The modulation of platelet function by growth hormone in growth hormone deficient Hypopituitary patients.

BACKGROUND: Growth hormone deficiency (GHD) has been implicated in increased cardiovascular and cerebrovascular disease risk seen in hypopituitarism, however the mechanism remains speculative. We hypothesise that platelet abnormalities may play a contributory role. Herein we examined platelet behaviour in GHD hypopituitary patients, pre- and post-growth hormone (GH) replacement. METHODS: This study utilizes a physiological flow-based assay to quantify platelet function in whole blood from patient cohorts under arterial shear. Thirteen GH Naïve hypopituitary adults with GHD and thirteen healthy matched controls were studied. Patients were assessed before and after GH treatment. All other pituitary replacements were optimised before the study. In addition to a full endocrine profile, whole blood was labelled and perfused over immobilised von Willibrand factor (vWF). Seven parameters of dynamic platelet-vWF interactions were recorded using digital image microscopy and analysed by customised platelet tracking software. RESULTS: We found a significantly altered profile of platelet-vWF interactions in GHD individuals compared to healthy controls. Specifically, we observed a marked increase in platelets shown to form associations such as tethering, rolling and adherence to immobilized vWF, which were reduced post GH treatment. Speed and distance platelets travelled across vWF was similar between controls and pre-therapy GHD patients, however, this was considerably increased post treatment. This may indicate reduced platelet signaling resulting in less stable adhesion of platelets post GH treatment. CONCLUSIONS: Taken together observed differences in platelet behaviour may contribute to an increased risk of thrombosis in GHD which can in part be reversed by GH therapy.

Benefits of Adhering to a Mediterranean Diet Supplemented with Extra Virgin Olive Oil and Pistachios in Pregnancy on the Health of Offspring at 2 Years of Age. Results of the San Carlos Gestational Diabetes Mellitus Prevention Study.

The intrauterine environment may be related to the future development of chronic diseases in the offspring. The St. Carlos gestational diabetes mellitus (GDM) prevention study, is a randomized controlled trial that evaluated the influence of the early (before 12th gestational week) Mediterranean diet (MedDiet) on the onset of GDM and adverse gestational outcomes. Out of 874 women assessed after delivery (440 control group (CG)/434 intervention group (IG)), 703 children were followed (365/338; CG/IG), with the aim to assess whether the adherence to a MedDiet during pregnancy induces health benefits for the offspring during the first two years of life. Logistic regression analysis showed that the IG in children of mothers with pre-gestational body mass index (BMI) < 25 kg/m2 and normal glucose tolerance (NGT), was associated with a lower risk (RR(95% CI)) of suffering from severe events requiring hospitalization due to bronchiolitis/asthma (0.75(0.58-0.98) and 0.77(0.59-0.99), respectively) or other diseases that required either antibiotic (0.80(0.65-0.98) and 0.80(0.65-0.99), respectively), corticosteroid treatment (0.73(0.59-0.90) and 0.79(0.62-1.00) respectively) or both (all p < 0.05). A nutritional intervention based on the MedDiet during pregnancy is associated with a reduction in offspring's hospital admissions, especially in women with pre-gestational BMI < 25 kg/m2 and NGT.

A Mediterranean Diet with an Enhanced Consumption of Extra Virgin Olive Oil and Pistachios Improves Pregnancy Outcomes in Women Without Gestational Diabetes Mellitus: A Sub-Analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study.

AIMS: The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy. METHODS: This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8-12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40-42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age. RESULTS: Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37-0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced. CONCLUSION: A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women. TRIAL REGISTRATION: Identifier ISRCTN84389045. The study was registered on September 27, 2013. Last edited on September 26, 2018.

A Mediterranean diet with additional extra virgin olive oil and pistachios reduces the incidence of gestational diabetes mellitus (GDM): A randomized controlled trial: The St. Carlos GDM prevention study.

