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Activating mutations in GNAQ/GNA11 occur in over 90% of uveal melanomas (UMs), the most lethal melanoma subtype; however, targeting these oncogenes has proven challenging and inhibiting their downstream effectors show limited clinical efficacy. Here, we performed genome-scale CRISPR screens along with computational analyses of cancer dependency and gene expression datasets to identify the inositol-metabolizing phosphatase INPP5A as a selective dependency in GNAQ/11-mutant UM cells in vitro and in vivo. Mutant cells intrinsically produce high levels of the second messenger inositol 1,4,5 trisphosphate (IP3) that accumulate upon suppression of INPP5A, resulting in hyperactivation of IP3-receptor signaling, increased cytosolic calcium and p53-dependent apoptosis. Finally, we show that GNAQ/11-mutant UM cells and patients' tumors exhibit elevated levels of IP4, a biomarker of enhanced IP3 production; these high levels are abolished by GNAQ/11 inhibition and correlate with sensitivity to INPP5A depletion. Our findings uncover INPP5A as a synthetic lethal vulnerability and a potential therapeutic target for GNAQ/11-mutant-driven cancers., (© 2024. The Author(s).)

Anti-CD19 chimeric antigen receptor T cells (CART) has rapidly been adopted as the standard third-line therapy to treat aggressive B-cell lymphomas (ABCL) after failure of second-line therapy despite the lack of direct comparisons with allogeneic hematopoietic cell transplantation (alloHCT)-based strategies. Using the Grupo Español de Trasplante y Terapia Celular (GETH-TC) registry, we selected patients with the following characteristics: CART or alloHCT performed between 2016 and 2021; ≥18 years old; ABCL diagnosis; ≥2 lines of therapy; and either anti-CD19 CART or alloHCT as therapy at relapse. The analysis included a total of 316 (CART = 215, alloHCT = 101) patients. Median follow-up was 15 and 36 months for the CART and alloHCT cohorts, respectively. In the multivariate analysis, CART was confirmed to be similar to alloHCT for the primary study endpoint (progression-free survival) (hazard ratio [HR] 0.92, CI95%:0.56-1.51, p = 0.75). Furthermore, when the analysis was limited to only patients with chemo-sensitive diseases (complete and partial response) at infusion (CART = 26, alloHCT=93), no differences were reported (progression-free survival at month +18: 65% versus 55%, p = 0.59). However, CART had lower non-relapse mortality (HR 0.34, 95% CI: 0.13-0.85, p = 0.02). Given the lower toxicity and similar survival outcomes, these results suggest the use of CART before alloHCT., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The internal transcribed spacers (ITS) exhibit concerted evolution by the fast homogenization of these sequences at the intragenomic level. However, the rate and extension of this process are unclear and might be conditioned by the number and divergence of the different ITS copies. In some cases, such as hybrid species and polyploids, ITS sequence homogenization appears incomplete, resulting in multiple haplotypes within the same organism. Here, we studied the dynamics of concerted evolution in 85 individuals of seven plant species of the genus Erysimum (Brassicaceae) with multiple ploidy levels. We estimated the rate of concerted evolution and the degree of sequence homogenization separately for ITS1 and ITS2 and whether these varied with ploidy. Our results showed incomplete sequence homogenization, especially for polyploid samples, indicating a lack of concerted evolution in these taxa. Homogenization was usually higher in ITS2 than in ITS1, suggesting that concerted evolution operates more efficiently on the former. Furthermore, the hybrid origin of several species appears to contribute to the maintenance of high haplotype diversity, regardless of the level of ploidy. These findings indicate that sequence homogenization of ITS is a dynamic and complex process that might result in varying intra- and inter-genomic diversity levels., (© 2022. The Author(s).)

