Emmanuel I. González-Moreno

Glycemic Variability and Acute Ischemic Stroke: The Missing Link?

Hyperglycemia is commonly encountered in both diabetic and non-diabetic patients in acute ischemic stroke. Hyperglycemia in stroke has been associated with poor clinical outcome, a phenomenon that has been studied in experimental models, where hyperglycemia was shown to enhance cortical toxicity, increase infarct volumes, promote inflammation, and affect the cerebral vasculature. This has led to many trials attempting to modulate the hyperglycemic response as a therapeutic and neuroprotective strategy. Intensive glycemic control has been evaluated in stroke patients, with conflicting results. The evidence linking hyperglycemia with neurotoxicity coupled with the failure of intensive glucose control regimens to improve functional outcomes in stroke suggests that novel approaches should be devised. Recent attention has been paid to another related phenomenon, that of glycemic variability, which has been proven to be a predictor of outcome in critically ill patients; however, its the impact in stroke has not been evaluated.

The treatment of diabetes mellitus of patients with chronic liver disease.

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.

Clinical Features and Outcome of Mucormycosis

Mucormycosis (MCM) is a life-threatening infection that carries high mortality rates despite recent advances in its diagnosis and treatment. The objective was to report 14 cases of mucormycosis infection and review the relevant literature. We retrospectively analyzed the demographic and clinical data of 14 consecutive patients that presented with MCM in a tertiary-care teaching hospital in northern Mexico. The mean age of the patients was 39.9 (range 5–65). Nine of the patients were male. Ten patients had diabetes mellitus as the underlying disease, and 6 patients had a hematological malignancy (acute leukemia). Of the diabetic patients, 3 had chronic renal failure and 4 presented with diabetic ketoacidosis. All patients had rhinocerebral involvement. In-hospital mortality was 50%. All patients received medical therapy with polyene antifungals and 11 patients underwent surgical therapy. Survivors were significantly younger and less likely to have diabetes than nonsurvivors, and had higher levels of serum albumin on admission. The clinical outcome of patients with MCM is poor. Uncontrolled diabetes and age are negative prognostic factors.

Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise.

Posterior Reversible Encephalopathy Syndrome Due to Malignant Hypercalcemia: Physiopathological Considerations

CONTEXT Posterior reversible encephalopathy syndrome (PRES) is a neurological entity characterized by seizures, headache, and reversible subcortical vasogenic edema. It is associated with many etiologies, most often hypertension, chronic renal failure, and chemotherapy. Hypercalcemia is rarely associated with PRES. OBJECTIVE The aim of this study is to describe and discuss a case of PRES that developed in a patient with malignant hypercalcemia, with emphasis on the possible pathophysiological mechanisms involved. PATIENTS AND METHODS A 38-year-old woman presented with altered mental status. She had a 2-month history of lumbar pain of moderate intensity, weight loss, and gastrointestinal complaints, in addition to a mass in her left breast. Her corrected serum calcium was 14.5 mg/dL. She was normotensive, had no focalizing signs, and her cerebrospinal fluid was normal. Despite treatment, her neurological state did not resolve, and she developed severe headaches at day 4 of her admission. Brain magnetic resonance imaging showed a bilateral and symmetric hyperintensity in the occipital and parietal lobes on T2-weighted and fluid-attenuated inversion recovery imaging, a characteristic highly suggestive of PRES. After correction of hypercalcemia, her symptoms and imaging abnormalities resolved. CONCLUSIONS The development of PRES in the setting of severe hypercalcemia is extremely rare. Hypercalcemia could lead to PRES in the absence of hypertension by various mechanisms, including vasospasm, endothelial dysfunction, and an inflammatory state. A high index of suspicion is needed in this setting because hypercalcemia can lead to neurological symptomatology, and prompt diagnosis is essential for adequate treatment.

Hepatogenous diabetes: Is it a neglected condition in chronic liver disease?

Diabetes mellitus (DM) that occurs because of chronic liver disease (CLD) is known as hepatogenous diabetes (HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus (HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.

Lack of consistency with the consensus recommendations for the diagnosis of eosinophilic esophagitis (EoE) in published prevalence studies. A clinical and systematic review.

According to consensus recommendations, the presence of esophageal symptoms, >15 eosinophils/high‐power field and unresponsiveness to proton pump inhibitors are required for a diagnosis of eosinophilic esophagitis (EoE). Nevertheless, inconsistency in using these guidelines has been reported in recent publications. The objective of this study was to assess compliance with EoE diagnostic guidelines in published studies on EoE prevalence and to evaluate other clinical and methodological parameters.

