•Many COVID-19 patients require ICU stay which can result in neuromuscular damage.•We describe a series of patients with the diagnosis of ICU acquired weakness.•Neurophysiology plays an essential ...role in the diagnosis of these patients.
Coronavirus disease 2019 (COVID-19) has a high incidence of intensive care admittance due to the severe acute respiratory syndrome (SARS). Intensive care unit (ICU)-acquired weakness (ICUAW) is a common complication of ICU patients consisting of symmetric and generalised weakness. The aim of this study was to determine the presence of myopathy, neuropathy or both in ICU patients affected by COVID-19 and whether ICUAW associated with COVID-19 differs from other aetiologies.
Twelve SARS CoV-2 positive patients referred with the suspicion of critical illness myopathy (CIM) or polyneuropathy (CIP) were included between March and May 2020. Nerve conduction and concentric needle electromyography were performed in all patients while admitted to the hospital. Muscle biopsies were obtained in three patients.
Four patients presented signs of a sensory-motor axonal polyneuropathy and seven patients showed signs of myopathy. One muscle biopsy showed scattered necrotic and regenerative fibres without inflammatory signs. The other two biopsies showed non-specific myopathic findings.
We have not found any distinctive features in the studies of the ICU patients affected by SARS-CoV-2 infection.
Further studies are needed to determine whether COVID-19-related CIM/CIP has different features from other aetiologies. Neurophysiological studies are essential in the diagnosis of these patients.
Uncontrolled extracellular matrix (ECM) production by fibroblasts in response to injury contributes to fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Reactive oxygen species (ROS) ...generation is involved in the pathogenesis of IPF. Transforming growth factor‐β1 (TGF‐β1) stimulates the production of NADPH oxidase 4 (NOX4)‐dependent ROS, promoting lung fibrosis (LF). Dysregulation of microRNAs (miRNAs) has been shown to contribute to LF. To identify miRNAs involved in redox regulation relevant for IPF, we performed arrays in human lung fibroblasts exposed to ROS. miR‐9‐5p was selected as the best candidate and we demonstrate its inhibitory effect on TGF‐β receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR‐9‐5p abrogates TGF‐β1‐dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin‐induced LF, miR‐9‐5p dramatically reduces fibrogenesis and inhibition of miR‐9‐5p and prevents its anti‐fibrotic effect both in vitro and in vivo. In lung specimens from patients with IPF, high levels of miR‐9‐5p are found. In omentum‐derived mesothelial cells (MCs) from patients subjected to peritoneal dialysis (PD), miR‐9‐5p also inhibits mesothelial to myofibroblast transformation. We propose that TGF‐β1 induces miR‐9‐5p expression as a self‐limiting homeostatic response.
Synopsis
miR‐9‐5p is discovered as an anti‐fibrotic miRNA that targets TGBR2 and NOX4 to inhibit the transformation of fibroblasts into myofibroblasts. TGF‐β1 itself is pro‐fibrogenic, but promotes miR‐9‐5p expression, thus inducing inhibition of its own pro‐fibrogenic role.
Reactive oxygen species and TGF‐β1 induce miR‐9‐5p expression.
miR‐9‐5p inhibits TGFBR2 and NOX4 expression by binding to their 3′‐UTRs.
miR‐9‐5p inhibits TGF‐β‐mediated pro‐fibrogenic signaling in human lung fibroblasts and attenuates the development of experimental pulmonary fibrosis.
Peritoneal mesothelial fibrogenesis is also significantly reduced by miR‐9‐5p.
miR‐9‐5p is discovered as an anti‐fibrotic miRNA that targets TGBR2 and NOX4 to inhibit the transformation of fibroblasts into myofibroblasts. TGF‐β1 itself is pro‐fibrogenic, but promotes miR‐9‐5p expression, thus inducing inhibition of its own pro‐fibrogenic role.
