The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy.

Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12 yr; 18 women), before and 6 mo after parathyroidectomy (PTx). We examined the relationships among CKD-mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-ß), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-ß (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1ß, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx.

Corneal and Coronary Calcification in Maintenance Hemodialysis: The Face Is No Index to the Heart.

Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly evaluated in this population. Whether CCC correlates with coronary artery calcification remains unknown since studies so far have relied on methods with low sensitivity. Our objective was to test the relationship between CCC and coronary calcification based on tomography. This was a cross-sectional study that included patients on maintenance dialysis. Clinical, demographic, and biochemical data (calcium, phosphorus, parathormone, alkaline phosphatase, and 25(OH)-vitamin D) were recorded. Hyperparathyroidism was defined as parathyroid hormone (PTH) > 300 pg/mL. CCC was evaluated by anterior segment optical coherence tomography (AS-OCT), and coronary calcium scores (Agatston method) were assessed by computed tomography. We compared no/mild with moderate/severe CCC. Twenty-nine patients were included (49.6 ± 15.0 years, 62.1% female, on hemodialysis for 5.7 [2.7-9.4] years, 17.2% with diabetes mellitus, 75.9% with hyperparathyroidism). CCC was found in 82.7% of patients, with median scores of 9 (3, 14.5), ranging from 0 to 16. CCC was classified as absent/mild, moderate, and severe in 27.6%, 20.7%, and 51.7%, respectively. Coronary calcification was found in 44.8% of patients, with median scores of 11 (0, 464), varying from 0 and 6456. We found no significant correlation between coronary calcium scores and CCC (r = 0.203, p = 0.282). Hyperphosphatemia was more frequent in patients with moderate/severe CCC than in those with absent/mild CCC. We concluded that CCC was frequent in patients with CKD on dialysis and did not correlate with coronary calcium scores. Hyperphosphatemia appears to contribute to CCC. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Older patients are less prone to fast decline of renal function: a propensity-matched study.

PURPOSE: Despite CKD is common among older patients, and although factors associated with CKD progression have been explored over decades, little is known about the decline of renal function specifically in older individuals. METHODS: We included adult patients with CKD on conservative management in a propensity-score matched study 1:1 older (> 65 year) and young (≤ 65 yr). Factors associated with the slope of the decline of eGFR such as proteinuria, initial eGFR, diabetes, sex, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor block (ACEI/ARB) were analyzed. Inclusion criteria were at least two consultations in the service and an initial eGFR lower than 45 ml/min/m2, in the period between January 2012 and December 2017. RESULTS: Crude analysis of eGFR decline shows a slower progression of older patients when compared to younger patients in both absolute change [- 2.0 (- 4.5, - 1.0) vs. -3.0 (- 7.0, - 1.0) ml/min/1.73m2, p < 0.001] and slope of eGFR reduction [- 2.2 (- 4.4, - 1.0) vs. 3.1 (- 6.7, - 1.2)) ml/min/1.73m2, p < 0.001]. Patients considered fast progressors (> 5 ml/min/1.73 m2/year decline in eGFR) were less likely to be older (35.2% young vs. 22.0% older, p < 0.001). Adjusted logistic multivariate regression confirmed that older patients had less odds ratio of eGFR decline, independently of the presence of proteinuria, diabetes, ACEI/ARB use, sex, baseline eGFR, baseline phosphate and baseline 25(OH) vitamin D. CONCLUSION: Older patients present slower CKD progression even after multiple adjustments. This information should be taken into consideration while treating these patients on conservative management and should be kept in mind while planning dialysis start.

Self-reported and objective sleep duration in patients with CKD: are they telling the same story? / Duração do sono autorrelatada e objetiva em pacientes com DRC: contam a mesma história?

