The Occurrence of Lymphoma in Patients with Long-standing Hyperthyroidism

1) Six patients have been presented who, subsequent to long-standinghyperthyroidism, developed a lymphoma (one lymphoblastic lymphosarcoma,one Hodgkin’s disease, one giant follicular lymphoma, and three lymphocyticlymphosarcoma or leukemia).

2) Experimental evidence suggests that hyperthyroidism stimulates andhypothyroidism inhibits lymphoid structures, and hyperthyroidism promotestumor growth in animals. The mechanism of this action is not clear.

3) Three additional cases of hyperthyroidism followed by the developmentof a lymphoma were found in the literature.

4) It is suggested that prolonged hyperthyroidism may be a contributoryfactor in the development of lymphomas or allied disorders in man.

Submitted on July 30, 1962 Accepted on October 17, 1962     

Leukokinetic Studies. VII. Morphology of the Bone Marrow and Blood of Dogs Given Vinblastine Sulfate

The effect of a single injection of vinblastine sulfate was studied in 50mongrel dogs. Nine of 34 dogs given 0.2 mg./Kg. of VLB died with gastrointestinal toxicity and the mortality rate increased as the dosage of VLB wasincreased. The morphologic pattern of leukocyte suppression and recovery inthe bone marrow and blood was studied in detail in surviving animals.

The cells of the bone marrow were markedly affected by VLB. Within 4hours there was an increase in the number of cells in metaphase and, by day1, virtually all proliferating leukocytes and erythrocytes had disappeared. Anorderly repopulation of the bone marrow followed.

The neutrophils, eosinophils, lymphocytes and monocytes of the blood wereall markedly altered in concentration after VLB. Each type of cell first decreased to abnormally small numbers and then increased to abnormally largenumbers in the blood. The curve of disappearance from and reappearance inthe blood differed for each cell type.

The changes in blood neutrophil number and morphology were correlatedwith changes in the blood neutrophil precursor cells of the marrow. The following conclusions were reached concerning the neutrophils and the assumptions implicit to these conclusions were detailed.

1. In the dog, the marrow contains enough post-mitotic granulocytes toreplace those lost from the blood for at least 3 to 4 days.

2. The release of mature neutrophils from the bone marrow is a functionof the rate at which blood neutrophils are lost and proceeds normally evenwhen the marrow granulocyte reserve is partially depleted.

Submitted on March 27, 1963 Accepted on August 20, 1963     

Atrial Support Pacing in Heart Failure: Results from the Multicenter PEGASUS CRT Trial

Atrial Pacing in Heart Failure. Introduction: Cardiac resynchronization therapy (CRT) efficacy trials to date used atrial‐synchronous biventricular pacing wherein there is no or minimal atrial pacing. However, bradycardia and chronotropic incompetence are common in this patient population. This trial was designed to evaluate the effect of atrial support pacing among heart failure patients receiving a CRT defibrillator. Methods and Results: PEGASUS CRT was a multicenter, 3‐arm, randomized study. At 6 weeks, patients were randomized to DDD mode at a lower rate of 40 bpm (DDD‐40; control arm), or one of the following 2 treatment arms: DDD‐70, or DDDR‐40. The primary endpoint was a clinical composite endpoint that included all‐cause mortality, heart failure events, NYHA functional class, and patient global self‐assessment. Subjects were classified as improved, unchanged, or worsened at 12 months. There were 1,433 patients randomized, of whom 66% were male, mean age was 67 ± 11 years, and mean left ventricular ejection fraction was 23 ± 7%. The average follow‐up time was 10.5 ± 3.5 months and 1,309 patients contributed to the primary endpoint. No significant differences were observed in the composite endpoint between either of the 2 treatment arms compared to the control arm (P>0.05 for both comparisons). Additionally, there were no differences among the groups in mortality or heart failure events. Conclusion: In advanced heart failure patients treated with CRT, atrial support pacing did not improve clinical outcomes compared to atrial tracking. However, atrial pacing did not adversely affect mortality or heart failure events. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1317‐1325, December 2012)     

