Raquitismo hipofosfatémico familiar ligado al cromosoma X: Reporte de Caso

El Fósforo es regulado por el riñón y el sistema óseo orquestado principalmente por la acción de la parathormona (PTH) y una molécula recientemente descrita como el factor de crecimiento fibroblástico 23 (FGF-23) . Presentamos los casos de dos pacientes madre-hijo con Raquitismo hipofosfatémico ligado al cromosoma X. Se realizó el estudio genético identificándose una mutación en el Gen PHEX: variante patogénica tipo splicing en hemicigosis: mutación previamente descrita como HGMD CS126536. El Raquitismo Hipofosfatémico forma parte de un grupo de tubulopatías caracterizadas hiperfosfaturia. La mutación del gen PHEX con pérdida de función conduce al aumento de FGF-23. PHEX degrada el FGF-23 en fragmentos inactivos, evitando la excreción excesiva de fosfatos y el desarrollo de hipofosfatemia. En un paciente con hipofosfatemia no dependiente de la hormona PTH o de la vitamina D y de presentación familiar debe considerarse el diagnóstico de Raquitismo hipofosfatémico ligado al cromosoma X.

Phosphate is regulated by the kidneys and the osseus system, mainly due to the action of parathyroid hormone (PTH) and a recently described molecule, fibroblast growth factor 23 (FGF-23). We present the cases of two patients, mother and son with X-chromosome linked hypophosphatemic rickets. The genetic study was performed, and a mutation in the PHEX gene was identified, a splicing type pathogenic variant in hemizygosis. This mutation was previously described as HGMD CS126536. Hypophosphatemic rickets belongs to a group of tubulopathies characterized by hyperphosphaturia. PHEX gene mutation with function loss leads to increased FGF-23 levels. PHEX degrades FGF-23 into inactive fragments, preventing excessive phosphate excretion and the development of hypophosphatemia. In patients with PTH or vitamin D non- dependent hypophosphatemia, a diagnosis of X-chromosome linked hypophosphatemic rickets should be considered.

Caffeine intoxication as a result of excessive consumption of bottled coffee products: a case report / Journal of Rural Medicine

Objectives: Most cases of caffeine intoxication result from the excessive intake of over-the-counter drugs and energy drinks. However, few cases of caffeine intoxication due to the excessive consumption of bottled coffee products have been reported. Herein, we present a case report of caffeine intoxication.Patient: A 39-year-old man experienced numbness and weakness in the extremities for three nights over five days.Results: Blood tests revealed hypophosphatemia and low 25-OH vitamin D concentration. The symptoms disappeared the next day without any additional treatment. A lifestyle interview revealed that he regularly consumed bottled coffee like it was water and had approximately 1 L of it from evening to night. He was diagnosed with weakness in the extremities due to hypophosphatemia caused by caffeine intoxication. Upon investigating some bottled coffee products, we found that only a few of them had labels disclosing caffeine content and warnings of the risks of excessive caffeine intake.Conclusion: We encountered a case of caffeine intoxication via coffee. Although rare in the past, caffeine intoxication might increase owing to the widespread use of bottled coffee products. The caffeine content of coffee products should be indicated on labels to warn consumers.

New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia

Abstract Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. Arch Endocrinol Metab. 2022;66(5):658-65

Enfermedad ósea metabólica del prematuro: revisión de tema / Metabolic bone disease of prematurity: topic review

Resumen La enfermedad ósea metabólica del prematuro es una patología multifactorial que representa una importante causa de morbilidad, cuya prevalencia ha aumentado. Su diagnóstico requiere criterios bioquímicos, radiológicos y, en etapas avanzadas, clínicos; por lo cual, muchos autores recomiendan estrategias de tamizaje y prevención. El objetivo del presente artículo es realizar una revisión de los aspectos más relevantes respecto a la enfermedad ósea metabólica del prematuro, con énfasis en la prevención y tratamiento precoz. Se realizó una revisión bibliográfica con términos MeSH, en las bases de datos de Pubmed, ClinicalKey, ScienceDirect, SciELO y LILACS. Aunque no hay consenso en las pautas de tamizaje, diagnóstico y tratamiento, la principal estrategia usada en la actualidad es el soporte nutricional individualizado que cubra las demandas de calcio, fósforo y vitamina D, asociado a métodos de intervención clínica y seguimiento de bebés de alto riesgo. La comprensión de esta patología permitirá mejorar las estrategias de tamización, diagnóstico precoz, y de esta forma evitará complicaciones.

Abstract Metabolic bone disease of prematurity is a multifactorial pathology that represents a significant cause of morbidity and has increased in prevalence. Its diagnosis requires biochemical, radiological, and, in advanced stages, clinical criteria; therefore, many authors recommend screening and prevention strategies. This article aims to review the most relevant aspects of the metabolic bone disease of prematurity, with emphasis on prevention and early treatment. A bibliographic review was carried out with MeSH terms in the Pubmed, ClinicalKey, ScienceDirect, SciELO, and LILACS databases. Although there is no consensus on screening, diagnosis and treatment guidelines, the main strategy currently used is to provide individualized nutritional support that covers the demands of calcium, phosphorus and vitamin D associated with clinical intervention methods and monitoring of high-risk babies. Understanding this pathology will improve screening strategies and early diagnosis and thus avoid complications.

