Publications by authors named "Elisa Sala"

51 Publications

Structural and compositional analysis of (InGa)(AsSb)/GaAs/GaP Stranski-Krastanov quantum dots.

Light Sci Appl 2021 Jun 15;10(1):125. Epub 2021 Jun 15.

Department of Applied Physics, Eindhoven University of Technology, 5612 AZ, Eindhoven, The Netherlands.

We investigated metal-organic vapor phase epitaxy grown (InGa)(AsSb)/GaAs/GaP Stranski-Krastanov quantum dots (QDs) with potential applications in QD-Flash memories by cross-sectional scanning tunneling microscopy (X-STM) and atom probe tomography (APT). The combination of X-STM and APT is a very powerful approach to study semiconductor heterostructures with atomic resolution, which provides detailed structural and compositional information on the system. The rather small QDs are found to be of truncated pyramid shape with a very small top facet and occur in our sample with a very high density of ∼4 × 10 cm. APT experiments revealed that the QDs are GaAs rich with smaller amounts of In and Sb. Finite element (FE) simulations are performed using structural data from X-STM to calculate the lattice constant and the outward relaxation of the cleaved surface. The composition of the QDs is estimated by combining the results from X-STM and the FE simulations, yielding ∼InGaAsSb, where x = 0.25-0.30 and y = 0.10-0.15. Noticeably, the reported composition is in good agreement with the experimental results obtained by APT, previous optical, electrical, and theoretical analysis carried out on this material system. This confirms that the InGaSb and GaAs layers involved in the QD formation have strongly intermixed. A detailed analysis of the QD capping layer shows the segregation of Sb and In from the QD layer, where both APT and X-STM show that the Sb mainly resides outside the QDs proving that Sb has mainly acted as a surfactant during the dot formation. Our structural and compositional analysis provides a valuable insight into this novel QD system and a path for further growth optimization to improve the storage time of the QD-Flash memory devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41377-021-00564-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203795PMC
June 2021

Tolvaptan in the Management of Acute Euvolemic Hyponatremia After Transsphenoidal Surgery: A Retrospective Single-Center Analysis.

Front Endocrinol (Lausanne) 2021 24;12:689887. Epub 2021 May 24.

Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Introduction: Syndrome of inappropriate antidiuresis (SIAD) can be a complication of hypothalamus-pituitary surgery. The use of tolvaptan in this setting is not well established, hence the primary aim of this study was to assess the sodium correction rates attained with tolvaptan compared with standard treatments (fluid restriction and/or hypertonic saline). Furthermore, we compared the length of hospital stay in the two treatment groups and investigated the occurrence of overcorrection and side effects including osmotic demyelination syndrome.

Methods: We retrospectively reviewed 308 transsphenoidal surgical procedures performed between 2011 and 2019 at our hospital. We selected adult patients who developed post-operative SIAD and recorded sodium monitoring, treatment modalities and outcomes. Correction rates were adjusted based on pre-treatment sodium levels.

Results: Twenty-nine patients (9.4%) developed post-operative SIAD. Tolvaptan was administered to 14 patients (median dose 15 mg). Standard treatments were employed in 14 subjects (fluid restriction n=11, hypertonic saline n=1, fluid restriction and hypertonic saline n=2). Tolvaptan yielded higher adjusted sodium correction rates (12.0 mmolL/24h and 13.4 mmolL/48h) than standard treatments (1.8 mmolL/24h, p<0.001, and 4.5 mmolL/48h, p=0.004, tolvaptan). The correction rate exceeded 10 mmolL/24h or 18 mmolL/48h in 9/14 and 2/14 patients treated with tolvaptan, respectively, and in no patient who received standard treatments. No side effects including osmotic demyelination occurred. Tolvaptan was associated with a shorter hospital stay (1115 days, p=0.01).

Conclusions: Tolvaptan is more effective than fluid restriction (with or without hypertonic saline) and allows for a shortened hospital stay in patients with SIAD after transsphenoidal surgery. However, its dose and duration should be carefully tailored, and close monitoring is recommended to allow prompt detection of overcorrection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.689887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181462PMC
May 2021

Clinical and hormonal findings in patients presenting with high IGF-1 and growth hormone suppression after oral glucose load: a retrospective cohort study.

Eur J Endocrinol 2021 Jul 1;185(2):289-297. Epub 2021 Jul 1.

Endocrinology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Objective: High insulin-like growth factor 1 (IGF-1) and unsuppressed growth hormone (GH) levels after glucose load confirm the diagnosis of acromegaly. Management of patients with conflicting results could be challenging. Our aim was to evaluate the clinical and hormonal evolution over a long follow-up in patients with high IGF-1 but normal GH nadir (GHn < 0.4 μg/L according to the latest guidelines).

Design: Retrospective cohort study.

Methods: We enrolled 53 patients presenting high IGF-1 and GHn < 0.4 μg/L, assessed because of clinical suspicion of acromegaly or in other endocrinological contexts (e.g. pituitary incidentaloma). Clinical and hormonal data collected at the first and last visit were analyzed.

Results: At the first evaluation, the mean age was 54.1 ± 15.4 years, 34/53 were females, median IGF-1 and GHn were +3.1 SDS and 0.06 μg/L, respectively. In the whole group, over a median time of 6 years, IGF-1 and GHn levels did not significantly change (IGF-1 mean of differences: -0.58, P = 0.15; GHn +0.03, P = 0.29). In patients with clinical features of acromegaly, the prevalence of acromegalic comorbidities was higher than in the others (median of 3 vs 1 comorbidities per patient, P = 0.005), especially malignancies (36% vs 6%, P = 0.03), and the clinical worsening overtime was more pronounced (4 vs 1 comorbidities at the last visit).