A Randomized‐Controlled Pilot Study Comparing ICD Implantation with and Without Intraoperative Defibrillation Testing in Patients with Heart Failure and Severe Left Ventricular Dysfunction: A Substudy of the RAFT Trial

Comparing ICD Implantation with and Without Intraoperative Defibrillation Testing. Introduction: The need to perform defibrillation testing (DT) at the time of implantable cardioverter defibrillator (ICD) insertion is controversial. In the absence of randomized trials, some regions now perform more than half of ICD implants without DT. Methods: During the last year of enrolment in the Resynchronization for Ambulatory Heart Failure Trial, a substudy randomized patients to ICD implantation with versus without DT. Results: Among 252 patients screened, 145 were enrolled; 75 randomized to DT and 70 to no DT. Patients were similar in terms of age (65.9 ± 9.3 years vs 67.9 ± 8.9 years); LVEF (24.7 ± 4.6% vs 23.6 ± 4.6%), QRS width (154.8 ± 23.5 vs 155.8 ± 23.6 ms), and history of atrial fibrillation (5% vs 6%). All 68 patients in the DT arm tested according to the protocol achieved a successful DT (≤25 J); 96% without requiring any system modification. No patient experienced perioperative stroke, myocardial infarction, heart failure (HF), intubation or unplanned ICU stay. The length of hospital stay was not prolonged in the DT group: 20.2 ± 26.3 hours versus 21.3 ± 23.0 hours, P = 0.79. One patient in the DT arm had a failed appropriate shock and no patient suffered an arrhythmic death. The composite of HF hospitalization or all‐cause mortality occurred in 10% of patients in the no‐DT arm and 19% of patients in the DT arm (HR = 0.53, 95% CI: 0.21–1.31, P = 0.14). Conclusions: In this randomized trial, perioperative complications, failed appropriate shocks, and arrhythmic death were all uncommon regardless of DT. There was a nonsignificant increase in the risk of death or HF hospitalization with DT. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1313‐1316, December 2012)     

Safety and Effectiveness of Transvenous Lead Extraction in Octogenarians

Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012)     

AA genotype of IL‐8 −251A/T is associated with low PaO2/FiO2 in critically ill patients and with increased IL‐8 expression

Background and Objective: Interleukin‐8 (IL‐8) is a central chemokine in acute respiratory distress syndrome (ARDS), and the IL‐8 gene contains a functional single nucleotide polymorphism (SNP) ?251A/T in its promoter region. We hypothesized that IL‐8 ?251A/T SNP is associated with PaO₂/FiO₂ in critically ill patients. Methods: We conducted genetic‐association studies in intensive care units at academic teaching centres using a derivation septic shock cohort (vasopressin and septic shock trial (VASST), n = 467) and a validation post‐cardiopulmonary bypass surgery cohort (CPB, n = 739) of Caucasian patients. Patients in both cohorts were genotyped for IL‐8 ?251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO₂/FiO₂ < 200. IL‐8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro. Results: The frequency of the patients with PaO₂/FiO₂ <200 was significantly greater in patients who had the AA genotype of ?251A/T than in patients who had the AT or TT genotypes in both VASST (AA = 60.8% vs AT and TT = 53.8% and 48.0%, P = 0.038) and the CPB cohort (AA = 37.0% vs AT and TT = 27.0% and 26.0%, P = 0.039). Patients having the AA genotype had a higher probability to remain on mechanical ventilation (P = 0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL‐8 mRNA expression than cells having the AT or TT genotype (P = 0.022). Conclusions: Critically ill Caucasian patients who had the AA genotype of IL‐8 ?251A/T had an increased risk of PaO₂/FiO₂ <200. The AA genotype was associated with greater IL‐8 mRNA expression than the AT or TT genotypes.