Secreted extracellular vesicles (EVs) influence the tumor microenvironment and promote distal metastasis. Here, we analyzed the involvement of melanoma-secreted EVs in lymph node pre-metastatic niche formation in murine models. We found that small EVs (sEVs) derived from metastatic melanoma cell lines were enriched in nerve growth factor receptor (NGFR, p75NTR), spread through the lymphatic system and were taken up by lymphatic endothelial cells, reinforcing lymph node metastasis. Remarkably, sEVs enhanced lymphangiogenesis and tumor cell adhesion by inducing ERK kinase, nuclear factor (NF)-κB activation and intracellular adhesion molecule (ICAM)-1 expression in lymphatic endothelial cells. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased lymph node metastasis and extended survival in pre-clinical models. Furthermore, NGFR expression was augmented in human lymph node metastases relative to that in matched primary tumors, and the frequency of NGFR + metastatic melanoma cells in lymph nodes correlated with patient survival. In summary, we found that NGFR is secreted in melanoma-derived sEVs, reinforcing lymph node pre-metastatic niche formation and metastasis., Competing Interests: Competing Interests Statement The authors have no conflict of interests.

Objective: The objective of this study was to analyse the results of the surgical treatment of coexisting cataract and glaucoma and its effects on corneal endothelial cell density (CECD)., Methods: We include two longitudinal prospective studies: one randomised that included 40 eyes with open angle glaucoma that received one- (n = 20) or two-step (n = 20) phacotrabeculectomy and another that included 20 eyes that received phacoemulsification. We assess the impact of surgery on different clinical variables and in particular in CECD using Confoscan 4™ confocal microscopy and semiautomatic counting methods., Results: Phacoemulsification and phacotrabeculectomy, but not trabeculectomy, increase significantly best-corrected visual acuity and anterior chamber depth and trabeculectomy and one- or two-step phacotrabeculectomy decreased similarly the intraocular pressure. We document percentages of endothelial cell loss of 3.1%, 17.9%, 31.6% and 42.6% after trabeculectomy, phacoemulsification and one- or two-step phacotrabeculectomy, respectively. The coefficient of variation did not increase significantly after surgery but the percentage of hexagonality decreased significantly after phacoemulsification and after two-step phacotrabeculectomy., Conclusions: Trabeculectomy, phacoemulsification and phacotrabeculectomy are surgical techniques that cause morphological changes and decrease the densities of the corneal endothelial cells. Trabeculectomy produces lesser endothelial cell loss than phacoemulsification, and phacoemulsification lesser cell loss than phacotrabeculectomy. Two-step phacotrabeculectomy (trabeculectomy followed 3 months later by phacoemulsification) causes more cell loss than one-step phacotrabeculectomy, and this could be due to the cumulative effects of two separate surgical traumas or to a negative conditioning lesion effect of the first surgery. For the treatment of coexisting glaucoma and cataract, one-step phacotrabeculectomy is the treatment of choice., (© 2020. The Author(s).)

In a subset analysis of data from a 6-month, multicenter, non-interventional study, we compared change in symptoms and quality of life (QoL), and treatment tolerability, in men with moderate to severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving tamsulosin (TAM, 0.4 mg/day) or the hexanic extract of Serenoa repens (HESr, 320 mg/day) as monotherapy. Symptoms and QoL were assessed using the IPSS and BII questionnaires, respectively. Patients in the treatment groups were matched using two statistical approaches (iterative and propensity score matching). Within the iterative matching approach, data was available from a total of 737 patients (353 TAM, 384 HESr). After 6 months, IPSS scores improved by a mean (SD) of 5.0 (4.3) points in the TAM group and 4.5 (4.7) points in the HESr group (p = 0.117, not significant). Improvements in QoL were equivalent in the two groups. TAM patients reported significantly more adverse effects than HESr patients (14.7% vs 2.1%; p < 0.001), particularly ejaculation dysfunction and orthostatic hypotension. These results show that HESr is a valid treatment option for men with moderate/severe LUTS/BPH; improvements in urinary symptoms and QoL were similar to those observed for tamsulosin, but with considerably fewer adverse effects., (© 2021. The Author(s).)

