Is it safe to perform controlled ovarian stimulation (COS) for fertility preservation before starting anticancer therapies or ART after treatments in young breast cancer patients?
Performing COS ...before, or ART following anticancer treatment in young women with breast cancer does not seem to be associated with detrimental prognostic effect in terms of breast cancer recurrence, mortality or event-free survival (EFS).
COS for oocyte/embryo cryopreservation before starting chemotherapy is standard of care for young women with breast cancer wishing to preserve fertility. However, some oncologists remain concerned on the safety of COS, particularly in patients with hormone-sensitive tumors, even when associated with aromatase inhibitors. Moreover, limited evidence exists on the safety of ART in breast cancer survivors for achieving pregnancy after the completion of anticancer treatments.
The present systematic review and meta-analysis was carried out by three blinded investigators using the keywords 'breast cancer' and 'fertility preservation'; keywords were combined with Boolean operators. Eligible studies were identified by a systematic literature search of Medline, Web of Science, Embase and Cochrane library with no language or date restriction up to 30 June 2021.
To be included in this meta-analysis, eligible studies had to be case-control or cohort studies comparing survival outcomes of women who underwent COS or ART before or after breast cancer treatments compared to breast cancer patients not exposed to these strategies. Survival outcomes of interest were cancer recurrence rate, relapse rate, overall survival and number of deaths. Adjusted relative risk (RR) and hazard ratio (HR) with 95% CI were extracted. When the number of events for each group were available but the above measures were not reported, HRs were estimated using the Watkins and Bennett method. We excluded case reports or case series with <10 patients and studies without a control group of breast cancer patients who did not pursue COS or ART. Quality of data and risk of bias were assessed using the Newcastle-Ottawa Assessment Scale.
A total of 1835 records were retrieved. After excluding ineligible publications, 15 studies were finally included in the present meta-analysis (n = 4643). Among them, 11 reported the outcomes of breast cancer patients who underwent COS for fertility preservation before starting chemotherapy, and 4 the safety of ART following anticancer treatment completion. Compared to women who did not receive fertility preservation at diagnosis (n = 2386), those who underwent COS (n = 1594) had reduced risk of recurrence (RR 0.58, 95% CI 0.46-0.73) and mortality (RR 0.54, 95% CI 0.38-0.76). No detrimental effect of COS on EFS was observed (HR 0.76, 95% CI 0.55-1.06). A similar trend of better outcomes in terms of EFS was observed in women with hormone-receptor-positive disease who underwent COS (HR 0.36, 95% CI 0.20-0.65). A reduced risk of recurrence was also observed in patients undergoing COS before neoadjuvant chemotherapy (RR 0.22, 95% CI 0.06-0.80). Compared to women not exposed to ART following completion of anticancer treatments (n = 540), those exposed to ART (n = 123) showed a tendency for better outcomes in terms of recurrence ratio (RR 0.34, 95% CI 0.17-0.70) and EFS (HR 0.43, 95% CI 0.17-1.11).
This meta-analysis is based on abstracted data and most of the studies included are retrospective cohort studies. Not all studies had matching criteria between the study population and the controls, and these criteria often differed between the studies. Moreover, rate of recurrence is reported as a punctual event and it is not possible to establish when recurrences occurred and whether follow-up, which was shorter than 5 years in some of the included studies, is adequate to capture late recurrences.
Our results demonstrate that performing COS at diagnosis or ART following treatment completion does not seem to be associated with detrimental prognostic effect in young women with breast cancer, including among patients with hormone receptor-positive disease and those receiving neoadjuvant chemotherapy.
Partially supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC; grant number MFAG 2020 ID 24698) and the Italian Ministry of Health-5 × 1000 funds 2017 (no grant number). M.L. acted as consultant for Roche, Pfizer, Novartis, Lilly, AstraZeneca, MSD, Exact Sciences, Gilead, Seagen and received speaker honoraria from Roche, Pfizer, Novartis, Lilly, Ipsen, Takeda, Libbs, Knight, Sandoz outside the submitted work. F.S. acted as consultant for Novartis, MSD, Sun Pharma, Philogen and Pierre Fabre and received speaker honoraria from Roche, Novartis, BMS, MSD, Merck, Sun Pharma, Sanofi and Pierre Fabre outside the submitted work. I.D. has acted as a consultant for Roche, has received research grants from Roche and Ferring, has received reagents for academic clinical trial from Roche diagnostics, speaker's fees from Novartis, and support for congresses from Theramex and Ferring outside the submitted work. L.D.M. reported honoraria from Roche, Novartis, Eli Lilly, MSD, Pfizer, Ipsen, Novartis and had an advisory role for Roche, Eli Lilly, Novartis, MSD, Genomic Health, Pierre Fabre, Daiichi Sankyo, Seagen, AstraZeneca, Eisai outside the submitted work. The other authors declare no conflict of interest. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.
