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Background and Aims A 21 year old boy with a diagnosis of Autosomal Recessive Polycystic Kidney Disease and Caroli disease reached a final stage of chronic kidney disease (CKD) and started haemodialysis. Method After 3 years in haemodialysis he underwent a kidney transplant from a cadaveric donor. His transplanted kidney worked fairly well until the patients was 31 year old when he developed graft dysfunction (serum creatinine from 2.7 to 5 mg/dL in a very short period). There was a concomitant increase in serum phosphate levels (8.3 mg/dl) and iPTH that progressively increased to 1032 pg/ml despite a traditional therapy. Results At age 32, the patient returned to haemodialysis treatment thrice weekly with a concomitant a progressive worsening of hyperparathyroidism with bone pain . Cinacalcet at a dosage of 30 mg daily treatment was initiated, then it was increased to 120 mg daily without any benefit. Two years later, being the clinical situation without any improvement and being the patient scarcely compliant to the therapy and because a further enlargement of parathyroid glands was observed, a Parathyroidectomy (PTX) was advised. Nevertheless, PTX was not performed because of patient’s refusal. Furthermore, despite Erythropoietic Stimulating Agent (ESA) therapy, he developed severe anemia that required regular and frequent blood transfusions. iPTH increased to 4500 pg/ml [Fig.1] with a parallel rise in alkaline phosphatase >600 UI/L [Fig.2]. A Computed Tomography scan showed multiple bone-thickening lesions. He thus initiated Etelcalcetide 5 mg e.v. 3 times a week, after the HD session but without any benefit. The dosage was then increased to 7.5 mg but the patient gradually became frail and developed pancytopenia and low-grade fever. Hematological evaluation with bone marrow biopsy was performed in December 2019. Bone marrow histology showed severe fibrosis [Myelofibrosis (MF) grade 3] with normal bone marrow cytogenetics. Blood samples for mutations in JAK-2, CALR, and MPL and BCR-ABL rearrangement were negative. There was no evidence for a myeloproliferative neoplasm (MPN) or metastatic lesions. During the following months, while on a 7,5 mg dose of etalcalcetide, there was a gradual reduction in iPTH [Fig.1] and serum alkaline phosphatase [Fig.2], up to 500 pg/dl and 200 IU/L respectively. The patient developed asymptomatic, often severe, hypocalcemia which was managed with therapy. The patient’s clinical conditions gradually improved, anemia responded to lower doses of ESAs. A bone marrow biopsy was repeated after one year (December 2020) and it showed a reduction in fibrosis (MF grade varying from 1-2). Then etelcalcetide dosage was reduced while serum calcium and phosphate levels were in the normal limit. Conclusion Myelofibrosis secondary to renal osteodystrophy is an uncommon complication. It has been rarely reported and usually is associated with primary hyperparathyroidism. Marrow fibrosis and pancytopenia is related to the excessive iPTH that upregulates production of cytokines and paracrine factors in the bone marrow (IL-1a, IL-6, FNF-a, TGF–b, and platelet-derived growth factor) and it has an important stimulatory effect on fibroblast proliferation. It is known that surgical parathyroidectomy is associated with a reduction of bone marrow fibrosis in primary hyperparathyroidism. To our knowledge, this is probably the first case of tertiary hyperparathyroidism in which the effect of etelcalcetide is comparable to parathyroidectomy as far as on calcium-phosphate balance, and a significant improvement in bone marrow fibrosis and hemoglobin. In conclusion, etelcalcetide at least in this patient seems as effective as PTX on bone balance, bone marrow and anemia.

Background and Objectives. About 5% of the world’s population is affected by diabetes; these patients must be further treated during medical and surgical treatments. These patients, due to the glycemic conditions, realize during their life multiorgan changes, in different body districts. Moreover, this condition obliges them to undertake hypoglycemic therapies. Diabetes is a risk factor for many diseases, including those concerning the oral district with immunological implications. Materials and Methods. A comprehensive review of the literature was conducted according to PRISMA guidelines accessing the NCBI PubMed database. Authors conducted the search of articles in English language. The results of the last 10 years have been considered, which present useful information regarding the oral conditions. A total of 17 relevant studies were included in the review. The study evaluated only papers with specific inclusion criteria regarding oral health. The works initially taken into consideration were 782; subsequently applying the inclusion and exclusion criteria, there were 42 works. After a careful analysis of the work obtained by two academics who have worked separately, there have been 17 studies. All data from the studies were compared and many of these confirmed alteration in the oral district. Results. The studies taken into consideration evaluated different factors, such as OHRQoL, QoL, and oral alterations, involving soft tissue, dental structures, and postrehabilitative complications, as well as immunological alterations. Conclusions. We can affirm, in conclusion, that this study has brought to light those that are complications due to diabetic pathology, from different points of view. The psychological and psychosocial alterations, certainly present in these patients, are probably due to local and systemic alterations; this is confirmed by the correlation between oral health and quality of life reported by the patients.

We introduce a general scheme to consistently truncate equations of motion for Green's functions. Our scheme is guaranteed to generate physical Green's functions with real excitation energies and positive spectral weights. There are free parameters in our scheme akin to mean field parameters that may be determined to get as good an approximation to the physics as possible. As a test case we apply our scheme to a two-pole approximation for the 2D Hubbard model. At half-filling we find an insulating solution with several interesting properties: it has low expectation value of the energy and it gives upper and lower Hubbard bands with the full non-interacting bandwidth in the large U limit. Away from half-filling, in particular in the intermediate interaction regime, our scheme allows for several different phases with different number of Fermi surfaces and topologies., Comment: 12 pages, 17 figures

Lung congestion and frank pulmonary edema are established complications of acute kidney injury (AKI) and early detection and monitoring of lung congestion may be useful for the clinical management of AKI patients.We compared standardized clinical criteria (including lung crackles and peripheral edema grading) and simultaneous chest ultrasound (US) to detect lung congestion in a series of 39 inpatients with AKI.At baseline, twelve patients (31%) were clinically euvolemic and twelve presented clear-cur cardiovascular congestion (31%) by clinical criteria. Fifteen patients (38%) were hypovolemic. The median number of US-B lines in patients with cardiovascular congestion was much higher (50, inter-quartile range 27-99) than in euvolemic (14, IQR 11-37) and hypovolemic patients (7, IQR 3-16, P 0.001). Remarkably, a substantial proportion of asymptomatic euvolemic (66%) and hypovolemic (46%) patients had lung congestion of moderate to severe degree ( 15 US-B lines) by lung US. Crackles severity and the number of US-B lines over time were inter-related (Spearman's ρ = 0.38, P 0.01) but the agreement (Cohen k statistics) between the two metrics was unsatisfactory. Forty-eight percent of patients had lung congestion of moderate to severe degree by lung US and this estimate by far exceeded that by clinical criteria (32%).This pilot study shows that chest US has potential for the detection of lung congestion at a pre-clinical stage in AKI. The results of this pilot study form the basis for a clinical trial testing the usefulness of this technique for guiding lung congestion treatment in patients with AKI.

This manuscript aims to highlight all the clinical features of the herpes virus, with a particular focus on oral manifestations and in the maxillofacial district about Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2). Oral herpes virus is a very common and often debilitating infectious disease for patients, affecting oral health and having important psychological implications. The collection of relevant data comes from the scientific databases Pubmed, Embase; initially this collection obtained an extremely high number of results, 1415. After applying the inclusion and exclusion criteria, as well as a manual screening, the results included in this review were limited to 14. The results were expressed by evaluating all the signs and symptoms that this pathology entails during the study, paying attention to the characteristics linked to the quality of life and the psychological implications. This pathology has numerous therapies, which often make the healing phase of the manifestations of this viral pathology more comfortable. The therapies currently used for the treatment of this viral infection are pharmacological, topical, systemic, or instrumental, for example with laser devices.