Partial migration, whereby some individuals migrate and some do not, is relatively common and widespread among animals. Switching between migration tactics (from migratory to resident or vice versa) occurs at individual and population levels. Here, we describe for the first time the movement ecology of the largest wintering population of Egyptian Vultures (Neophron percnopterus) in south-west Europe. We combined field surveys and GPS tracking data from December to February during four wintering seasons (2014-2018). The wintering population consisted on average of 85 individuals (range 58-121; 76% adults and 24% subadults). Individuals were counted at five different roosting sites located near farms, unauthorized carcass deposition sites and authorized carcass deposition sites. Our results show that vultures tend to remain close to the roosting site. Moreover, we observed that females exhibited smaller home range sizes than males, which suggests a possible differential use of food sources. Overall, birds relied more on farms than other available food resources, particularly subadult individuals which exploited more intensively these sites. Our results showed that Egyptian Vultures congregate in significant numbers at specific sites throughout the winter period in south-west Spain and that these roosting and feeding sites should be given some level of legal protection and regular monitoring. Furthermore, predictable food sources might be driving the apparent increase in the non-migratory population of Egyptian Vultures, as observed in other avian species which are also changing their migratory behavior.

Representing data as networks cuts across all sub-disciplines in ecology and evolutionary biology. Besides providing a compact representation of the interconnections between agents, network analysis allows the identification of especially important nodes, according to various metrics that often rely on the calculation of the shortest paths connecting any two nodes. While the interpretation of a shortest paths is straightforward in binary, unweighted networks, whenever weights are reported, the calculation could yield unexpected results. We analyzed 129 studies of ecological networks published in the last decade that use shortest paths, and discovered a methodological inaccuracy related to the edge weights used to calculate shortest paths (and related centrality measures), particularly in interaction networks. Specifically, 49% of the studies do not report sufficient information on the calculation to allow their replication, and 61% of the studies on weighted networks may contain errors in how shortest paths are calculated. Using toy models and empirical ecological data, we show how to transform the data prior to calculation and illustrate the pitfalls that need to be avoided. We conclude by proposing a five-point check-list to foster best-practices in the calculation and reporting of centrality measures in ecology and evolution studies.

Salinization is having a major impact on wetlands and its biota worldwide. Specifically, many migratory animals that rely on wetlands are increasingly exposed to elevated salinity on their nonbreeding grounds. Experimental evidence suggests that physiological challenges associated with increasing salinity may disrupt self-maintenance processes in these species. Nonetheless, the potential role of salinity as a driver of ecological carry-over effects remains unstudied. Here, we investigated the extent to which the use of saline wetlands during winter - inferred from feather stable isotope values - induces residual effects that carry over and influence physiological traits relevant to fitness in black-tailed godwits Limosa limosa limosa on their northward migration. Overwintering males and females were segregated by wetland salinity in West Africa, with females mostly occupying freshwater wetlands. The use of these wetlands along a gradient of salinities was associated with differences in immune responsiveness to phytohaemagglutinin and sized-corrected body mass in godwits staging in southern Europe during northward migration - 3,000 km from the nonbreeding grounds - but in males only. These findings provide a window onto the processes by which wetland salinity can induce carry-over effects and can help predict how migratory species should respond to future climate-induced increases in salinity.

Epidemics can spread across large regions becoming pandemics by flowing along transportation and social networks. Two network attributes, transitivity (when a node is connected to two other nodes that are also directly connected between them) and centrality (the number and intensity of connections with the other nodes in the network), are widely associated with the dynamics of transmission of pathogens. Here we investigate how network centrality and transitivity influence vulnerability to diseases of human populations by examining one of the most devastating pandemic in human history, the fourteenth century plague pandemic called Black Death. We found that, after controlling for the city spatial location and the disease arrival time, cities with higher values of both centrality and transitivity were more severely affected by the plague. A simulation study indicates that this association was due to central cities with high transitivity undergo more exogenous re-infections. Our study provides an easy method to identify hotspots in epidemic networks. Focusing our effort in those vulnerable nodes may save time and resources by improving our ability of controlling deadly epidemics.