Serum Calcium/Phosphorus Ratio in Biochemical Screening of Primary Hyperparathyroidism

SUMMARY OBJECTIVE: Primary hyperparathyroidism is a common endocrine disease and most cases are asymptomatic. Currently, in a hypercalcemic patient, the first laboratory investigation is serum primary hyperparathyroidism measurement. However, the primary hyperparathyroidism level cannot be measured in many primary healthcare centers in our country. In addition, serum calcium levels are normal in normocalcemic primary hyperparathyroidism patients, even if most centers have serum calcium levels measured. Therefore, a simple and inexpensive laboratory biochemical marker is required for the diagnosis of primary hyperparathyroidism. Recently, the calcium/phosphorus ratio has been proposed as a suitable tool for diagnosing primary hyperparathyroidism. This study aimed to investigate the diagnostic value of serum calcium/phosphorus ratio in primary hyperparathyroidism screening. METHODS: A total of 462 patients followed in our clinic with a diagnosis of primary hyperparathyroidism were reviewed in this retrospective study. Out of these patients, 148 with normal levels of serum parathyroid hormone, calcium, and phosphorus were selected as the control group. Serum calcium, corrected calcium, phosphorus, albumin, parathyroid hormone, 25-hydroxyvitamin D, and creatinine were evaluated. The diagnostic accuracy of the calcium/phosphorus ratio was investigated using receiver operating characteristic curve analysis. RESULTS: There were 404 (87.4%) females and 58 (12.6%) males in the primary hyperparathyroidism group. Calcium, parathyroid hormone, and calcium/phosphorus ratio were significantly higher in primary hyperparathyroidism than in controls (p<0.001 for each). Receiver operating characteristic curve analyses identified a cutoff value of 2.59 (3.35 if calcium and phosphorus are measured in mg/dL) for the calcium/phosphorus ratio, with a sensitivity of 90.5% and specificity of 93.2% (p<0.001). CONCLUSION: The calcium/phosphorus ratio is a simple and inexpensive method for primary hyperparathyroidism screening when a cutoff value of 2.59 is used.

The characteristics of nutritional intake and bone metabolism in preterm infants with very low birth weight and small gestational age / 中国新生儿科杂志

Objective:To study the differences in nutritional intake and bone metabolism between small gestational age infant (SGA) and appropriate gestational age infant (AGA) in very low birth weight (VLBW) preterm infants.Methods:From January 2015 to January 2020, infants admitted to the neonatal intensive care unit of our hospital immediately after birth and survived more than 4 weeks were retrospectively studied. The infants with GA<32 weeks, BW<1 500 g and small for gestational age were assigned into SGA group. Each SGA group infants were paired with an AGA infants The perinatal history was reviewed. Serum total calcium, blood phosphorus, blood magnesium, alkaline phosphatase and other nutritional intake indicators in the blood biochemistry were examined at 1 w, 2 w and 4 w after birth. SPSS 22.0 statistical software was used to analyze the relationship between nutritional intake and bone metabolism indexes.Results:A total of 80 cases were included in SGA group and AGA group, respectively. No significant difference existed in the incidence of hypophosphatemia within 2w after birth between the two groups ( P>0.05). SGA group had significantly lower incidence of hypophosphatemia at 4w than AGA group [36.3% (29/80 ) vs. 56.3% (45/80)]( P<0.05). SGA group showed significantly higher proportion of ALP>500 U/L cases than AGA group at 2 w and 4 w [16.3% (13/80) vs. 1.3% (1/80), 21.3% (17/80) vs. 2.5% (2/80)]( P<0.05). The two groups had similar serum magnesium level ( P>0.05). SGA group had higher incidence of delayed milk feeding [67.5% (54/80) vs. 26.2% (21/80)], longer parenteral nutrition duration [(49.4±14.4)d vs. (40.5±18.2)d] and slower increase of calorie intake and enteral nutrition than AGA group ( P<0.05). Conclusions:Among VLBW preterm infants, SGA infants have worse nutritional intake than AGA and are more vulnerable to abnormal bone metabolism.

Effect of hypophosphatemia on the prognosis of critically ill patients / 中华危重病急救医学

