28 research outputs found
High-intensity focused ultrasound in prostate cancer: Today's outcomes and tomorrow's perspectives
No full textHigh-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied for prostate cancer that capitalizes on the coagulation necrosis that occurs at temperatures greater than 60°C. Owing to a lack of long-term follow-up data the procedure is still considered experimental treatment. As primary therapy, HIFU is indicated in patients aged ≥70 years with clinical organ-confined disease, although it has also been used, with encouraging results, as first line salvage therapy after definitive treatment, and in locally advanced (T3-4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated with this treatment method appears to be low and includes urinary retention (1-9%), urethral stricture (4-14%), incontinence (1-15%), erectile dysfunction (13-53%) and rectourethral fistulae (0-3%). The risk of complications increases with repeated treatments. A few studies have recently been published on HIFU as focal therapy. HIFU technology can be enhanced using means such as ultrasound microbubble contrast agents for assessment of therapy efficacy, magnetic resonance imaging to guide the enhancement of heat rate, and localized drug and gene deliver
The Association Between Childhood Trauma, Emotional Dysregulation, and Depressive Symptoms’ Severity in Patients with Obesity Seeking Bariatric Surgery
No full textBackground: Patients with obesity seeking bariatric surgery often display high rates of depressive symptoms, which are linked to worse clinical and surgical outcomes. A comprehensive evaluation of depression-related features in this population is lacking. Therefore, this study investigated clinical and psychopathological factors associated with depressive symptoms’ severity in 946 outpatients with obesity undergoing pre-surgical evaluation. Methods: The sample (45.1 ± 12 years) was subdivided according to Patient Health Questionnaire-9 (PHQ-9) into ‘absent’, ‘mild’, and ‘moderate-to-severe depression’ groups, which were compared for sociodemographic characteristics, childhood trauma, and emotional dysregulation. Assessments included the Childhood Trauma Questionnaire-Short-Form (CTQ-SF) and Difficulties in Emotion Regulation Scales (DERS). Inflammatory levels were evaluated through the Systemic Immune-inflammatory Index (SII). Multinomial logistic regression and correlations were performed to evaluate predictors of depression severity and their interrelationship. Results: Beyond sociodemographic and clinical differences, patients with moderate-to-severe depression displayed higher childhood trauma, emotional dysregulation, and inflammatory levels. Logistic regression with 95% confidence intervals showed that higher CTQ-SF scores were significantly associated with moderate-to-severe vs. absent depression (p = 0.005, 95% CI: 1.02–1.09), while elevated DERS scores were a risk factor for both moderate-to-severe vs. mild (p < 0.001, 95% CI: 1.04–1.11) and vs. absent depression (p < 0.001, 95% CI: 1.11–1.18). Additionally, PHQ-9 was significantly correlated with CTQ-SF, DERS, and SII. Conclusions: A worse clinical picture was observed in patients with moderate-to-severe depression, and significant interactions were found between psychopathology and inflammatory indexes. Emotional dysregulation was primarily associated with depression severity. These preliminary results support the implementation of rigorous pre-operative screening to identify and deliver targeted psychotherapeutic/pharmacological interventions aimed at improving clinical and post-surgical outcomes
Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner
No full textHematopoietic stem cells (HSCs) residing in specialized niches in the bone marrow are responsible for the balanced output of multiple short-lived blood cell lineages in steady-state and in response to different challenges. However, feedback mechanisms by which HSCs, through their niches, sense acute losses of specific blood cell lineages remain to be established. While all HSCs replenish platelets, previous studies have shown that a large fraction of HSCs are molecularly primed for the megakaryocyte-platelet lineage and are rapidly recruited into proliferation upon platelet depletion. Platelets normally turnover in an activation-dependent manner, herein mimicked by antibodies inducing platelet activation and depletion. Antibody-mediated platelet activation upregulates expression of Interleukin-1 (IL-1) in platelets, and in bone marrow extracellular fluid in vivo. Genetic experiments demonstrate that rather than IL-1 directly activating HSCs, activation of bone marrow Lepr+ perivascular niche cells expressing IL-1 receptor is critical for the optimal activation of quiescent HSCs upon platelet activation and depletion. These findings identify a feedback mechanism by which activation-induced depletion of a mature blood cell lineage leads to a niche-dependent activation of HSCs to reinstate its homeostasis
Introductions to the Community: Early-Career Researchers in the Time of COVID-19
No full textCOVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers
SICOB-endorsed national Delphi consensus on obesity treatment optimization: focus on diagnosis, pre-operative management, and weight regain/insufficient weight loss approach
No full textPurpose: Overweight and obesity affects 60% of adults causing more than 1.2 million deaths across world every year. Fight against involved different specialist figures and multiple are the approved weapons. Aim of the present survey endorsed by the Italian Society of Bariatric Surgery (SICOB) is to reach a national consensus on obesity treatment optimization through a Delphi process. Methods: Eleven key opinion leaders (KOLs) identified 22 statements with a major need of clarification and debate. The explored pathways were: (1) Management of patient candidate to bariatric/metabolic surgery (BMS); (2) Management of patient not eligible for BMS; (3) Management of patient with short-term (2 years) weight regain (WR) or insufficient weight loss (IWL); (4) Management of the patient with medium-term (5 years) WR; and (5) Association between drugs and BMS as WR prevention. The questionnaire was distributed to 65 national experts via an online platform with anonymized results. Results: 54 out of 65 invited panelists (83%) respond. Positive consensus was reached for 18/22 statements (82%); while, negative consensus (s20.4; s21.5) and no consensus (s11.5, s17) were reached for 2 statements, respectively (9%). Conclusion: The Delphi results underline the importance of first-line interdisciplinary management, with large pre-treatment examination, and establish a common opinion on how to properly manage post-operative IWL/WR. Level of evidence V: Report of expert committees
Body Image in Bariatric surgery candidates
No full textIntroductionBody image is a multidimensional concept that has assumed a significant role in eating disorders in which affective and perceptual distortions have been documented. Obesity is not a psychiatric disorder according to DSM-5 but several studies highlighted the presence of body image diseases in obesity.ObjectivesThe aim of this work is to evaluate the presence of body uneasiness in obese seeking for Bariatric surgery and to correlate it with psychopathological symptoms, psychosocial and anamnestic variables.MethodsFrom June 2014 to June 2016, we enrolled 537 Bariatric surgery candidates. Body image was investigated using the Body Uneasiness Test (BUT-A), a 34-item self-report questionnaire which measures weight phobia (WP), body image concerns (BIC), avoidance (A), compulsive self-monitoring (CSM), detachment and depersonalization (D). Psychopathological symptoms and personality traits have been evaluated using SCL90R and MMPI-2.ResultsDescriptive analyzes showed that BUT subscales were altered in most of our sample. Correlations of Pearson underlined significant associations between BUT subscales and SCL90R subscales. No correlation was found between BMI, marital status and BUT scores, while young, female and unemployed people had more difficulties with body.ConclusionsOur data highlight the presence of considerable body uneasiness in obese, correlated with the severity of psychiatric symptoms but independent from the severity of obesity. This seems to reflect the mind-body split detected both in obesity and in eating disorders. Therefore, a multidisciplinary integrated approach including psychological work on cognitive, emotional and perceptual aspects of body image will help patients to improve coping with corporeal changes achieved through surgery.Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec
Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency
No full textDefects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8 + T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8 + lymphoblasts had reduced interferon-γ secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL
Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.
No full textEvidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation
