Anaemia in elective orthopaedic surgery - Royal Adelaide Hospital, Australia.

BACKGROUND: An anaemia clinic was established to improve the preoperative management of elective orthopaedic patients scheduled for arthroplasty. This paper is a report on the first 100 patients assessed. AIM: To assess the incidence and causes of anaemia in patients on a waiting list for elective arthroplasty in a public hospital and to assess the impact of anaemia detection in this patient population. METHODS: Patients attending an Anaemia Clinic for elective orthopaedic surgical patients, during March 2010 to June 2013 were studied. Outcome measures included change in haemoglobin preoperative results and perioperative transfusion rates by preoperative haemoglobin. RESULTS: Seventeen per cent of patients scheduled for elective surgery were found to be anaemic. Of the 100 patients who attended, approximately half were found to be iron deficient and the remainder had anaemia of chronic disease. Serum ferritin <30 µg/L alone did not identify iron deficiency in 80% of patients with iron deficiency. Patients with iron deficient anaemia were able to be treated, in all cases, to achieve a significant increase in preoperative haemoglobin. The general unavailability of erythropoietin limited effective intervention for the non-iron-deficient anaemic patients. Seven patients had their surgery cancelled because of the screening programme. CONCLUSIONS: Half of the anaemic patients in a joint replacement screening clinic were iron deficient, and treatment was effective in improving the pre-operative haemoglobin and reducing perioperative transfusion rates. This screening process should improve patient outcome. Another important finding in this group of patients is that ferritin levels cannot be reliably used as the sole indicator in the diagnosis of iron deficiency anaemia in this group of patients undergoing elective arthroplasty.

Treatment of patients with multiple myeloma who are not eligible for stem cell transplantation: position statement of the myeloma foundation of Australia Medical and Scientific Advisory Group.

Options for treatment of elderly patients with multiple myeloma have expanded substantially following the development of immunomodulatory drugs (IMiD), proteasome inhibitors and with enhancement in safety of high-dose therapy and autologous stem cell transplant (HDT + ASCT). The recognition of biological heterogeneity among elderly patients has made delivery of therapy more challenging. An individualised approach to treatment selection is recommended in an era in which highly efficacious treatment options are available for transplant-ineligible patients. Here, we summarise recommendations for patients who are considered unsuitable for HDT + ASCT, including pretreatment considerations, and induction, maintenance and supportive care therapies.

Treatment of patients with multiple myeloma who are eligible for stem cell transplantation: position statement of the Myeloma Foundation of Australia Medical and Scientific Advisory Group.

The survival of patients with multiple myeloma (MM) has improved substantially since the introduction in the late 1980s of high-dose chemotherapy (HDT) supported by autologous stem cell transplantation (ASCT). Further improvements have been observed following the availability of immunomodulatory drugs (IMiD) such as thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib. Here, we summarise the recommendations of the Medical Scientific Advisory Group to the Myeloma Foundation of Australia for patients considered suitable for HDT + ASCT as part of initial therapy. These recommendations incorporate the various phases of treatment: induction, HDT conditioning and maintenance therapy.

Management of systemic AL amyloidosis: recommendations of the Myeloma Foundation of Australia Medical and Scientific Advisory Group.

Systemic AL amyloidosis is a plasma cell dyscrasia with a characteristic clinical phenotype caused by multi-organ deposition of an amyloidogenic monoclonal protein. This condition poses a unique management challenge due to the complexity of the clinical presentation and the narrow therapeutic window of available therapies. Improved appreciation of the need for risk stratification, standardised use of sensitive laboratory testing for monitoring disease response, vigilant supportive care and the availability of newer agents with more favourable toxicity profiles have contributed to the improvement in treatment-related mortality and overall survival seen over the past decade. Nonetheless, with respect to the optimal management approach, there is a paucity of high-level clinical evidence due to the rarity of the disease, and enrollment in clinical trials is still the preferred approach where available. This review will summarise the Clinical Practice Guidelines on the Management of Systemic Light Chain (AL) Amyloidosis recently prepared by the Medical Scientific Advisory Group of the Myeloma Foundation of Australia. It is hoped that these guidelines will assist clinicians in better understanding and optimising the management of this difficult disease.

The rate of glove perforations in orthopaedic procedures: single versus double gloving. A prospective study.