Objective:To explore the impact of hypophosphatemia on the occurrence and prognosis of critically ill patient.Methods:The clinical data of critically ill patients admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from October 2021 to April 2022 were retrospectively analyzed. Patients were divided into hypophosphatemia group (serum phosphorus level < 0.80 mmol/L) and non-hypophosphatemia group (serum phosphorus level ≥ 0.80 mmol/L) when they were admitted to the ICU. The following variables were also collected, including gender, age, acute physiology and chronic health evaluationⅡ(APACHE Ⅱ), sequential organ failure assessment (SOFA), serum phosphorus level, serum calcium level, serum magnesium level, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), presence of infection and infection site, length of hospital stay, ICU stay, 28-day mortality, and mechanical ventilation time. Multivariate Logistic regression analysis was used to evaluate the relationship between each variable and the 28-day mortality. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) and 95% confidence interval (95% CI) were calculated to evaluate the predictive value of serum phosphorus levels for the prognosis of ICU patients. Results:A total of 263 patients were enrolled, including 54 patients with hypophosphatemia and 209 patients without. The SOFA score, LYM level and the infection rate of patients in the hypophosphatemia group were significantly higher than those in the non-hypophosphatemia group [SOFA score: 6.70±3.17 vs. 5.64±3.59, LYM (×10 9/L): 0.99±0.54 vs. 0.77±0.54, infection rate: 77.78% (42/54) vs. 59.33% (124/209), all P < 0.05], the NLR was significantly lower than that of the non-hypophosphatemia group [10.67 (7.08, 18.02) vs. 12.25 (7.25, 21.68), P < 0.05]. The length of hospital stay, ICU stay, and mechanical ventilation duration in the hypophosphatemia group were significantly longer than those in the non-hypophosphatemia group [length of hospital stay (days): 15 (11, 28) vs. 12 (6, 21), length of ICU stay (days): 10.35±7.80 vs 7.15±6.61, mechanical ventilation duration (days): 3 (0, 12) vs. 2 (0, 5), all P < 0.05]. There was no significant difference in the 28-day mortality between the hypophosphatemia group and the non-hypophosphatemia group [9.26% (5/54) vs. 11.00% (23/209), P > 0.05]. Multivariate Logistic regression analysis showed that APACHE Ⅱ score [odds ratio ( OR) = 1.188, 95% CI was 1.110-1.271], CRP ( OR = 1.016, 95% CI was 1.007-1.026), and NLR ( OR = 1.002, 95% CI was 0.996-1.008) were independent risk factors affecting the 28-day mortality of critically ill patients in ICU (all P < 0.05). ROC curve analysis showed that the AUC of serum phosphorus levels for predicting the length of hospital stay of critically ill patients in ICU > 10 days, ICU stay > 5 days, and mechanical ventilation duration > 5 days were 0.701 (95% CI was 0.632-0.770), 0.771 (95% CI was 0.691-0.852), 0.617 (95% CI was 0.541-0.692), respectively, all P < 0.01. Conclusion:Hypophosphatemia has some predictive value for the length of hospital and ICU stay and mechanical ventilation time in critically ill patients, but it cannot predict the 28-day mortality.

Raquitismo hipofosfatémico ligado al cromosoma X: un reto diagnóstico y terapéutico

La hipofosfatemia ligada al X es un desorden genético ocasionado por mutaciones del gen PHEX (phosphate regulating endopeptidase analog, X-linked). Esta afecta la codificación de una metaloproteasa que tiene como función inhibir el factor de crecimiento fibroblástico - 23 (FGF-23), promoviendo la pérdida renal de fosfato. A continuación, describimos el caso de un paciente de edad pediátrica a quien se le hace diagnóstico en la adolescencia con una mutación del gen PHEX. Posteriormente, la misma alteración genética fue encontrada en la madre, considerada como una mutación espontánea que fue trasmitida a su hijo. Esto aumenta la rareza del caso, donde el reto para diagnosticar esta patología necesita vencer dificultades administrativas, económicas y sociales. El diagnóstico y tratamiento oportuno ayudan a optimizar la talla final y minimizar todas las deformidades esqueléticas presentadas, tanto en la madre como en el hijo. En la actualidad se cuenta con el tratamiento tradicional y uno novedoso que fue ordenado para el paciente pediátrico de este reporte.

SUMMARY X-linked hypophosphatemia is a genetic disorder caused by PHEX gene mutations, which affects the encoding of a metalloprotease whose function is to inhibit fibroblastic growth factor-23 (FGF-23), promoting phosphate renal loss. Following we describe the case of a teenager diagnosed with a PHEX gene mutation. The same genetic alteration was found in the mother of the patient, considering a spontaneous mutation that was transmitted to her son, which makes the case, even rarer, where the diagnostic challenge needs to overcome administrative, economic and social difficulties. A timely diagnosis and treatment could help optimize the final height and minimize the skeletal deformities presented in both the mother and the child. Currently, there is a traditional treatment and a novel one that was ordered for the pediatric patient in this report.

Prevalência de hipofosfatemia e risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva / Prevalence of hypophosphatemia and risk of refeeding syndrome in elderly patients admitted to an intensive care unit

