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

ASO Author Reflections: The Liver-First Approach: A New Standard for Patients with Multiple Bilobar Colorectal Metastases?

The best surgical strategy for patients with colorectal cancer and synchronous liver metastases is a matter of endless debate. Technical and oncological issues must be considered but have often been confounded. In 2006, Mentha et al.1 proposed an innovative and convincing oncosurgical approach, whereby they reversed the strategy, focusing attention on the prognostically most relevant target, i.e. the liver. Even if appealing, the liver-first approach struggled to find its role and failed to demonstrate a benefit, except for the inclusion of chemoradiotherapy in the treatment schedule of patients with locally advanced rectal tumors. The proposers themselves reported non-inferiority (and not superiority) of the reverse strategy in comparison with the standard primary-first approach.2 A recent network meta-analysis ranked the liver-first approach as the best treatment option for its relative efficacy based on 5-year overall survival outcomes,3 but the evidence is too weak to impact current clinical practice

The effect of left fronto-parietal resections on hand selection: a lesion-tractography study

Strong right-hand preference on the population level is a uniquely human feature, although the neural basis for this is still not clearly defined. Recent behavioural and neuroimaging literature suggests that hand preference may be related to the orchestrated function and size of fronto-parietal white matter tracts bilaterally. Lesions to these tracts induced during tumour resection may provide an opportunity to test this hypothesis. In the present study, a cohort of seventeen neurosurgical patients with left hemisphere brain tumours were recruited to investigate whether resection of certain white matter tracts affects the choice of hand selected for the execution of a goal-directed task (assembly of jigsaw puzzles). Patients performed the puzzles, but also tests for basic motor ability, selective attention and visuo-constructional ability, preoperatively and one month after surgery. Diffusion tractography of fronto-parietal tracts (the superior longitudinal fasciculus) and the corticospinal tract were performed, to evaluate whether resection of tracts was significantly associated with changes in hand selection. A complementary atlas-based disconnectome analysis was also conducted. Results showed a shift in hand selection despite the absence of any motor or cognitive deficits, which was significantly associated with patients with frontal and parietal resections, compared with those with resections in other lobes. In particular, this effect was significantly associated with the resection of dorsal fronto-parietal white matter connections, but not with the ventral fronto-parietal tract. Dorsal white matter pathways contribute bilaterally, with specific lateralised competencies, to control of goaldirected hand movements. We show that unilateral lesions, by unbalancing the cooperation of the two hemispheres, can alter the choice of hand selected to accomplish movements

The X-ray outburst of the Galactic Center magnetar over six years of Chandra observations

The magnetar SGR J1745-2900 discovered at parsecs distance from the Milky Way central black hole, Sagittarius A*, represents the closest pulsar to a supermassive black hole ever detected. Furthermore, its intriguing radio emission has been used to study the environment of the black hole, as well as to derive a precise position and proper motion for this object. The discovery of SGR J1745-2900 has opened interesting debates about the number, age and nature of pulsars expected in the Galactic center region. In this work, we present extensive X-ray monitoring of the outburst of SGR J1745-2900 using the Chandra X-ray Observatory, the only instrument with the spatial resolution to distinguish the magnetar from the supermassive black hole (2.4" angular distance). It was monitored from its outburst onset in April 2013 until August 2019, collecting more than fifty Chandra observations for a total of more than 2.3 Ms of data. Soon after the outburst onset, the magnetar emission settled onto a purely thermal emission state that cooled from a temperature of about 0.9 to 0.6 keV over 6 years. The pulsar timing properties showed at least two changes in the period derivative, increasing by a factor of about 4 during the outburst decay. We find that the long-term properties of this outburst challenge current models for the magnetar outbursts.Comment: 11 pages, 6 figures. Accepted by Ap

A strongly magnetized pulsar within grasp of the Milky Way's supermassive black hole

