Κυριακή 20 Δεκεμβρίου 2020

Critical Ischemia

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Abstract

Critical ischemia is defined as the presence of ischemic symptoms at rest. It identifies patients with high risk of imminent tissue loss. Critical ischemia in SSc results from progressive microvascular insufficiency but occasionally it may result from macrovascular compromise by emboli, thrombosis or vasculitis. Outcome of critical ischemia is contingent on the duration of ischemia, presences of comorbidities, prompt institution of appropriate workup and therapy. Timely and comprehensive therapy is key to prevent loss of threatened tissues. Therapies vary based on location of ischemia and the severity of symptoms. Primary prevention and control of modifiable risk factors remain paramount in the ongoing care of patients.

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How to Assess a Patient for HSCT

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Abstract

Treatment of early diffuse cutaneous systemic sclerosis (dcSSc) patients can be challenging especially when organ involvement is present. Comprehensive screening is therefore necessary to determine the nature and extent of heart, lung and kidney involvement. This should include ECG, cardiac MRI, thoracic HRCT, lung function testing, right heart catheterisation and laboratory tests including NT-proBNP and hs-cTnI. Such patients may be considered for autologous hematopoietic stem cell transplantation (HSCT) if they do not respond to conventional immunosuppressive medication and have other features of poor prognosis. Clinical decision making may be difficult however in those patients with cardiac involvement who are deemed at risk of serious adverse events from HSCT including treatment-related death from heart/lung failure due to cardiotoxicity of high dose cyclophosphamide, cytokine-release syndrome from ATG and/or fluid overload.

We describe two cases of poor prognosis dcSSc with subclinical myocardial involvement who underwent autologous stem cell transplantation with favourable outcomes. These cases demonstrate that HSCT may be considered even in dcSSc patients with cardiac involvement but are probably best managed in tertiary referral centers.

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The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

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Abstract

Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disorders, although their exact roles in disease remain unclear. For example, nuclear receptor coactivator 7 (NCOA7) has been associated with autism, although almost nothing is known regarding the mode-of-action of this TLDc protein in the nervous system. Here we investigated the molecular function of NCOA7 in neurons and generated a novel mouse model to determine the consequences of deleting this locus in vivo. We show that NCOA7 interacts with the cytoplasmic domain of the vacuolar (V)-ATPase in the brain and demonstrate that this protein is required for normal assembly and activity of this critical proton pump. Neurons lacking Ncoa7 exhibit altered development alongside defective lysosomal formation and function; accordingly, Ncoa7 deletion animals exhibited abnormal neuronal patterning defects and a reduced expression of lysosomal markers. Furthermore, behavioural assessment revealed anxiety and social defects in mice lacking Ncoa7. In summary, we demonstrate that NCOA7 is an important V-ATPase regulatory protein in the brain, modulating lysosomal function, neuronal connectivity and behaviour; thus our study reveals a molecular mechanism controlling endolysosomal homeostasis that is essential for neurodevelopment.

Graphic abstract

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Autophagy and the endolysosomal system in presynaptic function

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Abstract

The complex morphology of neurons, the specific requirements of synaptic neurotransmission and the accompanying metabolic demands create a unique challenge for proteostasis. The main machineries for neuronal protein synthesis and degradation are localized in the soma, while synaptic junctions are found at vast distances from the cell body. Sophisticated mechanisms must, therefore, ensure efficient delivery of newly synthesized proteins and removal of faulty proteins. These requirements are exacerbated at presynaptic sites, where the demands for protein turnover are especially high due to synaptic vesicle release and recycling that induces protein damage in an intricate molecular machinery, and where replacement of material is hampered by the extreme length of the axon. In this review, we will discuss the contribution of the two major pathways in place, autophagy and the endolysosomal system, to presynaptic protein turnover and presynaptic function. Although clear ly different in their biogenesis, both pathways are characterized by cargo collection and transport into distinct membrane-bound organelles that eventually fuse with lysosomes for cargo degradation. We summarize the available evidence with regard to their degradative function, their regulation by presynaptic machinery and the cargo for each pathway. Finally, we will discuss the interplay of both pathways in neurons and very recent findings that suggest non-canonical functions of degradative organelles in synaptic signalling and plasticity.