Introdução: A presença de hipofosfatemia é fortemente relacionada à ocorrência de síndrome de realimentação em pacientes críticos, na qual um dos principais grupos de risco é a população idosa. Objetivos: Avaliar a prevalência de hipofosfatemia e o risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva. Métodos: Estudo observacional prospectivo, realizado numa unidade de terapia intensiva com pacientes idosos de ambos os sexos e em uso de terapia nutricional enteral. Foram coletados dados demográficos, clínicos e exames bioquímicos, e realizadas triagem e avaliação nutricional. As necessidades nutricionais foram calculadas e adotou-se o ponto de corte de 90% para estabelecer a adequação da oferta calórica. Para avaliar o risco e a ocorrência de síndrome de realimentação, foram utilizados os critérios propostos pelo grupo NICE. A análise estatística foi realizada com o auxílio do programa SPSS 13.0, com um intervalo de confiança (IC) de 95%. Resultados: Foram estudados 44 pacientes, dos quais 34,1% estavam em magreza; 86,4% dos pacientes iniciaram a terapia nutricional enteral em até 48 horas, com 43,2% de adequação calórica em até 72 horas. A hipofosfatemia foi encontrada em 9,1% dos pacientes na admissão e em 29,5% após o início da dieta. Com isso, 88,6% dos pacientes apresentaram algum risco para desenvolver síndrome de realimentação e 40,9% deles manifestaram a síndrome. Conclusão: Foi identificada elevada prevalência de hipofosfatemia após o início da terapia nutricional. Além disso, o risco de desenvolver síndrome de realimentação foi elevado e sua manifestação se assemelha aos dados encontrados na literatura. (AU)

Introduction: The presence of hypophosphatemia is strongly related to the occurrence of refeeding syndrome in critically ill patients, in which one of the main risk groups is the elderly population. Objectives: To assess the prevalence of hypophosphatemia and the risk of refeeding syndrome in elderly patients admitted to an intensive care unit. Methods: Prospective observational study carried out in an intensive care unit with elderly patients of both genders using enteral nutritional therapy. Demographic, clinical and biochemical data were collected, and nutritional screening and assessment were performed. The energy and nutrient requirements were calculated and a cutoff point of 90% was adopted to establish the adequacy of the caloric supply. To assess the risk and occurrence of refeeding syndrome, the criteria proposed by the NICE group were used. Statistical analyses were performed using the SPSS 13.0 program, with a 95% confidence interval (CI). Results: 44 patients were studied, of which 34.1% were malnourished; 86.4% of patients started enteral nutritional therapy within 48 hours, with 43.2% of caloric adequacy within 72 hours. Hypophosphatemia was found in 9.1% of patients on admission and in 29.5% after starting the diet. Thus, 88.6% of patients had some risk of developing the refeeding syndrome and 40.9% of them manifested the syndrome. Conclusion: A high prevalence of hypophosphatemia was identified after starting nutritional therapy. In addition, the risk of developing refeeding syndrome was high and its manifestation is similar to data found in the literature. (AU)

Impact of hypophosphatemia on weaning from mechanical ventilation / 中华危重病急救医学

Objective:To explore the influence of hypophosphatemia on weaning from mechanical ventilation.Methods:An observational study was conducted. The medical records of 30 mechanical ventilated patients with hypophosphatemia admitted to intensive care unit of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to August 2020 were analyzed; another 60 mechanical ventilated patients with normophosphatemia around the same time were enrolled as controls by 1∶2 case-control matching based on gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score. And then the duration of invasive mechanical ventilation, times of spontaneous breathing trial (SBT), the diaphragmatic ultrasonography movement indexes, and outcome of weaning and prognosis during hospitalization were compared between the two groups. Receiver operator characteristic curve (ROC curve) was plotted to calculate the areas under ROC curve (AUC) and cut-off values of serum phosphorus for successful weaning and hospital survival. The correlations between the diaphragmatic ultrasonography movement indexes and serum phosphorus were analyzed by Pearson partial correlation analysis.Results:Compared with normophosphatemic group, the duration of invasive mechanical ventilation in hypophosphatemia group was significantly longer [days: 13.0 (7.0, 22.0) vs. 10.0 (5.5, 14.0), P < 0.05], and SBT attempts were more often [times: 3 (0, 5) vs. 1 (1, 2), P < 0.01], while the rate of successful weaning was lower (53.3% vs. 91.7%, P < 0.01), and the hospital mortality was higher (20.0% vs. 1.7%, P < 0.01). ROC curve analysis showed that serum phosphorus could predict successful weaning of mechanical ventilated patients, the AUC was 0.795, and the optimum cut-off value of serum phosphorus was 0.85 mmol/L with sensitivity of 73.2% and specificity of 84.2%. Serum phosphorus could predict hospital survival of mechanical ventilated patients, the AUC was 0.782, and the optimum cut-off value of serum phosphorus was 0.48 mmol/L with sensitivity of 81.9% and specificity of 85.7%. Compared with normophosphatemic group, diaphragm thickness at the end of inspiration (DTei), diaphragm thickness at the end of expiration (DTee), diaphragm thickening fraction (DTF), diaphragm excursion (DE) in hypophosphatemia group were all significantly decreased [DTei (cm): 0.19±0.07 vs. 0.27±0.08, DTee (cm): 0.14±0.05 vs. 0.19±0.06, DTF: (33.55±16.17)% vs. (45.04±18.66)%, DE (cm): 1.17±0.49 vs. 2.28±0.69, all P < 0.01]. Pearson partial correlation analysis showed that linear correlations were found between serum phosphorus and DTei, DTee, DTF, DE ( r values were 0.442, 0.351, 0.293, 0.628 respectively, all P < 0.01). Conclusions:Serum phosphorus may have correlation with the diaphragmatic ultrasonography movement indexes. Hypophosphatemia may impair the contractile properties of diaphragm, induce more SBT attempts and longer duration of invasive mechanical ventilation, and affect outcome of weaning and prognosis.