Portal vein thrombosis in patients with cirrhosis: just a common finding or a predictor of poor outcome?

BACKGROUND & AIMS It is unclear whether portal vein thrombosis (PVT) unrelated to malignancy is associated with reduced survival or it is an epiphenomenon of advanced cirrhosis. The objective of this study was to assess clinical outcome in cirrhotic patients with PVT not associated with malignancy and determine its prevalence. MATERIAL AND METHODS Retrospective search in one center from June 2011 to December 2014. RESULTS 169 patients, 55 women and 114 men, median age 54 (19-90) years. Thirteen had PVT (7.6%). None of the patients received anticoagulant treatment. The PVT group was younger (49 [25-62] vs. 55 [19-90] years p = 0.025). Child A patients were more frequent in PVT and Child C in Non-PVT. Median Model for End Stage Liver Disease (MELD) score was lower in PVT (12 [8-21] vs. 19 [7-51] p ≤ 0.001) p ≤ 0.001). There was no difference between upper gastrointestinal bleeding and spontaneous bacterial peritonitis in the groups. Encephalopathy grade 3-4 (4 [30.8%] vs. 73 [46.8%] p = 0,007) and large volume ascites (5 [38.5%] vs. 89 [57.1%] p= 0,012) was more common in non-PVT. Survival was better for PVT (16.5 ± 27.9 vs. 4.13 ± 12.2 months p = 0.005). CONCLUSIONS We found that PVT itself does not lead to a worse prognosis. The most reliable predictor for clinical outcome remains the MELD score. The presence of PVT could be just an epiphenomenon and not a marker of advanced cirrhosis.

Causes of Infrequent Prevalence of Eosinophilic Esophagitis in Hispanics May Involve Social and Cultural Factors: Probable Role of Digestive Microbiota

We read with great interest the article by Yu Ch et al. who found in a cohort study that the prevalence of eosinophilic esophagitis (EoE) is significantly lower in Hispanic population compared to Caucasians. They also found that analysis of gene expression had similar results in subjects with EoE from both ethnic groups. The authors concluded that environmental, racial, and cultural factors should be studied to explain these marked differences [1]. A low prevalence of EoE has also been observed in our Latin American countries in the few studies published so far [2, 3]. In the light of current knowledge, we think that the prevalence of EoE in a given population is determined by the interaction of three factors with variable specific weight: (1) genetics, (2) environmental allergens, and (3) immunological susceptibility. Firstly, genetic factors have recently been identified [4]. The estimated sibling recurrence rate in EoE is approximately 80 percent, indicating a potentially significant role of genetics in this disease. In another study, the gene that encodes eotaxin-3 was the most upregulated gene in EoE [5]. Secondly, there exist some aeroallergens and food-based allergens that could have a central role. Notwithstanding, why foods and pollens that had been tolerated by humans for thousands of years now trigger EoE? Maybe sensitization of individuals (the third crucial factor) could explain this issue. This is also extended to other allergic diseases mediated through Th2 inflammatory response (implicated in the pathophysiology of EoE) such as asthma, atopic dermatitis, and allergic rhinitis. It has been shown that these allergic diseases have increased their incidence in developed countries in the last two or three decades [6]. The increase in sensitization could be the result of the modification of lifestyles as a consequence of the improvement of the socioeconomic levels in developed countries in the last decades. For example, it has been observed that the prevalence of EoE is inversely proportional to the prevalence of infection by Helicobacter pylori [7], which is still highly prevalent in Latin populations [8] and is related to low socioeconomic levels. Whether or not Helicobacter pylori could protect against EoE is a non-cleared issue. We think that the presence of the infection could be the reflection of modifications of the digestive microbiota, which is determined from birth and can suffer variations due to cesarean delivery, antibiotics use, type of diet, breast-feeding, repeated gastrointestinal infections, and rigorous aseptic codes. Along with these findings, the hygiene hypothesis postulates that the elimination of non-lethal bacterial infections mediated by the inflammatory reaction Th1 could increase the expression of inflammatory Th2 response [9]. Dysbiosis of the intestinal microbiota during the neonatal stage is linked to the development of atopy and asthma in childhood [10]. This linkage has not been studied for EoE. On the other hand, the microbiota of the stomach and esophagus have been poorly studied. In the future, these hot topics could be the subject of research to better understand the pathogenesis of EoE and the difference in prevalence among diverse populations throughout the world.

Elevated Serum Triglycerides Associated With Systemic Inflammatory Response Syndrome and Persistent Organ Failure in Acute Pancreatitis

Elevated Serum Triglycerides Associated With Systemic Inflammatory Response Syndrome and Persistent Organ Failure in Acute Pancreatitis