Glove perforation during surgery has always been a matter of concern as it increases the infection rate and the risk of transmission of blood borne diseases. To determine the common causes, the site and the awareness of glove perforations in orthopaedic surgery, a prospective study was conducted to assess the rate of glove perforation during 130 consecutive orthopaedic operations. All gloves worn by the surgical team were assessed after the surgery using the water-loading test. A total of 1452 gloves were tested, and the rate of perforation was 3.58%. Most of these perforations (61.5%) were unnoticed. The main surgeons had the most perforations (76.9%), followed by first assistants (13.5%) and second assistants (9.6%). Most perforations occurred at the non-dominant hand. The commonest site of perforation was the index finger followed by the thumb. Shearing force with instruments accounted for 45% of the noticed perforations. Majority of these occurred during nailing procedures (33%) and internal fixation without the use of wires (19%). Our rate of glove perforation is similar to other series. Most of them went unnoticed and were mainly due to shearing injuries rather than perforation by sharps. Therefore, there is an increased risk of contamination and break in asepsis during surgery.

Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: a prospective Australasian Leukaemia and Lymphoma Group Study.

This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a median follow-up duration of 4 years. Transplant conditioning was according to clinician preference. In all, 14 patients had pre-transplant abdominopelvic IFRT and 19 had post transplant IFRT (including three who had pre-transplant IFRT). Grade III-IV haematological toxicity from pre-transplant IFRT occurred in three patients and from post transplant IFRT in 10 patients. Pre-transplant IFRT had no effect on haematological recovery post transplant, but was associated with a trend towards increased gastrointestinal toxicity (P = 0.094). Pneumonitis due to post transplant thoracic IFRT occurred in one patient. Two patients failed in involved sites after completion of protocol radiotherapy. One case of myelodysplasia has been reported. As sequenced in this study, IFRT was feasible and produced a low incidence of severe pulmonary and haematological toxicities. Patient selection, field size and radiotherapy dose warrant further study.

Haematemesis resulting from ischaemic strangulating intestinal obstruction.

Although bleeding into the intestinal lumen may occur in strangulating intestinal obstruction, haematemesis is infrequently encountered. We report on a patient who presented with haematemesis and who had, in addition, clinical and radiological features of small bowel obstruction. Upper gastrointestinal endoscopy did not locate the source of bleeding. At laparotomy, which was performed because of clinical deterioration, gangrenous strangulated small bowel secondary to adhesive obstruction was found. In a patient with non-resolving intestinal obstruction, a deterioration in the condition is a clear indication for exploration. Haematemesis occurring concurrently may be a marker of intestinal strangulation, adds strength to the indication and highlights the urgency of the need for exploration.

Allogeneic CD34 selected peripheral stem cell transplant for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): rapid haemopoietic and biochemical reconstitution.

Severe Maroteaux-Lamy syndrome is usually fatal in teenage or early adult life. Until recently, allogeneic bone marrow transplantation was the only form of enzyme replacement. We report the first successful transplant using CD34 selected, mobilised allogeneic blood cells for an inborn error of metabolism. A busulphan, cyclophosphamide, melphalan and antithymocyte globulin conditioning regimen was used as myeloablative therapy. Allogeneic CD34 selected granulocyte colony-stimulating factor (G-CSF)-mobilised blood cells from a HLA-identical sibling were used for the transplant. Haemopoietic reconstitution occurred on day 10 post-transplant with normal N-acetylgalactosamine-4-sulphatase levels. Infectious and graft-versus-host disease (GVHD) complications were minimal. We suggest that CD34 selected, mobilised allogeneic blood cells are a safe form of enzyme replacement therapy in Maroteaux-Lamy syndrome and should be considered in other metabolic diseases where the benefits of haemopoietic transplantation are proven.

Enhanced levels and enhanced clonogenic capacity of blood progenitor cells following administration of stem cell factor plus granulocyte colony-stimulating factor to humans.