Prevalence and clinical characteristics of X-linked hypophosphatemia in Paraná, southern Brazil

ABSTRACT Objective: The aim of this cross-sectional study was to estimate the prevalence of XLH in Paraná, a state in southern Brazil, and report the clinical features and complications of the disease. Materials and methods: We invited all endocrinologists (n = 205), nephrologists (n = 221), orthopedic surgeons (n = 1020), and pediatricians (n = 1000) in Paraná to fill out an electronic survey with information on patients with X-linked hypophosphatemia (XLH), and searched the records of the state's health department for all calcitriol prescriptions in 2018. Results: In all, 244 (10%) specialists responded to the email, of whom 18 (7.4%) reported to be taking care of patients with XLH and answered the online survey. A total of 57 patients with XLH were identified (prevalence 5 per million inhabitants). The median age at diagnosis was 22 years, and 42.2% were children and adolescents. Fifteen patients had genetic testing showing a PHEX mutation. Overall, 91.2% had bone deformities, 30.8% had a history of fragility fractures, and 22.4% had renal complications. Conclusion: This study demonstrated a prevalence of XLH of 5 cases per million inhabitants in the state of Paraná, a rate lower than the one reported in other countries. Manifestations of renal calcification and bone fragility were frequent among the patients. This is the first epidemiological study evaluating the prevalence and clinical presentation of XLH in Latin America.

Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy / Tratamento do hiperparatireoidismo hipercalcêmico persistente pós-transplante renal: cinacalcete versus paratireoidectomia

ABSTRACT Background: Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet. Methods: A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities. Results: PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05). Conclusions: Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.

RESUMO Introdução: O hiperparatireoidismo persistente pós-transplante está associado a aumento na incidência de eventos cardiovasculares, fraturas e óbitos. O objetivo deste estudo foi comparar as opções terapêuticas disponíveis: paratireoidectomia (PTX) e o agente calcimimético cinacalcete. Métodos: Estudo retrospectivo de um único centro incluiu pacientes transplantados renais adultos que desenvolveram hipercalcemia devido a hiperparatireoidismo persistente. Critérios de inclusão: PTH > 65 pg/mL com cálcio sérico > 11,5 mg/dL a qualquer momento após o transplante, ou cálcio sérico persistentemente superior a 10,2 mg/dL um ano após o transplante. Os pacientes tratados com cinacalcete (n = 46) foram comparados aos pacientes tratados com paratireoidectomia (n = 30). O período de acompanhamento foi de um ano. Dados clínicos e laboratoriais foram analisados para comparar a eficácia e a segurança de ambas as modalidades terapêuticas. Resultados: a PTX controlou a calcemia mais rapidamente (mês 1 x mês 6) e atingiu níveis significativamente mais baixos no mês 12 (9,1 ± 1,2 v.s. 9,7 ± 0,8 mg/dL, p < 0,05); pacientes submetidos à PTX apresentaram níveis significativamente mais altos de fósforo sérico (3,8 ± 1,0 v.s. 2,9 ± 0,5 mg/dL, p < 0,05) e retornaram aos níveis normais de PTH (45 ± 51 pg/mL). O cinacalcete, apesar de controlar o cálcio e o fósforo no longo prazo, diminuiu, mas não corrigiu o PTH (197 ± 97 pg/mL). A proporção de pacientes que permaneceram com PTH acima da faixa normal foi de 95% no grupo cinacalcete e 22% no grupo PTX. Os pacientes tratados com cinacalcete apresentaram melhor função renal (creatinina 1,2 ± 0,3 v.s. 1,7 ± 0,7 mg/dL, p < 0,05). Conclusões: O tratamento cirúrgico foi superior ao cinacalcete para corrigir os distúrbios metabólicos do hiperparatireoidismo, apesar de estar associado a pior função renal no longo prazo. Cinacalcete provou ser um medicamento seguro e bem tolerado.

Hypophosphatemia and risk of refeeding syndrome in critically ill patients before and after nutritional therapy

Summary OBJECTIVE: To investigate the prevalence of hypophosphatemia as a marker of refeeding syndrome (RFS) before and after the start of nutritional therapy (NT) in critically ill patients. METHODS: Retrospective cohort study including 917 adult patients admitted at the intensive care unit (ICU) of a tertiary hospital in Cuiabá-MT/Brasil. We assessed the frequency of hypophosphatemia (phosphorus <2.5mg/dl) as a risk marker for RFS. Serum phosphorus levels were measured and compared at admission (P1) and after the start of NT (P2). RESULTS: We observed a significant increase (36.3%) of hypophosphatemia and, consequently, a greater risk of RFS from P1 to P2 (25.6 vs 34.9%; p<0.001). After the start of NT, malnourished patients had a greater fall of serum phosphorus. Patients receiving NT had an approximately 1.5 times greater risk of developing RFS (OR= 1.44 95%CI 1.10-1,89; p= 0.01) when compared to those who received an oral diet. Parenteral nutrition was more associated with hypophosphatemia than either enteral nutrition (p=0,001) or parenteral nutrition supplemented with enteral nutrition (p=0,002). CONCLUSION: The frequency of critically ill patients with hypophosphatemia and at risk for RFS on admission is high and this risk increases after the start of NT, especially in malnourished patients and those receiving parenteral nutrition.

