Clinical evaluation of hyponatremia and hypovolemia in critically ill adult neurologic patients: contribution of the use of cumulative balance of sodium

Purpose

Knowledge of the cumulative balance of sodium (CBS) is important for the diagnosis of salt disorders and water homeostasis and has the potential to predict hypovolemic status in acute neurological patients. However, an extensive application of the use of CBS is still lacking in the intensive care setting, where salt and water homeostasis represents a priority.

Methods

Records of consecutive series of acute neurological patients admitted to a neurointensive care unit over a 6-month period were retrospectively reviewed. CBS was calculated at the admission to the Emergency Department. Discrimination between cerebral salt-wasting syndrome (CSWS) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was performed on the basis of the classical criteria. Additionally, we used the findings of a negative CBS exceeding 2 mEq/kg for the diagnosis of CSWS. Two independent clinicians who were blinded to the CBS results performed diagnosis of the causes of hyponatremia and estimated the daily volemic status of the patients on the basis of clinical parameters. Logistic regression analysis was used to determine the independent prognostic factors of hypovolemia.

Results

Thirty-five patients were studied for a total of 418 days. Four patients (11.4 %) fitted the criteria of CSWS and three patients (8.5 %) had SIADH. The unavailability of the CBS led to a wrong diagnosis in three of the eight hyponatremic patients (37.5 %). The risk of developing hypovolemia in patients with negative CBS was 7.1 times higher (CI 3.86–13.06; p < 0.001). Multivariate analysis revealed that negative cumulative fluid balance, negative CBS >2 mEq/kg, and CVP ≤5 cmH₂O were independent prognostic factors for hypovolemia.

Conclusions

CBS is likely to be a useful parameter in the diagnosis of CSWS and a surrogate parameter for estimating hypovolemia in acute neurological patients.     

Aqueductal stenosis 9 years after mumps meningoencephalitis: treatment by endoscopic third ventriculostomy

Introduction Hydrocephalus due to aqueductal stenosis following mumps meningoencephalitis is a rare condition, reported only in 16 cases in the literature. The pathogenetic role of the mumps virus in inducing aqueductal stenosis has been demonstrated experimentally in animal models and clinically proven in a few cases. Although obstructive in nature, the post-infectious etiology raises the question as to whether third ventriculostomy is the appropriate treatment.Patient We report a case of hydrocephalus due to pure aqueductal stenosis occurring in an 11-year-old boy who suffered from mumps meningoencephalitis 9 years previously. The boy was successfully treated by endoscopic third ventriculostomy.Conclusions The present case offers further evidence of the purely obstructive nature of the hydrocephalus induced by paramyxovirus meningoencephalitis, even if it did occur several years after the infectious disease. The pathogenesis of mumps-induced hydrocephalus and the rationale of treatment are discussed, and the literature is reviewed.     

Immunohistochemical expression of p16(INK4a) is predictive of HR-HPV infection in cervical low-grade lesions.

The p16(INK4a) is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated. In this study, we investigated in parallel, p16 expression and HPV infection in 100 cervical biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous cancers). Results obtained demonstrated that none of the 17 normal cervical tissues, evaluated by immunohistochemistry, presented p16 positivity whereas, starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a constant and significant increase of protein overexpression (P<0.0001) was observed. In addition, p16 overexpression consistently showed elevated sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high positive predictive value (97%) and negative predictive value (86%). Of interest, 93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and further demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions.     

R0 resection in the treatment of gastric cancer: Room for improvement

Gastric carcinoma is one of the most frequent malignancies in the world and its clinical behavior especially depends on the metastatic potential of the tumor.In particular,lymphatic metastasis is one of the main predictors of tumor recurrence and survival,and current pathological staging systems reflect the concept that lymphatic spread is the most relevant prognostic factor in patients undergoing curative resection.This is compounded by the observation that two-thirds of gastric cancer in the Western world...     

Mitochondrial transporters of the SLC25 family and associated diseases: a review

To date, 14 inherited diseases (including phenotypes) associated to mitochondrial transporters of the SLC25 family have been well characterized biochemically and genetically. They are rare metabolic disorders caused by mutations in the SLC25 nuclear genes that encode mitochondrial carriers, a superfamily of 53 proteins in humans that shuttle a variety of solutes across the mitochondrial membrane. Mitochondrial carriers vary considerably in the nature and size of the substrates they transport, the modes of transport and driving forces. However, their substrate translocation mechanism at the molecular level is thought to be basically the same. Herein, the main structural and functional properties of the SLC25 mitochondrial carriers and the known carrier-related diseases are presented. Two of these disorders, ADP/ATP carrier deficiency and phosphate carrier deficiency, are caused by defects of the two mitochondrial carriers that provide mitochondria with ADP and phosphate, the substrates of oxidative phosphorylation; these disorders therefore are characterized by defective energy production by mitochondria. The mutations of SLC25 carrier genes involved in other cellular functions cause carnitine/acylcarnitine carrier deficiency, HHH syndrome, aspartate/glutamate isoform 1 and 2 deficiencies, congenital Amish microcephaly, neuropathy with bilateral striatal necrosis, congenital sideroblastic anemia, neonatal epileptic encephalopathy, and citrate carrier deficiency; these disorders are characterized by specific metabolic dysfunctions depending on the role of the defective carrier in intermediary metabolism.