Within plant populations, space-restricted gene movement, together with environmental heterogeneity, can result in a spatial variation in gene frequencies. In biennial plants, inter-annual flowering migrants can homogenize gene frequencies between consecutive cohorts. However, the actual impact of these migrants on spatial genetic variation remains unexplored. Here, we used 10 nuclear microsatellite and one plastid genetic marker to characterize the spatial genetic structure within two consecutive cohorts in a population of the biennial plant Erysimum mediohispanicum (Brassicaceae). We explored the maintenance of this structure between consecutive flowering cohorts at different levels of complexity, and investigated landscape effects on gene flow. We found that cohorts were not genetically differentiated and showed a spatial genetic structure defined by a negative genetic-spatial correlation at fine scale that varied in intensity with compass directions. This spatial genetic structure was maintained when comparing plants from different cohorts. Additionally, genotypes were consistently associated with environmental factors such as light availability and soil composition, but to a lesser extent compared with the spatial autocorrelation. We conclude that inter-annual migrants, in combination with limited seed dispersal and environmental heterogeneity, play a major role in shaping and maintaining the spatial genetic structure among cohorts in this biennial plant.

The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat's immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8 + T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4 + subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat's immunity, opening up new perspectives of therapeutic interventions for humans.

The psychological, sociological and evolutionary roots of conspecific violence in humans are still debated, despite attracting the attention of intellectuals for over two millennia. Here we propose a conceptual approach towards understanding these roots based on the assumption that aggression in mammals, including humans, has a significant phylogenetic component. By compiling sources of mortality from a comprehensive sample of mammals, we assessed the percentage of deaths due to conspecifics and, using phylogenetic comparative tools, predicted this value for humans. The proportion of human deaths phylogenetically predicted to be caused by interpersonal violence stood at 2%. This value was similar to the one phylogenetically inferred for the evolutionary ancestor of primates and apes, indicating that a certain level of lethal violence arises owing to our position within the phylogeny of mammals. It was also similar to the percentage seen in prehistoric bands and tribes, indicating that we were as lethally violent then as common mammalian evolutionary history would predict. However, the level of lethal violence has changed through human history and can be associated with changes in the socio-political organization of human populations. Our study provides a detailed phylogenetic and historical context against which to compare levels of lethal violence observed throughout our history.

Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.

Ecological interactions are crucial to understanding both the ecology and the evolution of organisms. Because the phenotypic traits regulating species interactions are largely a legacy of their ancestors, it is widely assumed that ecological interactions are phylogenetically conserved, with closely related species interacting with similar partners. However, the existing empirical evidence is inadequate to appropriately evaluate the hypothesis of phylogenetic conservatism in ecological interactions, because it is both ecologically and taxonomically biased. In fact, most studies on the evolution of ecological interactions have focused on specialized organisms, such as some parasites or insect herbivores, belonging to a limited subset of the overall tree of life. Here we study the evolution of host use in a large and diverse group of interactions comprising both specialist and generalist acellular, unicellular and multicellular organisms. We show that, as previously found for specialized interactions, generalized interactions can be evolutionarily conserved. Significant phylogenetic conservatism of interaction patterns was equally likely to occur in symbiotic and non-symbiotic interactions, as well as in mutualistic and antagonistic interactions. Host-use differentiation among species was higher in phylogenetically conserved clades, irrespective of their generalization degree and taxonomic position within the tree of life. Our findings strongly suggest a shared pattern in the organization of biological systems through evolutionary time, mediated by marked conservatism of ecological interactions among taxa.

The response to erythropoietin-stimulating agents (ESA) can vary among different patients and according to the different circumstances over time within a given individual. The aim of this study was to analyze the factors that can modify the response to epoetin in patients on hemodialysis (HD) and its influence on early mortality. Prospective and observational study including 1710 patients from 119 HD units in Spain with a follow-up of 12 months. To evaluate the dose-response effect of EPO therapy, we used the erythropoietin resistance index (ERI), calculated as the weekly weight-adjusted dose of EPO divided by the hemoglobin level. Patients were stratified in three groups according to ERI: group A, ERI <5; group B, ERI=5-15; group C, ERI>15 U/kg/week/g per 100 ml. Mean ERI for the entire group was 10.2+/-7.3 U/kg/week/g per 100 ml. ERI was directly related with incident comorbidity (Charlson Index), age, female gender and low body mass index with no relationship with etiology of chronic kidney disease. Patients with antecedents of heart failure, acute infection or malignant neoplasm had significantly higher ERI than those without. Transferrin saturation index, but not serum ferritin, was inversely related with ERI. Serum levels of albumin and cholesterol were related with lower ERI, but no relation was found with normalized protein catabolic rate. Patients with a permanent catheter for HD had significant higher values of ERI than those with native fistula (P=0.012). One year survival in all three groups of patients according to ERI was 0.916 in group A, 0.877 in group B and 0.788 in group C (log-rank=20.7, P<0.001). The resistance to ESA is directly related with incident comorbidity in patients on hemodialysis and it can be interpreted as a useful marker of early mortality.