BACKGROUND: Gestational diabetes mellitus (GDM) prevalence is increasing and becoming a major public health concern. Whether a Mediterranean diet can help prevent GDM in unselected pregnant women has yet to be studied. METHODS: We conducted a prospective, randomized controlled trial to evaluate the incidence of GDM with two different dietary models. All consecutive normoglycemic (<92 mg/dL) pregnant women at 8-12 gestational weeks (GW) were assigned to Intervention Group (IG, n = 500): MedDiet supplemented with extra virgin olive oil (EVOO) and pistachios; or Control Group (CG, n = 500): standard diet with limited fat intake. Primary outcome was to assess the effect of the intervention on GDM incidence at 24-28 GW. Gestational weight gain (GWG), pregnancy-induced hypertension, caesarean section (CS), preterm delivery, perineal trauma, small and large for gestational age (SGA and LGA) and admissions to neonatal intensive care unit were also assessed. Analysis was by intention-to-treat. RESULTS: A total of 874 women completed the study (440/434, CG/IG). According to nutritional questionnaires and biomarker analysis, women in the IG had a good adherence to the intervention. 177/874 women were diagnosed with GDM, 103/440 (23.4%) in CG and 74/434(17.1%) in IG, p = 0.012. The crude relative risk (RR) for GDM was 0.73 (95% CI: 0.56-0.95; p = 0.020) IG vs CG and persisted after adjusted multivariable analysis, 0.75(95% CI: 0.57-0.98; p = 0.039). IG had also significantly reduced rates of insulin-treated GDM, prematurity, GWG at 24-28 and 36-38 GW, emergency CS, perineal trauma, and SGA and LGA newborns (all p<0.05). CONCLUSIONS: An early nutritional intervention with a supplemented MedDiet reduces the incidence of GDM and improves several maternal and neonatal outcomes.

Adipsic diabetes insipidus in adult patients.

INTRODUCTION: Adipsic diabetes insipidus (ADI) is a very rare disorder, characterized by hypotonic polyuria due to arginine vasopressin (AVP) deficiency and failure to generate the sensation of thirst in response to hypernatraemia. As the sensation of thirst is the key homeostatic mechanism that prevents hypernatraemic dehydration in patients with untreated diabetes insipidus (DI), adipsia leads to failure to respond to aquaresis with appropriate fluid intake. This predisposes to the development of significant hypernatraemia, which is the typical biochemical manifestation of adipsic DI. METHODS: A literature search was performed to review the background, etiology, management and associated complications of this rare condition. RESULTS: ADI has been reported to occur in association with clipping of an anterior communicating artery aneurysm following subarachnoid haemorrhage, major hypothalamic surgery, traumatic brain injury and toluene exposure among other conditions. Management is very difficult and patients are prone to marked changes in plasma sodium concentration, in particular to the development of severe hypernatraemia. Associated hypothalamic disorders, such as severe obesity, sleep apnoea and thermoregulatory disorders are often observed in patients with ADI. CONCLUSION: The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.

Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304* ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275-5,000) years. tMRCA-based simulations predicted 432 (90-5,175) current carriers, including 86 affected (18-1,035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease.

The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single-centre study.

OBJECTIVE: The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency. DESIGN: Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium ≤ 130 mmol/l) between January 1st and October 1st 2015. PATIENTS: A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD. MAIN OUTCOME MEASURES: (i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency. RESULTS: Central nervous system diseases were the commonest cause of SIAD (n = 148, 26%) followed by pulmonary diseases (n = 111, 19%), malignancy (n = 105, 18%) and drugs (n = 47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration. CONCLUSIONS: In a large, prospective and well-defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co-occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.

Diagnosis and treatment of hyponatraemia in neurosurgical patients.

