Based on the profound biological insights of the last years into the molecular pathogenesis of mantle cell lymphoma and the clinical introduction of new targeted drugs, with high efficacy and a good ...safety profile, the therapeutic scenario for this tumor has been shown to be thoroughly favourable. No longer characterized by a uniformly dismal prognosis, mantle cell lymphoma has been revealed as a spectrum of different diseases, ranging from very indolent cases to highly aggressive and refractory ones. Thus, there is an urgent need to adapt therapy to accommodate the diverse presentations of the disease. High-dose chemotherapy, followed by autologous stem cell transplantation is the current standard of care for younger patients, generally providing high responses and long survival rates, but hampered by acute and long-term toxicity. In addition, some patients may be overtreated, while others could benefit from targeted approaches, based on the new, molecular-directed compounds. Such a personalized treatment based on the specific characteristics of individual patients may be guided by validated prognostic tools, such as the Mantle Cell Lymphoma International Prognostic Index and the Ki-67 Proliferative Index, as well as by early predictors of treatment response, like minimal residual disease analysis. Moreover, mutation screening of distinctive genomic alterations may provide new, predictive biomarkers, with an additional impact on clinical practice. Only after tailoring treatment according to the clinical and biological heterogeneity of the disease the role of transplantation and modern therapeutic options will be redefined in mantle cell lymphoma.
Human herpervirus-8/human immunodeficiency virus negative Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disorder sustained by a pro-inflammatory condition of ...hypercytokinemia mostly mediated by Interleukin-6 (IL-6). According to iMCD consensus guidelines, anti-IL-6 blockade should be the first-line therapy for iMCD. However, despite the existing therapeutic alternatives, a large proportion of iMCD patients still lacks an effective therapy.
Here, we report two real-life iMCD cases with a different response to IL-6 blockade. The first presented patient obtained a prompt resolution of symptoms and a complete regression of adenopathies after IL-6 blockade therapy administration. Conversely, the second patient did not respond neither to Rituximab and Etoposide association nor to IL-6 blockade therapy (both Siltuximab and Tocilizumab). Furthermore, Intravenous immunoglobulin, Cyclosporine A, Sirolimus and anti-Interleukin-1 Anakinra were all attempted without any results. Since no treatment was successful, after a further confirmation of iMCD diagnosis by a second lymph node biopsy, patient has been candidate for thalidomide, cyclophosphamide and prednisone association therapy.
The iMCD cases we reported are coherent with the evidences that IL-6 blockade is a safe and an effective therapy for iMCD. Despite this, more than half of patients do not respond to anti IL-6 drugs. In such cases, therapeutic alternatives could be represented by Sirolimus, targeting PI3K/AKT/mTOR signaling or by associations of conventional drugs such as thalidomide, cyclophosphamide and prednisone. However, the two reported iMCD cases, confirm the need to more deeply investigate iMCD pathogenesis and to better dissect the heterogeneity of the disease in order to develop novel, effective therapeutic strategies.
To explore the psychological status of infertile women and men who had in-vitro fertilization (IVF) treatment interrupted or postponed because of the COVID-19 emergency.
An electronic survey ...(NCT04395755) was e-mailed between April and June 2020 to couples whose IVF treatments have been interrupted or postponed due to the COVID-19 pandemic. The presence and severity of symptoms suggestive of anxiety and/or depression were assessed using the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Subjects with preexisting psychiatric disorders were excluded.
Overall, 524 out of 646 patients completed the survey. The prevalence of anxiety and/or depression feelings was significantly higher in women, mainly if aged more than 35 years and with a previous IVF attempt. The occurrence of these psychological symptoms was significantly associated with the time spent on COVID-19 related news per day and partner with evidence of psychological disorder and, in females, with a diagnosis of poor ovarian reserve, diagnosis of endometriosis or uterine fibroids.
The psychological impact of the COVID-19 pandemic on the infertile couples who should have undergone IVF treatment has been significant. IVF centers should systematically offer these couples adequate psychological counseling to improve mental health.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. ...Nevertheless, a proportion of MCL patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in MCL, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective
(high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of
and disruption of
by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding
mutations and
disruption to the MIPI-c backbone, we derived a new prognostic index, the "MIPI-genetic" ("MIPI- g"). The "MIPI-g" improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-year progression free survival and overall survival of 72.0% and 94.5%); ii) inter-mediate-risk patients (4-year progression free survival and overall survival of 42.2% and 65.8%) and iii) high-risk patients (4-year progression free survival and overall survival of 11.5% and 44.9%). Our results: i) confirm that
disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring
mutations share the same poor outcome as patients harboring
disruption; and iii) allow to develop a tool for the identification of high-risk MCL patients for whom novel therapeutic strategies need to be investigated. (
).
Introduction: Scientific evidence on subjects treated with statin or other lipid-lowering treatments has established that treatments aiming to lower low-density lipoprotein cholesterol (LDL-C) can ...reduce atherosclerosis. PCSK9 inhibitors (PCSK9-i), thanks to their efficacy in reducing LDL-C constitute a further step in the treatment of dyslipidemia and cardiovascular (CV) diseases.
Areas covered: The purpose of this narrative review is to summarize the current knowledge of PCSK9-i, with particular regard to pharmacodynamic, pharmacokinetic, and clinical data on evolocumab and alirocumab.