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We present a comprehensive review and outlook of silicon carbide (SiC) and gallium nitride (GaN) transistors available on the market for current and next-generation power electronics. Material ...properties and structural differences among GaN and SiC devices are first discussed. Based on the analysis of different commercially available GaN and SiC power transistors, we describe the state-of-the-art of these technologies, highlighting the preferential power conversion topologies and the key characteristics of each technological platform. Current and future fields of application for GaN and SiC devices are also reviewed. The article also reports on the main reliability aspects related to both technologies. For GaN HEMTs, threshold voltage stability, dynamic ON-resistance, and breakdown limitation are described, whereas for SiC MOSFETs the analysis also focuses on gate oxide failure and short-circuit (SC) robustness. Finally, we give an overview on the perspective of such materials in different fields of interest. An indication of possible future improvements and developments for both technologies is drawn. The requirements for hybrid converters, along with a careful optimization of performance and the use of innovative optimization tools, are underlined.
The perceived intensity of an intense stimulus as well as the startle reflex it elicits can both be reduced when preceded by a weak stimulus (prepulse). Both phenomena are used to characterise the ...processes of sensory gating in clinical and non-clinical populations. The latter phenomenon, startle prepulse inhibition (PPI), is conceptualised as a measure of pre-attentive sensorimotor gating due to its observation at short latencies. In contrast, the former, prepulse inhibition of perceived stimulus intensity (PPIPSI), is believed to involve higher-order cognitive processes (e.g., attention), which require longer latencies. Although conceptually distinct, PPIPSI is often studied using parameters that elicit maximal PPI, likely limiting what we can learn about sensory gating’s influence on conscious perception. Here, we tested an array of stimulus onset asynchronies (SOAs; 0–602 ms) and prepulse intensities (0–3× perceptual threshold) to determine the time course and sensitivity to the intensity of electrotactile PPIPSI. Participants were required to compare an ‘unpleasant but not painful’ electric pulse to their left wrist that was presented alone with the same stimulus preceded by an electric prepulse, and report which pulse stimulus felt more intense. Using a 2× perceptual threshold prepulse, PPIPSI emerged as significant at SOAs from 162 to 602 ms. We conclude that evidence of electrotactile PPIPSI at SOAs of 162 ms or longer is consistent with gating of perception requiring higher-level processes, not measured by startle PPI. The possible role of attentional processes, stimuli intensity, modality-specific differences, and methods of investigating PPIPSI further are discussed.
Hearing loss is the most frequent sensorineural disorder affecting 1 in 1000 newborns. In more than half of these babies, the hearing loss is inherited. Hereditary hearing loss is a very ...heterogeneous trait with about 100 gene localizations and 44 gene identifications for non‐syndromic hearing loss. Transmembrane channel‐like gene 1 (TMC1) has been identified as the disease‐causing gene for autosomal dominant and autosomal recessive non‐syndromic hearing loss at the DFNA36 and DFNB7/11 loci, respectively. To date, 2 dominant and 18 recessive TMC1 mutations have been reported as the cause of hearing loss in 34 families. In this report, we describe linkage to DFNA36 and DFNB7/11 in 1 family with dominant and 10 families with recessive non‐syndromic sensorineural hearing loss. In addition, mutation analysis of TMC1 was performed in 51 familial Turkish patients with autosomal recessive hearing loss. TMC1 mutations were identified in seven of the families segregating recessive hearing loss. The pathogenic variants we found included two known mutations, c.100C>T and c.1165C>T, and four new mutations, c.2350C>T, c.776+1G>A, c.767delT and c.1166G>A. The absence of TMC1 mutations in the remaining six linked families implies the presence of mutations outside the coding region of this gene or alternatively at least one additional deafness‐causing gene in this region. The analysis of copy number variations in TMC1 as well as DNA sequencing of 15 additional candidate genes did not reveal any proven pathogenic changes, leaving both hypotheses open.
The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial. Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly assigned to 2 experimental protocols: ...(1) rats were killed before (−24 h, n = 8) and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg/kg body weight) to determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX (4 mg/kg body weight/week) and were killed before the first injection (M0) and 1 week after each injection (M1, M2, M3, and M4) to determine the chronological effects. Animals used at M0 (n = 8) were also used at moment −24 h of acute study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology analyses were carried out at each time point. Single dose of DOX was associated with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed an effect of a cumulative dose on body weight (R = −0.99, p = 0.011), necrosis (R = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = −0.95, p = 0.049). DNA SBs damage was negatively associated with TAP (R = −0.98, p = 0.018), and necrosis (R = −0.97, p = 0.027). Our results suggest that oxidative damage is associated with acute cardiotoxicity induced by a single dose of DOX only. Increased resistance to the oxidative stress is plausible for the multiple dose of DOX. Thus, different mechanisms may be involved in acute toxicity versus chronic toxicity.