Thyroid cancer represents a heterogenous disease whose incidence has increased in the last decades. Although three main different subtypes have been described, molecular characterization is ...progressively being included in the diagnostic and therapeutic algorithm of these patients. In fact, thyroid cancer is a landmark in the oncological approach to solid tumors as it harbors key genetic alterations driving tumor progression that have been demonstrated to be potential actionable targets. Within this promising and rapid changing scenario, current efforts are directed to improve tumor characterization for an accurate guidance in the therapeutic management. In this sense, it is strongly recommended to perform tissue genotyping to patients that are going to be considered for systemic therapy in order to select the adequate treatment, according to recent clinical trials data. Overall, the aim of this article is to provide a comprehensive review on the molecular biology of thyroid cancer focusing on the key role of tyrosine kinases. Additionally, from a clinical point of view, we provide a thorough perspective, current and future, in the treatment landscape of this tumor.
Juvenile psammomatoid ossifying fibroma (JPOF) is an osteofibrous neoplasm that originates in the craniofacial skeleton typically during the first three decades of life. JPOFs usually involve the ...orbit, paranasal sinuses or the jaws. Extensive involvement of the anterior cranial base with compromised visual function is a rare phenomenon. In such clinical context, a definite diagnosis can only be made on the basis of histopathological findings, given the absence of pathognomonic radiological features. Despite being considered a benign entity, JPOFs present a locally aggressive behavior. Therefore, these neoplasms must be included in the differential diagnosis in every patient harboring a skull base osteofibrous lesion, and, once diagnosed, gross total surgical removal should be attempted. In this study, we present our experience in the diagnosis and treatment of a patient diagnosed with a giant JPOF involving the cranial base.
Abstract
Background
Primary cardiac lymphomas are extremely rare entities (< 2% of cardiac tumours) and the most frequent histologic type is diffuse large B-cell lymphoma (DLBCL). Fibrin-associated ...DLBCL (FA-DLBCL) is a very unusual form of DLBCL associated with chronic inflammation, and only case reports and small series have been described. In the heart, it usually occurs in the context of a cardiac myxoma or cardiac prostheses and it is not bulk forming. These lymphomas frequently present with non-germinal center phenotype and are associated with Epstein-Barr virus (EBV) type III latency.
Case presentation
We describe a case of FA-DLBCL arising in a cardiac myxoma, with plasmacytic differentiation and type I EBV latency.
Conclusions
Although they are very rare, FA-DLBCLs should be known for their diagnostic difficulty, due to its unspecified clinical manifestations, and for their more favourable prognosis, sometimes even without additional treatment after surgical resection.
To review the clinical relevance of pituitary adenoma (PA) consistency and its relationship to clinical presentation, radiologic and histopathological characteristics, and surgical outcomes.
PA ...consistency is a critical factor influencing operative planning, surgical outcomes, and patient counseling. There is no validated classification of PA consistency in the literature, and there are no current preoperative variables capable of predicting it.
We conducted a thorough literature review of the Medline, Embase, Web of Science, and Cochrane Library databases. The inclusion criteria were all articles that described PA consistency and correlated it with preoperative aspects, radiological, pathological, and operative findings, or clinical outcomes.
Although most authors differentiate easily aspirated (soft) tumors from those that are not (fibrous, might require prior fragmentation), there is no universally accepted PA consistency classification. Fibrous PA tends to be hypointense on T2WI and has lower apparent diffusion coefficient (ADC) values. Fibrous tumors seemed to present higher invasion into neighboring structures, including the cavernous sinus. Several articles suggest that dopamine agonists could increase PA consistency and that prior surgery and radiotherapy also make PA more fibrous. The anatomopathological studies identify collagen as being mainly responsible for fibrous consistency of adenomas.
Preoperative knowledge of PA consistency affords the neurosurgeon substantial benefit, which clearly appears to be relevant to surgical planning, risks, and surgery outcomes. It could also encourage the centralization of these high complexity tumors in reference centers. Further studies may be enhanced by applying standard consistency classification of the PA and analyzing a more extensive and prospective series of fibrous PA.
Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) show numerous alterations including inflammation, apoptosis, and necrosis of myofibers. However, the molecular mechanism that ...explains these changes remains largely unknown. Here, the involvement of hemichannels formed by connexins (Cx HCs) was evaluated in skeletal muscle of
mdx
mouse model of DMD. Fast myofibers of
mdx
mice were found to express three connexins (39, 43 and 45) and high sarcolemma permeability, which was absent in myofibers of
mdx
Cx43
fl/fl
Cx45
fl/fl
:Myo-Cre mice (deficient in skeletal muscle Cx43/Cx45 expression). These myofibers did not show elevated basal intracellular free Ca
2+
levels, immunoreactivity to phosphorylated p65 (active NF-κB), eNOS and annexin V/active Caspase 3 (marker of apoptosis) but presented dystrophin immunoreactivity. Moreover, muscles of
mdx
Cx43
fl/fl
Cx45
fl/fl
:Myo-Cre mice exhibited partial decrease of necrotic features (big cells and high creatine kinase levels). Accordingly, these muscles showed similar macrophage infiltration as control
mdx
muscles. Nonetheless, the hanging test performance of
mdx
Cx43
fl/fl
Cx45
fl/fl
:Myo-Cre mice was significantly better than that of control
mdx
Cx43
fl/fl
Cx45
fl/fl
mice. All three Cxs found in skeletal muscles of
mdx
mice were also detected in fast myofibers of biopsy specimens from patients with muscular dystrophy. Thus, reduction of Cx expression and/or function of Cx HCs may be potential therapeutic approaches to abrogate myofiber apoptosis in DMD.
The optimal planning of preoperative diagnosis, management and treatment of pituitary tumors (PT) candidates to pituitary surgery (PS) requires a multidisciplinary approach involving a team of ...endocrinologists, neurosurgeons, ENT, neuro-ophthalmologists and neuroradiologists with experience in pituitary diseases. Such teams improve surgical results, minimize complications and facilitate their correct treatment if occurring, and optimize the hormonal, ophthalmological and radiological preoperative and follow-up evaluation. We have developed a clinical practice protocol for patients with PT who are candidates to PS based on the most recent national and international guidelines and the relevant literature regarding PT published in the last years. The protocol has been elaborated by a multidisciplinary team of a Spanish Pituitary Tumor Center of Excellence (PTCE) that includes at least one neurosurgeon, ENT, neuroradiologist, neuro-ophthalmologist, endocrine pathologist and endocrinologist specialized in pituitary diseases. We elaborated this guideline with the aim of sharing our experience with other centers involved in the perioperative and surgical management of PT thereby facilitating the management of patients undergoing PS.
Purpose To evaluate whether presurgical treatment using long-acting somatostatin receptor ligands (SRL) may change pituitary tumor consistency and improve surgical outcome in GH-secreting pituitary ...macroadenomas. Methods Retrospective study of 40 patients with GH-secreting pituitary macroadenomas operated for the first time by endoscopic transsphenoidal approach. Tumor consistency was evaluated intraoperatively and then correlated with histopathological fibrosis parameters and surgical outcomes. Surgical remission was reported based on the 2010 criteria. Results The mean tumor size of GH-secreting macroadenomas was of 16.9 ± 8.2 mm and 25 were invasive pituitary adenomas (PAs). Presurgical treatment with long-acting SRL was performed in 17 patients (11 lanreotide, 6 octreotide). The cure rate was higher in those patients pre-treated with monthly doses ≥30 mg of octreotide or ≥90 mg of lanreotide than in those treated with lower doses or untreated (8/11 (72.7%) vs 11/29 (37.9%), P = 0.049). However, although the proportion of soft tumors increased as higher doses of SRL were considered in the pre-treated group, no statistical significance was reached, even when the highest approved monthly doses were used (6/6 (100%) vs 23/34 (67.7%), P = 0.102). Moreover, we found that the remission rate was similar between fibrous and soft tumors (P = 0.873) and also of surgical complications (P = 0.859), despite of the higher prevalence of Knosp >2 (P = 0.035) and very large PA (P = 0.025) in fibrous tumors than in soft tumors. Conclusions Although presurgical treatment with high doses of SRL was associated with a 2.2-fold greater chance of surgical remission, this benefit was not related with changes in tumor consistency induced by the presurgical treatment.
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