Maintenance of target hemoglobin (Hb) values in hemodialysis patients treated with erythropoiesis-stimulating agents (ESAs) remains difficult. We examined Hb variability in the clinical setting in hemodialysis patients. Hemodialysis patients treated with ESAs who maintained the recommended Hb range of 11-13 g per 100 ml over 3 months and were not admitted to hospital, did not require transfusion, and did not experience any major clinical event during this period were followed prospectively for 1 year. Anemia events, Hb variation events (any value out of +/-1.5 g per 100 ml of the median Hb level in the total follow-up period for the individual patient), risk factors for anemia, and Hb variation events were assessed. We studied 420 patients (63% males, mean age 61 years), 222 received short-acting erythropoietin (EPO) and 198 long-acting darbepoetin. A total of 4654 blood samples (mean 11.1 per patient-year) were analyzed. Only 3.8% of patients were maintained within the target Hb levels (11-13 g per 100 ml) during 1 year. Hb variation events occurred in 20.8% of laboratory values and anemia events in 14.7%, with a median time to the first event of 3 months. Treatment with short-acting EPO (vs long-acting darbepoetin), change of ESA dose in the previous visit, resistance index, and hospitalization were significant risk factors for both anemia events and Hb variation events. Our results show that Hb values are rarely maintained within the recommended guidelines even in more stable hemodialysis patients. Hb variability is frequently associated with clinical events or ESA dose changes. Long-acting darbepoetin achieved better Hb stability than short-acting EPO.

The atmospheres of the gas giant planets (Jupiter and Saturn) contain jets that dominate the circulation at visible levels. The power source for these jets (solar radiation, internal heat, or both) and their vertical structure below the upper cloud are major open questions in the atmospheric circulation and meteorology of giant planets. Several observations and in situ measurements found intense winds at a depth of 24 bar, and have been interpreted as supporting an internal heat source. This issue remains controversial, in part because of effects from the local meteorology. Here we report observations and modelling of two plumes in Jupiter's atmosphere that erupted at the same latitude as the strongest jet (23 degrees N). The plumes reached a height of 30 km above the surrounding clouds, moved faster than any other feature (169 m s(-1)), and left in their wake a turbulent planetary-scale disturbance containing red aerosols. On the basis of dynamical modelling, we conclude that the data are consistent only with a wind that extends well below the level where solar radiation is deposited.

Background: Excessive interdialytic weight gain (IDWG) is usually related to an overload of sodium and water, and is the most important factor for arterial hypertension in dialysis. On the other hand, food intake also contributes to IDWG, and is the basic factor for nutrition. The objective of this study is to assess the long-term prognostic effect of IDWG and its relationship with the nutritional status and blood pressure in patients in hemodialysis (HD)., Methods: We describe the results of a 5-year prospective observation study in which 134 HD patients were included (70 males and 64 females), with ages between 18 and 81. Initially, the average data were collected during 4 weeks, including total IDWG and percentages according to dry weight (IDWG%), nutritional parameters, and blood pressure. Patients were divided into 3 cohorts according to IDWG% (<2.9, 2.9-3.9, and >3.9%, respectively). Student t test, ANOVA, linear regression analysis, and Kaplan-Meier survival curves compared with log-rank test were used as statistical tools., Results: The mean IDWG% for the whole studied population was 3.5 +/- 1.1% (1.5-8.0%). It was not related to gender, but had an inverse correlation with age (P < 0.000) and serum bicarbonate level (P= 0.009). It was directly correlated with predialysis systolic and diastolic blood pressure, nPCR, urea and creatinine levels (P < 0.01 for all of them), and the body mass index (P < 0.000). Serum levels of albumin (44.7 +/- 4.0 g/dL) and prealbumin (31.9 +/- 7.4 mg/dL) had a direct correlation with total IDWG (P < 0.01). We found no significant relationship between or IDWG% and ferritin and transferrin levels. Five-year actuarial survival was 0.38, 0.52, and 0.63, respectively, in the 3 cohorts for IDWG% (P < 0.01)., Conclusion: Our results show that a greater IDWG is directly associated with a better nutritional status, although it is also associated with higher predialysis blood pressure. The greater the IDWG%, the better the long-term prognosis of the patients. The beneficial effects of IDWG on the nutritional status and prognosis are greater than the negative aspects that depend on its effects on blood pressure. One must distinguish clearly between some isolated instances of not complying with a diet from those situations where a higher IDWG is merely a reflection of a good nutritional status, and one must be careful so that dietary recommendations will not have a negative influence on nutritional aspects. One must watch and correct the trend towards higher acidosis in patients with a greater IDWG.