Abstract Introduction: There is disagreement between data on sleep duration obtained from questionnaires and objective measurements. Whether this is also true for individuals with CKD is unknown. Here we compared self-reported sleep duration with sleep duration obtained by actigraphy. Methods: This prospective study included adult individuals with stage 3 CKD recruited between September/2016 and February/2019. We evaluated subjective sleep duration by asking the following question: "How many hours of actual sleep did you get at night?" Results: Patients (N=34) were relatively young (51 ± 13 years). Self-reported and measured sleep duration were 7.1 ± 1.7 and 6.9 ± 1.6 hours, respectively, with no correlation between them (p=0.165). Although the mean difference between measurements was 0.21 h, the limits of agreement ranged from -3.7 to 4.1 h. Conclusion: Patients with CKD who are not on dialysis have an erroneous sleep perception. Data on sleep duration should be preferentially obtained from objective measurements in patients with CKD.

Resumo Introdução: Há discordância entre os dados sobre duração do sono obtidos a partir de questionários e medições objetivas. Não se sabe se isto também é verdade para indivíduos com DRC. Aqui comparamos a duração do sono autorrelatada com a duração do sono obtida por meio de actigrafia. Métodos: Este estudo prospectivo incluiu indivíduos adultos com DRC estadio 3 recrutados entre Setembro/2016 e Fevereiro/2019. Avaliamos a duração subjetiva do sono, fazendo a seguinte questão: "Quantas horas de sono real você teve à noite?" Resultados: Os pacientes (N=34) eram relativamente jovens (51 ± 13 anos). A duração do sono autorrelatada e mensurada foi de 7,1 ± 1,7 e 6,9 ± 1,6 horas, respectivamente, sem correlação entre elas (p=0,165). Embora a diferença média entre as medições tenha sido de 0,21 h, os limites de concordância variaram de -3,7 a 4,1 h. Conclusão: Pacientes com DRC que não estão em diálise apresentam uma percepção equivocada do sono. Dados sobre a duração do sono devem ser obtidos preferencialmente a partir de medições objetivas em pacientes com DRC.

Assessment of drinking water safety in the Netherlands using nationwide exposure and mortality data.

BACKGROUND: Although drinking water in the Netherlands is generally accepted as safe, public concern about health risks of long-term intake still exist. OBJECTIVE: The aim was to explore associations between drinking water quality for nitrate, water hardness, calcium and magnesium and causes-of-death as related to cardiovascular diseases amongst which coronary heart disease and colorectal cancer. METHODS: We used national administrative databases on cause-specific mortality, personal characteristics, residential history, social economic indicators, air quality and drinking water quality for parameters specified by the EU Drinking Water Directive. We put together a cohort of 6,998,623 persons who were at least 30 years old on January 1, 2008 and lived for at least five years on the same address. The average drinking water concentration over 2000-2010 at the production stations were used as exposure indicators. We applied age stratified Cox proportional hazards models. RESULTS: Magnesium was associated with a reduced risk for mortality due to coronary heart diseases: HR of 0.95 (95% CI: 0.90, 0.99) per 10 mg/L increase. For mortality due to cardiovascular diseases, a 100 mg/L increase in calcium was associated with a HR of 1.08 (95% CI: 1.03, 1.13) and an increase of 2.5 mmol/L of water hardness with a HR of 1.06 (95% CI: 1.01, 1.10). The results show an elevated risk for coronary heart disease mortality at calcium concentrations below 30 mg/L, but over the whole exposure range no exposure response relation was observed. For other combinations of drinking water quality parameters and cause-specific mortality studied, no statistical significant associations were identified. CONCLUSION: We identified in this explorative study a protective effect of magnesium for the risk of mortality to coronary heart disease. Also we found an increased risk of mortality due to cardiovascular disease associated with the concentration of calcium and the water hardness in drinking water.

Hyperuricemia is associated with secondary hyperparathyroidism in patients with chronic kidney disease.

