Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances

The role of cerebral amyloid angiopathy (CAA) in the pathogenesis of Alzheimer's disease (AD) is not fully understood. Here, we studied whether CAA is associated with alterations in microvascularisation in transgenic mouse models and in the human brain. APP23 mice at 25–26 months of age exhibited severe CAA in thalamic vessels whereas APP51/16 mice did not. Wild-type littermates were free of CAA. We found CAA-related capillary occlusion within the thalamus of APP23 mice but not in APP51/16 and wild-type mice. Magnetic resonance angiography (MRA) showed blood flow alterations in the thalamic vessels of APP23 mice. CAA-related capillary occlusion in the branches of the thalamoperforating arteries of APP23 mice, thereby, corresponded to the occurrence of blood flow disturbances. Similarly, CAA-related capillary occlusion was observed in the human occipital cortex of AD cases but less frequently in controls. These results indicate that capillary CAA can result in capillary occlusion and is associated with cerebral blood flow disturbances providing an additional mechanism for toxic effects of the amyloid β-protein in AD.     

Right Adrenal Metastases of Hepatocarcinoma After Liver Transplantation: Case Report and Literature Review

Background

Hepatocellular carcinoma (HCC) represents one of the most common malignancies globally, accounting for nearly one million new cases per year. Although the treatment of extrahepatic metastases from primary liver tumors is essentially palliative, a solitary metastasis from such tumors offers a possibility of cure by surgical resection. The adrenal gland is an uncommon site for metastasis from primary liver tumors.

Methods

We report a liver transplantation case of HCC and hepatitis B virus in a 23-year-old man with an excellent postoperative result. However, because an increased alpha-fetoprotein was evident and complete radiologic and blood tests were performed, all of which were normal. Three years posttransplantation, a right adrenal mass was identified by CT. PAAF was performed as well as adrenalectomy for a solitary adrenal metastasis from hepatocellular carcinoma.

Results

The patient underwent adrenalectomy for the right adrenal metastasis at 3 years following liver transplantation for HCC. He is presently alive and disease-free 24 months after adrenalectomy.

Conclusion

Carefully selected patients with solitary metastasis from HCC may be considered for resection.     

Tracing of temporo-entorhinal connections in the human brain: cognitively impaired argyrophilic grain disease cases show dendritic alterations but no axonal disconnection of temporo-entorhinal association neurons

Argyrophilic grain disease (AGD), a neurodegenerative disorder, is often associated with mild to moderate Alzheimer’s disease (AD)-related pathology. The development of dementia in AGD is associated with the extent of coexisting AD-related pathology. Therefore, the question arises whether the degenerative changes in the neuronal network of demented AGD-patients represent a distinct pattern or show similar changes of disconnection as considered for AD. We were able to apply DiI-tracing in two human autopsy cases with mild AD-related pathology (controls), in one AD-patient, in one non-demented patient with advanced AD-related pathology, and in three cognitively impaired AGD-patients. DiI-crystals were injected into the entorhinal cortex. Pyramidal neurons of layers III and V of the adjacent temporal neocortex (area 35) were retrogradely marked with the tracer and analyzed. The AD case did not exhibit any retrogradely labeled neurons in the temporal neocortex. In the non-demented case with advanced AD-related pathology, the number of traced neurons was reduced as compared to that in the two controls and in the three AGD cases. In contrast, all three cognitively impaired AGD cases exhibited labeled pyramidal neurons in area 35 in an almost similar number as in the controls. However, alterations in the dendritic tree were observed in the AGD cases. These results show the existence of temporo-entorhinal connections in the adult human brain similar to those reported in animal models. Furthermore, the present study based on seven cases is the first attempt to study changes in the neuronal network in a human tauopathy with targeted axonal tracing techniques. Our findings in three cognitively impaired AGD cases suggest that AGD-related dementia constitutes a distinct disorder with a characteristic pattern of degeneration in the neuronal network.     

Effectiveness of an early cognitive–behavioral treatment in patients with work disability due to musculoskeletal disorders

Objective

To evaluate whether an early cognitive–behavioral treatment complementary to a rheumatologic care program, for patients with recent‐onset temporary work disability caused by musculoskeletal disorders (MSDs) is effective.

Methods

Patients with an MSD‐related temporary work disability episode from 3–8 weeks' duration who were in a rheumatologic care program were randomized into a control group (rheumatologic care program) or an intervention group (rheumatologic care program plus cognitive–behavioral treatment). Enrollment lasted 24 months and followup lasted 6–24 months. Efficacy variables included duration of temporary work disability episodes, total number of work days saved, relative efficacy, and relative rate to return to work. An economic evaluation was also performed.