RESUMO OBJETIVO: Determinar a frequência de hipofosfatemia como marcador da síndrome de realimentação (SR) antes e após o início da TN em pacientes críticos. MÉTODOS: Coorte retrospectiva realizada com 917 pacientes adultos de um hospital terciário em Cuiabá-MT. Foi determinada a frequência de hipofosfatemia (fósforo <2,5 mg/dl) como marcador de risco de SR, para valores de fósforo sérico da admissão (P1) e após o início da TN (P2). RESULTADOS: Foi observado um aumento significativo (36,3%) da hipofosfatemia entre P1 e P2 e, consequentemente, do risco de SR (25,6% vs 34,9%; p<0,001) com o início da TN. Após o início da TN, pacientes desnutridos apresentaram maior queda do fósforo sérico. Os pacientes com TN apresentaram aproximadamente 1,5 vez mais chance de desenvolver hipofosfatemia e risco de SR (OR=1,44 IC95% 1,10-1,89; p=0,01) quando comparado aos com dieta oral. Nutrição parenteral foi mais associada à hipofosfatemia versus nutrição enteral (p=0,001) e nutrição enteral suplementada com parenteral (p=0,002). CONCLUSÃO: A frequência de pacientes críticos com hipofosfatemia e em risco de SR é alta e esse risco aumenta após o início da TN, especialmente nos desnutridos e naqueles recebendo nutrição parenteral.

Asociación entre hipoalbuminemia e hipofosfatemia con desnutrición en pacientes con Enfermedad Renal Crónica en hemodiálisis / Association Between Hypoalbuminemia And Hypophosphatemia With Malnutrition In Patients With Chronic Renal Disease Undergoing Hemodialysis

Introducción: La malnutrición en los pacientes en hemodiálisis es consecuencia de diversos factorescarenciales e hipercatabólicos y constituye un factor de riesgo de morbimortalidad. Objetivo:Determinar la asociación entre hipoalbuminemia e hipofosfatemia con la escala de valoración globalsubjetiva (VGS) tipo C en pacientes con enfermedad renal crónica en hemodiálisis. Métodos: Estudiotransversal analítico. Se estudiaron pacientes del servicio de hemodiálisis del hospital GuillermoAlmenara. Para la asociación entre variables continuas de malnutrición y los tipos de VGS se utilizóel test de Kruskal-Wallis y prueba de comparaciones múltiples y para las variables categóricashipoalbuminemia (≤3,5 g/dL) e hipofosfatemia (<3 mg/dL) se utilizó el chi cuadrado. Se analizó laasociación con la VGS tipo C. Resultados: Se incluyeron 131 pacientes y la edad mediana fue de 63años. El 34% presentó hipoalbuminemia, 27% presentó hipofosfatemia y el 14% una VGA tipo C. El52% (68) de los pacientes presentó alteración de al menos un biomarcador analizado. Se encontrarondiferencias entre VGS y albúmina (p<0,001) y fósforo (p=0,040). Los pacientes con VGS tipo C tuvieronuna media de albúmina de 3,1±0,74 de fósforo de 2,88±1,54 y tuvieron diferencia significativa encomparación con los de VGS tipo A (p<0,001 y p=0,011, respectivamente). El análisis de chi cuadradotambién demostró asociación significativa entre VGS e hipoalbuminemina (p=0,017) e hipofosfatemia(p=0,050). Conclusión: Existe asociación entre la VGS tipo C e hipoalbuminemia e hipofosfatemia enpacientes con enfermedad renal crónica en hemodiálisis.

Introduction: Malnutrition in hemodialysis patients is a consequence of various deficiency andhypercatabolic factors and constitutes a risk factor for morbidity and mortality. Objective: Determinethe association between hypoalbuminemia and hypophosphatemia with the Subjective globalassessment (SGA) C in patients with chronic renal disease on hemodialysis. Methods: Analytical cross-sectional study. Patients from the hemodialysis service of the Hospital Guillermo Almenara werestudied. The Kruskal-Wallis test and multiple comparisons test were used for the association betweencontinuous variables of malnutrition and the types of SGA. The square-chi test was used for thecategorical variables hypoalbuminemia (≤3.5 g/dL) and hypophosphatemia (<3 mg/dL). The associationwith SGA C was analyzed. Results: 131 patients were included and the median age was 63 years. 34%had hypoalbuminemia, 27% had hypophosphatemia and 14% had SGA C. 52% (68) of the patientspresented alteration of at least one analyzed biomarker. Differences were found between SGA andalbumin (p<0.001) and phosphorus (p=0.040). Patients with SGA C had a mean albumin of 3.1±0.74 andphosphorus of 2.88±1.54 and had a significant difference compared to those with SGA A (p<0.001 and P= 0.011, respectively). Chi-square analysis also demonstrated a significant association between SGA andhypoalbuminemia (p = 0.017) and hypophosphatemia (p=0.050). Conclusion: There is an associationbetween SGA C and hypoalbuminemia and hypophosphatemia in patients with chronic kidney diseaseundergoing hemodialysis.