PURPOSE: Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism. METHODS: This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65 pg/ml. RESULTS: Our patients were mostly Caucasian women, with a mean age of 64 ± 16 years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol. CONCLUSION: Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated.

Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis / Consequências esqueléticas e cardiovasculares de um balanço positivo de cálcio durante a hemodiálise

Abstract Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.

Resumo Pacientes em hemodiálise são expostos ao cálcio, por meio do dialisato, pelo menos três vezes por semana. As alterações no cálcio sérico variam de acordo com a transferência de massa de cálcio durante a diálise, que é dependente do gradiente entre a concentração de cálcio no plasma e no dialisato (d [Ca]) e o estado de renovação do esqueleto que altera a capacidade do osso de incorporar cálcio. Embora subestimado, o d [Ca] pode potencialmente causar balanço positivo de cálcio que leva a danos em órgãos sistêmicos, incluindo associações com mortalidade, disfunção miocárdica, tolerabilidade hemodinâmica, calcificação vascular e arritmias. A fisiopatologia desses efeitos adversos inclui alterações do cálcio sérico, supressão do hormônio da paratireóide e calcificação vascular por meio de efeitos diretos e indiretos. Alguns órgãos são mais suscetíveis a alterações na homeostase do cálcio. Nesta revisão, discutimos os dados existentes e os mecanismos potenciais que ligam o d [Ca] ao equilíbrio do cálcio com a consequente disfunção no esqueleto, miocárdio e artérias.

The disparity of measuring bone mineral content using bioimpedance and dual-energy absorptiometry in the context of hyperparathyroidism / A disparidade nos valores do conteúdo mineral ósseo medido usando bioimpedância e absorciometria de dupla energia no contexto do hiperparatireoidismo

Abstract Introduction: Body composition is critical for the evaluation of patients with Chronic Kidney Disease (CKD) and can be obtained from either multifrequency bioelectrical impedance analysis (BIA) or dual-energy absorptiometry (DXA). Although the discrepancy between the results obtained from both methods has already been described, reasons are unknown, and might be related to secondary hyperparathyroidism, which is associated with bone loss. Methods: We have evaluated 49 patients (25 males and 24 females): 20 with CKD not on dialysis and 29 on maintenance hemodialysis [18 with severe hyperparathyroidism (HD-SHPT) and 11 submitted to parathyroidectomy (HD-PTX)]. All patients underwent DXA and BIA. Results: The median age and body mass index (BMI) were 49 years and 25.6 kg/m2, respectively. Patients exhibited low bone mineral content (BMC) measured by DXA, particularly those from the HD-SHPT group. The largest BMC measurement disagreement between DXA and BIA was found in the HD-SHPT group (p=0.004). Factors independently associated with this discrepancy in BMC measurement were serum phosphate (p=0.003) and patient group (p=0.027), even after adjustments for age, BMI, and gender (adjusted r2=0.186). PTX attenuated this difference. Discussion: BIA should be interpreted with caution in patients with SHPT due to a loss of accuracy, which can compromise the interpretation of body composition.

Resumo Introdução: A composição corporal é fundamental para a avaliação de pacientes com Doença Renal Crônica (DRC), e pode ser obtida por análise de impedância bioelétrica por multifrequência (BIA) ou absorciometria de dupla energia (DXA). Embora a discrepância entre os resultados obtidos pelos dois métodos já tenha sido descrita, os motivos são desconhecidos e podem estar relacionados ao hiperparatireoidismo secundário, devido à perda óssea. Métodos: Avaliamos 49 pacientes (25 homens e 24 mulheres): 20 com DRC não em diálise e 29 em hemodiálise de manutenção [18 com hiperparatireoidismo grave (HD-SHPT) e 11 submetidos à paratireoidectomia (HD-PTX)]. Todos os pacientes foram submetidos à DXA e BIA. Resultados: A mediana da idade e do índice de massa corporal (IMC) foram de 49 anos e 25,6 kg/m2, respectivamente. Os pacientes exibiram baixo conteúdo mineral ósseo (CMO) medido pelo DXA, particularmente aqueles do grupo HD-SHPT. A maior discordância da medida do CMO entre DXA e BIA foi encontrada no grupo HD-SHPT (p = 0,004). Os fatores independentemente associados a essa discrepância na medida do CMO foram fosfato sérico (p = 0,003) e grupo de pacientes (p = 0,027), mesmo após ajustes para idade, IMC e sexo (r2 ajustado = 0,186). PTX atenuou essa diferença. Discussão: A BIA deve ser interpretada com cautela em pacientes com HPTS devido a uma perda de precisão, o que pode comprometer a interpretação da composição corporal.