Conclusions: In patients presenting high IGF-1 but GHn < 0.4 μg/L, a hormonal progression is improbable, likely excluding classical acromegaly in its early stage. However, despite persistently low GH nadir values, patients with acromegalic features present more acromegalic comorbidities whose rate increases over time. Close clinical surveillance of this group is advised.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-21-0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284905PMC
July 2021

Investigational immunotherapy targeting CD19 for the treatment of acute lymphoblastic leukemia.

Expert Opin Investig Drugs 2021 Jul 13;30(7):773-784. Epub 2021 Jul 13.

Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany.

Introduction: The anti-CD19 immunotherapy for the treatment of B-precursor acute lymphoblastic leukemia (B-ALL) underwent an expansion in the last decade. CD19 is widely expressed on B-ALL and nearly ideal for immunotherapy because of strong 'on target' ─ but manageable 'off target' effects.

Areas Covered: We review the major advances in the field, including data on CD19 monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engaging antibodies and adoptive cellular therapies such as chimeric antigen receptor T cells (CAR-Ts). We discuss novel strategies on approved anti-CD19 immunotherapies. The focus is on experimental anti-CD19 antibodies or CAR-Ts, which might overcome the limitations of toxicity, rapid clearance or resistance.

Expert Opinion: The potential of new anti-CD19 antibodies in ALL is limited. The most promising results were achieved with novel cellular constructs. Bi- or multi-specific CAR-Ts might overcome the immune escape by antigen loss. Modified constructs with lower peak expansion or longer persistence provide better control of the toxicity and might improve the efficacy. Finally, the allogeneic 'off the shelf' constructs from healthy donors avoid the time-consuming preparation and the exhaustion of immune cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13543784.2021.1928074DOI Listing
July 2021

Sarcopenia Screening Allows Identifying High-Risk Patients for Allogenic Stem Cell Transplantation.

Cancers (Basel) 2021 Apr 8;13(8). Epub 2021 Apr 8.

Center for Internal Medicine, Division of Sports and Rehabilitation Medicine, Ulm University Medical Center, 89073 Ulm, Germany.

Allogenic stem cell transplantation (aSCT) is the only potentially curative treatment for high-risk hematological diseases. Despite advancements in supportive measures, aSCT outcome is still affected by considerable transplant-related mortality. We implemented a new sarcopenia assessment prior to aSCT to evaluate its predictive capability for all-cause and non-relapse mortality. Therefore all patients initially scheduled for aSCT within a 25-month period were screened during pre-transplantation-routine for muscle mass, grip strength, and aerobic capacity (AC) by measuring peak oxygen uptake (VO2peak). Patients were assigned to one of five groups adapted according current sarcopenia guidelines. Primary endpoints were all-cause and non-relapse mortality within a follow up time of up to 12 months. A total of 178 patients were included and rated as normal ( = 48), impaired aerobic capacity ( = 56), pre-sarcopenic ( = 26), sarcopenic ( = 27), and severe sarcopenic ( = 22) without significant age-differences between groups. Patients presenting with sarcopenia showed a significant three-fold increase in all-cause and non-relapse mortality compared to patients with normal screening results. AC showed to be the strongest single predictor with a more than two-fold increase of mortality for low AC. We conclude that risk stratification based on combination of muscle mass, grip strength, and AC allowed identifying a subgroup with increased risk for complications in patients undergoing aSCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13081771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068111PMC
April 2021

Challenges of Hematopoietic Stem Cell Transplantation in the Era of COVID-19.

Exp Clin Transplant 2021 Feb 24. Epub 2021 Feb 24.

From the Surgery Working Group, Society of Junior Doctors, Athens, Greece.

The coronavirus disease 2019 (COVID-19) pandemic raised unprecedented concerns in the hematopoietic stem cell transplant community. The diagnosis of COVID-19 in these transplant recipients may require extensive laboratory testing and high clinical suspicion, as atypical clinical manifestations or other respiratory viral infections are common in this patient population. The underlying malignancies, immunosuppressed state, frequently observed coinfections, and advanced age in some patients may also predispose them to worse clinical outcomes. Similar outcomes have been previously described with other human coronaviruses, including the severe acute respiratory syndrome coronavirus and the Middle East respiratory syndrome coronavirus. Many hematopoietic stem cell transplant organizations have issued elaborative guidelines that aim to prevent transmission and hence adverse patient outcomes. All potential donors are thoroughly screened, and donated products are cryopreserved in advance. Potential hematopoietic stem cell transplant recipients are also screened, and most nonurgent transplant cases with low risk of progression and/or death are deferred. Current hematopoietic stem cell transplant recipients should adhere to precaution and isolation measures, while their transplant units should also follow strict safety protocols, similar to other infectious outbreaks. The prolonged susceptibility of hematopoietic stem cell transplant recipients to respiratory viral infections might necessitate extending these measures even after the peak of the outbreak until a gradually return to normality is possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6002/ect.2020.0326DOI Listing
February 2021

Pituitary tumors: genetic and molecular factors underlying pathogenesis and clinical behavior.

Neuroendocrinology 2021 Feb 1. Epub 2021 Feb 1.

Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neoplasms. Although generally benign, they can show a clinically aggressive course, with local invasion, recurrences and resistance to medical treatment. No universally accepted biomarkers of aggressiveness are available yet, and predicting clinical behavior of PitNETs remains a challenge. In rare cases the presence of germline mutations in specific genes predisposes to PitNETs formation, as part of syndromic diseases or familial isolated pituitary adenomas (FIPA), and associates to more aggressive, invasive and drug resistant tumors. The vast majority of cases is represented by sporadic PitNETs. Somatic mutations in the  subunit of stimulatory G protein gene (gsp) and in the ubiquitin-specific protease 8 (USP8) gene have been recognized as pathogenetic factors in sporadic GH- and ACTH-secreting PitNETs, respectively, without an association with a worse clinical phenotype. Other molecular factors have been found to significantly affect PitNETs drug responsiveness and invasive behavior. These molecules are cytoskeleton and/or scaffold proteins whose alterations prevent proper functioning of the somatostatin and dopamine receptors, targets of medical therapy, or promote the ability of tumor cells to invade surrounding tissues. The aim of the present review is to provide an overview of the genetic and molecular alterations that can contribute to determine PitNETs clinical behavior. Understanding subcellular mechanisms underlying pituitary tumorigenesis and PitNETs clinical phenotype will hopefully lead to identification of new potential therapeutic targets and new markers predicting the behavior and the response to therapeutic treatments of PitNETs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000514862DOI Listing
February 2021

Vertebral Fractures Associated with Spinal Sagittal Imbalance and Quality of Life in Acromegaly: A Radiographic Study with EOS 2D/3D Technology.

Neuroendocrinology 2021 25;111(8):775-785. Epub 2020 Sep 25.

Endocrinology, Diabetology and Andrology Unit - Metabolic Bone Diseases and Osteoporosis Section, Milan, Italy.

Introduction: Acromegaly is commonly complicated by arthropathy and skeletal fragility with high risk of vertebral fractures (VFs).

Objective: This study aimed to assess whether VFs may be associated with sagittal spine deformities, arthropathy, impaired quality of life (QoL), pain, and disability.

Methods: Thirty-eight patients with acromegaly (median age: 55 years, 20 males) and 38 matched control subjects were evaluated by a low-dose sagittal and coronal planes, X-ray imaging system (EOS®-2D/3D) for morphometric VFs, radiological signs of spine arthropathy, and spine deformities (Cobb thoracic index ≥40°, pelvic incidence minus lumbar lordosis ≥10°, pelvic tilt >20°, and sagittal vertical axis ≥4 cm) determining sagittal spine imbalance. Acromegalic patients were also evaluated by questionnaires for QoL (Acromegaly QoL Questionnaire [AcroQoL] and Short Form-36 [SF-36]) and pain and disability (Western Ontario and McMaster University [WOMAC]).

Results: Acromegalic patients showed higher prevalence of thoracic hyperkyphosis (i.e., Cobb thoracic index ≥40°; p = 0.04) and pelvic tilt >20° (p = 0.02) than control subjects. VFs were found in 34.2% of acromegalic patients (p = 0.003 vs. control subjects), in relationship with higher prevalence of hyperkyphosis (p = 0.03), pelvic tilt >20° (p = 0.04), sagittal vertical axis ≥4 cm (p = 0.03), and moderate/severe subchondral degeneration (p = 0.01). Moreover, patients with VFs had lower AcroQoL general health (p = 0.007) and SF-36 general health (p = 0.002) scores and higher WOMAC pain (p = 0.003) and global (p = 0.009) scores than patients who did not fracture.

Conclusions: In acromegaly, VFs may be associated with spine deformities and sagittal imbalance, spine arthropathy, impaired QoL, and disability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000511811DOI Listing
September 2020

COVID-19 cardiac involvement in a 38-day old infant.

Pediatr Pulmonol 2020 08 18;55(8):1879-1881. Epub 2020 Jun 18.

Department of Pediatrics, IRCCS San Raffaele Scientific Institute, Milano, Italy.

The spectrum of clinical manifestations of coronavirus disease 2019 in children is yet to be fully elucidated. We report the case of an infant who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developed mild cardiovascular inflammation, a novelty for patients of very young age, that contributes to defining the puzzling nature of this disease in pediatric patients. The potential cardiovascular involvement of SARS-CoV-2 in children should always be taken into account.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.24895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323066PMC
August 2020

First-line pembrolizumab in advanced non-small cell lung cancer patients with poor performance status.

Eur J Cancer 2020 05 25;130:155-167. Epub 2020 Mar 25.

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Department of Oncology and Hemato-Oncology, Università Degli Studi di Milano, Milan, Italy.

Background: Pembrolizumab is the first-line standard of care for advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score (TPS) ≥ 50%. Eastern Cooperative Oncology Group performance status (PS) 2 patients may receive pembrolizumab, despite the absence of sustaining evidence.

Patients And Methods: GOIRC-2018-01 is a multicentre, retrospective, observational study. PS 2 NSCLC patients with a PD-L1 TPS ≥50% receiving first-line pembrolizumab from June 2017 to December 2018 at 21 Italian institutions were included. Clinical-pathological characteristics were correlated with disease response and survival outcomes; adverse events were recorded. The primary objective was 6-months progression-free rate (6-months PFR).