Hyperparathyroidism (HPT) is common in patients on dialysis, and parathyroidectomy (PTx) is often required. We present a retrospective, descriptive analysis of data corresponding to 148 patients on dialysis undergoing PTx due to severe refractory HPT (PTH 1401 +/- 497 pg/mL, Ca 10.6 +/- 0.8 mg/dL, P 6.9 +/- 1.7 mg/dL). Demographic data were compared with those recorded in 309 patients on dialysis not subjected to PTx who were managed at the same hospital. In the PTx group, the factors age (49.3 +/- 14 years), male gender (48.6%), and diabetes (0.7%) were significantly lower than in the non-PTx group (61.5 +/- 14.9 years, male gender 59%, diabetes 19.4%), while time on dialysis was longer (8.6 +/- 5.8 vs. 5.5 +/- 5.4 years). In 129 of the study patients (87.4%), four or more glands were identified, and total PTx plus autotransplantation (AT) in the forearm was performed. In the remaining 19 patients, two to three glands were identified, and AT was not undertaken. Four of the 19 patients were successfully operated on again for persistent HPT, seven showed PTH levels <250 pg/mL, and eight maintained severe HPT. Perioperative complications included one death due to cardiac insufficiency, two repeat operations due to bleeding, and one patient with chronic hoarseness. Hospital stay was prolonged in 20% of patients due to a hungry bone syndrome. Among those patients with PTx and AT, HPT recurred in 21 patients (16.2%) at 3.1 +/- 2.3 years. In 13 of these patients, autograft was removed at 7.5 +/- 2.9 years. Serum calcium and phosphate levels improved after PTx, and these results were maintained for 5 years (9.6 +/- 0.8 and 4.2 +/- 1.2 mg/dL, respectively). In conclusion, PTx with AT is a safe option for the treatment of severe HPT that is accompanied by low morbidity and mortality and a good outcome. Medical treatment should not be prolonged at the expense of long repeated bouts of hypercalcemia and/or hyperphosphatemia with their irreversible consequences.

Partial correction of anemia in patients with chronic kidney disease (CKD) improves anemia-related symptoms. However, controversy remains as to whether total correction of anemia provides benefits over and above those afforded by partial correction. There is some evidence showing that normalization of hemoglobin (Hb) concentrations may improve the cardiac hyperdynamic state in CKD patients and reduce the diameter of the left ventricle. Further studies have shown that normalization of Hb improves cognitive function and physical capacities as measured by quality of life (QoL) tests. Large studies have shown that in dialysis patients there is a close inverse relationship between hematocrit (Hct) levels and mortality and morbidity. Moreover, there is evidence suggesting that Hct levels higher than those recommended by European Best Practice Guidelines (EBPG) and the National Kidney Foundation Dialysis Outcome and Quality Initiative (NKF-DOQI provide better outcomes for patients with CKD. However, when Hb concentrations are increased to normal in selected patients with cardiac disease, congestive heart failure, or ischemic cardiopathy, higher mortality rates are evident. Therefore, while the majority of patients with CKD may experience significant benefits when Hb is normalized, it seems prudent to recommend individualized target Hb concentrations for each patient, taking into account factors such as age, sex, employment status, physical activity, and co-morbidities.