The center of our Galaxy hosts a supermassive black hole, Sagittarius (Sgr) A*. Young, massive stars within 0.5 pc of SgrA* are evidence of an episode of intense star formation near the black hole a few Myr ago, which might have left behind a young neutron star traveling deep into SgrA*'s gravitational potential. On 2013 April 25, a short X-ray burst was observed from the direction of the Galactic center. Thanks to a series of observations with the Chandra and the Swift satellites, we pinpoint the associated magnetar at an angular distance of 2.4+/-0.3 arcsec from SgrA*, and refine the source spin period and its derivative (P=3.7635537(2) s and \dot{P} = 6.61(4)x10^{-12} s/s), confirmed by quasi simultaneous radio observations performed with the Green Bank (GBT) and Parkes antennas, which also constrain a Dispersion Measure of DM=1750+/-50 pc cm^{-3}, the highest ever observed for a radio pulsar. We have found that this X-ray source is a young magnetar at ~0.07-2 pc from SgrA*. Simulations of its possible motion around SgrA* show that it is likely (~90% probability) in a bound orbit around the black hole. The radiation front produced by the past activity from the magnetar passing through the molecular clouds surrounding the Galactic center region, might be responsible for a large fraction of the light echoes observed in the Fe fluorescence features.Comment: ApJ Letters in pres

CD73 expression and clinical significance in human metastatic melanoma.

CD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target. CD73 expression was detected in TC in 54% of melanoma metastases, involving < 50% TC in the majority of the cases, with variable intensity. CD73 expression was significantly associated with a lower Breslow's depth of the primary lesion and was more frequent in patients having received prior non-surgical therapies. In an adjusted analysis, CD73 expression in TC (H-score > 37.5 or intensity > 1) significantly correlated to decreased overall survival (OS) from biopsy. Of the samples containing TIMC, 35% presented CD73+ TIMC. Highly infiltrated tumors were more likely to contain CD73+ TIMC. CD73 expression in TIMC (percentage ≥1%) significantly correlated with improved OS from biopsy. Immunohistochemistry detected CD73 expression in more than half of metastatic melanomas. While CD73 expression in TC significantly correlated with decreased OS, CD73 expression in TIMC significantly associated with improved OS. These results encourage the study of anti-CD73 therapies for metastatic melanoma patients. CD73 expression was assessed by immunohistochemistry in metastatic melanomas from 114 patients. Immunostainings were evaluated in tumor cells (TC) (percentage, intensity (1-3) and H-score) and in tumor-infiltrating mononuclear cells (TIMC) (percentage)

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

Mirna reference genes in extracellular vesicles released from amniotic membrane-derived mesenchymal stromal cells

Human amniotic membrane and amniotic membrane-derived mesenchymal stromal cells (hAMSCs) have produced promising results in regenerative medicine, especially for the treatment of inflammatory-based diseases and for different injuries including those in the orthopedic field such as tendon disorders. hAMSCs have been proposed to exert their anti-inflammatory and healing potential via secreted factors, both free and conveyed within extracellular vesicles (EVs). In particular, EV miRNAs are considered privileged players due to their impact on target cells and tissues, and their future use as therapeutic molecules is being intensely investigated. In this view, EV-miRNA quantification in either research or future clinical products has emerged as a crucial paradigm, although, to date, largely unsolved due to lack of reliable reference genes (RGs). In this study, a panel of thirteen putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p, miR-660-5p and U6 snRNA) that were identified in different EV types was assessed in hAMSC-EVs. A validated experimental pipeline was followed, sifting the output of four largely accepted algorithms for RG prediction (geNorm, NormFinder, BestKeeper and \u394Ct method). Out of nine RGs constitutively expressed across all EV isolates, miR-101-3p and miR-22-5p resulted in the most stable RGs, whereas miR-423-5p and U6 snRNA performed poorly. miR-22-5p was also previously reported to be a reliable RG in adipose-derived MSC-EVs, suggesting its suitability across samples isolated from different MSC types. Further, to shed light on the impact of incorrect RG choice, the level of five tendon-related miRNAs (miR-29a-3p, miR-135a-5p, miR-146a-5p, miR-337-3p, let-7d-5p) was compared among hAMSC-EVs isolates. The use of miR-423-5p and U6 snRNA did not allow a correct quantification of miRNA incorporation in EVs, leading to less accurate fingerprinting and, if used for potency prediction, misleading indication of the most appropriate clinical batch. These results emphasize the crucial importance of RG choice for EV-miRNAs in hAMSCs studies and contribute to the identification of reliable RGs such as miR-101-3p and miR-22-5p to be validated in other MSC-EVs related fields