Results: One hundred fifty-three patients (median age 70 years) were enrolled. At a median follow-up of 18.2 months, median progression-free survival (PFS) and overall survival (OS) were 2.4 (95% confidence interval, 95% CI, 1.6-2.5) and 3.0 months (95% CI 2.4-3.5), respectively. 6-months PFR was 27% (95% CI 21-35%). Patients with a PS 2 determined by comorbidities (n = 41) had significantly better outcomes compared with disease burden-induced PS 2 (n = 112). Indeed, 6-months PFR was 49% versus 19%, median PFS 5.6 versus 1.8 months and OS 11.8 versus 2.8 months, respectively. Additional potential prognostic factors (radiotherapy, antibiotics, steroids received before pembrolizumab) correlated with clinical outcomes. The determinant of PS 2 resulted the only factor independently impacting on both PFS and OS. No toxicity issues emerged.

Conclusions: Outcomes of PS 2 NSCLC patients with PD-L1 TPS ≥50% receiving first-line pembrolizumab were globally dismal but strongly dependent on the reason conditioning the poor PS itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.02.023DOI Listing
May 2020

Respiratory syncytial virus and human metapneumovirus after allogeneic hematopoietic stem cell transplantation: Impact of the immunodeficiency scoring index, viral load, and ribavirin treatment on the outcomes.

Transpl Infect Dis 2020 Aug 6;22(4):e13276. Epub 2020 Apr 6.

Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.

Introduction: Respiratory viral infections are a major cause of morbidity and mortality among stem cell transplant recipients. While there is a substantial amount of information on prognostic factors and response to ribavirin therapy is available for RSV infections, this information is largely lacking for hMPV.

Patients And Methods: In total, 71 patients were included in this study: 47 patients with RSV and 24 with hMPV. Forty-one patients presented as an upper respiratory tract infection (URTI) and 30 as a primary lower respiratory tract infection (LRTI). Patients were stratified as per ISI criteria into low-, moderate-, and high-risk groups. Twenty-two patients in the URTI cohort received treatment with ribavirin (mainly oral), and 19 patients received no antiviral therapy. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. The viral load was assessed indirectly by using the CT value of the RT-PCR.

Results: In the cohort, as whole 11.5% suffered a virus-associated death, 5% in the URTI group, and 20% in the LRTI group. Sixty-day mortality was significantly higher in the ISI high-risk group (log-rank P = .05). Mortality was independent of the type of virus (P = .817). Respiratory failure with an indication for mechanical ventilation developed in 11.5%, this risk was independent of the type of virus. Progression from URTI to LRTI was observed in 24% of cases with a significantly higher risk (75%) in the ISI high group (log-rank P = .001). In the ISI high-risk group, treatment with ribavirin significantly reduced the risk of progression (log-rank P < .001). Neither the type of virus nor the viral load in the nasopharyngeal swab impacted the risk of progression (P = .529 and P = .141, respectively). The detection of co-pathogens in the BAL fluid was borderline significant for mortality (P = .07).

Conclusions: We could detect no differences between RSV and hMPV with respect to progression to LRTI, risk of respiratory failure or need for mechanical ventilation and virus-associated death. The ISI index is of predictive value in hMPV patients with a high ISI score and treatment with oral ribavirin has an equivalent protective effect in RSV and hMPV patients. Treatment of LRTI with intravenous ribavirin results in a similar outcome in RSV- and hMPV-infected patients. We could not detect any benefit of adjunctive treatment with immunoglobulins in both primary and secondary LRTI. No role of viral load as an independent prognostic marker could be detected either for progression to LRTI or death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13276DOI Listing
August 2020

Cushing's disease: a prospective case-control study of health-related quality of life and cognitive status before and after surgery.

J Neurosurg 2019 Nov 15:1-11. Epub 2019 Nov 15.

2Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan.

Objective: Some studies have highlighted psychological and neuropsychological difficulties and a potential reduction in health-related quality of life (HRQOL) in patients with pituitary tumors, despite hormone deficits or excess. To the authors' knowledge, this study is the first prospective longitudinal case-control study with the aim of simultaneously testing whether HRQOL and psychiatric and neuropsychological disabilities are related to neural dysfunction due to hypercortisolism per se, or tumor mass and/or surgery in patients with Cushing's disease (CD). The authors evaluated a homogeneous cohort of patients with CD and nonfunctioning pituitary adenomas (NFPAs) before and after neurosurgery and compared these patients with healthy controls.

Methods: Twenty patients (10 with NFPA and 10 with CD) were evaluated using 3 validated questionnaires (SF-36, Beck Depression Inventory-II [BDI-II], and Minnesota Multiphasic Personality Inventory-II [MMPI-II]) to assess HRQOL and psychological status preoperatively and 12 months after neurosurgery. Neuropsychological tests were assessed preoperatively, 3-7 days postoperatively, and 12 months postoperatively. Twenty healthy matched controls were recruited.

Results: Preoperatively, the NFPA and CD subgroups had worse HRQOL scores than controls on the basis of SF-36 scores, although the NFPA subgroup experienced significant recovery 12 months postoperatively. Preoperatively, CD patients had depressive symptoms according to the BDI-II and MMPI-II that persisted 12 months postoperatively, together with social introversion and hypochondriasis; NFPA patients were similar to controls except for hypochondriasis scores that were clinically significant at all timepoints. Preoperatively and 3-7 days postoperatively, both subgroups showed significant neuropsychological disabilities compared with controls, but only the CD subgroup did not completely recover over time.