Variación en los niveles séricos de Calcio, Fósforo, Magnesio, Cobre y Zinc durante las distintas etapas productivas en cabras de leche en un tambo caprino del noroeste argentino / Variation in serum levels of Calcium, Phosphorous, Magnesium, Copper and Zinc across productive stages of dairy goats in northwestern Argentina

Resumen El objetivo de este trabajo fue evaluar los niveles séricos de calcio (Ca), fósforo (P), magnesio (Mg), cobre (Cu), y zinc (Zn) en cabras lecheras en diferentes etapas productivas. Se seleccionaron 20 cabras de raza Saanen en diferentes estadios productivos: preparto (1 a 2 semanas previas al parto), posparto (1 a 2 semanas de lactancia), pico de lactancia (6 a 8 semanas de lactancia posparto) y período de seca (15 a 30 días de finalizada la lactancia) de un establecimiento lechero del valle de Lerma, Salta. Se colectaron muestras de sangre y se midieron los niveles séricos de Ca, Mg, Cu, y Zn empleando espectrofotometría de absorción atómica y P por colorimetría. Se identificó hipocalcemia (7,7±0,2 mg/dL) e hipofosfatemia (3,4±0,4 mg/dL) durante todas las etapas productivas. El Mg, por el contrario, presentó niveles adecuados durante todo el ensayo (2,5±0,06 mg/dL). Con respecto a los microminerales evaluados, solo los niveles séricos de Zn fueron inferiores a los recomendaros en todos los periodos productivos (53±4 µg/dL). Los niveles de Cu estuvieron dentro de los límites normales (53±4 µg/dL). Estos resultados permitieron identificar anormalidades en los niveles de Ca, P y Zn durante los periodos productivos evaluados. La información sobre deficiencias minerales en cabras es escasa y debe estudiarse más al respecto.

Abstract The aim of this study was to evaluate the serum levels of calcium (Ca), phosphorus (P), magnesium (Mg), copper (Cu), and zinc (Zn) in dairy goats in different productive periods. Twenty Saanen breed goats were selected at different productive stages: prepartum (1 to 2 weeks before partum), postpartum (1 to 2 weeks of lactation), peak of lactation (6 to 8 weeks postpartum) and dry period (15 to 30 days of the final lactation) of a dairy farm in the Valle de Lerma, in the province of Salta. Blood samples were collected and then, Ca, Mg, Cu and Zn levels were measured using atomic absorption spectrophotometry, and P was measured by colorimetric. Hypocalcaemia (7,7±0,2 mg/dL) and hypophosphatemia (3,4±0,4 mg/dL) were found in all production stages. In contrast, Mg levels did not present variation during all the samplings (2.5 ± 0.06 mg / dL). In evaluated micro-minerals, only the serum levels of Zn were lower than those recommended in all the productive periods (53 ± 4 µg / dL). Serum cupper levels were within normal limits (53 ± 4 µg / dL). The obtained results allowed identifying abnormalities in Ca, P and Zn levels during the evaluated productive periods. Information about mineral deficiency in goats is restricted and it is needed to study more about it.

Hipofosfatemia inducida por drogas: fierro carboximaltosa e imatinib. Casos clínicos / Hypophosphatemia induced by carboxymaltose iron and imatinib. Report of two cases

Hypophosphatemia is a relatively frequent and a potentially serious adverse drug effect. Clinically it is characterized by bone pain and muscle weakness. There are several mechanisms by which a drug can induce hypophosphatemia and they can be classified according to whether or not they are mediated by an excess of Fibroblast Growth Factor 23 (FGF23). We report two patients with the condition: (i) A 49-year-old woman with Chronic Myeloid Leukemia (CML) and gastric sleeve surgery at 46 years of age. After receiving intravenous carboxymaltose iron in one occasion due to refractory anemia, she developed symptomatic hypophosphatemia. Urinary phosphate losses associated with high FGF23 levels were confirmed. Plasma phosphate returned to normal values 90 days after the iron administration. (ii) A 40-year-old man with a history of CML in whom imatinib was started. He developed symptomatic hypophosphatemia due to non FGF23-mediated hyperphosphaturia. As treatment with imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake. These cases illustrate the importance of recognizing and treating drug-induced hypophosphatemia in a timely manner, and thus avoid the morbidity associated with this entity.

Risk of refeeding syndrome. case report

ABSTRACT Introduction: Refeeding syndrome (RS) is an acute metabolic disorder that occurs during nutritional repletion. Although it has been known for years, the early detection of risk factors for its onset and the implementation of measures to prevent it are not common in nutritional care. Case presentation: 48-year-old male patient, in critical care for 6 days, with suspected Wernicke-Korsakoff encephalopathy and high risk of refeeding syndrome according to criteria of the United Kingdom National Institute of Health and Clinical Excellence. The subject received enteral nutrition with 14 kcal/kg for the first 3 days, with subsequent increases aiming to achieve a nutritional goal of 25 kcal/kg on day 5. He also received daily supplementation of thiamine 600mg, folic acid 5mg and pyridoxine 50mg. Blood phosphorus decreased from 3 mg/dL to 2 mg/dL the day after initiating the nutritional plan and normalized by day 3. Discussion: The patient did not present severe hypophosphatemia or clinical manifestations of refeeding syndrome. Hypophosphatemia was resolved by maintaining a stable caloric restriction during the first days. Some professionals consider this restriction as very conservative, and others think that it may lead to achieve significant improvements in mortality reduction. Conclusions: The strategy for assessing the risk of refeeding syndrome, nutritional management and implemented follow-up were successful in preventing the patient from developing a refeeding syndrome.