An alternatively spliced transcript of human AQP4 that lacks exon 4 is identified. In transfected cells, AQP4-Δ4 shows no water transport properties, is retained in the ER, and has a dominant-negative effect on full-length AQP4. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein in different muscles., Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue. Here we report the identification and functional analysis of an alternatively spliced transcript of human AQP4, AQP4-Δ4, that lacks exon 4. In transfected cells AQP4-Δ4 is mainly retained in the endoplasmic reticulum and shows no water transport properties. When AQP4-Δ4 is transfected into cells stably expressing functional AQP4, the surface expression of the full-length protein is reduced. Furthermore, the water transport activity of the cotransfectants is diminished in comparison to transfectants expressing only AQP4. The observed down-regulation of both the expression and water channel activity of AQP4 is likely to originate from a dominant-negative effect caused by heterodimerization between AQP4 and AQP4-Δ4, which was detected in coimmunoprecipitation studies. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein and is physiologically associated with different types of skeletal muscles. The expression of AQP4-Δ4 may represent a new regulatory mechanism through which the cell-surface expression and therefore the activity of AQP4 can be physiologically modulated.

INTRODUCTION Hypertension remains a major problem in hemodialysis (HD) patients. METHODS We performed a pragmatic trial (Pragmatic Clinical Intervention on Blood Pressure Driven by Audit [CLINIDEA]) testing the effectiveness and safety of a 6-month multimodal intervention in hypertensive HD patients regarding the application of higher ultrafiltration (UF) rates or longer or more frequent dialyses in UF-intolerant patients, and an educational intervention to encourage patients to lower their salt and fluid intake. RESULTS Blood pressure (BP) in hypertensive patients (n=32) fell from 156.8 ± 13.3 / 81.1 ± 8.9 mm Hg to 147.9 ± 18.8 / 77.5 ± 11.1 mm Hg. UF intensification was well tolerated, and the BP goal was achieved without resorting to longer or more frequent dialyses. BP changes were paralleled by a consistent (p

Adiponectin is markedly increased in patients with nephrotic series of proteins spanning from TNF- and angiotensin- syndrome and is related to metabolic risk factors. ogen to plasminogen activator inhibitor type-1 and leptin. Background. Adiponectin (ADPN), the gene product of These proteins impinge upon important body functions apM1, is the most abundant secretory protein of the adipose ranging from inflammation, hematopoiesis, and immu- tissue in human plasma. Altered regulation (reduced synthesis) nomodulation, to sympathetic activity (1). Of particular of this substance may be relevant to endothelial dysfunction and cardiovascular complications in patients with ESRD. interest is the emerging hypothesis that disordered endo- Methods. We investigated the relationship between plasma crine function of the adipocyte may contribute to cardio- ADPN, glomerular filtration rate (GFR) (plasma iohexol clear- vascular disease (2), a concept supported by the observa- ance), and metabolic risk factors in 16 patients with nephrotic tion that high fat mass is associated to raised plasma syndrome, in 25 patients with chronic nephropathies without concentration of vasculotoxic cytokines, such as TNF, nephrotic syndrome, and in 31 healthy subjects. Results. Plasma ADPN was much higher (P 0.01) in pa- and to high circulating levels of leptin, which is a recog- tients with nephrotic syndrome (24.4 14.9 g/mL) than in nized sympathetic trigger and a predictor of cardiovascu- patients with chronic nephropathies without nephrotic syndrome lar events (3). Adiponectin (ADPN) is the most abundant (12.3 7.2 g/mL) and healthy subjects (5.9 2.6 g/mL). In adipose tissue protein in human plasma (4). ADPN is a the aggregate 24-hour, proteinuria (r 0.53, P 0.01) and particularly interesting compound because it may have serum cholesterol (r 0.53, P 0.01) were strong and direct correlates of plasma ADPN, while serum albumin correlated a protective influence on the cardiovascular system. In- inversely (r 0.46, P 0.01) with this protein. Proteinuria deed, it suppresses the attachment of monocytes to endo- appeared to be an important confounder of the relationship thelial cells and modulates the endothelial response to between ADPN and the GFR because in the whole patient inflammatory stimuli (5) The potential protective role population (with and without nephrotic syndrome), this rela- tionship emerged only after data adjustment for 24-hour pro- of adiponectin in human diseases is supported by the teinuria (partial r0.31, P 0.05), while no such relationship observation that plasma ADPN is low in patients with was demonstrable on crude data analysis (r 0.03, P 0.87). coronary artery disease (5) and in patients with type 2 Conclusions. ADPN is markedly increased in patients with diabetes mellitus (6). nephrotic syndrome, and proteinuria is strongly related to cir- Renal insufficiency is a notorious trigger of cardiovas- culating ADPN in patients with nephrotic and non-nephrotic renal diseases. The relationships between plasma ADPN, se- cular complications because, in this condition, endothe- rum cholesterol, and serum albumin suggest that this adipocyte lial dysfunction and atherosclerosis are almost universal. protein may serve to mitigate endothelial damage triggered by Preliminary observations in our laboratory indicated that dyslipidemia and other risk factors in patients with chronic ADPN is inversely related to creatinine clearance (7); renal diseases. this finding has been recently confirmed in a large survey in patients with dyslipidemia (8). Furthermore, we have also shown that ADPN is markedly increased in patients In the last decade substantial evidence has been ac- with ESRD (9). However, it is unknown whether the crued showing that the adipose tissue produces a large increase in plasma ADPN observed in patients with renal diseases depends purely on accumulation of this protein † Deceased. or represents a counter-regulatory response to the sev- eral metabolic and hemodynamic risk factors of renal