Hyponatraemia is the most common electrolyte imbalance in neurosurgical patients. Acute hyponatraemia is particularly common in neurosurgical patients after any type of brain insult, including brain tumours and their treatment, pituitary surgery, subarachnoid haemorrhage or traumatic brain injury. Acute hyponatraemia is an emergency condition, as it leads to cerebral oedema due to passive osmotic movement of water from the hypotonic plasma to the relatively hypertonic brain which ultimately is the cause of the symptoms associated with hyponatraemia. These include decreased level of consciousness, seizures, non-cardiogenic pulmonary oedema or transtentorial brain herniation. Prompt treatment is mandatory to prevent such complications, minimize permanent brain damage and therefore permit rapid recovery after brain insult. The infusion of 3% hypertonic saline is the treatment of choice with different rates of administration based on the severity of symptoms and the rate of drop in plasma sodium concentration. The pathophysiology of hyponatraemia in neurotrauma is multifactorial; although the syndrome of inappropriate antidiuresis (SIADH) and central adrenal insufficiency are the commonest causes encountered. Fluid restriction has historically been the classical treatment for SIADH, although it is relatively contraindicated in some neurosurgical patients such as those with subarachnoid haemorrhage. Furthermore, many cases admitted have acute onset hyponatraemia, who require hypertonic saline infusion. The recently developed vasopressin receptor 2 antagonist class of drug is a promising and effective tool but more evidence is needed in neurosurgical patients. Central adrenal insufficiency may also cause acute hyponatraemia in neurosurgical patients; this responds clinically and biochemically to hydrocortisone. The rare cerebral salt wasting syndrome is treated with large volume normal saline infusion. In this review, we summarize the current evidence based on the clinical presentation, causes and treatment of different types of hyponatraemia in neurosurgical patients.

Symptoms of gonadal dysfunction are more predictive of hypopituitarism than nonspecific symptoms in screening for pituitary dysfunction following moderate or severe traumatic brain injury.

OBJECTIVE: The economic and logistic burden of screening for hypopituitarism following moderate/severe traumatic brain injury (TBI) is considerable. A key recommendation in published guidelines is to prioritize for screening those patients with symptoms suggestive of pituitary dysfunction. The purpose of this study was to evaluate the utility of targeted screening for hypopituitarism in long-term survivors after moderate/severe TBI using referrals on the basis of symptoms. DESIGN: In group 1 (G1), consecutive, unselected patients were screened from the Irish National Neurosurgery Centre, whereas in group 2 (G2) patients were targeted based on the presence of symptoms suggestive of pituitary dysfunction. PATIENTS: A total of 137 patients (113 male) were systematically screened (G1) and compared to 112 patients (77 male) referred for pituitary evaluation on the basis of suggestive symptoms (G2). MAIN OUTCOME MEASURES: The rate of GH, ACTH, gonadotrophin (GT), TSH and ADH deficiency was compared among groups. RESULTS: Patients referred with menstrual dysfunction had more GH (50% vs 11%, P = 0·001), ACTH (60% vs 14%, P < 0·0001), GT (90% vs 16%, P < 0·0001) deficiency and any pituitary hormone deficit (80% vs 33%, P = 0·003) than G1. Men with symptoms of hypogonadism had more GH (33% vs 11%, P = 0·003), GT (58% vs 16%, P < 0·0001) and TSH (16% vs 1%, P = 0·03) deficiency than G1. Patients with nonspecific symptoms were no more likely to have hypopituitarism than those consecutively screened. CONCLUSIONS: Symptoms of hypogonadism are sufficiently predictive of hypopituitarism to justify screening for hypopituitarism after moderate/severe TBI. Nonspecific symptoms of hypopituitarism are no more predictive than unselected screening.

The relevance of hyponatraemia to perioperative care of surgical patients.

