Calcaneotibial screws for immobilisation of the tarsocrural joint of dogs in extension: effect of the angle of screw placement on the force to failure in a canine cadaveric model.

AIMS: To compare the force to failure under axial loading of a calcaneotibial screw placed approximately perpendicular to the tibia with that of a screw placed perpendicular to the calcaneus, when used to immobilise the tarsus in an ex vivo canine model. METHODS: Twelve pairs of cadaveric hindlimbs from large breed dogs, without orthopaedic or soft tissue disease, were prepared by transecting the limb at the level of the stifle and stripping the limbs of all musculature from the stifle to mid-metatarsus, including removal of the common calcaneal tendon from all limbs. The limbs in each pair were randomly assigned to receive a calcaneotibial screw placed perpendicular to the long axis of either the calcaneus (C group) or the tibia (T group) with the tarsus in full extension. The distal limb was potted in resin and the proximal tibia was pinned to allow biomechanical testing in compressive loading. Testing was performed to apply an axial load using a material testing machine in a proximodistal direction through the tibia, advancing at a rate of 10 mm/second. The force to failure was recorded in kN and compared between groups. RESULTS: The median force to failure of the C group was 0.86 (min 0.50; max 1.64) kN which was higher than the T group which had a median force to failure of 0.74 (min 0.26, max1.05) kN (p = 0.004). All modes of failure were by screw pull-out. CONCLUSIONS: A calcaneotibial screw placed at an angle approximately perpendicular to the long axis of the calcaneus, has a higher force to failure under axial loading than a calcaneotibial screw that is placed at an angle approximately perpendicular to the tibia, in a canine cadaveric model. CLINICAL RELEVANCE: A temporary calcaneotibial screw is a common method of immobilising the tarsus in extension to protect primary repair of a common calcaneal tendon injury. Placing a calcaneotibial screw perpendicular to the calcaneus may be a more reliable option for immobilisation of the tarsus to protect a common calcaneal tendon repair compared to screws placed perpendicular to the tibia. However extrapolation of these results into a clinical setting requires caution.

Analysis of a potential cluster of rhinovirus infections in patients and staff on two haemato-oncology wards.

BACKGROUND: Human rhinoviruses (HRV) cause the common cold, increased mortality in patients attending elderly care facilities and significant morbidity as well as mortality in the post-transplantation setting. OBJECTIVES: The aim of the study was to determine if there had been a breakdown in infection control practice in a large haemato-oncology centre. Molecular techniques had detected increased numbers of HRV in respiratory samples from patients and staff over a 6-week period. Typing was performed to investigate the possibility of transmission between individuals. STUDY DESIGN: This was a retrospective study having detected HRV RNA in combined nose and throat swab samples that were collected from 13 individuals: 8 patients and 5 staff members, in the haemato-oncology wards of a tertiary referral centre in January and February 2011. The 5'NTR and the VP4/VP2 region were used for HRV typing. RESULTS: All 3 HRV species were detected with 7 HRV-A, 1 HRV-B, 4 HRV-C and 1 untyped. None of the individuals were infected by the same HRV serotype. Three individuals had multiple samples collected: 1 patient had an HRV-B infection over a 4-week period, 1 patient had an HRV-A infection over 3 months and 1 staff member had an HRV-C infection over 1 week, each shedding an unchanged serotype throughout the whole period. CONCLUSION: Nucleotide sequence analysis confirmed that there was no breakdown in infection control measures. No transmission incidents had occurred between patients and/or between staff and patients.

Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity conditioning allogeneic hematopoietic SCT for patients with high-risk myelodysplastic syndrome and AML.

We report a retrospective analysis of 128 consecutive patients with high-risk myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reduced-intensity conditioning hematopoietic SCT (RIC HSCT). The median recipient age was 53 years (range 21-72 years). A total of 49 (38%) recipients had a sibling donor and 79 (62%) had a volunteer-unrelated donor. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was assigned to all patients with a score of 0 in 40 (31%), of 1-2 in 45 (35%) and >or=3 in 43 (34%) patients. The 3-year non-relapse mortality (NRM) was 31%, disease-free survival (DFS) was 41% and overall survival (OS) was 46%. The 3-year NRM for patients with a HCT-CI score of 0, 1-2 or >or=3 was 16, 24 and 42%, respectively. The 3-year DFS and OS by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1-2) and 24 and 32% (score >or=3), respectively. On multivariate analysis, HCT-CI was an independent variable affecting 3-year NRM, DFS and OS (P-value=0.04, 0.01 and <0.01, respectively). Although the disease stage at the time of transplant was an additional independent predictive variable on transplant outcomes, recipient age (>or<50 years) did not have a significant predictive impact. In MDS or AML patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI provides an important means of stratifying patients with a high risk of inferior transplant outcomes.

