Second transplantation using allogeneic peripheral blood stem cells in a β-thalassaemia major patient featuring stable mixed chimaerism

Allogeneic bone marrow transplantation (BMT) for β-thalassaemia major carries the risks of disease recurrence due to residual thalassaemic stem cells or true immune-mediated rejection. We report a thalassaemic patient who displayed stable mixed chimaerism with only 5% donor-derived cells for about 5 years after BMT. Displacement of host cells was accomplished by ambulatory non-myeloablative conditioning and allogeneic G-CSF mobilized peripheral blood stem cell transplantation from the same donor, resulting in full reconstitution. Patients featuring stable mixed chimaerism after BMT may benefit from allogeneic cell therapy with immunocompetent lymphocytes and stem cells, whilst avoiding supralethal conditioning.     

Second transplantation using allogeneic peripheral blood stem cells in a β-thalassaemia major patient featuring stable mixed chimaerism

Allogeneic bone marrow transplantation (BMT) for β-thalassaemia major carries the risks of disease recurrence due to residual thalassaemic stem cells or true immune-mediated rejection. We report a thalassaemic patient who displayed stable mixed chimaerism with only 5% donor-derived cells for about 5 years after BMT. Displacement of host cells was accomplished by ambulatory non-myeloablative conditioning and allogeneic G-CSF mobilized peripheral blood stem cell transplantation from the same donor, resulting in full reconstitution. Patients featuring stable mixed chimaerism after BMT may benefit from allogeneic cell therapy with immunocompetent lymphocytes and stem cells, whilst avoiding supralethal conditioning.     

Paroxysmal A trial Fibrillation:

Classification of Atrial Fibrillation. Introduction: Clinical aspects of paroxysmal atrial fibrillation are heterogeneous. The attacks of atrial fibrillation may differ in their duration frequency and presence and severity of symptoms. Therefore, a proposal for a clinical classification of paroxysmal atrial fibrillation may be helpful. We tested a new classification system in a cohort of 51 consecutive hospitalized patients with paroxysmal atrial fibrillation. Methods and Results: Paroxysmal atrial fibrillation was subdivided into three classes. Class I included a first attack of symptomatic atrial fibrillation either with spontaneous termination (IA) or requiring cardioversion because of poor tolerance (IB). Class II included recurrent attacks in untreated patients within three subgroups: IIA with no symptoms, IIB with < 1 symptomatic attack per 3-month period, and IIC > with 1 symptomatic attack per 3-month period. Class III included recurrent atrial fibrillation unresponsive to one or more antiarrhythmic agents for prevention of recurrences. Class III also consisted of three subgroups: IIIA with no or mild symptoms, IIIB with < 1 symptomatic attack per 3-month period, and IIIC with > 1 symptomatic attack per 3-month period. The criteria for paroxysmal atrial fibrillation (episode > 2 minutes and < 7 days in duration) were fulfilled by 51 patients (29 men, 22 women; mean age 61 ± 14 years). Structural heart disease was present in 31 patients; the atrial fibrillation was idiopathic in 18 (35%). All 51 patients could be classified within the three classes and their subgroups: 14 patients (27%) in Class I, 13 (25%) in Class II, and 24 (47%) in Class III. The incidences of idiopathic atrial fibrillation were 21%, 30%, and 45% of the patients in Classes I, II, and III, respectively. Conclusions: Based on this new classification system, all hospitalized patients with paroxysmal atrial fibrillation could be classified. This classification may be useful to delineate better the clinical subgroups of patients with paroxysmal atrial fibrillation, to characterize better the patient population in future studies, and to improve treatment strategies.     

Endocavitary Structures in the Outflow Tract: Anatomy and Electrophysiology of the Conus Papillary Muscles

Catheter ablation is an increasingly used and successful treatment choice for right ventricular outflow tract (RVOT) arrhythmias. While the role of endocavitary structures and the regional morphology of the ventricular inflow tract and the right atrium as a cause for difficulty with successful ablation are well described, similar issues within the RVOT are not well understood. It is also not commonly appreciated that one of the papillary muscles is located within the proximal RVOT. We report 3 patients in which ventricular arrhythmia was targeted and ablated in the conus papillary muscle. The anatomic features, potential role of the fascicular conduction system, and unique challenges with mapping arrhythmia arising from this structure are discussed.     