Expert opinion: PCSK9-I are effective in reducing atherosclerotic events through their significant LDL-C-lowering action similarly to statins. Furthermore, these drugs can be considered safe and well-tolerated. However, some controversies remain with regard to their efficacy in reducing mortality and the paucity of data on both pleiotropic effects and long-term safety of these drugs. However, future studies will focus on understanding the effects of very low cholesterol levels on health. At present, we know that the genetic model of PCSK9 deficiency is characterized by very low LDL-C levels without particular health problems. Yet, we do not know the effect of prolonged PCSK9 inhibition induced by antibody action during the lifetime of normal subjects.
Sentinel node mapping (SLNM) has replaced lymphadenectomy for staging surgery in apparent early-stage endometrial cancer (EC). Here, we evaluate long-term survival of three different approaches of ...nodal assessment in EC.
This is a multi-institutional retrospective study evaluating long-term outcomes (at least 3 years) of EC patients having lymphadenectomy, SLNM followed by lymphadenectomy and SLNM alone. In order to reduce possible confounding factors we applied a propensity-matched algorithm. Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard models.
Applying a propensity score matching algorithm we selected 180 patients having SLNM (90 SLNM vs. 90 SLNM followed by lymphadenectomy). Additionally, a control group of 180 patients having lymphadenectomy was selected using the same criteria. Overall, 10% of patients were diagnosed with positive nodes. Low volume disease was observed in 16 cases (5 micrometastasis and 11 isolated tumor cells). Patients having SLNM followed by lymphadenectomy had a higher possibility to be diagnosed with a stage IIIC disease in comparison to lymphadenectomy alone (p=0.02); while we did not observe difference in the diagnostic value of SLNM followed by lymphadenectomy and SLNM (p=0.389). Median follow-up time was 69 months (range, 7–206). The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p=0.570, log-rank test) and overall survival (p=0.911, log-rank test); Similarly, they did not impact on survival outcomes after stratification by low, intermediate and high risk patients.
Our study highlighted that SLNM provides similar long-term oncologic outcomes than lymphadenectomy. Further evidence is warranted to assess the prognostic value of low-volume disease detected by ultrastaging in patients following SLNM.
•Sentinel node mapping allows a more accurate identification of patients with nodal disease compared to lymphadenectomy.•Patients having sentinel node mapping experience similar outcomes than patients having lymphadenectomy.•Even in high-risk group sentinel node mapping ensures the oncologic safety of lymphadenectomy.
Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. ...Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+).
This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models.
Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with 5-year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001).
HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.
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•HPV persistence correlates with an increased risk of 5-year recurrence in women undergoing cervical conization•Patients undergoing laser conization experience a slightly lower risk of recurrence in comparison to LEEP•Further evidence regarding fertility and obstetrical issues is necessary
Lynch syndrome (LS) is a hereditary condition associated with an increased risk of colorectal and endometrial cancer. This study aimed to assess the knowledge, attitudes, and beliefs of women with LS ...regarding combined hormonal contraceptive (CHC) use compared to a control group of healthy women.OBJECTIVELynch syndrome (LS) is a hereditary condition associated with an increased risk of colorectal and endometrial cancer. This study aimed to assess the knowledge, attitudes, and beliefs of women with LS regarding combined hormonal contraceptive (CHC) use compared to a control group of healthy women.Pre-menopausal women with LS (n = 43) and an age-matched control group of healthy women (n = 128) participated in this prospective, cross-sectional study (NCT05909410). Participants completed an electronic questionnaire evaluating perceptions of CHC use and its impact on various cancers, medical conditions, and symptoms. Statistical analysis compared responses between the two groups, with reported p-values.METHODSPre-menopausal women with LS (n = 43) and an age-matched control group of healthy women (n = 128) participated in this prospective, cross-sectional study (NCT05909410). Participants completed an electronic questionnaire evaluating perceptions of CHC use and its impact on various cancers, medical conditions, and symptoms. Statistical analysis compared responses between the two groups, with reported p-values.Women with LS were less likely to use CHCs compared to the control group (p = 0.03) and had a more negative perception of CHCs' impact on colorectal cancer (p = 0.023) and endometrial cancer (p = 0.028). Limited knowledge was observed in both groups regarding the protective effects of CHCs against colorectal and ovarian cancer. Perceptions of CHC use and its impact on symptoms and chronic diseases did not significantly differ between the groups (p > 0.05). CHC use was not associated with greater awareness of the protective effect against colorectal (p = 0.89) and endometrial cancer (p = 0.47), but it was associated with a desire for contraception (OR 21.25; 95% CI 1.16 to 388.21; p = 0.039).RESULTSWomen with LS were less likely to use CHCs compared to the control group (p = 0.03) and had a more negative perception of CHCs' impact on colorectal cancer (p = 0.023) and endometrial cancer (p = 0.028). Limited knowledge was observed in both groups regarding the protective effects of CHCs against colorectal and ovarian cancer. Perceptions of CHC use and its impact on symptoms and chronic diseases did not significantly differ between the groups (p > 0.05). CHC use was not associated with greater awareness of the protective effect against colorectal (p = 0.89) and endometrial cancer (p = 0.47), but it was associated with a desire for contraception (OR 21.25; 95% CI 1.16 to 388.21; p = 0.039).This study highlights contrasting perceptions of CHCs and their implications in oncology between women with LS and healthy women. Tailored counselling and support strategies are crucial for empowering women with LS to make informed decisions about their gynaecologic health.CONCLUSIONThis study highlights contrasting perceptions of CHCs and their implications in oncology between women with LS and healthy women. Tailored counselling and support strategies are crucial for empowering women with LS to make informed decisions about their gynaecologic health.
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