in those of YACR; TI did not differ significantly between the two groups. Together with these findings, hemodynamic dysfunction, namely heightened end-diastolic pressure (EDP) and lowered coronary flow (CF), occurred in the AR hearts. Notably, such pattern of hemodynamic dysfunction associated with myocardial oxidant damage occurred in the hearts of other YACR perfused in the presence of a cell-permeable form of iron, i.e., the iron/hydroxyquinoline complex, pointing to the involvement of catalytic iron in the aged heart damage. Moreover, as shown in other AR, heart perfusion in the presence of the iron chelator deferoxamine (0.6mM or 3.6mM) reduced the myocardial levels of LMWI, without significantly affecting those of NHI, HI, and TI; concomitantly, in AR deferoxamine lowered myocardial lipid and protein oxidation, and reduced EDP with a tendency to augment CF. Instead, deferoxamine, even at high concentration of 3.6mM, had no significant effects in the YACR. In conclusion, altered iron status with catalytic LMWI burden occurs in the aged rabbit heart, eventually resulting in iron-dependent cardiac oxidative stress and hemodynamic dysfunction.

Migraine is a highly disabling neurological condition, and preventative treatment still remains problematic, due to aspecificity of the majority of the currently available prophylactic drugs. Calcitonin-gene-related peptide (CGRP) plays a crucial role in migraine pathophysiology; agents aimed at blocking its activity have, therefore, been developed in recent years, among which are monoclonal antibodies (mAbs) against CGRP, to prevent migraine. Erenumab is the only mAb that targets the CGRP receptor instead of the ligand, with high specificity and affinity of binding. This review will report on the most recent data on erenumab characteristics and on the results of clinical trials on its employment in the prevention of episodic migraine (4-14 monthly migraine days): one Phase II and two Phase III trials (completed) and one Phase III trial (ongoing). Monthly subcutaneous administration (70 mg or 140 mg) of erenumab vs placebo for 3-6 months showed significantly higher efficacy in reducing the mean monthly number of migraine days and the use of migraine-specific medication, and in decreasing physical impairment and impact of migraine on everyday activities (P

It is not known whether aging alters glutathione metabolic status of the mammalian arterial tissue favoring vascular oxidative stress and dysfunction. Thus we assessed total, reduced and oxidized glutathione (TG, GSH and GSSG, respectively), the glutathione redox ratio (GRR, namely [GSSG]/[GSH+2GSSG]×100), and the activities of the glutathione status-regulating enzymes glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS) and γ-glutamyl transpeptidase (γ-GT) in the aortic tissue of 9 young adult control rabbits (YACR, about 4months old) and 9 aged rabbits (AR, about 4.5years old); aortic lipid and protein oxidation and H2O2 were also determined as oxidative stress indicators. Vascular function was assessed on aortic ring preparations. TG and GSH concentrations, together with γ-GCS and γ-GT activities, were significantly lower, while GSSG content and the GRR higher, in the AR than in the YACR aortas; GSSG-Red activity did not differ significantly between the two groups. Heightened levels of lipid and protein oxidation and H2O2 occurred in the AR aortas, indicating age-dependent vascular oxidative stress. Moreover, in the whole population of 18 rabbits, the aortic values of GSH and related enzyme activities were inversely and significantly correlated with those of lipid and protein oxidation and H2O2, highlighting the antioxidant role of GSH and related enzymes in the vascular tissue. Aortic endothelium-dependent vasodilation was lower in the AR than in the YACR. In conclusion, glutathione metabolic status is altered in the aged rabbit aorta reflecting depressed γ-GCS- and γ-GT-related GSH biosynthesis and GSSG burden eventually favoring vascular oxidative stress and dysfunction.

Many pain conditions in patients tend to co-occur, influencing the clinical expressions of each other in various ways. This paper summarizes the main concurrent pain conditions by analyzing the major interactions observed. In particular, co-occurrence will be examined in: visceral pain (especially ischemic heart disease, irritable bowel syndrome, dysmenorrhea/endometriosis and urinary pain), fibromyalgia, musculoskeletal pain and headache. Two concurrent visceral pains from internal organs sharing at least part of their central sensory projection can give rise to viscero-visceral hyperalgesia, i.e., enhancement of typical pain symptoms from both districts. Visceral pain, headache and musculoskeletal pains (myofascial pain from trigger points, joint pain) can enhance pain and hyperalgesia from fibromyalgia. Myofascial pain from trigger points can perpetuate pain symptoms from visceral pain conditions and trigger migraine attacks when located in the referred pain area from an internal organ or in cervico-facial areas, respectively. The pathophysiology of these pain associations is complex and probably multifactorial; among the possible processes underlying the mutual influence of symptoms recorded in the associations is modulation of central sensitization phenomena by nociceptive inputs from one or the other condition. A strong message in these pain syndrome co-occurrence is that effective treatment of one of the conditions can also improve symptoms from the other, thus suggesting a systematic and thorough evaluation of the pain patient for a global effective management of his/her suffering.