ST segment depression in aVL: a sensitive marker for acute inferior myocardial infarction

In a substantial percentage of patients with acute myocardialinfarction, especially in those with inferior wall involvement,no ST elevation is detected on the electrocardiogram. In manyof them, ST depression is found in leads oriented to remotesegments of the heart. The importance of those reciprocal changesfor early diagnosis of acute inferior myocardial infarctionin patients without ST elevation has not been stressed. In orderto find the prevalence of reciprocal ST depression, we evaluatedthe admission electrocardiograms of 107 consecutive patientswith evolving first acute inferior mvocardial infarction. Ninety-threepatients had ST elevation of at least 0.1 mV in at least oneof the inferior leads: II, III or a VF (group A) and in 14 patientsST displacement did not reach 0·1 mV in any of theseleads (group B). In both groups, reciprocal ST depression occurredmore frequently in a VL than in any other lead. Only three patientshad no ST depression in a VL. in eight patients (7·5%ST depression in a VL was the sole early electrocardiographicsign of the inferior infarction, a VL is the only lead thatis facing the superior part of the left ventricle and thus isthe only lead that is truly opponent to the inferior wall. Itseems that ST depression in a VL, by contrast to that in theprecordial leads, is found in the majority of patients withevolving inferior wall myocardial infarction and is not influencedby extension of the infarclion to the right ventricle or tothe posterior wall. We conclude that transient ST depressionin a VL is a sensitive early electrocardiographic sign of acuteinferior wall myocardial infarction.     

Relationships among initial hospital triage,disease progression and mortality in community‐acquired pneumonia

Background and objective: Appropriate triage of patients with community‐acquired pneumonia (CAP) may improve morbidity, mortality and use of hospital resources. Worse outcomes from delayed intensive care unit (ICU) admission have long been suspected but have not been verified. Methods: In a retrospective study of consecutive patients with CAP admitted from 1996–2006 to the ICUs of a tertiary care hospital, we measured serial severity scores, intensive therapies received, ICU‐free days, and 30‐day mortality. Primary outcome was mortality. We developed a regression model of mortality with ward triage (and subsequent ICU transfer within 72 h) as the predictor, controlled by propensity for ward triage and radiographic progression. Results: Of 1059 hospital‐admitted patients, 269 (25%) were admitted to the ICU during hospitalization. Of those, 167 were directly admitted to the ICU without current requirement for life support, while 61 (23%) were initially admitted to the hospital ward, 50 of those undergoing ICU transfer within 72 h. Ward triage was associated with increased mortality (OR 2.6, P = 0.056) after propensity adjustment. The effect was less (OR 2.2, P = 0.12) after controlling for radiographic progression. The effect probably increased (OR 4.1, P = 0.07) among patients with ≥ 3 severity predictors at admission. Conclusions: Initial ward triage among patients transferred to the ICU is associated with twofold higher 30‐day mortality. This effect is most apparent among patients with ≥ 3 severity predictors at admission and is attenuated by controlling for radiographic progression. Intensive monitoring of ward‐admitted patients with CAP seems warranted. Further research is needed to optimize triage in CAP.     

Mycosis fungoides—a disease of antigen persistence

The function of B- and T-lymphocytes in nineteen patients with classical Alibert's mycosis fungoides (MF) was studied. In general there was no evidence of immune depression, not even in those with the disease for many years. The distribution of B-cells in the peripheral blood was normal. No immunoglobulin- bearing lymphocytes were detected in freshly liberated cells from the skin lesions or on direct immunofluorescence microscopy of those lesions. Serum IgE levels were significantly elevated, even though only two of the patients were atopic. ‘Auto-antibodies’ were detected in thirteen patients. Two cases of malignant lymphoma and one of Sézary syndrome contrasted strikingly with the mycosis fungoides (MF) group. Our findings support the hypothesis that mycosis fungoides (MF) is a chronic granulomatous response to persistent unidentified antigen(s), upon which immune imbalance can develop resulting in ‘auto-immune’ phenomena and, in a few cases, the emergence of various lymphoreticular neoplasms.