Predictive biomarkers for the early detection and management of heart failure.

Cardiovascular disease (CVD) is a serious public health concern whose incidence has been on a rise and is projected by the World Health Organization to be the leading global cause of mortality by 2030. Heart failure (HF) is a complicated syndrome resulting from various CVDs of heterogeneous etiologies and exhibits varying pathophysiology, including activation of inflammatory signaling cascade, apoptosis, fibrotic pathway, and neuro-humoral system, thereby leading to compromised cardiac function. During this process, several biomolecules involved in the onset and progression of HF are released into circulation. These circulating biomolecules could serve as unique biomarkers for the detection of subclinical changes and can be utilized for monitoring disease severity. Hence, it is imperative to identify these biomarkers to devise an early predictive strategy to stop the deterioration of cardiac function caused by these complex cellular events. Furthermore, measurement of multiple biomarkers allows clinicians to divide HF patients into sub-groups for treatment and management based on early health outcomes. The present article provides a comprehensive overview of current omics platform available for discovering biomarkers for HF management. Some of the existing and novel biomarkers for the early detection of HF with special reference to endothelial biology are also discussed.

Evaluation of a protocol-based treatment strategy for postoperative diabetes insipidus in craniopharyngioma.

BACKGROUND: Postoperative diabetes insipidus (DI) is a significant cause of morbidity in craniopharyngiomas (CP) and its effective management improves outcome. OBJECTIVE: The objective was to determine the efficacy of a treatment protocol in the management of early postoperative DI in CP. MATERIALS AND METHODS: The quality of postoperative DI control in a prospective cohort of 26 patients treated utilizing a strict protocol (Group 1) was compared with a retrospective cohort of 34 patients (Group 2) managed without a protocol. A 6-h urine output more than 4 ml/kg/h or serum sodium (Na+) more than 145 mEq/L was diagnosed as DI. The quality of DI control was assessed by determining the incidence of serum Na+ values above 150 mEq/L or below 130 mEq/L and the incidence of wide (>10 mEq/L) intra-day fluctuations of serum Na+ levels. RESULTS: The occurrence of high and low serum Na+ levels was significantly lower in Group 1(P = 0.032). The incidence of serum Na+ exceeding 150 mEq/L on postoperative days 2 and 3 was significantly higher in Group 2 as compared with those in Group 1 (25% vs. 7.6%, P = 0.0008). Hyponatremia was more frequent in Group 2 and tended to occur on postoperative days 6, 7, and 8 (14.2% vs. 3.2%; P = 0.004). The same patients who had hypernatremia in the early part of the week later developed hyponatremia. Although the incidence of wide intra-day fluctuations (>10 mEq/L) was higher in Group 2, it did not reach statistical significance. CONCLUSION: A strict protocol based management results in better control of postoperative DI in CP.

Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays.

BACKGROUND: Early detection of residual disease may benefit management strategies in patients undergoing transsphenoidal surgery for acromegaly. This requires establishing objective thresholds for early postoperative growth hormone (GH) assays, and incorporating these parameters into a scale for outcome prediction. METHOD: We analyzed a database containing the records of 86 patients who had undergone gross total transsphenoidal resection of GH-secreting pituitary adenomas. Early postoperative biochemical testing included a morning fasting basal GH assay on the first postoperative day (POD1) and a second GH assay following suppression with 100 g of oral glucose on the seventh postoperative day (POD7). Remission was defined as a normal IGF-1 with either a GH nadir <0.4 ng/ml following suppression with oral glucose or a basal fasting GH <1 ng/ml on follow-up dated >3 months after surgery. Receiver operator characteristic (ROC) curves identified optimal thresholds for all biochemical parameters. Logistic regression analysis assessed the statistical significance of factors associated with cure. A point system was developed, employing regression coefficients obtained from the multivariate statistical model to quantify the impact of each predictor on cure. RESULTS: Remission was achieved in 34.6 % of patients and was associated with smaller, non-invasive tumors with lower preoperative, POD1 and POD7 GH levels. Optimal thresholds obtained from the ROC analysis suggested that lower POD1 and POD7 GH values provided good sensitivity and specificity for cure, despite modest predictive values. The model with the best ability to predict outcome included size, POD1 GH and POD7 GH levels, with a score of ≥95 demonstrating high specificity for prediction of remission. CONCLUSION: Early postoperative GH assays are highly sensitivity and specific. The scoring system that we propose provided excellent predictive value and requires further validation in larger cohorts and in different populations. The model may help guide the intensity of follow-up and enable early identification of residual disease.

Improvement in intraoperative transcranial electrical motor-evoked potentials in tethered cord surgery: an analysis of 45 cases.