New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome—and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.

The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for $3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP’s Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain. ispartof: PAIN vol:160 issue:1 pages:53-59 ispartof: location:United States status: published

Chronic pain is a major source of suffering. It interferes with daily functioning and often is accompanied by distress. Yet, in the International Classification of Diseases, chronic pain diagnoses are not represented systematically. The lack of appropriate codes renders accurate epidemiological investigations difficult and impedes health policy decisions regarding chronic pain such as adequate financing of access to multimodal pain management. In cooperationwith theWHO,an IASP Working Group has developed a classification system that is applicable in awide range of contexts, including pain medicine, primary care, and low-resource environments. Chronic pain is defined as pain that persists or recurs formore than 3months. In chronic pain syndromes, pain can be the sole or a leading complaint and requires special treatment and care. In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in itsownright; in our proposal,we call this subgroup “chronic primary pain.” In 6 other subgroups, pain is secondary to an underlying disease: chronic cancer-related pain, chronic neuropathic pain, chronic secondary visceral pain, chronic posttraumatic and postsurgical pain, chronic secondary headache and orofacial pain, and chronic secondary musculoskeletal pain. These conditions are summarized as “chronic secondary pain” where pain may at least initially be conceived as a symptom. Implementation of these codes in the upcoming 11th edition of International Classification of Diseases will lead to improved classification and diagnostic coding, thereby advancing the recognition of chronic pain as a health condition in its own right. ispartof: PAIN vol:160 issue:1 pages:19-27 ispartof: location:United States status: published

Chronic visceral pain is a frequent and disabling condition. Despite high prevalence and impact, chronic visceral pain is not represented in ICD-10 in a systematic manner. Chronic secondary visceral pain is chronic pain secondary to an underlying condition originating from internal organs of the head or neck region or of the thoracic, abdominal, or pelvic regions. It can be caused by persistent inflammation, by vascular mechanisms or by mechanical factors. The pain intensity is not necessarily fully correlated with the disease process, and the chronic visceral pain may persist beyond successful treatment of the underlying cause. This article describes how a new classification of chronic secondary visceral pain is intended to facilitate the diagnostic process and to enable the collection of accurate epidemiological data. Furthermore, it is hoped that the new classification will improve the tailoring of patient-centered pain treatment of chronic secondary visceral pain and stimulate research. Chronic secondary visceral pain should be distinguished from chronic primary visceral pain states that are considered diseases in their own right.

The recent COVID-19 pandemic has dramatically changed the world in the last months, leading to a serious global emergency related to a novel coronavirus infection that affects both sexes of all ages ubiquitously. Advanced age, cardiovascular comorbidity, and viral load have been hypothesized as some of the risk factors for severity, but their role in patients affected with other diseases, in particular immune disorders, such as sarcoidosis, and the specific interaction between these two diseases remains unclear. The two conditions might share similar imaging findings but have distinctive features that are here described. The recent development of complex imaging softwares, called deep learning techniques, opens new scenarios for the diagnosis and management.

microRNAs (miRNAs) are a broad group of endogenous small non-coding molecules that reduce the transcription of mRNA and play a key role in post-transcriptional gene processes. miRNAs are involved in onset and progression of several human disorders such as infectious and immune non-infectious diseases, cancers, metabolic and cardiovascular disorders. They regulate the expression of gene targets (e.g. oncogenes and tumor suppressor genes) and act as gene repressors with mRNA binding and cleavage. The increasing evidence that miRNAs play a key role in the pathogenesis of cardiovascular conditions could radically change the future management approach to these disorders. This review focuses on current knowledge about the influence of miRNAs on cardiovascular disease, with particular regard to common conditions such as atherosclerosis, diabetes and migraine. Key messages miRNAs are a group of endogenous small non-coding RNA segments measuring 19-25 nucleotides that are involved in physiologic processes and onset and progression of disorders such as infectious and immune non-infectious diseases, cancers, metabolic and cardiovascular disorders. miRNAs expression guarantees vascular integrity, by regulating apoptosis, VEGF pathway and VCAM 1 expression (-126), and is involved in atherosclerotic plaque formation process and progression. Hyperglycemia, overt diabetes, and their complications are associated with overexpression of several miRNAs. An altered expression of miRNAs has also been postulated in migraine patients, although only a few preliminary studies have so far been performed with this respect.

Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Monoclonal antibodies against CGRP (LY2951742, ALD-403, and LBR-101/TEV-48125) or its receptor (AMG334) were subsequently developed. As reviewed in this study, numerous phase 1 and 2 trials and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Being macromolecules, these mAbs are not suitable for oral administration; however, their intravenous or subcutaneous delivery can be performed at relatively low frequency-every month or even quarterly-which enhances patients' compliance. Although not all migraineurs respond to this treatment, and longer administration periods will be needed to assess long-term effects, the results so far obtained are extraordinarily promising. The future introduction of mAbs on the market will probably represent a turning point for prevention similar to that represented by triptans for abortive treatment in migraine.