Results

One hundred eighty‐one patients were included (66 control and 115 intervention patients), generating 222 episodes of MSD‐related temporary work disability. Episodes tended to be shorter in the intervention group than in the control group (mean 98 versus 127 days; P = 0.053), with a relative efficacy of 22.9%. There were no differences in duration of the first episode between groups (mean 105 versus 110 days; P = 0.79), but relapse episodes were significantly shorter in the intervention group (mean 63 days versus 197 days; P = 0.0002). Costs were also lower in the intervention group. To save 1 day of temporary work disability, $13.50 had to be invested in the program. Each dollar invested generated a benefit of $4.08. The program had a net benefit of $172,607.

Conclusion

Early cognitive–behavioral treatment complementary to a rheumatologic care program is cost‐effective, adds >20% efficacy to the rheumatologic care program, and reduces the duration of relapses.     

Efficacy of a self-management education programme on patients with type 2 diabetes in primary care: A randomised controlled trial

Aim

The purpose of this study was to assess the efficacy of the Spanish Diabetes Self-Management Program (SDSMP) versus usual care in adults with type 2 diabetes mellitus (T2DM) residing in a Spanish region.

Insuring continuity of care for chronic disease patients after a disaster: key preparedness elements

BACKGROUND: Care for patients with chronic diseases is a challenge after a disaster. This is particularly true for individuals from health disparate populations as they are less likely to evacuate, have fewer financial resources and often depend on resource-strapped institutions for their care. The specific aim of the study presented here was to elicit challenges and solutions in the provision of health care to those with chronic diseases after Hurricane Katrina in coastal Alabama and Mississippi. METHODS: Focusing on agencies providing care to health disparate populations, a qualitative methodology was employed using in-depth interviews with health and social service providers. Participants identified key elements essential to disaster preparedness. RESULTS: Predisaster issues were patient education and preparedness, evacuation, special needs shelters, and health care provider preparedness. Postdisaster issues were communication, volunteer coordination, and donation management. CONCLUSIONS: Lessons learned from those on the ground administering health care during disasters should inform future disaster preparations. Furthermore, the methodological approach used in this study engendered collaboration between health care institutions and may enhance future interagency disaster preparedness.     

Nutritional Status,Body Surface,and Low Lean Body Mass/Body Mass Index Are Related to Dose Reduction and Severe Gastrointestinal Toxicity Induced by Afatinib in Patients With Non‐Small Cell Lung Cancer

Background.

The main reason for dose reduction of afatinib is gastrointestinal toxicity (GT). In a phase II study, we analyzed anthropometrical, nutritional, and biochemical factors associated with GT induced by afatinib.

Materials and Methods.

Patients diagnosed with non-small cell lung cancer who progressed to prior chemotherapy received 40 mg of afatinib. Malnutrition was determined by Subjective Global Assessment, and lean body mass (LBM) was determined by computed tomography scan analysis using a pre-established Hounsfield unit threshold. Toxicity was obtained during four cycles by Common Terminology Criteria for Adverse Events.

Results.

Eighty-four patients were enrolled. Afatinib was administered as the second, third, and fourth line of treatment in 54.8%, 38.1%, and 7.12% of patients, respectively. Severe diarrhea, mucositis, and overall severe GT were present in 38.9%, 28.8%, and 57.5%, respectively. Of the patients, 50% developed dose-limiting toxicity (DLT). Patients with malnutrition have higher risk for severe GT. Patients with lower LBM and body mass index developed more DLT (71.4% vs. 18.8%).

Conclusion.

Malnutrition is associated with a higher risk of severe GT induced by afatinib. Determination of nutritional status and body composition are helpful in identifying patients at higher risk of severe GT and could allow initiating treatment with lower doses according to tolerance.

Implications for Practice:

Body composition analysis, specifically lean body mass quantification, and nutritional status assessment are significant clinical variables to take into account when assessing oncological patients. This study on patients with non-small cell lung cancer treated with afatinib showed the important impact that malnutrition and low lean body mass have on the risk for developing dose-limiting toxicity and severe gastrointestinal toxicity. Still more research needs to be done to explore dose adjustment according to lean body mass, especially in drugs that are given at fixed doses, such as afatinib. However, this study presents evidence for the clinical oncologist to have a closer follow-up with malnourished patients and even to consider a lower starting dose until therapeutic dose is achieved.     

Recomendaciones para el uso de la ecografía y la resonancia magnética en pacientes con espondiloartritis,incluyendo la artritis psoriásica,y en pacientes con artritis idiopática juvenil

Objective

To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging in patients with spondyloarthritis, including psoriatic arthritis, and juvenile idiopathic arthritis.