Clonal gammopathies following alemtuzumab-based reduced intensity conditioning haematopoietic stem cell transplantation: association with chronic graft-versus-host disease and improved overall survival.

The presence of clonal gammopathies (CG) has been reported following both conventional myeloablative and autologous haematopoietic stem cell transplantation (HSCT). We monitored the occurrence of CG in a cohort of patients with myeloid malignancies receiving FBC (fludarabine-busulphan-alemtuzumab)-based reduced intensity conditioned (RIC) HSCT, and assessed its correlation with infections, graft-versus-host disease (GvHD) and survival. Serial serum protein electrophoresis was analysed in a total of 138 patients and CG were detected in 49 patients (36%). The predominant Ig isotype was IgG (82%). There was no difference in the incidence of viral infections between patient groups. However, patients with gammopathies were more likely to have had prior chronic GvHD (OR 2.7, 95% CI 1.3-5.5, P<0.001). On multivariate analysis, the only factors that were found to influence overall survival (OS) were presence of gammopathies, which was associated with an improved OS (OR 0.35 95% CI 0.14-0.86, P=0.02) as well as disease stage, patients with advanced disease having a higher risk of death (OR 2.20 95% CI 1.18-4.11, P=0.02). Disease stage was the only variable that influenced relapse incidence on multivariate analysis (OR 4.22 95% CI 1.82-9.78, P<0.01). Clonal gammopathies are a frequent but benign occurrence following alemtuzumab-based RIC HSCT, and their appearance may define a group of patients with a favourable overall outcome.

Sclerodermatous graft-versus-host disease: clinical spectrum and therapeutic challenges.

Sclerodermatous graft-versus-host disease (GVHD) is a rare complication of bone marrow transplantation. While GVHD is often associated with the beneficial graft vs. tumour effect, it also contributes towards significant morbidity and mortality. No reliably effective treatment has yet been established. We present 10 patients with haematological malignancies who underwent an allogeneic stem cell transplant and developed sclerodermatous GVHD. Donor lymphocyte infusion administered for relapse or reducing donor T-cell chimerism was a known trigger for sclerodermatous GVHD in four of the patients. Treatment with immunosuppressants, psoralen plus ultraviolet A (PUVA) and extracorporeal photopheresis has been largely unsuccessful in their management. Intensive immunosuppression including the use of anti-CD20 monoclonal antibody may have contributed to relapse of leukaemia in one patient 10 years after her transplant. Sclerodermatous GVHD may occur without a preceding lichenoid stage. Clinical heterogeneity is common, although sclerodermatous GVHD has a predilection for the limbs. Treatment options are largely unsatisfactory if conventional immunosuppression fails. PUVA may give some symptomatic benefit and extracorporeal photopheresis seems to be less efficacious than previously published work suggests.

Lamivudine prophylaxis and treatment of hepatitis B Virus-exposed recipients receiving reduced intensity conditioning hematopoietic stem cell transplants with alemtuzumab.

Individuals with past exposure to hepatitis B virus (HBV) may reactivate HBV following bone marrow transplantation. Alemtuzumab (CAMPATH)-based reduced intensity conditioning bone marrow transplantation has been associated with a high incidence of viral infections. Lamivudine prophylaxis for HBV should be instituted in this setting. The management of 240 CAMPATH-based reduced intensity conditioning bone marrow transplantation, carried out over an 8-year period at Kings College Hospital, was reviewed. Hepatitis B core total antibody (anti-HBc) testing identified recipients and donors with previous HBV exposure. Fifteen donor-recipient pairs were identified as being at risk of HBV reactivation. Eight recipients of anti-HBc negative donors were HBsAg negative, anti-HBc positive pre-transplantation. Five anti-HBc negative recipients received transplants from HBsAg negative, anti-HBc positive donors. Two HBV carrier recipients had one anti-HBc negative and one positive donor, respectively. Pre-transplant lamivudine prophylaxis was given to 8/10 (80%) anti-HBc positive recipients. Although HBsAg and HBV DNA were detected 4 months after bone marrow transplantation in one patient who did not receive prophylaxis, a good antiviral response was documented on starting lamivudine. The two HBV carrier recipients had stopped lamivudine at 8 and 31 months post-bone marrow transplantation, respectively, and died of liver failure with a sharp rise in HBV DNA levels. The five anti-HBc negative recipients with anti-HBc positive donors remained HBsAg and HBV DNA negative. Although lamivudine prophylaxis prevented HBV reactivation, it is unclear at what stage post-transplantation prophylaxis can be discontinued. Close monitoring of liver function tests (LFTs), HBsAg, and HBV DNA must be undertaken even after stopping antiviral prophylaxis.

