Cerebral venous hemodynamic abnormalities in episodic and chronic migraine

Alterations of cerebral venous drainage have been demonstrated in chronic migraine (CM), suggesting that cerebral venous hemodynamic abnormalities (CVHAs) play a role in this condition. The aim of the present study was to look for a correlation between CM and CVHAs. We recruited 33 subjects suffering from CM with or without analgesic overuse, 29 episodic migraine (EM) patients with or without aura, and 21 healthy subjects as controls (HCs). CVHAs were evaluated by transcranial and extracranial echo-color Doppler evaluation of five venous hemodynamic parameters. CVHAs were significantly more frequent in the CM and EM patients than in the HCs. In the migraine patients, CVHAs were not correlated with clinical features. Cerebral venous hemodynamic abnormalities in episodic and chronic migraine The significantly greater frequency of CVHAs observed in the migraineurs may reflect a possible relationship between migraine and these abnormalities. Prospective longitudinal studies are needed to investigate whether CVHAs have a role in the processes of migraine chronification

Time to redefine endometriosis including its pro-fibrotic nature

Endometriosis is currently defined as presence of endometrial epithelial and stromal cells at ectopic sites. This simple and straightforward definition has served us well since its original introduction. However, with advances in disease knowledge, endometrial stromal and glands have been shown to represent only a minor component of endometriotic lesions and they are often absent in some disease forms. In rectovaginal nodules, the glandular epithelium is often not surrounded by stroma and frequently no epithelium can be identified in the wall of ovarian endometriomas. On the other hand, a smooth muscle component and fibrosis represent consistent features of all disease forms. Based on these observations, we believe that the definition of endometriosis should be reconsidered and reworded as 'A fibrotic condition in which endometrial stroma and epithelium can be identified'. The main reasons for this change are: (1) to foster the evaluation of fibrosis in studies on endometriosis pathogenesis using animal models; (2) to limit potential false negative diagnoses if pathologists stick stringently to the current definition of endometriosis requiring the demonstration of endometrial stromal and glands; (3) to consider fibrosis as a potential target for treatment in endometriosis. This opinion article is aimed at boosting the attention paid to a largely neglected aspect of the disease. We hope that targeting the fibrotic process might increase success in developing new therapeutic approaches

Ovarian stimulation and endometriosis progression or recurrence: a systematic review

Available evidence on the impact of ovarian stimulation on the progression of endometriosis or its recurrence was systematically reviewed. Data from ovarian stimulation alone, or associated with intrauterine insemination (IUI) or IVF, were included. Sixteen studies were selected. Initial case reports (n = 11) documented some severe clinical complications. However, subsequent observational studies were more reassuring. Overall, five conclusions can be drawn: (i) IVF does not worsen endometriosis-related pain symptoms (moderate quality evidence); (ii) IVF does not increase the risk of endometriosis recurrence (moderate quality evidence); (iii) the impact of IVF on ovarian endometriomas, if present at all, is mild (low quality evidence); (iv) IUI may increase the risk of endometriosis recurrence (low quality evidence); (v) deep invasive endometriosis might progress with ovarian stimulation (very low quality evidence). In conclusion, available evidence is generally reassuring (at least for IVF) and does not justify aggressive clinical approaches such as prophylactic surgery before assisted reproductive technology treatment to prevent endometriosis progression or recurrence. However, further evidence is required before being able to reach definitive conclusions. In particular, the potential effects on deep invasive endometriosis and the possible synergistic effect of stimulation and pregnancy are two areas that need to be explored further

Evaluation of the weight loss of raw beef cuts vacuum-packaged with two different techniques