Corneal and Conjunctival Calcification in a Dialysis Patient Reversed by Parathyroidectomy.

Mineral and bone metabolism disorders are relatively common among patients with end-stage renal disease on maintenance hemodialysis. Corneal and conjunctival calcification is the main extravascular site for calcification. Recently, this form of calcification has been linked to vascular calcification. Secondary hyperparathyroidism can lead to high levels of calcium and phosphorus and increase the risk of calcification. Here, we report a case of a 38-year-old female with severe hyperparathyroidism who underwent eye examination before and after parathyroidectomy. Anterior segment optical coherence tomography showed an improvement in the number and size of ocular calcifications 6 months after surgery. This case calls attention to the importance of eye examination in patients on dialysis and brings the possibility of recovery of calcification in a short-term follow-up.

Association of parathormone and alkaline phosphatase with bone turnover and mineralization in children with CKD on dialysis: effect of age, gender, and race.

BACKGROUND: Studies investigating bone histology in children with chronic kidney disease (CKD) are scarce. METHODS: Forty-two patients, mean age 11.3 ± 4.3 years with stage 5 CKD on dialysis, underwent double tetracycline labeling bone biopsy and the relationship between clinical features, biochemical markers, and bone densitometry (DXA) was investigated. RESULTS: Low bone turnover was present in 59% of patients, abnormal mineralization in 29%, and low bone volume in 7%. Higher bone formation rate was found in non-Caucasian patients, whereas abnormal mineralization occurred in older and shorter children. We found no impact of gender and etiology of renal disease in our population. Parathormone (PTH) and alkaline phosphatase (AP) showed positive associations with bone turnover. ROC curve analysis showed a fair performance of biomarkers to predict TMV status. PTH < 2 times ULN independently associated with low bone turnover (RR 5.62, 95% CI 1.01-31.24; p = 0.049), in a model adjusted for race, calcitriol dosage, and calcium. It was also associated with abnormal mineralization (RR 1.35, 95% CI 1.04-1.75; p = 0.025), in a model adjusted for BMD scores, AP, age, and calcitriol. PTH and AP significantly predicted turnover and mineralization defect, although with low specificity and sensitivity, reaching a maximum value of 64% and 67%, respectively. CONCLUSIONS: While PTH and AP were associated with turnover and mineralization, we recognize the limitation of their performance to clearly distinguish high from low/normal bone turnover and normal from abnormal mineralization. Our results reinforce the need to expand knowledge about renal osteodystrophy in pediatric population through prospective bone biopsy studies. Graphical abstract.

Mortality of Patients on Maintenance Hemodialysis Submitted to Coronary Artery Bypass Surgery.

