Acute renal embolism. Forty-four cases of renal infarction in patients with atrial fibrillation

Acute renal embolus is rarely reported in the medical literature; thus, accurate data regarding presentation, laboratory tests, diagnostic techniques, and treatment are lacking. To better define this condition, we examined the medical records of all patients admitted to Kaplan Medical Center and Sheba Medical Center in central Israel from 1984 to 2002 who had a diagnosis of renal infarction and atrial fibrillation. We noted demographic, clinical, and laboratory parameters; method of diagnosis; treatment received; and patient outcome. We identified 44 cases of renal embolus: 23 females and 21 males, with an average age of 69.5 +/- 12.6 years. Thirty (68%) patients had abdominal pain, and 6 (14%) had a previous embolic event. Nine patients were being treated with warfarin on admission, 6 (66%) of whom had an international normalized ratio (INR) < 1.8. Hematuria was present in 21/39 (54%), and 41 (93%) patients had a serum lactate dehydrogenase (LDH) level > 400 U/dL. The mean LDH was 1100 +/- 985 U/dL. Diagnostic techniques included renal isotope scan, which was abnormal in 36/37 cases (97%); contrast-enhanced computed tomography (CT) scan, which was diagnostic in 12/15 cases (80%); and ultrasound, which was positive in only 3/27 cases (11%). Angiography was positive in 10/10 cases (100%). Twenty-three (61%) of 38 patients had normal renal function on follow-up. The 30-day mortality was 11.4%. Renal embolus was diagnosed mainly in patients aged more than 60 years, some of whom had a previous embolic event. Most of those receiving anticoagulant therapy had a subtherapeutic INR. Abdominal pain was common, as well as hematuria and an elevated LDH. These patients are at risk of subsequent embolic events to other organs. The most sensitive diagnostic technique in this population is a renal isotope scan, but contrast-enhanced CT scan requires further assessment.     

Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.     

Mycoplasma-pneumoniae-induced thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the plasma von Willebrand factor-cleaving protease resulting in unusually large von Willebrand factor multimers that later on initiate the cascade of TTP. In this communication, we present a unique association between infection with Mycoplasma pneumoniae and TTP. We believe that the emergence of antibodies that cross-react with Mycoplasma and the protease might elucidate in this case the pathogenesis of TTP.     

Cytokine levels and phagocytic activity in patients with Alzheimer's disease

BACKGROUND: Clinical observations indicate that patients with Alzheimer's disease show a greater susceptibility to infections. One possible explanation is that this predisposition is due to alterations in their immune system. OBJECTIVE: To investigate this assumption, pro- and anti-inflammatory cytokines, as well as the phagocytic activity and superoxide anion generation was examined in aged individuals with and without Alzheimer's disease. METHODS: The production of IL-1beta, IL-2, IL-6, TNFalpha and IL-10 by peripheral blood mononuclear cells from 12 patients with Alzheimer's disease was compared with that of 12 age-matched individuals without any signs of dementia and 12 middle-aged healthy volunteers who served as an additional control. The engulfing capacity of the phagocytic cells was detected by counting cells containing latex beads and the number of particles internalized by each individual cell. RESULTS: The secretion of IL-2 was markedly low in the demented patients, compared with both elderly and middle-aged subjects. IL-1beta and TNFalpha production was similar in the individuals of the 3 groups. The production of IL-6 and IL-10 was significantly lower when compared to that of the middle-aged, but did not differ between the elderly patients with and without dementia. The phagocytic function of both polymorphonuclear cells and monocytes was decreased in individuals of the elderly groups with a low number of engulfed latex particles by each individual polymorphonuclear cell. The production of superoxide anions was increased only by monocytes from the elderly groups. CONCLUSIONS: The results suggest that although the impaired immune function in patients with Alzheimer's disease is related to the aging process, the significant low IL-2 production in these patients may play a role in their increased susceptibility to infections.     

Molecular Imaging of Membrane Transporters’ Activity in Cancer: a Picture is Worth a Thousand Tubes

Molecular imaging allows the non-invasive assessment of membrane transporter expression and function in living subjects. Such technologies have the potential to become diagnostic and prognostic tools, allowing detection, localization, and prediction of response of tumors and their metastases to therapy. Beyond tumors, imaging can also help understand the role of transporters in adverse drug effects and drug clearance. Here, we review molecular imaging technologies that monitor transporter-mediated processes. We emphasize emerging probe substrates and potential clinical applications of imaging the function of membrane transporters in cancer.KEY WORDS: membrane transporters, molecular imaging, multidrug resistance, near infrared, optical imaging     

Medical scribes have no impact on the patient experience of an emergency department

Objective

We aimed to evaluate patient perceptions of medical scribes in the ED and to test for scribe impacts on ED Net Promoter Scores, Press Ganey Surveys and other patient‐centred topics.