In the present study, 25 cuts of shank form adult cattle coming from the same slaughtering batch, were withdrawn just after manual sectioning/deboning, and each divided into two pieces (Prox and Dist) of approximately the same weight, that were vacuum packaged by using two different packaging systems: vacuum chamber machine with a bag material and a thermo-forming packaging machine with top and bottom webs named BAG and THF respectively. The packed cuts were stored at 2-3\ub0C for 20 days. The drip loss was calculated at the end of the storage as the difference between drained weight and net. Internal muscle pH and pH of the exudate present in the package and microbiological analyses (by pooling the samples) were performed at T0 and at the end of the storage. The drip loss, was significantly lower with BAG packaging: this difference was evident after 20 days of storage (average \ub1 STD BAG vs THF = 1.04\ub10.36% vs 1.71\ub10.42%; P<0.01). The values were, in general, low for both the packaging systems, never above 2%. Moreover, shrink bag packages are characterized by better overall pack appearance and less plastic weight per pack. Forming step reduce the thickness of ther-moforming material lowering the mechanical resistance and the barrier to oxygen, on the contrary after shrinking bag materials are thickened. The pH of muscles was stable, although a slight increase was evidenced after 20 (average \ub1 STD BAG vs THF= 5.73\ub10.05 vs 5.78\ub10.09; P<0.01), due to the ageing of meat. The pH of the exudate was equal at T20 (average \ub1 STD BAG vs THF = 5.34\ub10.20 vs 5.33\ub10.17). The drip loss didn\u2019t influence the development of all the microflora; in particular LAB, that represented the main microbial population, showed a gradual increase from T0 (2.20\ub10.41 Log CFU/g) to T20 (average \ub1 STD BAG vs THF= 4.76\ub10.29 Log CFU/g vs 4.75\ub10.0.15 Log CFU/g). No Enterobacteriaceae showed an increase, if compared to the initial counts, due to the prolonged storage and the gradual growth of ephemeral microorganisms, without differences among the two series (Enterobacteriaceae: T0=<1.7 Log CFU/g to T20 average \ub1 STD BAG vs THF = 2.83\ub10.77 Log CFU/g vs 3.09\ub10.0.70 Log CFU/g). In conclusion, the use of the BAG system demonstrated to have an effect in reducing the drip loss of beef cuts during the refrigerated storage, with only slight influence on the other characteristics of raw meat

Short-term effects of focal muscle vibration on motor recovery after acute stroke: a pilot randomized sham-controlled study

Repetitive focal muscle vibration (rMV) is known to promote neural plasticity and long-lasting motor recovery in chronic stroke patients. Those structural and functional changes within the motor network underlying motor recovery occur in the very first hours after stroke. Nonetheless, to our knowledge, no rMV-based studies have been carried out in acute stroke patients so far, and the clinical benefit of rMV in this phase of stroke is yet to be determined. The aim of this randomized double-blind sham-controlled study is to investigate the short-term effect of rMV on motor recovery in acute stroke patients. Out of 22 acute stroke patients, 10 were treated with the rMV (vibration group–VG), while 12 underwent the sham treatment (control group–CG). Both treatments were carried out for 3 consecutive days, starting within 72 h of stroke onset; each daily session consisted of three 10-min treatments (for each treated limb), interspersed with a 1-min interval. rMV was delivered using a specific device (Cro®System, NEMOCO srl, Italy). The transducer was applied perpendicular to the target muscle's belly, near its distal tendon insertion, generating a 0.2–0.5 mm peak-to-peak sinusoidal displacement at a frequency of 100 Hz. All participants also underwent a daily standard rehabilitation program. The study protocol underwent local ethics committee approval (ClinicalTrial.gov NCT03697525) and written informed consent was obtained from all of the participants. With regard to the different pre-treatment clinical statuses, VG patients showed significant clinical improvement with respect to CG-treated patients among the NIHSS (p < 0.001), Fugl-Meyer (p = 0.001), and Motricity Index (p < 0.001) scores. In addition, when the upper and lower limb scales scores were compared between the two groups, VG patients were found to have a better clinical improvement at all the clinical end points. This study provides the first evidence that rMV is able to improve the motor outcome in a cohort of acute stroke patients, regardless of the pretreatment clinical status. Being a safe and well-tolerated intervention, which is easy to perform at the bedside, rMV may represent a valid complementary non-pharmacological therapy to promote motor recovery in acute stroke patients