Conclusions: HRQOL and neuropsychological impairments were observed in all patients at early timepoints, independent of hypercortisolism, tumor mass, and successful surgery. Over time, CD patients showed persistent changes in HRQOL, in particular in social activities. In this light, CD seems to have a strong impact on HRQOL and to be associated with more psychological and neuropsychological comorbidities than NFPA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.8.JNS19930DOI Listing
November 2019

Clinically Nonfunctioning Pituitary Incidentalomas: Characteristics and Natural History.

Neuroendocrinology 2020 13;110(7-8):595-603. Epub 2019 Sep 13.

Endocrinology, Diabetology and Medical Andrology Unit, Humanitas Clinical and Research Hospital, Rozzano, Italy.

Introduction: Available data on pituitary incidentalomas mostly derive from small-scale studies, with heterogeneous inclusion criteria and limited follow-up. No paper has focused specifically on clinically nonfunctioning pituitary in-cidentalomas (CNFPIs).

Objective: To describe the charac-teristics and the natural history of patients diagnosed with CNFPIs.

Methods: Retrospective multicenter cohort study evaluating hormonal, imaging, and visual field characteristics at diagnosis and during follow-up of CNFPIs investigated in 2 Pituitary Centers.

Results: Three hundred and seventy-one patients were included (50.9% microadenomas, 35.6% males). Men were older and more likely to have a macroadenoma (p < 0.01). Totally, 23.7% of patients presented secondary hormonal deficits (SHDs), related to tumor size (higher in macroadenomas; p < 0.001) and age (higher in older patients; p < 0.001). Hypogonadism was the most frequent SHD (15.6%). Two hundred and ninety-six patients had follow-up data, 29.1% required surgery after first evaluation, and 97 had at least 3 years of follow-up. In total, 15.3% adenomas grew (more macroadenomas), but only in microadenomas patients with longer follow-up showed a higher growth trend. Totally, 5.2% of patients developed new SHDs (micro- vs. macroadenomas p = 1.000), and in 60% of them this was not associated with an increase in tumor size. Thirteen additional patients required surgery during follow-up (1 microadenoma at diagnosis).

Conclusions: Macroadenomas and age are risk factors for SHD in CNFPIs, which occur at diagnosis in a quarter of patients. During follow-up, macroadenomas tend to grow more often, but microadenomas display higher growth trend as follow-up increases. Deterioration of pituitary function is not always related to adenoma growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000503256DOI Listing
July 2021

Chimeric antigen receptor (CAR) T-cell therapy as a treatment option for patients with B-cell lymphomas: perspectives on the therapeutic potential of Axicabtagene ciloleucel.

Cancer Manag Res 2019 25;11:2393-2404. Epub 2019 Mar 25.

Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany.

Axicabtagene lisoleucel (Axi-cel) is the second approved gene-alterating cancer treatment and the first in aggressive lymphoma using the "chimeric antigen receptor" (CAR) technology. T-cells from patients were transfected with CARs and reinfused after a lymphodepleting chemotherapy. CAR T-cells are "living drugs" with the ability to persist and expand after a single infusion. Axi-cel is a "second generation" CAR product characterized by the use of a retroviral gene vector transfer and by CD28 as costimulatory domain. In a phase II trial with heavily pretreated patients with aggressive B-cell lymphoma, the overall response rate was 82% with an ongoing complete response rate of 40% after 6 months - with expectations of long-term remissions and cure, even though follow-up data are still limited. There are some prominent side effects like cytokine release syndrome (Grade 3-5: 13%) and neurotoxicity (Grade 3-5: 28%). Novel strategies for prediction, prevention and treatment of these critical side effects are warranted. There are new concepts to enhance the efficacy and prevent resistance in lymphomas. CAR T-cells represent an extremely evolving field with an inestimable potential in general and particularly in aggressive lymphoma. However, we are still learning how to use Axi-cel and other CAR-T cells compounds effectively to optimize the long-term results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S163225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489634PMC
March 2019

International prospective observational study on intracranial pressure in intensive care (ICU): the SYNAPSE-ICU study protocol.

BMJ Open 2019 04 20;9(4):e026552. Epub 2019 Apr 20.

Department of Public Health, Erasmus MC, Rotterdam, Netherlands.

Introduction: Intracranial pressure (ICP) monitoring is commonly used in neurocritical care patients with acute brain injury (ABI). Practice about indications and use of ICP monitoring in patients with ABI remains, however, highly variable in high-income countries, while data on ICP monitoring in low and middle-income countries are scarce or inconsistent. The aim of the SYNAPSE-ICU study is to describe current practices of ICP monitoring using a worldwide sample and to quantify practice variations in ICP monitoring and management in neurocritical care ABI patients.

Methods And Analysis: The SYNAPSE-ICU study is a large international, prospective, observational cohort study. From March 2018 to March 2019, all patients fulfilling the following inclusion criteria will be recruited: age >18 years; diagnosis of ABI due to primary haemorrhagic stroke (subarachnoid haemorrhage or intracranial haemorrhage) or traumatic brain injury; Glasgow Coma Score (GCS) with no eye opening (Eyes response=1) and Motor score ≤5 (not following commands) at ICU admission, or neuro-worsening within the first 48 hours with no eye opening and a Motor score decreased to ≤5. Data related to clinical examination (GCS, pupil size and reactivity, Richmond Agitation-Sedation Scale score, neuroimaging) and to ICP interventions (Therapy Intensity Levels) will be recorded on admission, and at day 1, 3 and 7. The Glasgow Outcome Scale Extended (GOSE) will be collected at discharge from ICU and from hospital and at 6-month follow-up. The impact of ICP monitoring and ICP-driven therapy on GOSE will be analysed at both patient and ICU level.