Methods

Exploratory semi‐structured interviews were conducted in the ED during wait times after scribed consultations. Interview results were used to derive topics relating to scribes. Items addressing these topics from validated surveys were combined with items from widely used patient satisfaction questionnaires. Questionnaires were administered in the ED by face‐to‐face approach while patients were waiting for admission/discharge or test results. Patients and doctors were blinded to the purpose of the questionnaire. The survey evaluated for non‐inferiority of scribed consultations, using Net Promoter Scores, Press Ganey questions and questions specific to the presence of the scribe.

Results

Patient interviews did not identify any negative views regarding the presence of scribes during consultations. Thematic saturation was achieved after seven interviews. Two hundred and fifty‐eight patients were approached to complete the questionnaire, and 215 participated (83%); 95 and 118 participants in the scribed and non‐scribed groups, respectively. There was no difference between scribed and non‐scribed consultations on the following measures of satisfaction: the Net Promoter Score, Press Ganey questions, quality of information received from doctors, communication, privacy concerns or inhibition about revealing private information and room crowding.

Conclusion

We found no evidence that scribes reduce patient satisfaction during emergency consultations, nor prompt discomfort that might cause a patient to withhold information.     

Extracardiac ice formation during CoolLoop cryoablation of atrial fibrillation

A 75‐year‐old male patient was referred for longstanding atrial fibrillation ablation. We performed this procedure combining an epicardial and endocardial approach. Under general anesthesia and via a left‐sided thoracoscopic approach, we isolated the pulmonary veins (PVs) and the roofline and inferior line were created using a radiofrequency tool. To isolate the endocardial PVs, a transseptal puncture was performed via the groin, and a cryoablation CoolLoop catheter (AFreeze GmbH, Innsbruck, Austria) was advanced into the left atrium. Ice crystals started to appear on the epicardial surface of the left inferior PV antrum after 121 seconds later, those crystals had formed an ice plaque. For the first time in humans, we were able to visualize the transmural effects of cryothermal energy ablation via a CoolLoop catheter on the epicardial surface of the ostium of the PV.     

Colchicine for large pericardial effusion

On the basis of our reported experience with colchicine for recurrent pericarditis, we administered colchicine to two patients with large pericardial effusions complicating idiopathic pericarditis. The first was a 26-year-old male who showed clinical deterioration following emergency pericardiocentesis and aspirin (3 g/day) for 10 days; the second was a 2-year-old girl who was unsuccessfully treated with aspirin (100 mg/kg/day) for 2 weeks, followed by corti-costeroids for 7 months. Administration of colchicine (1 mg/ day) instead of aspirin in the first case, and with a rapid tapering-off of the corticosteroids in the second case, led to complete regression of the pericardial effusion on echocardiography within 1 week and 1 month, respectively. Colchicine was discontinued after 1 month in the first patient and was continued for 6 months in the child. Neither has had a recurrence at 24 and 6 months of follow-up, respectively. No side effects of colchicine were observed. We conclude that colchicine may be effective in the treatment of large pericardial effusion when therapy with nonsteroidal anti-inflammatory drugs and/or corticosteroids fails.     

Tracing environmental markers of autoimmunity: introducing the infectome

We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of adaptive mechanisms in the body. These studies complement genome-wide association studies, which establish the genetic predisposition to disease. The infectome is a component which spans the whole life and may begin at the earliest stages right up to the time when the first symptoms manifest, and may thus contribute to the understanding of the pathogenesis of autoimmunity at the prodromal/asymptomatic stages. We provide practical examples and research tools as to how we can investigate disease-specific infectomes, using laboratory approaches employed from projects studying the “immunome” and “microbiome”. It is envisioned that an understanding of the infectome and the environmental factors that affect it will allow for earlier patient-specific intervention by clinicians, through the possible treatment of infectious agents as well as other compounding factors, and hence slowing or preventing disease development.     

Genetics and autoantibodies

Autoimmune diseases (ADs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens. The pathogenic hypothesis comprises a complex interaction between genetic, environmental and hormonal factors that interact with an individual over time generating a dysregulation of the immune system leading to disease development. Several polymorphic genes contribute to the development of ADs. Furthermore, age and gender play a major role by influencing hormone levels that can represent the fulcrum unbalancing from susceptibility to protection. Evidences suggest that while all these steps occur, the susceptible individual develops autoantibodies over a long time lapse. Such autoantibody production is genetically determined and finally, their presence seems to determine the clinical presentation of ADs. The genetic predisposition to the developments of autoantibodies and toward the disease process may overlap. The unveiling of these mechanisms could allow not only to treat but also to prevent the development of autoimmune diseases.