Ethical, Legal and Social Issues of Big Data - A Comprehensive Overview

The ELSI White Paper is the final achievement of the ELSI Task Force for the National Research Programme “Big Data” (NRP 75). It is an informational document that provides an overview of the key ethical, legal, and social challenges of big data and provides guidance for the collection, use, and sharing of big data. The document aims to bring together the expertise of the ELSI Task Force members rather than exhaustively covering all topics in big data relating to ethical, legal, and social issues (ELSI). The white paper comprises two parts: main articles and commentaries on it. The main articles give an overview of the major concerns associated with the use of big data, based on the assessment of the participating researchers. The commentary articles either examine in depth one or more of the issues that are presented in the main articles or highlight other issues that are considered relevant by their authors but are not covered in the main articles. The main articles are divided into three sections corresponding to the three ELSI levels of analysis. In the section on ethics, Marcello Ienca explores the threat of big data to ethics commissions, privacy rights, personal autonomy, and equality in the healthcare sector and biomedical research. Bernice Elger focuses on the need to address informed consent differently and complement it with additional mechanisms in the big data context. In the legal section, Christophe Schneble explores whether current Swiss data protection laws adequately regulate and protect individuals’ data. Eleonora Viganò analyses the threat of big data to state sovereignty and explore the two contrasting acceptations of the term “digital sovereignty” in the context of big data. In the section on social issues, Markus Christen addresses the big data divide, namely, the uneven distribution of benefits and harms from big data and the connected issue of the transparency asymmetry between data givers and data owners. Michele Loi delves into the debate on fair algorithms, presenting the risks of discriminating against certain groups when adopting big data-based predictive algorithms, such as those for predicting inmates’ recidivism. The second part of the ELSI White Paper contains three commentaries. In the first, Mira Burri focuses on the viability of new approaches to global trade governance that seek to address big data issues and makes recommendations for a better informed and more proactive Swiss approach. In the second commentary, David Shaw explores the lack of protection for vulnerable groups in big data research and the temporospatial and moral distance between researchers and participants that increases the risk of exploitation. In the third commentary, Christian Hauser tackles big data from the perspective of business ethics and provides guidance to companies employing big data. Keywords: Big data, informed consent, data protection law, big data divide, digital sovereignty, health data, discrimination, big data research, big data in industry JEL Classification: O3, F1

Model-assisted predictions on prognosis in HNSCC: do we learn?

Dedicated software packages incorporating prognostic models are meant to aid physicians in making accurate predictions of prognosis. This study concerns 742 predictions of 5-year survival on consecutive newly diagnosed patients with head- and neck squamous cell carcinoma. The 5-year survival predictions made by the physicians are not compared with actual survival, but with a prediction made by OncologIQ, a dedicated software package. We used a linear regression and a linear mixed-effects model to look at absolute differences between both predictions and possible learning effects. Predictions made by the physicians were optimistic and inaccurate. Using the linear regression and linear mixed-effects models, the physicians’ learning effect showed little improvement per successive prediction. We conclude that prognostic predictions in general are imprecise. When given feedback on the model’s predicted survival, the accuracy increases, but only very modestly

Terminal ileum ileoscopy and histology in patients undergoing high-definition colonoscopy with virtual chromoendoscopy for chronic nonbloody diarrhea : a prospective, multicenter study