Migraine is a common and highly disabling neurological disorder whose acute treatment remains problematic and unsatisfactory in a high percentage of cases. Consequently, there remains a need for new symptomatic therapies that can be easily handled by patients (i.e. by oral administration).This review reports on compounds currently under development for the oral treatment of acute migraine attacks, focusing on Calcitonin-Gene-Related-Peptide receptor antagonists, specifically ubrogepant and rimegepant. This article is based on literature obtained from PubMed and publicly available clinical trial data.Both reviewed compounds meet the need for rapid and effective pain control, combined with the control of associated bothersome symptoms while also lacking significant adverse events and safety concerns. Though further studies should assess the profile of these compounds comparatively with existing and available treatments (namely triptans), the currently available data points to these new therapies as being very promising new symptomatic oral treatments of migraines.

Background In migraine patients with cervical myofascial trigger points whose target areas coincide with migraine sites (M + cTrPs), TrP anesthetic injection reduces migraine symptoms, but the procedure often causes discomfort. This study evaluated if a topical TrP treatment with 3% nimesulide gel has similar efficacy as the injection but produces lesser discomfort with higher acceptability by the patients. Methods Retrospective analysis of medical charts of M + cTrPs patients in the period January 2012–December 2016 at a single Headache Center. Three groups of 25 patients each were included, all receiving migraine prophylaxis (flunarizine 5 mg/day) for 3 months and symptomatic treatment on demand. Group 1 received no TrP treatment, group 2 received TrP injections (bupivacaine 5 mg/ml at basis, 3rd, 10th, 30th and 60th day), group 3 received daily TrP topical treatment with 1.5 g of 3% nimesulide gel for 15 consecutive days, 15 days interruption and again 15 consecutive days. The following were evaluated: monthly number of migraine attacks and rescue medications, migraine intensity; pain thresholds to skin electrical stimulation (EPTs) and muscle pressure stimulation (PPTs) in TrP and target (basis, 30th, 60th and 180th days); discomfort from, acceptability of and willingness to repeat treatment (end of study). ANOVA for repeated measures and 1-way ANOVA were used to assess temporal trends in each group and comparisons among groups, respectively. Significance level was set at p

Migraine is a highly disabling neurological condition, and preventative treatment still remains problematic, due to aspecificity of the majority of the currently available prophylactic drugs. Calcitonin-gene-related peptide (CGRP) plays a crucial role in migraine pathophysiology; agents aimed at blocking its activity have, therefore, been developed in recent years, among which are monoclonal antibodies (mAbs) against CGRP, to prevent migraine. Erenumab is the only mAb that targets the CGRP receptor instead of the ligand, with high specificity and affinity of binding. This review will report on the most recent data on erenumab characteristics and on the results of clinical trials on its employment in the prevention of episodic migraine (4-14 monthly migraine days): one Phase II and two Phase III trials (completed) and one Phase III trial (ongoing). Monthly subcutaneous administration (70 mg or 140 mg) of erenumab vs placebo for 3-6 months showed significantly higher efficacy in reducing the mean monthly number of migraine days and the use of migraine-specific medication, and in decreasing physical impairment and impact of migraine on everyday activities (

Objective : To investigate enzymatic reactive aldehyde-scavenging enzyme capacity together with lipid peroxidation as expression of oxidative stress in atherosclerotic plaques of cigarette smokers and nonsmokers. Methods : We have assessed specific enzymatic activities of class 1, 2, and 3 aldehyde dehydrogenase (ALDH1, ALDH2, and ALDH3, respectively), glutathione S -transferase (isozyme A4-4, GSTA4-4), and aldose reductase (AR), namely the major reactive aldehyde-scavenging enzymes, together with lipid peroxidation, i.e., fluorescent damage products of lipid peroxidation (FDPL), in carotid atherosclerotic plaques surgically removed from 17 cigarette smokers and 17 nonsmokers. Results : The enzymatic activities of ALDH1 plus ALDH2, ALDH3, GSTA4-4, and AR were significantly lower in the atherosclerotic plaques of smokers than in those of nonsmokers, while plaque FDPL levels were significantly higher in the smokers than in the nonsmokers. The amount of cigarette smoking was correlated inversely with the aforementioned plaque enzymatic activities and directly with plaque FDPL content. Plaque FDPL levels were inversely correlated with plaque enzymatic activities in smokers and nonsmokers. The degree of carotid atherosclerotic stenosis, as expression of atherosclerosis severity, was correlated inversely with plaque enzymatic activities and directly with plaque FDPL levels in smokers and nonsmokers; moreover, the degree of carotid stenosis was directly correlated with the amount of cigarette smoking. Conclusion : atherosclerotic lesions of cigarette smokers are endowed with a depressed enzymatic reactive aldehyde-scavenging capacity eventually favoring oxidative stress and the severity of atherosclerosis.