Ten year survival after heart transplantation: palliative procedure or successful long term treatment?

OBJECTIVE: To investigate the long term outcome and prognostic factors after heart transplantation. SETTING: University hospital. SUBJECTS: 120 heart transplant patients (98 male, 22 female; underlying disease: dilated cardiomyopathy in 69, coronary artery disease in 42, miscellaneous in nine) who had undergone heart transplantation between October 1984 and October 1987. Immunosuppressive treatment was comparable in all patients and rejection episodes were treated in a uniform manner. METHODS: Functional status, quality of life, and potential predictors for long term survival were investigated. RESULTS: Actuarial survival rates were 65% at five years and 48% at 10 years; 58 patients survived > 10 years. The major causes of death were cardiac allograft vasculopathy (39%), acute rejection (18%), infection (11%), and malignancy (11%). Long term survivors had good exercise tolerance assessed by the New York Heart Association classification: 47 (81%) in grade I/II; 11 (19%) in grade III/IV. Echocardiography showed good left ventricular function in 48 patients. On angiography, severe allograft vasculopathy was present in only 16 patients (28%). Renal function was only slightly impaired, with mean (SD) serum creatinine of 148.5 (84.9) micromol/l. Multiple potential predictors of long term survival were analysed but none was found useful. CONCLUSIONS: Heart transplantation represents a valuable form of treatment. Survival for more than 10 years with a good exercise tolerance and acceptable side effects from immunosuppression can be achieved in about 50% of patients.     

The role of bridge to transplantation: should LVAD patients be transplanted?

PURPOSE OF REVIEW: The decrease in useable donor organs means an increasing number of patients are requiring support with a left ventricular assist device (LVAD) for survival when their clinical status deteriorates before transplantation. We address whether these patients should be transplanted, if so, with what priority, and when and if they are not transplanted, what are the alternatives? RECENT FINDINGS: The perioperative mortality and morbidity of LVAD insertion remains high. Infection and device failure still limit the safety of long periods of bridging and might necessitate earlier transplantation. Early results suggest that the smaller impeller pumps may be associated with a lower incidence of device failure and infection, but with more thromboembolic and hemorrhagic complications. Transplantation of LVAD patients results in survival rates as good as those with conventional transplantation, and the survival benefit is better than for non-LVAD-supported patients. A small number of LVAD patients have shown a significant improvement in myocardial function, sufficient enough to allow explantation of the device. The proportion of these patients has previously been reported to be as low as 5%, but a strategy to maximize recovery has allowed pump removal in approximately two thirds of dilated cardiomyopathy patients. In a recent destination therapy trial, survival in LVAD patients was superior to those on medical therapy, but the frequency of infection, bleeding, and malfunction of the device was higher. SUMMARY: LVAD technology is continuing to evolve quickly, while transplantation is here to stay. The interaction between these two powerful modalities requires continued thoughtful evaluation for maximal benefit to patients.     

Quality of Life in Cushing's disease: A long term issue?

The purpose of this review is to describe how quality of life (QoL) is impaired in patients with hypercortisolism due to Cushing's syndrome of any aetiology, including pituitary-dependent Cushing's disease. It is worse in active disease, but improvement after successful therapy is often incomplete, due to persistent physical and psychological co-morbidities, even years after endocrine “cure”. Physical symptoms like extreme fatigability, central obesity with limb atrophy, hypertension, fractures, and different skin abnormalities severely impair the affected patients’ everyday life. Psychological and cognitive problems like bad memory, difficulties to concentrate and emotional distress, often associated with anxiety and depression, make it difficult for many patients to overcome the aftermath of treated Cushing's syndrome. Recent studies have shown diffuse structural abnormalities in the central nervous system during active hypercortisolism, thought to be related to the wide distribution of glucocorticoid receptors throughout the brain. Even though they improve after treatment, normalization is often not complete. Shortening the exposure to active Cushing's syndrome by reducing the often long delay to diagnosis and promptly receiving effective treatment is highly desirable, together with preparing the patient for the difficult periods, especially after surgery. In this way they are prepared for the impairments they perceive in every day life, and live with the hope of later improvement, which can be therapeutic in many instances.     

Bile duct cyst in adults:Interventional treatment,resection,or transplantation?

Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree,within the liver,or in both of these locations simultaneously.Presentation in adults is often associated with complications.The therapeutic possibilities have changed considerably over the last few decades.If possible,complete resection of the cyst(s)can cure the symptoms and avoid the risk of malignancy.According to the type of bile duct cyst,surgical procedures include the Roux-en-Y hepaticojejunostomy and variable types of hepatic resection.However,the diffuse forms of Todani type Ⅴ cysts(Caroli disease and Caroli syndrome)in particular remain a therapeutic problem,and liver transplantation has become an important option.The mainstay of interventional treatment for Todani typeⅢbile duct cysts is via endoscopic retrograde cholangiopancreatography.The diagnostic term"bile duct cyst"comprises quite different pathological and clinical entities.Interventional therapy,hepatic resection,and liver transplantation all have their place in the treatment of this heterogeneous disease group.They should not be seen as competitive treatment modalities,but as complementary options.Each patient should receive individualized treatment after all of the clinical findings have been considered by an interdisciplinary team.     

Increase of body mass index in a tight controlled methotrexate‐based strategy with prednisone in early rheumatoid arthritis: Side effect of the prednisone or better control of disease activity?

Objective

To clarify whether increase of body weight in patients with early rheumatoid arthritis (RA) upon administration of prednisone is a side effect of prednisone or a result of better control of disease activity, we examined the association of prednisone and disease activity with a subsequent change in body mass index (BMI).

Methods

In the Computer Assisted Management in Early Rheumatoid Arthritis Trial‐II, patients ages ≥18 years with early RA (disease duration <1 year and no prior use of disease‐modifying antirheumatic drugs) had been randomized to a methotrexate (MTX)–based tight control strategy with either 10 mg of prednisone (MTX + prednisone) or placebo (MTX + placebo). The MTX + prednisone group had lower disease activity, but gained more weight than the MTX + placebo group (mean ± SD 2.9 ± 4.2 kg versus 1.3 ± 5.3 kg; P = 0.03). Data from patients with monthly measurements of disease activity (Disease Activity Score in 28 joints [DAS28]) and BMI were analyzed with a longitudinal regression (mixed model) analysis with BMI as the dependent variable and treatment strategy and DAS28 as the independent variables, correcting for baseline BMI and possible confounders (sex, age, and rheumatoid factor status).

Results

There was no independent association of glucocorticoid therapy with a change in BMI, but a lower DAS28 was associated with an increased BMI 6 months later. The association of the DAS28 with BMI was most strongly present in postmenopausal women. Clinical cutoff points showed a clear association between DAS28 level and the change in BMI 6 months later.

Conclusion

Weight gain during treatment with prednisone seems attributable to a reduction of disease activity and is probably, at least partly, regained weight.     

Is there a predisposition for the development of autoimmune diseases in patients with fibromyalgia? Retrospective analysis with long term follow-up

The objectives of the study were to evaluate the prevalence of antinuclear antibodies (ANA) in patients with fibromyalgia (FM) and the probability of the development of clinically overt connective tissue diseases. Four hundred and fifty FM patients were compared to 129 healthy matched blood donors. ANA testing was performed by immunofluorescence on rat tissue sections; in case of highly positive results, ANA were specified further by ELISA and immunodiffusion. All ANA positive FM patients were invited for a control examination. The ANA negative patients received a questionnaire, which was designed to identify those patients with possible connective tissue diseases (CTD). There was no significant difference in the frequency of ANA or thyroid antibodies between patients and controls (11.6% vs. 7%). Two patients had developed SLE: one was already ANA/anti-dsDNA positive at time of first diagnosis of FM; in the other, specific antibodies and SLE-related symptoms developed after 4.5 years. The probability for FM patients to develop CTD (SLE) within one year is 0.0027%, which is comparable to the incidence of SLE in the general population (0.005%). The risk of CTD is not increased in FM. The detection of ANA does not predict the development of CTD. However, in individual cases, FM may be an early sign of an autoimmune disease.     

Will immunotherapy lead to a breakthrough in the treatment of older adults with ALL?

Historically, older adults with B-cell acute lymphoblastic leukemia (ALL) have done poorly with chemotherapy-based treatment. Therefore, new innovative approaches are urgently needed to improve outcomes for this population. CD19-targeted immunotherapies such as blinatumomab and chimeric antigen receptor (CAR) T cell therapy have produced remarkable responses in relapsed/refractory (r/r) B-cell ALL, including clearance of minimal residual disease (MRD). Available data support the efficacy and safety of blinatumomab in older adults with advanced B-cell ALL. Therefore, its application is being extended to frontline regimens for B-cell ALL, particularly in older adults. There are several studies actively examining the role of blinatumomab alone or in combination with attenuated dosing of conventional chemotherapy or novel agents in older adults with newly diagnosed ALL and early data are encouraging. While CD19-targeted CAR (CD19CAR) T cell therapy is active in children and young adults with r/r B-cell ALL, data supporting its efficacy and safety in older adults with ALL is scarce. Furthermore, the commercially FDA approved CD19CAR T cell therapy product for r/r ALL is restricted only to patients ≤25 years of age. Although there are concerns about older adults tolerating the expected toxicities associated with CAR T cell therapy, which may be life threatening, tailored approaches for prophylactic and pre-emptive interventions combined with utilization of safer CAR T cell platforms may improve tolerability and further extend the use of this promising treatment to older patients with ALL. In this review, we will discuss the progress in immunotherapies for older adults with B-cell ALL and their potential for transforming frontline therapy for newly diagnosed patients.