Administration of hematopoietic growth factors is being used increasingly to obtain populations of blood progenitor/stem cells (PBPC) for clinical transplantation. Here we examined the effect of combining stem cell factor (SCF ) and granulocyte colony-stimulating factor (G-CSF ) versus G-CSF alone in a randomized clinical study involving 62 women with early-stage breast cancer. In the first patient cohorts, escalating doses of SCF were administered for 7 days with concurrent G-CSF administration. At baseline, levels of progenitor cells in the bone marrow or blood were comparable in the different patient groups. As with administration of G-CSF alone, the combination of SCF plus G-CSF did not alter the wide variation in levels of PBPC observed between individuals and did not alter the selective nature of PBPC release, with preferential release of day-14 granulocyte-macrophage colony-stimulating factor (GM-CFC) versus day-7 GM-CFC. However, SCF acted to sustain the levels of PBPC after cessation of growth factor treatment; levels of PBPC were elevated 100-fold at later timepoints compared with G-CSF alone. In addition, the maximum levels of PBPC observed were increased approximately fivefold at day 5 of growth-factor administration. The increased levels of PBPC resulted in significantly increased levels of PBPC obtained by leukapheresis. In a subsequent patient cohort, 3-days pretreatment with SCF was introduced and followed by 7 days concurrent SCF plus G-CSF. The 3-days pretreatment with SCF resulted in an earlier wave of PBPC release in response to commencement of G-CSF. In addition, maximum PBPC levels in blood and PBPC yield in leukapheresis products were further increased. Unexpectedly however, SCF pretreatment resulted in progenitor cells with enhanced self-generation potential. Recloning assays documented the ability of approximately 30% of primary granulocyte-macrophage (GM) colonies from control cell populations to generate secondary GM colonies (n = 1,106 primary colonies examined). In contrast approximately 90% of GM colonies from PBPC after SCF pretreatment generated secondary clones and 65% generated secondary colonies. The action of SCF was not explicable in terms of altered SCF, GM-CSF, or G-CSF responsiveness, but SCF pretreatment was associated with maximum serum SCF levels at the time G-CSF was commenced. These results show that PBPC populations mobilized by different growth factor regimens can differ in their functional properties and caution against solely considering number of harvested progenitor cells without regard to their function.

Divalent cations and heparin/heparan sulfate cooperate to control assembly and activity of the fibroblast growth factor receptor complex.

Polypeptides of the fibroblast growth factor (FGF) family are ubiquitous bioregulators within tissues whose activity is controlled by heparan sulfates within the pericellular matrix. FGF and the ectodomain of their transmembrane tyrosine kinase receptors (FGFR) exhibit heparin-binding domains that when juxtaposed in a FGF middle dotFGFR complex can accommodate a single, potentially bivalent, decameric polysaccharide chain in a ternary complex. Here we show that the interaction of heparin with FGF ligands is not affected by divalent cations. In contrast, the high affinity interaction (apparent Kd = 10 nM) of heparin with FGFR requires Ca2+ or Mg2+ at physiological concentrations. Divalent cations maintain FGFR in a heparan sulfate-dependent state in respect to FGF binding and an FGF- and heparan sulfate-dependent state in respect to autophosphorylation. A model is proposed where divalent cations and heparan sulfate cooperate to maintain FGFR in a conformation that restricts trans-phosphorylation between intracellular kinase domains. The restriction is overcome by FGF or constitutively as a common consequence of diverse mutations in FGFR associated with skeletal and craniofacial abnormalities.

An incremental response to high-dose therapy in multiple myeloma.

Results of conventional chemotherapy for multiple myeloma are disappointing. High-dose chemoradiotherapy with auto-transplantation is increasingly reported and some results are encouraging. We report the results of peripheral blood stem cell transplantation (PBSCT) for multiple myeloma at a single institution over a 6-year period. Forty patients, including 18 de novo patients, received debulking chemotherapy consisting of vincristine, adriamycin, and dexamethasone or methyl-prednisolone followed by stem cell mobilization with high-dose cyclophosphamide. Twenty-nine patients received PBSCT following high-dose chemoradiotherapy. Following PBSCT 92% of evaluable patients obtained at least a partial remission and 29% reached complete remission. Objective treatment responses, defined as at least a 50% reduction in serum paraprotein or marrow plasma cells, were observed following each treatment step of debulking chemotherapy, mobilization and PBSCT in 50, 42 and 71% of patients, respectively. The median overall survival from diagnosis in patients transplanted was 50 months and the median overall and progression-free survivals following transplant were 26 and 18 months, respectively. Median follow-up was 28 months. Overall treatment-related mortality was 20% but was significantly lower in de novo vs previously treated patients at 6 and 33% respectively (P = 0.027). De novo patients were more likely to obtain complete remission and had a longer overall survival following transplant but overall survival from diagnosis was similar to previously treated patients. A low serum B2M before mobilization predicted a longer progression-free survival. PBSCT needs to be considered early following diagnosis to maximise treatment response and reduce the high treatment-related mortality seen in heavily pretreated patients. In this treatment program a dose response effect in multiple myeloma was observed possibly suggesting that more intensive therapy than a single transplant may effect greater disease response.