BACKGROUND: Hyponatraemia is the most common electrolyte disturbance in hospitalized patients. There is an increasing awareness of the impact of hyponatraemia on the perioperative management of surgical patients. METHODS: We performed a literature review. We have included relevant data from different surgical disciplines for analysis. In this review we discuss the differential diagnosis of hyponatraemia, and explain the specific relevance of hyponatraemia to pre-, peri- and post-operative care. RESULTS: Hyponatraemia is common during the preoperative period and is associated with an increase in subsequent peri-operative complications, such as wound infection, pneumonia, higher mortality rate and higher direct and indirect costs. Furthermore, data shows poorer surgical outcomes when plasma sodium concentration drops. Careful preoperative evaluation of the hyponatraemic patient enables assessment of surgical risk and individualization of the management of hyponatraemia. CONCLUSIONS: We outline a practical guide to the assessment of the cause of hyponatraemia, which dictates the correct management of hyponatraemia and the correct selection of perioperative fluids. Finally, for the therapeutic role of the new vasopressin antagonist drugs in the treatment of surgical hyponatraemia is discussed in two illustrative surgical clinical cases.

Fat-soluble vitamin deficiencies after bariatric surgery could be misleading if they are not appropriately adjusted.

OBJECTIVE: To evaluate the differences in frequency of fat-soluble vitamin deficiencies if we adjust their levels by its main carriers in plasma in patients undergoing Biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB). RESEARCH METHODS & PROCEDURES: We recruited 178 patients who underwent RYGB (n = 116 patients) and BPD (n = 62 patients) in a single centre. Basal data information and one-year after surgery included: anthropometric measurements, fat-soluble vitamins A, E and D, retinol binding protein (RBP) and total cholesterol as carriers of vitamin A and E respectively. Continuous data were compared using T-Student and proportions using chisquare test. RESULTS: There was a vitamin D deficiency of 96% of all patients, 10% vitamin A deficiency and 1.2% vitamin E deficiency prior to surgery. One year after surgery, 33% of patients were vitamin A deficient but the frequency reduced to 19% when we adjusted by RBP. We found a vitamin E deficiency frequency of 0% in RYGB and 4.8% in DBP one year after surgery. However, when we adjusted the serum levels to total cholesterol, we found an increased frequency of 8.7% in RYGB group for vitamin E deficiency and 21.4% in DBP (p = 0.04). CONCLUSION: We have found a different frequency of deficit for fat-soluble vitamin both in BPD and RYGB once we have adjusted for its main carriers. This is clinically relevant to prevent from overexposure and toxicity. We suggest that carrier molecules should be routinely requested when we assess fat-soluble vitamin status in patients who undergo malabsorptive procedures.

OBJETIVO: Evaluar las diferencias en la frecuencia de las deficiencias de vitaminas liposolubles si ajustamos sus concentraciones mediante sus principales transportadores plasmáticos en pacientes sometidos a derivación biliopancreática (DBP) y derivación gástrica en Y de Roux (DGYR). MÉTODOS DE INVESTIGACIÓN Y PROCEDIMIENTOS: Reclutamos a 178 pacientes sometidos a DGYR (n = 116 pacientes) y DBP (n = 62 pacientes) en un único centro. Los datos de información basal y al año de la cirugía incluyeron: mediciones antropométricas, vitaminas liposolubles A, E y D, proteína de unión al retinol (PUR) y el colesterol total como transportadores de las vitaminas A y E, respectivamente. Los datos continuos se compararon utilizando la t de Student y para las proporciones el test chi cuadrado. RESULTADOS: Hubo una deficiencia de vitamina D en el 96% de todos los pacientes, de vitamina A en el 10% y de vitamina E en el 1,2% antes de la cirugía. Un año después de la cirugía, el 33% de los pacientes tenía deficiencia de vitamina A pero la frecuencia se redujo al 19% cuando ajustamos para la PUR. Encontramos una frecuencia de deficiencia de vitamina E en el 0% de los pacientes con DGYR y en el 4,8% de aquellos con DBP un año después de la cirugía. Sin embargo, cuando ajustamos las concentraciones séricas de colesterol total, encontramos un aumento de la frecuencia de hasta el 8,7% de deficiencia de vitamina E en el grupo con DGYR y del 21,4% en el grupo con DBP (p = 0,04). CONCLUSIÓN: Encontramos una frecuencia diferente de déficit de vitaminas liposolubles tanto en DBP como en DGYR una vez que ajustamos para sus principales transportadores. Esto es clínicamente relevante para evitar la sobreexposición y la toxicidad. Sugerimos que se deberían solicitar de forma rutinaria las moléculas transportadoras a la hora de evaluar el estado de vitaminas liposolubles en pacientes sometidos a procedimientos que entrañan malabsorción.

