Last Marrow Standing: Bone Marrow Transplantation for Acquired Bone Marrow Failure Conditions

Paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome are a spectrum of acquired marrow failure, having a common pathologic thread of both immune dysregulation and the development of abnormal hematopoiesis. Allogeneic hematopoietic cell transplantation plays a critical role in the treatment of these disorders and, for many patients, is the only treatment modality with demonstrated curative potential. In recent years, there have been many breakthroughs in the understanding of the pathogenesis of these uncommon disorders. The subsequent advances in non-transplant therapies, along with concurrent improvement in outcomes after hematopoietic cell transplantation, necessitate continual appraisal of the indications, timing, and approaches to transplantation for acquired marrow failure syndromes. We review here contemporary and critical new findings driving current treatment decisions.     

The SMART‐COP score performs well for pneumonia risk stratification in Australia’s Tropical Northern Territory: a prospective cohort study

Objective To prospectively compare a modified pneumonia severity scoring system, SMARTACOP, with other severity scores in patients presenting with pneumonia to the emergency department (ED) of a tertiary referral hospital in tropical Australia. Methods We conducted a prospective observational study of adult patients presenting with radiologically confirmed pneumonia over a 12‐month period. The sensitivity of risk stratification scores were assessed against the need for intensive respiratory or vasopressor support (IRVS). Results There were 367 ED attendances for pneumonia of whom 77.1% were admitted to hospital, 10% required intensive respiratory or vasopressor support and 2.8% died. Mean age was 50.0 years, 52% were men and 59% were Indigenous. The sensitivity of a SMART‐COP score ≥3, a SMARTACOP score ≥3 and a pneumonia severity index (PSI) class ≥3 for predicting IRVS was 97%, 97% and 78% respectively. Conclusions We found no significant advantage of the SMARTACOP over the SMART‐COP score for the prediction of intensive respiratory or vasopressor support, but both scores significantly outperformed PSI. The SMART‐COP score should replace the PSI in tropical Australia and should be assessed in other tropical areas for pneumonia risk stratification in emergency departments.     

Natural history of parathyroid function and calcium metabolism after kidney transplantation: a single-centre study.

BACKGROUND: The natural history of parathyroid function after successful renal transplantation (RT) and the factors predisposing to persistent hyperparathyroidism (HPT) are not well established. A better knowledge of these data may be helpful in the development of algorithms for optimal surveillance and treatment of HPT after successful RT. Our aim was to evaluate the post-transplant natural history of parathyroid function and calcium metabolism in patients with a functional renal graft and to identify risk factors for persistent HPT. METHODS: Charts of 1165 allograft kidney recipients transplanted between 1989 and 2000 were reviewed. Patients with an intact parathyroid hormone (iPTH) level available at the time of transplantation were identified. The charts of the latter patients were checked for a variety of demographic and clinical data, and all determinations of the iPTH concentration available since transplantation were recorded. Serum levels of calcium, phosphorus, alkaline phosphatases and creatinine, concurrently determined, were also registered. RESULTS: After an initial fall, iPTH levels showed a slow but steady decline towards the upper normal limit. The prevalence of persistent HPT, defined as an iPTH level > or =2.5 times the upper normal limit or the need for parathyroidectomy following transplantation, remained stable at approximately 17% up to 4 years after transplantation. Patients with persistent HPT had significantly elevated serum levels of iPTH, calcium and phosphorus at the time of RT, and had spent a longer time on dialysis. Post-transplant iPTH levels correlated significantly with transplant kidney function. CONCLUSION: Kidney transplant recipients with a high iPTH and calcium x phosphate product at the time of transplantation are at risk for persistent HPT especially when renal function is suboptimal. Therapy for persistent HPT, if considered, should be initiated 3 months post-transplantation since further spontaneous improvement of parathyroid function thereafter is limited.     

