Chronic somatoparaphrenia: a follow-up study on two clinical cases

Somatoparaphrenia consists in abnormal or bizarre verbal reports about some parts of the body. Such a pathological condition usually lasts for days or weeks and is variably associated with other cognitive defects. In the present paper we describe exceptionally long-lasting somatoparaphrenia in two focal brain-damaged patients: GA who had a right hemorrhagic fronto-parieto-temporal stroke and AC who developed a left ischemic parieto-occipital lesion. The presence and severity of somatoparaphrenia did not change in either patient during a 2-year follow-up, whereas the two patients showed different evolution of anosognosia for motor disorders, severity of extrapersonal neglect and cognitive impairments. Moreover, impairment of position sense was associated with somatoparaphrenia in one patient only; neither patient showed personal neglect. The reported clinical observations suggest that somatoparaphrenia can be observed as a body-related chronic disorder and can outlast other cognitive defects, even if it arose in conjunction with them.     

Filling the gap between science & clinical practice: prevention of stroke recurrence

Because of its high recurrence rate, active secondary prevention is mandatory once an episode of stroke has occurred. In non-cardioembolic stroke, in addition to lifestyle changes and to targeted treatments, current guidelines recommend Aspirin, Clopidogrel or Aspirin+extended-release dipyridamole. In cardioembolic stroke (due to atrial fibrillation or flutter [AF]), Vitamin K antagonists (VKAs) are recommended in most of patients. A favorable risk/benefit ratio of these treatments has been demonstrated also in elderly patients. However, registry data emphasize that such interventions are often under-used, especially in AF patients. A poor knowledge of current guidelines may play a role in hampering their application in clinical practice. The risk of major bleeding associated with antithrombotic drugs, their inherent limitations, such as socio-demographic (age > 80 years, living alone) and clinical (previous or recent bleeding, trauma, cancer, dementia) features, may account for the gap between current guidelines for stroke/TIA prevention and clinical practice.The objective of the present report is to evaluate the gap between current recommendations/guidelines for stroke/TIA prevention and clinical practice (registry findings). In our opinion new antithrombotic drugs and detailed educational programs (especially devoted to general practitioners and to some medical specialists), concerning efficacy, safety and limitations of these strategies, are needed to better manage stroke epidemics in the third millennium.     

Aspirin resistance, platelet turnover, and diabetic angiopathy: a 2011 update

In 2004 an editorial article on the so-called “aspirin resistance” and diabetic angiopathy as related to platelet turnover was published by one of us. An update of this issue is now presented.The evidence of an incomplete inhibition of platelet function by aspirin, despite doses of the drug proved to be clinically effective are employed, was first reported in the ‘80s, in studies devoted to platelet turnover. Based on this concept, the possibility of monitoring the entry of newly formed platelets into the circulation after aspirin ingestion was documented by measuring the return of thromboxane biosynthesis by platelets challenged in vitro by pairs of aggregating agents. The data obtained showed that platelets with intact cyclooxygenase activity could be detected into the circulation of control individuals as early as 4-6 hrs after aspirin ingestion, but at shorter time intervals in diabetic angiopathy. In the latter setting, it was concluded that “schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation”.As many as 25 years after its original publication, the clinical relevance of an accelerated platelet turnover as to “aspirin resistance” has been confirmed and extended to other clinical settings at high risk of ischemic events. Newer aspirin dosing and scheduling, tailored at reducing the individual patient risk related to an incomplete inhibition of platelet function by a standard aspirin dose should now be defined.     

Severe abdominal pain as a presenting symptom of probable catastrophic antiphospholipid syndrome

Catastrophic antiphospholipid syndrome (APS) in pediatric medicine is rare. We report 3 adolescents who presented with acute onset of severe abdominal pain as the first manifestation of probable catastrophic APS. The 3 patients, 2 male patients and 1 female patient were 14 to 18 years old. One had been diagnosed with systemic lupus erythematosus in the past, but the other 2 had no previous relevant medical history. All presented with excruciating abdominal pain without additional symptoms. Physical examination was noncontributory. Laboratory results were remarkable for high inflammatory markers. Abdominal ultrasonography was normal, and abdominal computed tomography scan showed nonspecific findings of liver infiltration. Only computed tomography angiography revealed evidence of extensive multiorgan thrombosis. All patients had elevated titers of antiphospholipid antibodies. The patients were treated with full heparinization, high-dose steroids, and intravenous immunoglobulin with a resolution of symptoms. One patient was resistant to the treatment and was treated with rituximab. In conclusion, severe acute abdominal pain can be the first manifestation of a thromboembolic event owing to catastrophic APS even in previously healthy adolescents. Diagnosis requires a high index of suspicion with prompt evaluation and treatment to prevent severe morbidity and mortality.     

