Deferred
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Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients with transplant-ineligible or transplant-deferred NDMM were randomly assigned to eight cycles of D-VRd or VRd followed by D-Rd or Rd until progression. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10-5 by next-generation sequencing. Major secondary endpoints included complete response (CR) or better (≥CR) rate, progression-free survival and sustained MRD-negativity rate at 10-5. At a median follow-up of 58.7 months, the MRD-negativity rate was 60.9% with D-VRd versus 39.4% with VRd (odds ratio, 2.37; 95% confidence interval (CI), 1.58-3.55; P < 0.0001). Rates of ≥CR (81.2% versus 61.6%; P < 0.0001) and sustained MRD negativity (≥12 months; 48.7% versus 26.3%; P < 0.0001) were significantly higher with D-VRd versus VRd. Risk of progression or death was 43% lower for D-VRd versus VRd (hazard ratio, 0.57; 95% CI, 0.41-0.79; P = 0.0005). Adverse events were consistent with the known safety profiles for daratumumab and VRd. Combining daratumumab with VRd produced deeper and more durable MRD responses versus VRd alone. The present study supports D-VRd quadruplet therapy as a new standard of care for transplant-ineligible or transplant-deferred NDMM. ClinicalTrials.gov registration: NCT03652064 .
- MeSH
- bortezomib * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- dexamethason * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- lenalidomid * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * farmakoterapie diagnóza mortalita patologie MeSH
- monoklonální protilátky * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- reziduální nádor MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- bortezomib * MeSH
- daratumumab MeSH Prohlížeč
- dexamethason * MeSH
- lenalidomid * MeSH
- monoklonální protilátky * MeSH
BACKGROUND: The loss or mutilation of a breast as a result of surgical treatment of neoplastic disease always represents a negative impact on a woman's psyche and negatively influences the quality of the woman's remaining life. The goal of our work was to implement deferred breast reconstruction into routine practice and the objectification of the influence of reconstruction on bodily integrity, quality of life, and the feeling of satisfaction in women. METHODS AND RESULTS: Women in remission from neoplastic disease after a radical mastectomy were indicated for breast reconstruction. Between January 2002 and December 2011 deferred breast reconstruction was carried out 174 × on 163 women, with an average age of 49.2 and an age range of 29-67 years. The most frequently used reconstruction method was a simple gel augmentation of the breast or a Becker expander/implant - 51 (29.3%) and 37 (21.3%), or in combination with a lateral thoracodorsal flap (31; 17.8% and 47; 27%); reconstruction using a free DIEP flap was carried out 7 × (4%). Complications occurred in 19 operations (10.9%) with a dominance of inflammation and pericapsular fibrosis, in a subjective analysis, satisfaction with the results prevailed, along with an increased quality of life after reconstruction. CONCLUSION: A growing number of deferred breast reconstructions, women's satisfaction with the results, the positive influence of renewed bodily integrity on the feeling of life satisfaction and the quality of life have elevated breast reconstructions to a qualitatively higher level.
- MeSH
- časové faktory MeSH
- chirurgické laloky MeSH
- dospělí MeSH
- implantace prsní náhrady metody MeSH
- kvalita života * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mamoplastika metody psychologie MeSH
- mastektomie metody psychologie MeSH
- nádory prsu chirurgie MeSH
- senioři MeSH
- spokojenost pacientů * MeSH
- tkáňové expandéry MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- akutní nemoc MeSH
- časové faktory MeSH
- cholecystektomie * MeSH
- lidé MeSH
- metody MeSH
- nemoci žlučníku chirurgie MeSH
- odpočinek MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Radical nephroureterectomy (RNU) with bladder cuff excision is a standard of care in patients with high-risk upper tract urothelial carcinoma (UTUC). Although several recommendations and guidelines on the delayed treatment of urologic cancers exist, the evidence on UTUC is scarce and ambiguous. The present systematic review aimed to summarize the available evidence on the survival outcomes after deferred RNU in patients with UTUC. A systematic literature search of the three electronic databases (PubMed, Embase, and Cochrane Library) was conducted until 30 April 2022. Studies were found eligible if they reported the oncological outcomes of patients treated with deferred RNU compared to the control group, including those patients treated with RNU without delay. Primary endpoints were cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In total, we identified seven eligible studies enrolling 5639 patients. Significant heterogeneity in the definition of "deferred RNU" was found across the included studies. Three out of five studies reporting CSS showed that deferring RNU was associated with worse CSS. Furthermore, three out of four studies reporting OS found a negative impact of delay in RNU on OS. One out of three studies reporting RFS found a negative influence of delayed RNU on RFS. While most studies reported a 3 month interval as a significant threshold for RNU delay, some subgroup analyses showed that a safe delay for RNU was less than 1 month in patients with ureteral tumors (UT) or less than 2 months in patients with hydronephrosis. In conclusion, long surgical waiting time for RNU (especially more than 3 months after UTUC diagnosis) could be considered as an important risk factor having a negative impact on oncological outcomes in patients with UTUC; however, the results of the particular studies are still inconsistent. The safe delay for RNU might be shorter in specific subsets of high-risk patients, such as those with UT and/or hydronephrosis at the time of diagnosis. High-quality additional studies are required to establish evidence for valid recommendations.