A weak stimulus presented immediately before a more intense one reduces both the N1-P2 cortical response and the perceived intensity of the intense stimulus. The former effect is referred to as ...cortical prepulse inhibition (PPI), the latter as prepulse inhibition of perceived stimulus intensity (PPIPSI). Both phenomena are used to study sensory gating in clinical and non-clinical populations, however little is known about their relationship. Here, we investigated 1) the possibility that cortical PPI and PPIPSI are associated, and 2) how they are affected by attentional load. Participants were tasked with comparing the intensity of an electric pulse presented alone versus one preceded 200 ms by a weaker electric prepulse (Experiment 1), or an acoustic pulse presented alone with one preceded 170 ms by a weaker acoustic prepulse (Experiment 2). A counting task (easy vs. hard) manipulating attentional load was included in Experiment 2. In both experiments, we observed a relationship between N1-P2 amplitude and perceived intensity, where greater cortical PPI was associated with a higher probability of perceiving the ‘pulse with prepulse’ as less intense. Moreover, higher attentional load decreased observations of PPIPSI but had no effect on N1-P2 amplitude. Based on the findings we propose that PPIPSI partially relies on the allocation of attentional resources towards monitoring cortical channels that process stimulus intensity characteristics such as the N1-P2 complex.
•PPI and PPIPSI reflect sensory gating.•Attention reduces PPIPSI but not cortical responses (N1-P2 complex).•Perceptual decisions depend on attention to cortical channels.
Several mechanisms may contribute to the degradation of GaN transistors; in this paper we discuss the main processes that limit the lifetime of GaN power devices, with focus on the following relevant ...aspects: (i) the degradation/breakdown induced by off-state bias; (ii) the origin of vertical leakage and breakdown; (iii) the failure of the gate stack in MIS-HEMTs and in transistors with p-type gate. The data reviewed in this paper help the reader understanding the main issues related to the development of GaN-based transistors, and give hints on possible strategies to improve device reliability. The signatures of the main deep levels in gallium nitride, which can influence the reliability of the devices, are critically reviewed and summarized.
The aim of the present study was to evaluate DNA damage (micronucleus) in cytokinesis-blocked lymphocytes and exfoliated buccal mucosa cells from children with malignant tumours and under ...chemotherapy. Micronucleated cells (MNCs) were assessed from children before and during chemotherapy. A total of 21 healthy children (controls), matched for gender and age, were used as control. The results pointed out higher frequencies of micronucleated lymphocytes in children with malignant tumour before any therapy when compared to healthy probands. Furthermore an increase of micronucleated lymphocytes during chemotherapy was detected when compared to the data obtained before chemotherapy. No statistically significant increases of MNCs were noticed in buccal mucosa cells at any of the timepoints evaluated. Taken together, these data indicate that the presence of malignant tumours may increase the frequency of DNA damage in circulating lymphocytes, these cells being more sensitive for detecting chromosome aberrations caused by anti-cancer drugs.
Toenail fungal infections account for half of all nail disease cases, and a highly negative impact on patient quality of life. Our aim was to compare the efficacy and safety of commercially available ...oral antifungals for onychomycosis.
A systematic review was performed in PubMed and Scopus. Randomized controlled trials evaluating the effect of oral antifungals on mycological cure, discontinuation and adverse events were included. Network meta-analyses were built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals (CrI). Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA).
We included 40 trials (n = 9568). Albaconazole 400 mg (OR 0.02 95% CrI 0.01-0.07 versus placebo), followed by posaconazole 200-400 mg and terbinafine 250-350 mg were considered the best therapies (SUCRA probabilities over 75%). For the networks of discontinuation and individual adverse events, few significant differences among treatments were observed, but itraconazole 400 mg was considered the safest drug (SUCRA around 25%). Albaconazole 400 mg, posaconazole 200-400 mg, and terbinafine 250-350 mg were the most effective therapies for onychomycosis, while itraconazole 400 mg was the safest.
The profile of albaconazole and posaconazole compared to current first-line therapies should be further investigated in well-designed trials.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Although haemolytic factor is known to be a putative virulence factor contributing to pathogenicity in Candida species, its production by Candida tropicalis is poorly understood. In this ...study, we analysed the culture conditions under which C. tropicalis can display haemolytic factor on plate assay and the secretion of haemolytic factor in liquid medium by clinical isolates obtained from different specimens. All the tested isolates exhibited an internal translucent ring, resembling beta‐haemolysis, surrounding by a peripheral greenish‐grey halo on sheep blood agar medium. Similar haemolytic pattern was observed on human blood enriched medium. Furthermore, incubation either under normal atmosphere or under increased CO2 had no effect on haemolysis. Overall, no differences were observed on beta‐haemolytic activities (P > 0.05) among tested isolates of C. tropicalis. In glucose‐limited medium (RPMI 1640 with 0.2% glucose), none of the isolates induced haemolysis on red blood cells. Similarly to found on plate assays, there were no significant differences (P > 0.05) in the activity of secreted haemolytic factor in liquid medium among C. tropicalis isolates. However, after growth, the number of yeast cells varied among isolates revealing different efficiencies of haemolytic factor production. Haemolytic activity was neither inhibited by heat treatment (100 °C) nor by the addition of pepstatin A. The obtained results extend our knowledge about haemolytic factor production by Candida species.
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