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Anatomical basis of erector spinae plane block: a dissection and histotopographic pilot study

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Abstract

Purpose

Erector spinae plane (ESP) block is an interfascial blockade used in different clinical scenarios. This study investigated the ventral extent of dye diffusion in ESP block.

Methods

The ultrasound-guided ESP block was bilaterally performed with an injection at the T5 vertebral level (21-Gauge, 50 mm needle), using diluted black tissue marking dye (20 mL; 1:4 ratio with standard saline solution) instead of local anesthetic on two fresh-frozen corpses within the body donation program of the University of Padova. Subsequently, the gross anatomical dissection was performed by a combined posterior plus anterior approach, and the histotopographic examination completed.

Results

Macroscopically by gross anatomical dissection, the dye spreading ranged on the dorsal side of the chest from T2/3 to T10/11 with an extension up to 10 cm laterally, and on the ventral side of the chest from T2/3–T9/10. Microscopically by histotopographic examination, the dye diffused ventrally to the intercostal spaces (2–3 and 5–6 spaces on the right and left, respectively) by following the blood vessels coupled to the dorsal nerve passing through the costotransverse foramen.

Conclusions

The anterior pathway of dye diffusion from the site of injection within the erector spinae muscle group during an ESP block seems to follow the blood vessels and dorsal rami of spinal nerves, suggesting the passing through the costotransverse foramen to reach the anterior paravertebral space and the intercostal nerves. These findings display an anterior histotopographic diffusion of dye resembling a paravertebral block.

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Topical Probiotics in Dermatological Therapy and Skincare: A Concise Review

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Abstract

Recent studies have produced an increasing body of evidence that the intestinal microbiome plays an essential role in modulating systemic inflammation and skin diseases. The gut microbiome influences and modulates the host immune system, enabling immune tolerance of environmental and dietary antigens and protecting against pathogens. Emerging scientific evidence has demonstrated that oral probiotics can help treat certain skin diseases, such as acne, atopic dermatitis, photoaging, psoriasis, and wound healing. The aim of this paper is to review the current scientific evidence on topical probiotics and their effects on dermatological diseases and skincare and to clarify if the application of exogenous probiotics could also have the same benefit as oral probiotics in promoting positive bacterial balance to treat dermatologic conditions.

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Surgical management of symptomatic cavum septum pellucidum cysts: systematic review of the literature

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Abstract

Cavum septum pellucidum (CSP) and cavum vergae (CV) cysts are commonly found incidentally. They are usually asymptomatic but may present with symptoms related to obstructive hydrocephalus. There is no consensus about the management of symptomatic CSP and CV cysts. We present, to the best of our knowledge, the first systematic review of the different treatment options for symptomatic CSP and CV cysts. We conducted a literature review using PubMed database, searching for cases of symptomatic CSP and CV cysts managed surgically, and published until April 2019. Preoperative characteristics, surgical procedure, and postoperative outcome were analyzed using SPSS® software (Statistical Package for Social Sciences, IBM®). We found 54 cases of symptomatic CSP and CV cysts managed surgically (34 males, 20 females, 1.7/1 male to female ratio). Mean age was 24.3 ± 20.1 years. The most common presentation was headaches (34 patients, 62%), followed by psychiatric s ymptoms (27 patients, 49.1%). Preoperative radiological hydrocephalus was present in 30 patients (54.5%). The most common surgical procedure was endoscopic fenestration (39 patients, 70.9%), followed by shunting (10 patients, 18.2%), open surgery (3 patients, 5.5%), and stereotactic fenestration (1 patient, 1.8%). Complete resolution of symptoms was achieved in 36 patients (65.5%) and partial resolution in 7 patients (12.7%), and symptoms were unchanged in 2 patients. The present review suggests that surgical treatment could provide resolution of the symptoms in most of the cases, regardless of the procedure performed. Although mean follow-up was short among the studies, recurrence rate was low.

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