Simultaneous lung resection for cancer and myocardial revascularization without cardiopulmonary bypass (off-pump coronary artery bypass grafting)

Backround

Patients with resectable lung cancer and unstable coronary heart disease are at high risk of postoperative death or severe cardiovascular complications. The aim of this study was to present the early results of radical lung resection for cancer with simultaneous myocardial revascularization on the beating heart (off-pump coronary artery bypass [OPCAB]).

Methods

From 1999 to 2002, thirteen patients (9 men and 4 women, aged 54 to 71 years, mean age 64 yrs) with resectable lung cancer and unstable angina or a recent history of myocardial infarction, were operated on. All of them underwent coronary angiography and neither coronary angioplasty nor stenting were feasible. Eight lobectomies, three pneumonectomies, and two wedge resections were carried out together with aortocoronary graft implantation (mean number of grafts: 1.7 per patient). Myocardial revascularization without cardiopulmonary bypass (OPCAB) preceded the lung resections. The preferred approach to the heart and lung was by sternotomy.

Results

There were no postoperative deaths in this group of patients. The most frequent postoperative complication was prolonged air leakage and one patient required respiratory support for two days. In one patient, significant blood loss was observed with a need for rethoracotomy. Transient supraventricular cardiac arrhythmias occurred in three patients. None of the patients showed evidence of myocardial ischemia after surgery. Patients were followed up for 7 to 36 months. None had acute myocardial infarction. In one patient, who underwent lobectomy, local recurrence was found. In another patient, who underwent pneumonectomy, distant metastases occurred in the third year of observation.

Conclusions

Lung resection carried out simultaneously with OPCAB is a safe and effective method for the treatment of lung cancer and myocardial ischemia.     

Increased oxidative stress in the mouse adriamycin model of glomerulosclerosis is accompanied by deposition of ferric iron and altered GGT activity in renal cortex

Chronic renal failure evolves inevitable towards glomerular and tubulo-interstitial sclerosis. This pathological process involves a disturbed redox status of the kidney tissue, leading to irreversible damage. In this study we investigate in an adriamycin model of chronic renal failure in mice the evolution of in vivo hydrogen peroxide production, and the possible role of gamma-glutamyl transpeptidase and ferric iron in the process. Histological changes and ferric iron deposits are evaluated by histochemical staining. To evaluate oxidative stress residual catalase activity, TBARS formation and gamma-glutamyl transpeptidase activity are measured spectrophotometrically. While catalase activity remains the same, a decreased residual catalase activity indicates an increased formation of hydrogen peroxide. Both the activity of gamma-glutamyl transpeptidase and TBARS formation is increased at early stages of the disease. Ferric iron is clearly present in the proximal tubule. Twenty days after adriamycin injection all parameters decrease, probably due to the destruction of the tissue. Our data show the involvement of oxidative stress in the progression of adriamycin induced renal failure in mice. Both radical production and oxidative damage are measurable, while the altered activity of gamma-glutamyl transpeptidase and the deposition of ferric iron suggest the involvement of these factors in the development of a disturbed redox status in the kidney cortex.     

Anti-inflammatory and immunomodulatory properties of azithromycin involved in treatment and prevention of chronic lung allograft rejection

Chronic lung allograft rejection is the single most important cause of death in lung transplant recipients after the first postoperative year, resulting in a 5-year survival rate of approximately 50%, which is far behind that of other solid organ transplantations. Spirometry is routinely used as a clinical marker for assessing pulmonary allograft function and diagnosing chronic lung allograft rejection after lung transplantation (LTx). As such, a progressive obstructive decline in pulmonary allograft function (forced expiratory volume in 1 sec [FEV1]) in absence of all other causes (currently defined as bronchiolitis obliterans syndrome [BOS]) is considered to reflect the evolution of chronic lung allograft rejection. BOS has a 5-year prevalence of approximately 45% and is thought to be the final common endpoint of various alloimmunologic and nonalloimmunologic injuries to the pulmonary allograft, triggering different innate and adaptive immune responses. Most preventive and therapeutic strategies for this complex process have thus far been largely unsuccessful. However, the introduction of the neomacrolide antibiotic azithromycin (AZI) in the field of LTx as of 2003 made it clear that some patients with established BOS might in fact benefit from such therapy due to its various antiinflammatory and immunomodulatory properties, as summarized in this review. Particularly in patients with an increased bronchoalveolar lavage neutrophilia (i.e., 15%-20% or more), AZI treatment could result in an increase in FEV1 of at least 10%. More recently, it has become clear that prophylactic therapy with AZI actually may prevent BOS and improve FEV1 after LTx, most likely through its interactions with the innate immune system. However, one should always be aware of possible adverse effects related to AZI when implementing this drug as prophylactic or long-term treatment. Even so, AZI therapy after LTx can generally be considered as safe.     