Ethics And Dissemination: The study has been approved by the Ethics Committee 'Brianza' at the Azienda Socio Sanitaria Territoriale (ASST)-Monza (approval date: 21 November 2017). Each National Coordinator will notify the relevant ethics committee, in compliance with the local legislation and rules. Data will be made available to the scientific community by means of abstracts submitted to the European Society of Intensive Care Medicine annual conference and by scientific reports and original articles submitted to peer-reviewed journals.

Trial Registration Number: NCT03257904.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-026552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500252PMC
April 2019

Cabergoline Withdrawal Before and After Menopause: Outcomes in Microprolactinomas.

Horm Cancer 2019 06 18;10(2-3):120-127. Epub 2019 Apr 18.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Natural course of prolactinomas after menopause is not fully elucidated. The aim of this study was to compare recurrence rate after cabergoline withdrawal in premenopausal vs. postmenopausal women with microprolactinoma. Sixty-two women with microprolactinoma treated with cabergoline for at least 1 year and followed for 2 years after drug withdrawal were retrospectively selected. Patients were divided into two groups: 48 patients stopped cabergoline before menopause ("PRE" group), while 14 after menopause ("POST" group). Recurrence was defined by prolactin levels above normal, confirmed on two occasions. Overall, 39/62 women relapsed. Patients who relapsed apparently had higher prolactin before withdrawal (median 216.2, range 21.2-464.3 mIU/L) compared with those in long-term remission (94.3, 29.7-402.8 mIU/L; p < 0.05), and the risk of recurrence seemed lower in POST women (4/14, 29%) than in PRE ones (35/48, 73%, p < 0.005, OR 0.149, 95% CI 0.040-0.558). However, none of the factors (prolactin before withdrawal, menopausal status, treatment duration, complete adenoma regression) showed a correlation with recurrence risk in multivariate analysis. The best strategy able to optimize CBG treatment and withdrawal's outcomes is still to be defined in microprolactinomas. Postmenopausal status cannot reliably predict long-term remission, and follow-up is needed also in women of this age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12672-019-00363-4DOI Listing
June 2019

Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

Neuroendocrinology 2019 13;108(3):211-218. Epub 2019 Jan 13.

Endocrinology Unit, Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda, Milan, Italy.

Background: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI).

Objective: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD.

Patients And Methods: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention.

Results: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence.

Conclusion: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000496846DOI Listing
December 2019

Somatostatin analogs regulate tumor corticotrophs growth by reducing ERK1/2 activity.

Mol Cell Endocrinol 2019 03 3;483:31-38. Epub 2019 Jan 3.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Endocrine Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Pasireotide has been associated with tumor shrinkage in patients with Cushing's disease subjected to long term treatment. However, to date the implicated molecular mechanisms are poorly elucidated. Here, we tested pasireotide-mediated cytostatic and cytotoxic effects in ACTH-secreting primary tumor cultures and murine corticotroph tumor cell line, AtT-20 cells. We found somatostatin receptor type 5 (SST5) expressed in 17 different ACTH-secreting tumors and SST2 detectable in 15 out of the 17 tissues. Pasireotide caused a slight but significant in vitro inhibition of cell growth in 3 out of 6 ACTH-secreting primary cultures (-12.1 ± 4.3%, P < 0.01 at 10 nM), remarkably reduced phospho-ERK1/2 levels in 5 out of 8 samples (-36.4 ± 20.5%, P < 0.01 at 1 μM) and triggered an increase of caspase 3/7 activity in 2 of 4 tumors (17 ± 3.6%, P < 0.05 at 1 μM). Accordingly, in AtT-20 cells, pasireotide significantly inhibited cell proliferation (-10.5 ± 7.7% at 10 nM, P < 0.05; -13.9 ± 10.9% at 100 nM, P < 0.05; -26.8 ± 8.9% at 1 μM, P < 0.01). Similar antiproliferative actions were exerted by BIM23206 and BIM23120 (SST5&2 selective ligands, respectively), whereas octreotide was effective when used at 1 μM (-13.3 ± 9.1%, P < 0.05). Moreover, a reduction of phospho-ERK1/2 was observed upon pasireotide and BIM23206 treatment (-8.4 ± 28.6%, P < 0.01 and -51.4 ± 15.9%, P < 0.001 at 10 nM, respectively) but not after octreotide and BIM23120 incubation. Finally, pasireotide was able to induce cell apoptosis in AtT-20 cells at lower concentration than octreotide. Altogether these data indicate a downstream implication of SST5-mediated phospho-ERK1/2 inhibition by pasireotide resulting in ACTH-secreting tumor cells proliferation reduction. Moreover, we describe for the first time a pro-apoptotic effect of pasireotide in corticotrophs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mce.2018.12.022DOI Listing
March 2019

Fate of manuscripts rejected by Intensive Care Medicine from 2013 to 2016: a follow-up analysis.

Intensive Care Med 2018 Dec 8;44(12):2300-2301. Epub 2018 Oct 8.

Medical Intensive Care Unit, Hôpital Saint-Louis, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-018-5407-2DOI Listing
December 2018

Natural history of Rathke's cleft cysts: A retrospective analysis of a two centres experience.

Clin Endocrinol (Oxf) 2018 Aug 12;89(2):178-186. Epub 2018 Jun 12.