BACKGROUND: Patients with chronic kidney disease (CKD) are less likely to be submitted to coronary artery bypass grafting (CABG) then clinical medical treatment based on the potential high risk of mortality. However, whether patients on maintenance dialysis who underwent an elective CABG experience high hospital- and long-term mortality is still debatable. METHODS: This is a prospective observational study that evaluated patients who underwent elective CABG. Three groups were compared: reference (n = 167, estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2), CKD3-4 (n = 84, eGFR 15-59 mL/min/1.73 m2), and maintenance hemodialysis (n = 31). Demographic, clinical, biochemical, fluid balance data, and Sequential Organ Failure Assessment (SOFA) scores were assessed daily for the same observer from day 1 (surgery) to hospital discharge. RESULTS: The main outcomes were in-hospital and 1-year mortality. Patients aged 63 ± 10, 63 ± 8, and 65 ± 6 years old, in reference, CKD3-4, and dialysis groups, respectively (p = 0.605). Patients from the reference group had a lower prevalence of diabetes (p = 0.010) and hypertension (p = 0.021). SOFA scores were higher in CKD3-4 and dialysis groups (p = 0.001), though this difference disappeared without the renal component (p = 0.326). In-hospital mortality (n = 17) was similar across groups (p = 0.955). There was no difference in 1-year mortality among groups even after adjustments for age, diabetes, intraoperative blood loss, and time on ventilation. CONCLUSIONS: CABG short-term mortality seems not to be greater among selected patients on maintenance dialysis. A multidisciplinary team has been helping cardiologists and cardiac surgeons in the decision-making process regarding the best approach in coronary artery disease, and CABG should be considered a worthy therapeutic option.

Comparison of serum levels with bone content and gene expression indicate a contradictory effect of kidney transplantation on sclerostin.

In an attempt to clarify the mechanisms of post-transplant bone disease we investigated the bone content and gene expression of several bone-related proteins. After a successful kidney transplant, the content of sclerostin in bone biopsies was found to be increased as measured by immunohistochemistry, multiplex assay, and gene expression despite a concomitant decrease of sclerostin in the serum. The phosphorylation of beta-catenin was increased, confirming Wnt pathway inhibition, an effect accompanied by an increase of the receptor activator of nuclear factor kappa-Β ligand (RANKL) and a decrease of osteoprotegerin protein levels in both serum and bone. Thus, changes in circulating biomarkers after kidney transplantation cannot be easily extrapolated to concomitant changes occurring in the bone. Hence, overall treatment decisions post kidney transplant should not be based on serum biochemistry alone.

Occurrence of pesticides in Dutch drinking water sources.

We determined pesticide occurrence in groundwater and surface water sources used for drinking water production in The Netherlands, using both routine monitoring data from Dutch drinking water companies and by studying the presence of newly authorized pesticides in drinking water sources. An analytical LC-MS/MS method was developed for 24 recently authorized pesticides, selected based on their mobility and persistence, and applied in a Dutch/Belgian ground- and surface water monitoring campaign. 15 of these pesticides were detected, including seven in concentrations above the water quality standard from the Water Framework Directive. Two neonicotinoids were detected in highest concentrations: acetamiprid (1.1 µg/L) and thiamethoxam (0.4 µg/L). The routine monitoring data was collected over 2010-2014 in The Netherlands, covering 408 pesticides and 52 metabolites. 63 pesticides and 6 metabolites were prioritized according to their presence in groundwater, surface water and drinking water. The vast majority of the pesticides in routine monitoring has not been detected or only in low concentrations. Overall, the study shows that pesticides are of major concern in drinking water sources across the Netherlands. In two third of the abstraction areas pesticides and/or metabolites have been detected. In one third of the abstraction areas pesticide and/or metabolites concentration exceeded water quality standards according to the Water Framework Directive. The results emphasize that monitoring should focus on priority pesticides, since the vast majority of the pesticides has a low priority. The occurrence of recently authorized pesticides in drinking water sources demonstrates the importance to keep routine monitoring methods up to date.

Clinical and radiographic outcomes in patients operated for complex open tibial pilon fractures.

