Publications by authors named "M C Salerno"

796 Publications

Growth Hormone Receptor (Ghr) 6ω Pseudoexon Activation: A Novel Cause Of Severe Growth Hormone Insensitivity (Ghi).

J Clin Endocrinol Metab 2021 Jul 28. Epub 2021 Jul 28.

Centre for Endocrinology, William Harvey Research Institute: Barts and The London School of Medicine and Dentistry William Harvey Research Institute.

Context: Severe forms of Growth Hormone Insensitivity (GHI) are characterized by extreme short stature, dysmorphism and metabolic anomalies.

Objective: Identification of the genetic cause of growth failure in 3 'classical' GHI subjects.

Design: A novel intronic GHR variant was identified, and in vitro splicing assays confirmed aberrant splicing. A 6Ω pseudoexon GHR vector and patient fibroblast analysis assessed the consequences of the novel pseudoexon inclusion and the impact on GHR function.

Results: We identified a novel homozygous intronic GHR variant (g.5:42700940T>G, c.618 + 836T> G), 44bp downstream of the previously recognized intronic 6Ψ GHR pseudoexon mutation in the index patient. Two siblings also harbored the novel intronic 6Ω pseudoexon GHR variant in compound heterozygosity with the known GHR c.181C>T (R43X) mutation. In vitro splicing analysis confirmed inclusion of a 151bp mutant 6Ω pseudoexon not identified in wild-type constructs. Inclusion of the 6Ω pseudoexon causes a frameshift resulting in a non-functional truncated GHR lacking the transmembrane and intracellular domains. The truncated 6Ω pseudoexon protein demonstrated extracellular accumulation and diminished activation of STAT5B signaling following growth hormone stimulation.

Conclusion: Novel GHR 6Ω pseudoexon inclusion results in loss of GHR function consistent with a severe GHI phenotype. This represents a novel mechanism of Laron syndrome and is the first deep intronic variant identified causing severe postnatal growth failure. The 2 kindreds originate from the same town in Campania, Southern Italy, implying common ancestry. Our findings highlight the importance of studying variation in deep intronic regions as a cause of monogenic disorders.
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http://dx.doi.org/10.1210/clinem/dgab550DOI Listing
July 2021

Image-Guided Thermal Ablation in De Novo Renal Tumor Arising in Kidney Allograft: 3-Year Follow-Up. A Case Report.

Transplant Proc 2021 Jul 24. Epub 2021 Jul 24.

Dipartimento di Scienze mediche e chirurgiche, Area di Urologia, Nefrologia e Trapianto Renale, IRCCS Agostino Gemelli, Rome, Italy.

De novo tumors in renal allograft recipients are a severe complication during long-term follow-up after transplantation and may require transplantectomy. Herein we present a case of de novo renal tumor arising in the renal allograft, treated with the less invasive image-guided radiofrequency ablation (RFA) with long-term follow-up. A tumor was detected during the routine annual follow-up in a patient with good renal function who underwent renal transplantation in 1989. Computed tomography (CT) showed a mass in the allograft whose shape, vascularization, and density suggested the presence of a solid, malignant mass, located in the upper renal pole, that measured 17 mm. CT-guided RFA was performed successfully, and the outcome was verified by an immediate control CT after the intervention. No residual pathologic tissue, major bleeding, or damage to the adjacent parenchyma was evidenced. The patient was discharged with stable renal function. CT scan and ultrasound were performed 3, 6, 12, 18, 24, and 36 months after RFA. No signs of change in renal function, recurrence, neovascularization, or damage to the adjacent microcirculation were observed during the 3-year follow-up. In conclusion, percutaneous RFA of small renal tumors occurring in renal allografts can be considered a function-sparing, safe, and effective therapeutic option when difficult surgical removal may be anticipated. Our experience also supports the need for yearly renal allograft ultrasound follow-up for early identification of small neoplasm than can be treated less invasively.
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http://dx.doi.org/10.1016/j.transproceed.2021.05.004DOI Listing
July 2021

Hypogonadism in male and female: which is the best treatment?

Minerva Pediatr (Torino) 2021 Jul 26. Epub 2021 Jul 26.