Department of Neurological Surgery, Stanford University Hospital, Stanford, CA, USA.

Objective: Rathke's cleft cyst (RCC) is a common sellar lesion which may cause visual impairment, hypopituitarism and headaches from mass effect. The natural history of these lesions is currently unclear. We investigated the natural history of RCCs and compared surgically treated patients with those treated conservatively.

Methods: We performed a retrospective cohort study of patients diagnosed with a RCC between 1996 and 2016 at Stanford University and Ospedale Maggiore Policlinico di Milano.

Results: Patients were divided into 2 cohorts: Group A, 72 subjects who underwent surgical resection of a symptomatic RCC, and Group B, 62 subjects managed conservatively. Compared to Group B, Group A subjects had larger RCCs (79% vs 22% had a largest diameter >10 mm, P < .001) and were more likely (41.5% vs 16%, P < .001) to present with hypopituitarism and diabetes insipidus (DI) (18% vs 1.6%, P = .002). In Group A, after a mean follow-up of 53.7 months, 12.5% of patients had recurrence and a second surgery. After surgery, 35% of patients recovered pituitary function. Hyperprolactinemia (26.6%) and hypogonadism (66.6%) resolved more commonly that did DI (20.1%). New pituitary deficits appeared in 16.6% of patients after surgery. In Group B, with a mean follow-up of 41 months, only 6.4% had cyst enlargement, none underwent surgery, and none developed a pituitary deficit.

Conclusion: Our data offer guidance in decision-making regarding the management of RCC patients and confirm the safety of conservative treatment in asymptomatic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cen.13744DOI Listing
August 2018

CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center's experience.

J Neurooncol 2018 Jun 10;138(2):291-298. Epub 2018 Feb 10.

Department of Neurological Surgery, Stanford Medical Center, Stanford University, Palo Alto, CA, USA.

Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5-50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6-84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-018-2793-9DOI Listing
June 2018

CyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing Disease.

World Neurosurg 2018 Apr 31;112:e425-e430. Epub 2018 Jan 31.

Department of Neurosurgery, Stanford Medical Center, Stanford University, Palo Alto, California, USA; Department of Medicine, Stanford Medical Center, Stanford University, Palo Alto, California, USA. Electronic address:

Background: Surgery is the primary treatment for Cushing disease. When surgery is unsuccessful in normalizing hypercortisolism, adjuvant radiation, such as stereotactic radiosurgery, may be useful to improve biochemical control.

Methods: This retrospective study included a cohort of consecutive patients treated with CyberKnife (CK) radiosurgery for active Cushing disease at Stanford Hospital and Clinics.

Results: As first-line treatment, all patients underwent transsphenoidal surgery with histologic demonstration of an adrenocorticotropic hormone-producing pituitary adenoma. CK was performed as adjuvant therapy for persistent or recurrent disease. The median time between surgery and CK was 14 ± 34 months. Before CK, median maximal diameter of tumors was 9 mm (range, 7-32 mm), with cavernous sinus invasion in all patients (100%) and abutment of the optic chiasm in 1 patient (14.2%). With an average follow-up of 55.4 months, normalization of hypercortisolism was achieved in 4 patients (57.1%): 2 patients (28.5%) achieved normalization of the hypothalamic-pituitary-adrenal axis without glucocorticoid replacement, and 2 patients developed hypoadrenalism (28.5%). The median time to biochemical remission was 12.5 months. Hypopituitarism occurred in only 1 patient (14.2%), and no patients had visual complications. Time between surgery and radiotherapy of <14 months was associated with a significantly improved biochemical remission rate (P = 0.02).

Conclusions: In a cohort of patients with Cushing disease, we demonstrate that CK is an effective treatment with rare complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2018.01.057DOI Listing
April 2018

Hematopoietic Cell and Renal Transplantation in Plasma Cell Dyscrasia Patients.

Cell Transplant 2016;25(6):995-1005. Epub 2015 Jul 8.

Department of Experimental Diagnostic and Specialty Medicine (DIMES), Nephrology, Dialysis and Renal Transplant Unit, St Orsola Hospital, University of Bologna, Bologna, Italy.

Gammopathies, multiple myeloma, and amyloidosis are plasma dyscrasias characterized by clonal proliferation and immunoglobulin overproduction. Renal impairment is the most common and serious complication with an incidence of 20-30% patients at the diagnosis. Kidney transplant has not been considered feasible in the presence of plasma dyscrasias because the immunosuppressive therapy may increase the risk of neoplasia progression, and paraproteins may affect the graft. However, recent advances in clinical management of multiple myeloma and other gammopathies allow considering kidney transplant as a possible alternative to dialysis. Numerous evidence indicates the direct relationship between hematological remission and renal function restoring. The combination of kidney and hematopoietic cell transplant has been reported as a promising approach to reestablish end-organ function and effectively treat the underlying disease. This review describes current protocols used to perform kidney transplantation in patients with plasma dyscrasias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3727/096368915X688560DOI Listing
March 2017

Hypothalamic-Pituitary Axis in Non-Functioning Pituitary Adenomas: Focus on the Prevalence of Isolated Central Hypoadrenalism.

Neuroendocrinology 2015;102(4):267-273. Epub 2015 Apr 29.

Endocrinology and Diabetology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Introduction: Non-functioning pituitary adenomas (NFPA) account for about 40% of pituitary tumors. Pituitary deficiencies are present at diagnosis in 60-80% of NFPA, and, classically, growth hormone (GH) secretion is lost first, while adrenocorticotropic hormone is expected to disappear last. The aim of this study was to evaluate the incidence of multiple or isolated pituitary deficiencies in a large series of NFPA.