AIM: To report clinical and radiographic results of treatment of patients with complex open tibial pilon fractures. METHODS: A retrospective analysis in 14 patients with complex open pilon fractures treated between 2010 and 2015 was conducted. The injuries were graded according to AO Classification and the Gustillo-Anderson system. Routine follow-up was performed at 1, 3, 6, 12 month with an annual evaluation thereafter. All patients were included for the assessment of the rate of infection, wound and fracture-healing. Functional outcome assessment was performed in all patients according to the American Orthopedic Foot and Ankle Score (AOFAS) at 12 months after the injury. The radiological outcome was evaluated through standard XR using the criteria proposed by Burwell and Charnley. RESULTS: Analysis were conducted in 12 men and 2 women, with a mean age of 50.4 years (20-77) who were followed up for an average 34 months (range: 9-60 months). All patients had a AO type 43C fracture. There were three Gustilo Type IIIA injuries, seven Type III B and four Type III C. The mean time to fracture healing was 6.3 months. 4 patients underwent definitive treatment with external fixation at the time of the initial irrigation and debridement. 10 patients underwent delayed definitive surgery: in 10 patients ORIF was used. Soft-tissue coverage by vascularized muscle flap was necessary in 4 patients (28%) and was typically performed on the day of definitive fixation. One patient required iliac crest bone-grafting. 4 patients (28%) had a deep infection.6 patients (43%) had a superficial pin infection or cellulitis. 6 patients (43%) presented delayed union. The average AOFAS score was 71.5 (40-95). According to the Burwell-Charnley score, the anatomical reduction of the fracture was obtained in 50% of patients and a good reduction in 86% of cases. 5 patients (35.7%) had loss of joint congruity and evidence of osteoarthritis on radiographs at final follow-up. No patient needed arthrodesis or amputation. CONCLUSION: The results of our study suggest that open tibial pilon fractures can be safely managed with low rate of complications using intensive debridement, antibiotics, adequate devices and patient-tailored timing of definitive surgical treatment.

Antifungal properties of silver coating on tumour endoprostheses: an in vitro study.

OBJECTIVE: We tested and quantified the in vitro effect of silver coating on preventing development of fungal biofilm over titanium, as found in some megaprosthesis used for musculoskeletal oncological reconstruction, to evaluate the antiseptic effect of this additional feature on this class of pathogens. MATERIALS AND METHODS: Different strains and species of Candida (C. albicans, C. tropicalis, C. parapsilosis) were cultured over 6 silver-coated and 6 non silver-coated titanium (Ti-6Al-4V) samples following a standardized procedure. Then spectrophotometrical analysis and viability assay were conducted after 5 days of incubation to quantify the different extension of biofilm produced by pathogens RESULTS: Significant differences between groups (p<0.05) were found in terms of biofilm extension and pathogens viability over the different materials for any single experiment reported, with silver-coating group showing substantially lower values in terms of fungal development in all conducted assays. CONCLUSIONS: The results suggest that silver coating is a reliable and effective implementation for antifungal purpose, in addition to its widely known and demonstrated antibacterial potential. Therefore, the use of silver-coated implants may be an even wiser choice in an oncological surgical procedure where patients are particularly at risk for this infective complication due to immunosuppression caused by pharmacological treatments, although the relevant antifungal potential here shown needs to be confirmed in vivo.

Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis.

BACKGROUND: An overview of promising prognostic variables and predictive subgroups concerning the curative treatment of esophageal and gastric cancer from randomized controlled trials (RCTs) is lacking. Therefore, we conducted a systematic review and meta-analysis. METHODS: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to March 2019 for RCTs on the curative treatment of esophageal or gastric cancer with data on prognostic and/or predictive factors for overall survival. Prognostic factors were deemed potentially clinically relevant according to the following criteria; (1) statistically significant (p < 0.05) in a multivariate analysis, (2) reported in at least 250 patients, and (3) p < 0.05, in ≥ 33% of the total number of patients in RCTs reporting this factor. Predictive factors were potentially clinically-relevant if (1) the p-value for interaction between subgroups was <0.20 and (2) the hazard ratio in one of the subgroups was significant (p < 0.05). RESULTS: For gastric cancer, 39 RCTs were identified (n = 13,530 patients) and, for esophageal cancer, 33 RCTs were identified (n = 8618 patients). In total, we identified 23 potentially clinically relevant prognostic factors for gastric cancer and 16 for esophageal cancer. There were 15 potentially clinically relevant predictive factors for gastric cancer and 10 for esophageal cancer. CONCLUSION: The identified prognostic and predictive factors can be included and analyzed in future RCTs and be of guidance for nomograms. Further validation should be performed in large patient cohorts.