Background and aims: Ileo-colonoscopy is the procedure of choice for chronic nonbloody diarrhea (CNBD) of unknown origin. Histological evaluation at different colonic sites is mandatory to assess the presence of microscopic colitis. However, the value of routine ileal biopsy on normal-appearing mucosa as assessed by means of standard-resolution white-light ileoscopy is controversial given its reported low diagnostic yield. Hence, we have assessed for the first time the accuracy of retrograde ileoscopy using high-definition and dyeless chromoendoscopy (HD + DLC), thereby calculating the impact and cost of routine ileal biopsy in CNBD. Methods: Patients with CNBD of unknown origin were prospectively enrolled for ileo-colonoscopy with HD + DLC at five referral centers. Multiple biopsies were systematically performed on each colorectal segment and in the terminal ileum for histopathological analysis. Results: Between 2014 and 2017, 546 consecutive patients were recruited. Retrograde ileoscopy success rate was 97.6%. A total of 492 patients (mean age: 53 \ub1 18 years) fulfilled all the inclusion criteria: Following endoscopic and histopathological work-up, 7% had lymphoid nodular hyperplasia and 3% had isolated ileitis. Compared to the histopathology as the gold standard, retrograde ileoscopy with HD + DLC showed 93% sensitivity, 98% specificity and 99.8% negative predictive value. In patients with normal ileo-colonoscopy, ileum histology had no diagnostic gain and resulted in a cost of US $26.5 per patient. Conclusions: Retrograde ileoscopy with HD + DLC predicts the presence of ileitis in CNBD with excellent performance. The histopathological evaluation of the terminal ileum is the gold standard for the diagnostic assessment of visible lesions but has no added diagnostic value in CNBD patients with negative ileo-colonoscopy inspection using modern endoscopic imaging techniques

Autologous Microfragmented Adipose Tissue Reduces the Catabolic and Fibrosis Response in an in Vitro Model of Tendon Cell Inflammation

Background. Mesenchymal stem cells (MSCs) emerged as a promising therapy for tendon pathologies. Microfragmented adipose tissue (\u3bcFAT) represents a convenient autologous product for the application of MSC-based therapies in the clinical setting. In the present study, the ability of \u3bcFAT to counteract inflammatory processes induced by IL-1\u3b2 on human tendon cells (TCs) was evaluated. Methods. Cell viability and proliferation were evaluated after 48 hours of transwell coculture of TCs and autologous \u3bcFAT in the presence or absence of IL-1\u3b2. Gene expression of scleraxis, collagen type I and type III, metalloproteinases-1 and -3, and cyclooxygenase-2 was evaluated by real-time RT-PCR. The content of VEGF, IL-1Ra, TNF\u3b1, and IL-6 was evaluated by ELISA. Results. IL-1\u3b2-treated TCs showed augmented collagen type III, metalloproteases, and cyclooxygenase-2 expression. \u3bcFAT was able to reduce the expression of collagen type III and metalloproteases-1 in a significant manner, and at the same time, it enhanced the production of VEGF, IL-1Ra, and IL-6. Conclusions. In this in vitro model of tendon cell inflammation, the paracrine action of \u3bcFAT, exerted by anti-inflammatory molecules and growth factors, was able to inhibit the expression of fibrosis and catabolic markers. Then, these results suggest that the application of \u3bcFAT may represent an effective conservative or adjuvant therapy for the treatment of tendon disorders

Disarming the guarded prognosis: predicting survival in newly referred patients with incurable cancer

People affected by cancer want information about their prognosis but clinicians have trouble estimating and talking about it. We sought to determine the nature and accuracy of medical oncologists' estimates of life expectancy in newly referred patients with incurable cancer. With reference to each patient, medical oncologists estimated how long they thought 90, 50, and 10% of similar patients would live. These proportions were chosen to reflect worst case, predicted, and best case scenarios suitable for discussions. After a median follow-up of 35 months, 86 of the 102 patients had died with an observed median survival of 12 months. Oncologists' estimates of each patient's worst case, predicted and best case scenarios were well-calibrated: 10% of patients lived for fewer months than estimated for the worst 10% of similar patients; 50% lived for at least as long as estimated for 50% of similar patients (predicted survival), and 17% lived for more months than estimated for the best 10% of similar patients. Oncologists' estimates of each patient's predicted survival were imprecise: 29% were within 0.67–1.33 times the patient's actual survival, 35% were too optimistic (>1.33 times the actual survival), and 39% were too pessimistic (<0.67 times the actual survival). The proportions of patients with actual survival times bounded by simple multiples of their predicted survival were as follows: 61% between half to double their predicted, 6% at least three to four times their predicted, and 4% no more than 1/6 of their predicted; similar to the proportions in an exponential distribution (about 50%, 10% and 10% respectively). Ranges based on simple multiples of the predicted survival time appropriately convey prognosis and its uncertainty in newly referred people with incurable cancer