BACKGROUND: Improvement of transcranial electrical motor-evoked potentials (TeMEPs) following untethering during tethered cord surgery (TCS) and its clinical significance have not been analyzed in the literature. METHODS: Forty-five consecutive cases of tethered cord were operated on with multimodality intraoperative neurophysiological monitoring (IONM) between February 2005 and January 2012. Intraoperative TeMEP change was classified as improvement, worsening or no change. Motor, sensory, bladder and bowel symptoms and signs were evaluated preoperatively, in the first week post-surgery and at the last follow-up (maximum of 2 years). RESULTS: Patient age ranged from 5 to 44 years (mean, 16 ± 10 years), with 30 children. Intraoperative MEPs improved in 23 (51 %), remained the same in 21 (46.7 %) and worsened in 1 (2 %) patient. Motor improvement occurred in 7 patients and clinical improvement in 17 patients in the immediate postoperative period. Postoperative neurological worsening occurred in one patient (2.2 %). Improved and stable MEPs correlated with the motor (p = 0.002) and clinical improvement (p = 0.02) in the immediate postoperative period. Follow-up was available in 35 patients (77.7 %), ranging from 5 to 24 months (median, 21 months; mean, 17.7 ± 6.8 months). There was late clinical improvement in 73.5 % of the patients in whom the intraoperative MEP had remained the same or improved. However, there was no statistically significant correlation between MEP change and long-term outcome. CONCLUSIONS: Intraoperative MEP improvement occurs in about 50 % of the patients following successful untethering. This finding probably provides support to the ischemic theory of tethered cord syndrome.

Incidence, predictors and early post-operative course of diabetes insipidus in paediatric craniopharygioma: a comparison with adults.

PURPOSE: This study aims to determine the incidence, predictors, early post-operative course of diabetes insipidus (DI) in paediatric craniopharyngiomas(CP) and compare the findings with adults. METHODS: Retrospective analysis of clinical, biochemical, radiological and operative data for 102 consecutive CP surgeries (45 paediatric and 57 adult cases) was done. Bivariate and multivariate analyses were done to determine the predictors of DI. The incidence of the triphasic response and electrolyte abnormalities in the first post-operative week was compared between children and adults. RESULTS: Children had larger tumours and higher incidence of cystic tumours and hydrocephalus. Preoperative DI was close to 15 % in both the age groups. Radical/subtotal excision was achieved in 58 % of children and 53 % of adults. The incidence of post-operative DI was 80 % and 63 % in children and adults, respectively. Children had significantly higher incidence of permanent DI (55.6 %). Radical excision in children (p = 0.000); previous tumour surgery (p = 0.014) and new onset hypopituitarism (p = 0.019) in adults were associated with permanent DI. The triphasic response (23 %), wide intra-day serum sodium fluctuations and hyponatraemia were more common in children. CONCLUSIONS: Post-operative DI is a frequent and significant cause of morbidity in children undergoing surgery for CP. Children have a higher incidence of permanent DI. Radical excision is a predictor of permanent DI in children, whereas previous tumour excision and new onset hypopituitarism were predictors of permanent DI among adults. The management of post-operative DI is more difficult in children and the treating physician needs to be alert to detect the triphasic response.

The current role of transcranial surgery in the management of pituitary adenomas.

The aim of this study was to determine the factors influencing the use of a transcranial (TC) approach in pituitary adenomas and suggest a decision-making tree for the surgical strategy. The data for 23 (4.6%) patients who underwent TC surgery from amongst 494 pituitary adenomas were retrospectively analyzed. Eight factors on magnetic resonance imaging (MRI) that could predict a difficult transsphenoidal (TS) surgery were noted. Adverse findings at TS surgery leading to a 2nd stage TC surgery were documented. Eighteen of the 23 cases were giant adenomas. Thirteen patients underwent TC surgery alone or as an initial approach when combined with TS while 10 underwent 2nd stage TC surgery following a TS approach. Most cases in the first group had 3 or more radiological factors in combination with a small sella. The 2nd group had higher sellar tumor volumes and fewer unfavourable radiological factors that led to the initial use of the TS approach. A hard, fibrous consistency or a significant residue obscured from the surgeon's view, and difficulty in hemostasis were additional factors prompting the use of a TC approach. Tumor excision ≥90% could be achieved in 13 cases (56.5%). Post-operative RT was administered in 12 patients. There were 2 deaths (8.7%) and the major morbidity rate was 43 %. Despite advances in endoscopic surgery the TC approach may be required in 5% of cases. A study of the preoperative MRI for factors that predict difficulty with the TS approach might encourage the surgeon to consider a TC surgery either as an initial approach or combined with a TS surgery.

Choroid plexus papilloma presenting as a non-contrast-enhancing fourth ventricular mass in a child.

Choroid plexus papilloma (CPP) is a rare benign tumor of the central nervous system with a propensity for location within the lateral ventricle in children. We report a case of a 14-year-old girl who presented with transient facial paresis and ataxia. Her imaging showed a non-enhancing intra fourth ventricular mass, the histology of which was reported as CPP. The atypical clinical and radiological features in this case are discussed. Choroid plexus papillomas should be considered in the differential diagnosis of non-enhancing fourth ventricular masses.