Pediatric Endocrinology Unit, Department of Public Health and Pediatric Sciences, Regina Margherita Children Hospital, University of Turin, Turin, Italy -

Background: Subjects with hypo-or hypergonadotropic hypogonadism need hormone replacement therapy (HRT) to initiate puberty and maintain it with a normal hormonal status. While general recommendations for the management of HRT in adults have been published, no systematic suggestions focused on adolescents and young adults. The focus of this review is the HRT in males and females with hypogonadism, from puberty to late reproductive age, covering the different management options, encompassing sex steroid or gonadotropin therapy, with discussion of benefits, limitations and specific considerations of the different treatments.

Methods: We conducted an extensive search in the 3 major scientific databases (PubMed, EMBASE and Google Scholar) using the keywords "hormonal replacement therapy", "hypogonadism", "bone mineral density", "estradiol/testosterone", "puberty induction", "delayed puberty". Case-control studies, case series, reviews and meta-analysis published in English from 1990 to date were included.

Results: By considering the available opportunities for fertility induction and preservation, we hereby present the proposals of practical schemes to induce puberty, and a decisional algorithm to approach HRT in post-pubertal adolescents.

Conclusions: A condition of hypogonadism can underlie different etiologies involving the hypothalamic-pituitary-gonadal axis at different levels. Since the long-terms effects of hypogonadism may vary and include not only physical outcomes related to sex hormone deficiencies, but also psychological problems and implications on fertility, the initiation, maintenance and consolidation of puberty with different pharmaceutical options is of utmost importance and beside pubertal development, optimal uterine and testicular growth and adequate bone health should consider also the psychosocial wellbeing and the potential fertility.
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http://dx.doi.org/10.23736/S2724-5276.21.06534-4DOI Listing
July 2021

Venoarterial Extracorporeal Membrane Oxygenation for Acute Massive Pulmonary Embolism: a Meta-Analysis and Call to Action.

J Cardiovasc Transl Res 2021 Jul 19. Epub 2021 Jul 19.

Department of Medicine, Cardiovascular Division, University of Virginia, 1215 Lee Street, Charlottesville, VA, USA.

Venoarterial extracorporeal membrane oxygenation (ECMO) has been used to treat acute massive pulmonary embolism (PE) patients. However, the incremental benefit of ECMO to standard therapy remains unclear. Our meta-analysis objective is to compare in-hospital mortality in patients treated for acute massive PE with and without ECMO. The National Library of Medicine MEDLINE (USA), Web of Science, and PubMed databases from inception through October 2020 were searched. Screening identified 1002 published articles. Eleven eligible studies were identified, and 791 patients with acute massive PE were included, of whom 270 received ECMO and 521 did not. In-hospital mortality was not significantly different between patients treated with vs. without ECMO (OR = 1.24 [95% CI, 0.63-2.44], p = 0.54). However, these findings were limited by significant study heterogeneity. Additional research will be needed to clarify the role of ECMO in massive PE treatment. In-hospital mortality for patients with acute massive pulmonary embolism was not significantly different (OR of 1.24, p = 0.54) between those treated with and without venoarterial ECMO.
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http://dx.doi.org/10.1007/s12265-021-10158-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288068PMC
July 2021

Towards Replacing Late Gadolinium Enhancement with Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy.

Circulation 2021 Jul 7. Epub 2021 Jul 7.

Oxford Centre for Clinical Magnetic Resonance Research, Oxford BRC NIHR, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for non-invasive myocardial tissue characterization, but requires intravenous contrast agent administration. It is highly desired to develop a contrast-agent-free technology to replace LGE for faster and cheaper CMR scans. A CMR Virtual Native Enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1-maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multi-center Hypertrophic Cardiomyopathy Registry (HCMR), using HCM as an exemplar. The datasets were randomized into two independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement and myocardial lesion burden quantification. Image quality was compared using nonparametric Wilcoxon test. Intra- and inter-observer agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC. 1348 HCM patients provided 4093 triplets of matched T1-maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development, and 345 for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets, p<0.001, Wilcoxon test). VNE revealed characteristic HCM lesions in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyper-intensity myocardial lesions (r=0.77-0.79, ICC=0.77-0.87; p<0.001) and intermediate-intensity lesions (r=0.70-0.76, ICC=0.82-0.85; p<0.001). The native CMR images (cine plus T1-map) required for VNE can be acquired within 15 minutes. Producing a VNE image takes less than one second. VNE is a new CMR technology that resembles conventional LGE, without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.054432DOI Listing
July 2021
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