Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer’s Disease

In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer''s disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.     

The opportunity costs of caring for people with dementia in Southern Spain

Objective

The aim of this paper is to study the opportunity costs (OC) that are involved in being a caregiver and to compare them with the direct costs assumed by the State and the families. We evaluate direct cost (those that imply a payment-out-of-pocket) and indirect cost (those that imply a dedication in time). We hypothesized that costs increase with the severity of the dementia, with the educational level and active occupational situation of caregiver. They are greater if the caregiver is male, but if the patient and caregiver cohabit they are reduced.

Intussusception in a premature neonate: A rare and often misdiagnosed clinical entity

Intussusception is a very rare cause of intestinal obstruction in neonates. It is of extremely rare occurrence among premature neonates. We present a case of 11-day-old premature neonate who presented with abdominal distension, intolerance to feeds, vomiting, significant bilious aspirate and bleeding per rectum. The initial diagnosis of necrotizing enterocolitis (NEC) led to a delay in the diagnosis. On exploratory laparotomy, it turned out to be a case of ileo-colic intussusception with Meckel''s diverticulum as a lead point. This site of intussusception (ileo-colic) and presence of a lead point among premature neonate is of exceedingly rare occurrence and very few such cases have been reported.In this article, the published work about clinical features and management on intussusceptions in premature neonates has been reviewed. The authors intend to highlight the difficulty in distinguishing the NEC and intussusception. Subtle clinical and radiological features which can help in differentiating the two conditions have been emphasized. This can avoid the delay in diagnosis and management which can prove critical. High index of suspicion with timely intervention is the key for optimizing outcome. A diagnosis of intussusception should always be considered in any preterm infant with suspected NEC.