Sentinel node biopsy in pediatric soft tissue sarcomas of extremities

Background

Sentinel Node Biopsy is an established staging technique in many adult malignancies. However, only few reports describe this procedure for the evaluation of regional lymph nodes in childhood and adolescents. Our experience with sentinel node biopsy in soft tissue sarcomas of extremities in children is reported.

Methods

Seventeen children were evaluated with sentinel node biopsy between 2002 and 2007: 11 at initial surgery, 5 at primary re‐excision, 1 at local relapse. The diagnosis was rhabdomyosarcoma in 5 and other soft tissue sarcomas in 12: Ewing/PNET sarcoma 6, epithelioid sarcoma 1, malignant peripheral‐nerve‐sheath tumor 1, undifferentiated sarcoma 1, myxoid liposarcoma 2, adult‐type fibrosarcoma 1. Primary sites included lower limbs (8), upper limbs (9). Mapping of nodes was performed with lymphoscintigraphy plus intra‐operative injections with blue‐dye in 14 cases, with lymphoscintigraphy and intra‐operative injections alone in 2 and 1, respectively.

Results

Of the 17 lymphatic regions (9 axilla, 8 inguinal), 16 were identified with lymphoscintigraphy, 15 by intra‐operative injections. Thirty‐five lymph nodes were removed. Nodes were positive for metastasis in two patients with alveolar rhabdomyosarcoma and undifferentiated sarcoma. There were no complications. No further lymph node metastases were recognized either at diagnosis or during the follow‐up (6–78 months).

Conclusions

Sentinel node biopsy was technically feasible, reliable, and free of complications. It could be an alternative to aggressive or random biopsies for extremity rhabdomyosarcoma and it can contribute to define those non‐rhabdomyosarcoma soft tissue sarcomas that spread to regional nodes. Pediatr Blood Cancer 2009;52:51–54. © 2008 Wiley‐Liss, Inc.     

New Users of Metformin Are at Low Risk of Incident Cancer: A cohort study among people with type 2 diabetes

OBJECTIVE

The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase (AMPK). Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels. We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes.

RESEARCH DESIGN AND METHODS

In an observational cohort study using record-linkage databases and based in Tayside, Scotland, U.K., we identified people with type 2 diabetes who were new users of metformin in 1994–2003. We also identified a set of diabetic comparators, individually matched to the metformin users by year of diabetes diagnosis, who had never used metformin. In a survival analysis we calculated hazard ratios for diagnosis of cancer, adjusted for baseline characteristics of the two groups using Cox regression.

RESULTS

Cancer was diagnosed among 7.3% of 4,085 metformin users compared with 11.6% of 4,085 comparators, with median times to cancer of 3.5 and 2.6 years, respectively (P < 0.001). The unadjusted hazard ratio (95% CI) for cancer was 0.46 (0.40–0.53). After adjusting for sex, age, BMI, A1C, deprivation, smoking, and other drug use, there was still a significantly reduced risk of cancer associated with metformin: 0.63 (0.53–0.75).

CONCLUSIONS

These results suggest that metformin use may be associated with a reduced risk of cancer. A randomized trial is needed to assess whether metformin is protective in a population at high risk for cancer.Recent research suggests that the antidiabetic drug metformin, which exerts its effects by activating the AMP-activated protein kinase (AMPK), may have potential for the treatment of cancer in humans (1). The hypothesis that metformin may have anticancer effects is supported by laboratory studies showing that metformin is associated with reduced incidence of pancreatic cancer in hamsters (2) and delays onset of mammary (3) and other tumors (4) in tumor-prone mice. Metformin also inhibits growth of human breast cancer cells (5). Although the potential for prevention of cancer in humans using metformin has not been explored, we previously reported the results of a pilot case-control study that identified a reduced risk of cancer among patients with type 2 diabetes who had used metformin (6). However, the outcome was limited to hospital admissions for cancer, and the date of diagnosis was assumed to be date of first hospital admission.Other diabetic drugs may also have cancer-related effects. An independent epidemiological study found that users of sulfonylureas were at higher risk of cancer-related mortality than metformin users (7). Sulfonylureas (and insulin) increase circulating insulin levels, and hyperinsulinemia may promote carcinogenesis (8). Treatments such as metformin and glitazones reduce insulin resistance, with insulin resistance possibly associated with increased risk of cancer (9). The objective of this study was to test the hypothesis that metformin use is associated with a reduced risk of cancer in people with type 2 diabetes using a national cancer registry to ensure valid diagnoses of cancer with precise dates of diagnosis. We also adjusted results for the effects of exposure to other diabetic drugs.