The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis.

Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38⁻0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58⁻1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28⁻0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.

Comparison of clinical, biochemical and histomorphometric analysis of bone biopsies in dialysis patients with and without fractures.

Chronic kidney disease-mineral bone disorders (CKD-MBD) are associated with increased risk of fracture. Studies report about 3% of fractures in CKD patients, and these occur earlier than in the general population, namely 16 and 13 years earlier for men and women, respectively. Better understanding of the pathophysiology of fractures would probably contribute to new therapeutic approaches. This study aimed to evaluate report of long bone fractures from a bone biopsies bank from patients on hemodialysis and compare clinical and biochemical characteristics, as well as the results of the histomorphometric analysis of trabecular and cortical bone of these patients with a control group (without fractures), paired for age, gender, and time on hemodialysis. Bone proteins (SOST, DMP1 and MEPE) were evaluated by immunohistochemistry. Seventeen patients with fracture and controls were studied. Fracture prevalence was 0.82/1000 patients/year. Serum phosphorus levels were significantly lower in the fracture group. Histomorphometric analysis revealed that all the patients had high turnover disease, and the fracture group had smaller volume and trabecular thickness, greater osteoid surface, smaller eroded surface, smaller mineralizing surface, formation rate and longer mineralization lag time when compared to controls; the DMP1 expression in the cortical bone was smaller and the SOST in the trabecular bone was higher in fractured patients. As conclusion, we found low prevalence of fractures. Both groups had high turnover disease, but the fractured ones presented more impaired bone microarchitecture, as well as lower formation and greater mineralization defect. Bone proteins expression correlated with parameters involved in bone remodeling.

Quality of life after surgery in secondary hyperparathyroidism, comparing subtotal parathyroidectomy with total parathyroidectomy with immediate parathyroid autograft: Prospective randomized trial.

BACKGROUND: No prospective randomized data exist about the impact of various strategies of parathyroidectomy in secondary hyperparathyroidism patients on quality of life and its possible relationship with metabolic status after the operation. METHOD: In a prospective randomized trial, the Short Form 36 Health Survey Questionnaire was applied to 69 patients undergoing parathyroidectomy through various approaches: subtotal parathyroidectomy (n = 23), total parathyroidectomy (PTx) with autotransplantation of 45 fragments (n = 25) and PTx with autotransplantation of 90 fragments (n = 21). The questionnaire was completed at three moments: (1) preoperatively, (2) 6 months after surgery, and (3) 12 months after surgery. RESULTS: Quality of life improved significantly in the physical component summary score in all three groups. Subtotal parathyroidectomy scores changed from 30.6 preoperatively to 51.7 6 months after surgery and 53.7 12 months after surgery. Total arathyroidectomy with autotransplantation of 45 fragments scores changed from 33.8 preoperatively to 52.6 6 months after surgery and 55.2 12 months after surgery. Total parathyroidectomy with autotransplantation of 90 fragments scores changed from 31.8 preoperatively to 50.5 6 months after surgery and 55.2 12 months after surgery (all groups P < .0001). No significant difference was detected in the physical component summary score change among the three groups. The physical component summary score was negatively correlated to age, parathormone, and alkaline phosphatase preoperatively. CONCLUSION: Parathyroidectomy significantly improves quality of life in hemodialysis patients with secondary hyperparathyroidism, regardless of the type of operation.