Hepatic Portal Venous Gas: A Warning Sign!?

A case of an overwhelming amount of hepatic portal venous gas caused by intestinal ischemia is described.     

Hypermobility of the first metatarsal bone in patients with Rheumatoid arthritis treated by lapidus procedure

ABSTRACT: BACKGROUND: Foot deformities and related problems of the forefoot are very common in patients with rheumatoid arthritis. The laxity of the medial cuneometatarsal joint and its synovitis are important factors in the development of forefoot deformity. The impaired joint causes the first metatarsal bone to become unstable in the frontal and sagittal planes. In this retrospective study we evaluated data of patients with rheumatoid arthritis who underwent Lapidus procedure. We evaluated the role of the instability in a group of patients, focusing mainly on the clinical symptoms and X-ray signs of the instability. METHODS: The study group included 125 patients with rheumatoid arthritis. The indications of the Lapidus procedure were a hallux valgus deformity greater than 15 degrees and varus deformity of the first metatarsal bone with the intermetatarsal angle greater than 15 degrees on anterio-posterior weight-bearing X-ray. RESULTS: Data of 143 Lapidus procedures of 125 patients with rheumatoid arthritis, who underwent surgery between 2004 and 2010 was evaluated. Signs and symptoms of the first metatarsal bone instability was found in 92 feet (64.3 %) in our group. The AOFAS score was 48.6 before and 87.6 six months after the foot reconstruction. Nonunion of the medial cuneometatarsal joint arthrodesis on X-rays occurred in seven feet (4.9 %). CONCLUSION: The Lapidus procedure provides the possibility to correct the first metatarsal bone varus position and its instability, as well as providing the possibility to achieve a painless foot for walking. We recommend using the procedure as a preventive surgery in poorly symptomatic patients with rheumatoid arthritis in case of the first metatarsal bone hypermobility.     

Decreased Hypoxia-Inducible Factor-1α in Gastrocnemius Muscle in Rats with Chronic Kidney Disease

Background/Aims: Hypoxia-inducible factor (HIF)-1α is responsible for increased expression of genes engaged in angiogenesis. Our previous study indicated capillary rarefaction and atrophy of glycolytic fibers, mainly in locomotor muscles of uremic animals. Perhaps these changes are secondary to disturbances of HIF-1α in skeletal muscles. Methods: Expression of HIF-1α at mRNA and protein levels, as well as mRNA of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), in gastrocnemius muscle (MG) and longissimus thoracic muscle (ML) were measured by RT-PCR and Western blot. Rats were randomized to subtotal nephrectomy (CKD5/6), uninephrectomy (CKD1/2) or sham operation (controls). Results: For CKD5/6 versus controls, mRNA levels for HIF-1α, VEGF-A, VEGFR-1 and VEGFR-2 were significantly reduced only in MG, while eNOS was significantly decreased and iNOS was significantly increased only in ML. Western blot analysis indicated significantly increased HIF-1α protein levels in MG and ML from CKD1/2 animals versus controls, whereas in the CKD5/6 group, the level of HIF-1α protein decreased significantly in MG and increased significantly in ML versus controls and CKD1/2. Conclusion: The reduced expression of HIF-1α mRNA and protein in locomotor muscle from CKD5/6 animals may be involved in the pathogenesis of uremic myopathy. Increased expression of iNOS in the postural muscles may act as a protective factor through HIF-1α stabilization.