Hematocrit and Prohepcidin: Causation or Simply Association?

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Is Nephrology More at Ease Than Oncology with Erythropoiesis-Stimulating Agents? Treatment Guidelines and an Update on Benefits and Risks

Abstract Erythropoiesis-stimulating agents (ESAs), which promote RBC production, have been extensively used to reduce transfusion requirements and improve quality of life (QoL) in both cancer patients and those with chronic kidney disease (CKD). However, the likelihood of response and duration of treatment differ in the two settings. In renal anemia, ESAs act straightforwardly as hormone-replacement therapy. The anemia of cancer, however, relates not to a lack of endogenous erythropoietin production but to diverse aspects of the disease (including a relevant inflammatory component) and chemotherapy. Response to ESAs is slower and less certain than in nephrology. In both settings, early studies showed that reversal of severe anemia was accompanied by substantial improvement in QoL. However, again in both settings, subsequent studies indicated that efforts to normalize hemoglobin might worsen outcome. In the context of cancer, this concern was reinforced by the suggestion that malignant cells had erythropoietin receptors and that its administration might therefore accelerate tumor growth, and moreover that cancer patients are more susceptible to venous thrombosis. The absence of these concerns for nephrologists, and their greater experience in managing ESAs and patients' iron status, may make them more at ease with ESAs than their counterparts in oncology. However, both groups of specialists have had to deal with reversals in recommended thresholds for intervention and restrictions imposed by regulatory authorities. In both specialties, the broad consensus now emerging is that the optimum balance of benefits and risks lies in using ESAs aimed at a hemoglobin level in the range of 11–12 g/dl, although for CKD patients there is still room for an individualized approach

Influence of ellagitannins extracted by pomegranate fruit on disulfide isomerase PDIA3 activity

Pomegranate fruit is a functional food of high interest for human health due to its wide range of phytochemicals with antioxidant properties are implicated in the prevention of inflammation and cancer. Ellagitannins, such as punicalagin and ellagic acid, play a role as anti-atherogenic and neuroprotective molecules in the complex fighting against the degenerative diseases. The aim of this work was to evaluate the composition in punicalagins and ellagic acid of differently obtained extracts from whole fruit, peels and juices, prepared by squeezing or by centrifugation, of pomegranate belonging to different cultivars. Moreover, a wider phenolic fingerprint was also determined. The bioactivity of the extracts was tested on the redox activity of PDIA3 disulfide isomerase, an enzyme involved in the regulation of several cellular functions and associated with different diseases such as cancer, prion disorders, Alzheimer’s and Parkinson’s diseases. The results demonstrate that the different ratios between punicalagin and ellagic acid modulate the enzyme activity and other ellagitannins could interfere with this activity

Inhibition of the Renin-Angiotensin System in Chronic Kidney Disease: A Critical Look to Single and Dual Blockade

The clinical benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) are well established in chronic kidney disease (CKD) patients with diabetic and non-diabetic nephropathies. But despite appearance, the magnitude of this effect has been questioned particularly in mild, proteinuric nephropathies. Given that the single agents can achieve only partial and not durable suppression of the renin-angiotensin system (RAS), it has been hypothesized that dual blockage with ACE inhibitors and ARBs would be most beneficial in the management of progressive CKD than either agent alone. Available evidence indicates significant anti-proteinuric effect, but long-term data in CKD patients are lacking. Recently, the findings of the ONTARGET trial even questioned the safety of this therapeutic approach. Given that preventing cardiovascular complications is extremely important in CKD and RAS inhibition may be useful in this setting, benefits of RAS blockade must be weighed against its possible adverse effects particularly in elderly patients

Clinical benefits of slowing the progression of renal failure

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Translate First Reorder Later: Leveraging Monotonicity in Semantic Parsing

Prior work in semantic parsing has shown that conventional seq2seq models fail at compositional generalization tasks. This limitation led to a resurgence of methods that model alignments between sentences and their corresponding meaning representations, either implicitly through latent variables or explicitly by taking advantage of alignment annotations. We take the second direction and propose TPol, a two-step approach that first translates input sentences monotonically and then reorders them to obtain the correct output. This is achieved with a modular framework comprising a Translator and a Reorderer component. We test our approach on two popular semantic parsing datasets. Our experiments show that by means of the monotonic translations, TPol can learn reliable lexico-logical patterns from aligned data, significantly improving compositional generalization both over conventional seq2seq models, as well as over a recently proposed approach that exploits gold alignments.Comment: 8 pages, 4 figures, 4 table

Endoscopic Endonasal Odontoidectomy Preserving Atlantoaxial Stability: a Pediatric Case

Abstract Objectives We illustrate endoscopic endonasal odontoidectomy for the Chiari-I malformation respecting craniovertebral junction (CVJ) stability. Design Case report of a 12-year-old girl affected by the Chiari-I malformation. Magnetic resonance imaging (MRI) showed tonsillar herniation, basilar invagination, and dental retroversion, causing angulation and compression of the bulbomedullary junction. Patient underwent endoscopic third ventriculostomy (ETV) with reduction of ventricular size and resolution of gait disturbances, but she complained the Valsalva-induced headaches, hiccup, and dysesthesias in the lower limbs. Endoscopic endonasal odontoidectomy was chosen to decompress the cervicomedullary junction. Setting The research was conducted at University Hospital "Ospedale di Circolo," Department of Neurosurgery at Varese in Italy. Participants Patients were from neurosurgical and ENT (ear, nose, and throat) skull base team. Main Outcome Measures A bilateral paraseptal approach was performed, using a four-hand technique. After resection of posterior edge of the nasal septum, the choana is entered and a rhinopharynx muscle–mucosal flap is dissected subperiosteal and transposed in oral cavity. The CVJ is exposed and, using neuronavigation and neuromonitoring, odontoidectomy is fulfilled until dura is reached, preserving the anterior arch of C1. Reconstruction is obtained suturing the flap previously harvested. Results Postoperative course was unremarkable and the patient experienced improvement of symptoms. Postoperative MRI documented the appearance of tight cerebrospinal fluid (CSF) film anterior to bulbomedullary junction and in retrotonsillar spaces, opening of the bulbomedullary angle, and slight tonsils reduction. No CVJ instability was occurred with any need of posterior fixation. Conclusion Endoscopic endonasal odontoidectomy is a feasible approach for CVJ malformation. In this case, bulbar decompression was achieved preserving CVJ stability and avoiding posterior fixation.The link to the video can be found at: https://youtu.be/VIobocHfCuc