RESUMEN Introducción. El síndrome de realimentación (SR) es un trastorno metabólico agudo que ocurre durante la repleción nutricional. Aunque ha sido conocido por años, la detección precoz de factores de riesgo para su desarrollo y la instauración de medidas para prevenirlo no son una práctica habitual en la atención nutricional. Presentación del caso. Paciente masculino de 48 años en cuidado crítico por 6 días, con sospecha de encefalopatía de Wernicke-Korsakoff y riesgo alto de SR según criterios del Instituto Nacional de Salud y Excelencia Clínica del Reino Unido. El sujeto recibió nutrición enteral con 14 kcal/kg los 3 primeros días, con aumentos posteriores que pretendían una meta de 25 kcal/kg al día 5 y suplementación diaria de tiamina 600mg, ácido fólico 5mg y piridoxina 50mg. El fósforo en sangre disminuyó de 3 mg/dL a 2 mg/dL al día siguiente del inicio de la nutrición y se normalizó para el día 3. Discusión. El paciente no presentó manifestaciones clínicas de SR ni hipofosfatemia severa; esta última se resolvió manteniendo estable la restricción calórica los primeros días. Para algunos profesionales dicha restricción puede ser muy conservadora; sin embargo, para otros puede llevar a mejoras significativas en la reducción de la mortalidad. Conclusiones. La estrategia para valorar el riesgo de SR, el manejo nutricional y el seguimiento implementado fueron acertados para evitar que el paciente desarrollara el síndrome.

Changes in serum phosphorous level during inpatient treatment of children with severe acute malnutrition

Background: SAM children have increased requirements for phosphorus during recovery. If requirements are not met, they may develop refeeding hypophosphatemia leading to increased morbidity and mortality. However, no much studies known about the effect of current therapeutic diets (F-75 and F-100) on serum phosphate in SAM children.Methods: Prospective observational study, in which measuring serum phosphate at admission, at end of stabilization phase and at discharge in SAM children between 6-59 months.Results: Among 35 children enrolled, mean serum phosphate was 4.3 '0.6 mg/dl at admission, 4.1' 0.8mg/dl at end of stabilization phase and 4.4'0.7mg/dl at discharge. 17% of children had hypophosphatemia at admission, 31% at end of stabilization phase and 17% at discharge. mean weight gain in hypophosphatemia and normophosphatemia groups are 1.3'1.46mg/kg/day and 2.51'2.63mg/kg/day (p=0.1) respectively. Mean duration of stay in hypophosphatemia and normophosphatemia groups are 11.6'1.26 and 10.26'1.54 days respectively (p=0.016).Conclusions: Hypophosphatemia was common among children with SAM at admission and increased at end of stabilization phase. Serum phosphate remains subnormal in about 1/5th of the children at discharge. This could be problematic for further recovery as phosphorus is needed for catch-up growth and bioavailability of phosphorus is low in local diets. Hence, authors suggest phosphorus supplementation in SAM children.

Tumor-Induced Osteomalacia: A Case Study Of A Nasal Tumor

Oncogenous osteomalacia, which is also known as tumor-induced osteomalacia, is a condition where a neoplasm isassociated with systemic bone demineralization and renal phosphaturia. We report a case who presented with a bleedingnasal mass, generalized fatigue, and cramps in her leg. Excision was done, and histopathologically, it was diagnosed tobe a phosphaturic mesenchymal tumor. The cramps disappeared soon after surgery and she is on regular follow-up forthe past 2 years.

Design and expression of FGF23 inhibitor in Pichia pastoris / 药学学报

Hypophosphatemia is a common metabolism disease in humans. Fibroblast growth factor 23 (FGF23) inhibits phosphate reabsorption by targeting on the renal tubules. FGF23C-tail contains 73 amino acids from C-terminus of FGF23, serves as an inhibitor of FGF23, and can increase phosphate reabsorption. Therefore, FGF23C-tail is an important drug for hypophosphatemia. In this paper, we constructed a fusion protein of FGF23C-tail with HSA, and investigated the expression of the fusion protein in the Pichia pastoris system. The recombinant gene was constructed by fusion PCR. A high-yield strain was selected by G418 resistance and fermentation yield, and the expression yield was 43.7 mg·L-1 in flask. In 5 L fermenters, the highest expression yield could reach 265.6 mg·L-1. FGF23C-tail-HSA could be used as an inhibitor for FGF23, and could significantly increase blood phosphorus levels in rats. The procedures for care and use of animals were approved by the Ethics Committee of YiChun University. This paper provided a basis research for further studying physiological activity of FGF23C-tail-HSA.