Materials And Methods: We retrospectively analyzed data on 218 NFPA cases (59% females, 59% with macroadenomas, average age: 50.2 ± 17 years) followed up at our center from 1990 to 2013. At diagnosis all patients had a complete evaluation of pituitary function in basal conditions and provocative tests for the hypothalamic-pituitary-adrenal axis, while tests for GH deficiency (GHD) were carried out in 38%.

Results: 52.3% of patients (65.6% of macroadenomas, 33.3% of microadenomas) presented at least 1 pituitary deficiency: isolated deficiency in 29.8%, multiple deficiencies in 30% and panhypopituitarism in 9%. Isolated deficiencies were hypogonadism in 11.5% of patients (8% in micro-, 14% in macroadenomas), hypoadrenalism in 10.1% (14% in micro-, 7% in macroadenomas) and GHD in 8.3% (8.9% in micro-, 7.8% in macroadenomas). About 30% of microadenomas had at least 1 pituitary deficiency at diagnosis, independently of tumor localization within the sellar region.

Conclusions: The presence of isolated hypoadrenalism suggests that the order of appearance of hypopituitarism does not always follow the one expected. Given the relatively high prevalence of isolated hypoadrenalism even in microadenomas, we suggest a full assessment of basal and dynamic pituitary function in all NFPA regardless of tumor size.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000430815DOI Listing
April 2015

Reevaluation of Acromegalic Patients in Long-Term Remission according to Newly Proposed Consensus Criteria for Control of Disease.

Int J Endocrinol 2014 21;2014:581594. Epub 2014 Dec 21.

Endocrinology and Diabetology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Padiglione Granelli, Via F. Sforza 35, 20122 Milan, Italy ; Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.

Acromegaly guidelines updated in 2010 revisited criteria of disease control: if applied, it is likely that a percentage of patients previously considered as cured might present postglucose GH nadir levels not adequately suppressed, with potential implications on management. This study explored GH secretion, as well as hormonal, clinical, neuroradiological, metabolic, and comorbid profile in a cohort of 40 acromegalic patients considered cured on the basis of the previous guidelines after a mean follow-up period of 17.2 years from remission, in order to assess the impact of the current criteria. At the last follow-up visit, in the presence of normal IGF-I concentrations, postglucose GH nadir was over 0.4 μg/L in 11 patients (Group A) and below 0.4 μg/L in 29 patients (Group B); moreover, Group A showed higher basal GH levels than Group B, whereas a significant decline of both GH and postglucose GH nadir levels during the follow-up was observed in Group B only. No differences in other evaluated parameters were found. These results seem to suggest that acromegalic patients considered cured on the basis of previous guidelines do not need a more intensive monitoring than patients who met the current criteria of disease control, supporting instead that the cut-off of 0.4 mcg/L might be too low for the currently used GH assay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/581594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283389PMC
January 2015

The pharmacist and the management of arterial hypertension: the role of blood pressure monitoring and telemonitoring.

Expert Rev Cardiovasc Ther 2015 Feb 12;13(2):209-21. Epub 2015 Jan 12.

Clinical Research Unit, Italian Institute of Telemedicine, Via Colombera 29, 21048 Solbiate Arno (Varese), Italy.

Randomized controlled trials have documented that a team of health care professionals which includes a physician, a nurse and a community pharmacist may improve the benefit and adherence of anti-hypertensive therapy. If such a health care model relies on blood pressure telemonitoring, it can promote a stronger relationship between health care professionals and patients, and further improve BP control of hypertension. The major benefit of this collaborative approach is to center the patient's management in a tailored way, providing comprehensive and preventive care based on health information technologies. In this review, the authors summarize recent clinical studies that evaluate the role of the community pharmacist in BP measurements, and in hypertension screening and control. The authors also describe the advantages of using blood pressure telemonitoring in home and ambulatory settings to evaluate potential alternatives to primary care in hypertension management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1586/14779072.2015.1001368DOI Listing
February 2015

Potential advantages of acute kidney injury management by mesenchymal stem cells.

World J Stem Cells 2014 Nov;6(5):644-50

Francesca Bianchi, Laboratory of Molecular Biology and Stem Cell Engineering - National Institute of Biostructures and Biosystems, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.

Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury (AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. After AKI, inflammation, oxidative stress and excessive deposition of extracellular matrix are the molecular events that ultimately cause the end-stage renal disease. Despite numerous improvement of supportive therapy, the mortality and morbidity among patients remain high. Therefore, exploring novel therapeutic options to treat AKI is mandatory. Numerous evidence in animal models has demonstrated the capability of mesenchymal stem cells (MSCs) to restore kidney function after induced kidney injury. After infusion, MSCs engraft in the injured tissue and release soluble factors and microvesicles that promote cell survival and tissue repairing. Indeed, the main mechanism of action of MSCs in tissue regeneration is the paracrine/endocrine secretion of bioactive molecules. MSCs can be isolated from several tissues, including bone marrow, adipose tissue, and blood cord; pre-treatment procedures to improve MSCs homing and their paracrine function have been also described. This review will focus on the application of cell therapy in AKI and it will summarize preclinical studies in animal models and clinical trials currently ongoing about the use of mesenchymal stem cells after AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4252/wjsc.v6.i5.644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178265PMC
November 2014
-->