Platysma flap: an alternative to free flaps.

OBJECTIVE: The objective of this paper is to show that platysma flaps have good results and should be an alternative in reconstructive surgery for oral tumors when microsurgery is not possible. It is a versatile, portable, and thin flap, is easy to perform, and can be obtained during neck dissection, with a primary closure of the donor site. METHODS: Five cases are presented, three men and two women, 51 and 71 years old, with medium size (2-4 cm) defects of oral cavity after the excision of squamous cell carcinomas. All of them were reconstructed with a platysma flap after neck dissection. This reconstruction technique was chosen because of the poor conditions of these patients to allow a microsurgical reconstruction. RESULTS: Non-local complications occurred with this technique. Overall aesthetic results were acceptable in all the patients. There were no cases of total necrosis flap, dehiscence, fistula or fibrosis. Only one case of partial necrosis occurred in one end of the flap, which was resolved with excision of necrotic tissue and closure by secondary intention. CONCLUSION: The platysma flap is a good method to reconstruct small and medium sized defects of oral cavity, especially in patients where a microsurgery reconstruction is not possible.

[Interleukin-6 and tumor necrosis factor-alpha as markers of vertically-transmitted neonatal bacterial infection]. / Interleucina-6 y factor de necrosis tumoral-alpha como marcadores de infección neonatal de transmisión vertical.

INTRODUCTION: Neonatal infection is a major cause of morbidity in the neonatal period. Several parameters have been used to assess neonatal sepsis. C-reactive protein (CRP) shows high specificity for bacterial infections, but an increase in CRP is often not detected until 12 to 24 hours after onset of the infection. OBJECTIVE: To evaluate the usefulness of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in the early diagnosis of vertically-transmitted neonatal bacterial infection. METHODS: Thirty-four newborns admitted to the neonatal intensive care unit with an initial diagnosis of respiratory distress were included. Twelve newborns presented the criteria for clinical sepsis or pneumonia (group I) and six had positive blood culture. The remaining patients did not present the clinical criteria for infection (group II). IL-6, TNF-alpha, CRP levels and the ratio between immature and mature neutrophil count were assessed at 8.8 +/- 7.3 hours of life. In 17 patients the same parameters were assessed at 67.4 +/- 24.8 hours of life. The statistical analysis was performed using the Mann-Whitney test. The sensitivity and specificity of these markers were assessed. RESULTS: No differences were found in the perinatal features of either group. Analysis of markers of infection revealed the following significant differences: ratio between immature and mature neutrophil count: (0.25 +/- 0.21 vs 0.12 +/- 0.09; p=0.048), CRP first determination (1.4 +/- 0.8 mg/dL vs 1 +/- 0.5 mg/dL; p=0.036), CRP second determination: (3.8 +/- 1.8 mg/dL vs 1.4 +/- 1.1 mg/dL; p=0.008), IL-6 first determination: (582.2 +/- 810.5 pg/mL vs 31.3 +/- 24.2 pg/mL; p=0.000). Sensitivity/specificity (%): ratio between immature and mature neutrophil count: 41.6/83.6; CRP first determination: 16.6/90.9; CRP second determination: 83.3/87.5; IL-6 (optimum cut-off value: 55 pg/mL): 100/72.7, and TNF-alpha: 16.6/85. CONCLUSIONS: IL-6 determination in the first hours of life is a more sensitive early marker of neonatal infection than other classical markers because of its early elevation. Like CRP, early TNF-alpha determination has high specificity but low sensitivity.