From an evolutionary perspective, Darwinian selection has favored insulin-resistant individuals, ie, those with a trait ensuring brain functioning in situations of extreme fuel deprivation. The ability to mount a powerful inflammatory response to infection was another survival advantage in our ancestors, and we now have solid evidence showing that these 2 traits, insulin resistance and inflammation (as measured by serum C-reactive protein [CRP]), are associated in modern human beings. In an analysis of 192 nondiabetic hemodialysis patients, leptin and adiponectin were related in an opposite fashion with insulin sensitivity in end-stage renal disease (ESRD) and interacted in determining insulin resistance in these patients. The risk of insulin resistance was about 6 times higher in ESRD patients with an unfavorable combination of the 2 adipokines (high leptin and low adiponectin) than in those with a favorable combination (low leptin and high adiponectin). Low adiponectin but not high leptin predicted incident cardiovascular events in this cohort. Neither leptin nor adiponectin were associated with CRP in a cross-sectional analysis, but they were linked in an opposite fashion to CRP in a longitudinal study in 21 patients with acute inflammation secondary to infection. High sympathetic activity predicts adverse cardiovascular outcomes in ESRD. Of note, we found that the risk for cardiovascular events is more than 3 times higher in patients with high sympathetic activity and low adiponectin than in those with high adiponectin and low sympathetic activity. The adipocyte hormones leptin and adiponectin are associated in an opposite fashion to insulin sensitivity and inflammation in ESRD patients. Relatively lower plasma adiponectin levels are associated with a higher rate of incident cardiovascular events. Finally, low adiponectin and high norepinephrine seem to be interacting factors in the dismal cardiovascular outcomes with ESRD.

ALTAMURA, G., ET AL.: Emergency Cardiac Pacing for Severe Bradycardia. Our study included the treatment of transcutaneous cardiac pacing (TCP) in 32 patients: (A) 19 patients were treated in the emergency area for complete symptomatic AV block before endocavitary pacing; (B) five patients were in asystole following DC shock or out-of-hospital cardiac arrest; and (C) eight patients were affected by bifascicular block undergoing emergency surgery and were treated in order to prevent complete AV block. Two transcutaneous stimulators were used. PaceAid-CRC model 50/52 with 20-msec pulse width; the electrodes were positioned on the V, ECG position and on the back. Results: in all but two patients, it was possible to obtain stable cardiac capture; in one patient arrived in hospital in asystole after prolonged cardiac arrest and in the other one was affected by complete AV block, TCP was ineffective. In groups A and B, TCP was maintained for a mean time of 15 minutes; in group C, TCP was tested in all patients, but performed in only one patient during surgery. Mean threshold was 81 mA. Stimulation was well tolerated in all but five patients. TCP is a reliable, noninvasive method that offers the possibility to initiate pacing within seconds and can be used by medical staff. In our opinion, it should be considered as the first choice emergency treatment of severe symptomatic bradycardia. In asystole, beneficial effects can be obtained only if TCP is performed early enough after the onset of arrhythmia.