- Klíčová slova
- deferred, delay, oncological outcomes, radical nephroureterectomy, upper tract urothelial carcinoma,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: To summarize the available evidence on the survival and pathologic outcomes after deferred radical prostatectomy (RP) in men with intermediate- and high-risk prostate cancer (PCa). METHODS: The PubMed database and Web of Science were searched in November 2020 according to the PRISMA statement. Studies were deemed eligible if they reported the survival and pathologic outcomes of patients treated with deferred RP for intermediate- and high-risk PCa compared to the control group including those patients treated with RP without delay. RESULTS: Overall, nineteen studies met our eligibility criteria. We found a significant heterogeneity across the studies in terms of definitions for delay and outcomes, as well as in patients' baseline clinicopathologic features. According to the currently available literature, deferred RP does not seem to affect oncological survival outcomes, such as prostate cancer-specific mortality and metastasis-free survival, in patients with intermediate- or high-risk PCa. However, the impact of deferred RP on biochemical recurrence rates remains controversial. There is no clear association of deferring RP with any of the features of aggressive disease such as pathologic upgrading, upstaging, positive surgical margins, extracapsular extension, seminal vesicle invasion, and lymph node invasion. Deferred RP was not associated with the need for secondary treatments. CONCLUSIONS: Owing to the different definitions of a delayed RP, it is hard to make a consensus regarding the safe delay time. However, the current data suggest that deferring RP in patients with intermediate- and high-risk PCa for at least around 3 months is generally safe, as it does not lead to adverse pathologic outcomes, biochemical recurrence, the need for secondary therapy, or worse oncological survival outcomes.
- Klíčová slova
- COVID-19, Deferred, PCa, Prostate cancer, RP, Radical prostatectomy,
- MeSH
- čas zasáhnout při rozvinutí nemoci * MeSH
- lidé MeSH
- míra přežití MeSH
- nádory prostaty mortalita patologie chirurgie MeSH
- prostatektomie * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.
- Klíčová slova
- cytoreductive nephrectomy, deferred nephrectomy, immunotherapy, renal carcinoma, tyrosine kinase inhibitors,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns.
- MeSH
- lidé MeSH
- odložení výhody * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Self-control underlies goal-directed behaviour in humans and other animals. Delayed gratification - a measure of self-control - requires the ability to tolerate delays and/or invest more effort to obtain a reward of higher value over one of lower value, such as food or mates. Social context, in particular, the presence of competitors, may influence delayed gratification. We adapted the 'rotating-tray' paradigm, where subjects need to forgo an immediate, lower-quality (i.e. less preferred) reward for a delayed, higher-quality (i.e. more preferred) one, to test social influences on delayed gratification in two corvid species: New Caledonian crows and Eurasian jays. We compared choices for immediate vs. delayed rewards while alone, in the presence of a competitive conspecific and in the presence of a non-competitive conspecific. We predicted that, given the increased risk of losing a reward with a competitor present, both species would similarly, flexibly alter their choices in the presence of a conspecific compared to when alone. We found that species differed: jays were more likely to select the immediate, less preferred reward than the crows. We also found that jays were more likely to select the immediate, less preferred reward when a competitor or non-competitor was present than when alone, or when a competitor was present compared to a non-competitor, while the crows selected the delayed, highly preferred reward irrespective of social presence. We discuss our findings in relation to species differences in socio-ecological factors related to adult sociality and food-caching (storing). New Caledonian crows are more socially tolerant and moderate cachers, while Eurasian jays are highly territorial and intense cachers that may have evolved under the social context of cache pilfering and cache protection strategies. Therefore, flexibility (or inflexibility) in delay of gratification under different social contexts may relate to the species' social tolerance and related risk of competition.
- MeSH
- cystoskopie MeSH
- cytodiagnostika * MeSH
- hematurie diagnóza MeSH
- karcinogeny MeSH
- lidé středního věku MeSH
- lidé MeSH
- metody MeSH
- nemoci z povolání diagnóza MeSH
- urogenitální nádory diagnóza MeSH
- urografie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- karcinogeny MeSH