Koebnerizing sclerodermatous graft-versus-host disease caused by donor lymphocyte infusion and interferon-alpha.

Graft-versus-host disease (GvHD) is a common sequel to allogeneic bone marrow transplants, which may be accompanied by desirable graft-versus-tumour effects. Sclerodermatous GvHD is a rare subtype that is very difficult to treat. We report the first case of sclerodermatous GvHD as part of the Koebner phenomenon. We propose that donor lymphocyte infusion and interferon-alpha were involved in the pathogenesis of this case.

Cardiac presentation of ALK positive anaplastic large cell lymphoma.

Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We report the case of an immunocompetent 29-year-old male who presented with syncope and arrythmias secondary to a ventricular cardiac mass. Transcutaneous cardiac biopsy was non-diagnostic, therefore an open cardiac biopsy was performed from which a provisional diagnosis of a cardiac inflammatory pseudotumour was made. Six months after presentation, he developed several subcutaneous lesions with systemic symptoms. Histological and immunophenotypic review of the initial cardiac biopsy revealed features consistent with a diagnosis of CD30, ALK1 positive anaplastic large cell lymphoma (ALCL). Despite intensive treatment with combination chemotherapy, there was significant progression of disease, and he died 11 months after diagnosis. The overall prognosis of cardiac lymphoma remains poor, which may be due to the often late presentation of the tumour. To our knowledge, this is the first reported case of a cardiac ALK positive ALCL. Although rare, cardiac presentation of ALCL should be added to the list of differential diagnoses of cardiac lymphomas.

PNP with Waldenström's macroglobulinaemia.

We describe a 65-year-old Caucasian man with Waldenstrom's macroglobulinaemia who developed paraneoplastic pemphigus (PNP) 3 years after his haematological diagnosis. This is a very rare malignancy that is associated with PNP. The evolution of PNP in this patient appears to exhibit the postulated immunological phenomenon of epitope spreading.

Patient, carer and health service outcomes of nurse-led early discharge after breast cancer surgery: a randomised controlled trial.

Patients with breast cancer who require axillary clearance traditionally remain in hospital until their wound drains are removed. Early discharge has been shown to improve clinical outcomes, but there has been little assessment of the psychosocial and financial impact of early discharge on patients, carers and the health service. This study aimed to evaluate the effectiveness of a nurse-led model of early discharge from hospital. Main outcome measures were quality of life and carer burden. Secondary outcomes included patient satisfaction, arm morbidity, impact on community nurses, health service costs, surgical cancellations and in-patient nursing dependency. A total of 108 patients undergoing axillary clearance with mastectomy or wide local excision for breast cancer were randomised to nurse-led early discharge or conventional stay. Nurse-led early discharge had no adverse effects on quality of life or patient satisfaction, had little effect on carer burden, improved communication between primary and secondary care, reduced cancellations and was safely implemented in a mixed rural/urban setting. In total, 40% of eligible patients agreed to take part. Nonparticipants were significantly older, more likely to live alone and had lower emotional well being before surgery. This study provides further evidence of the benefits of early discharge from hospital following axillary clearance for breast cancer. However, if given the choice, most patients prefer to stay in hospital until their wound drains are removed.

Reduced-intensity rituximab-BEAM-CAMPATH allogeneic haematopoietic stem cell transplantation for follicular lymphoma is feasible and induces durable molecular remissions.

The indolent non-Hodgkin's lymphomas are theoretically curable through allogeneic haematopoietic stem cell transplantation (allo-HSCT). The applicability of standard conditioning allo-HSCT is, however, restricted by its toxicity. Recently, reduced-intensity conditioning regimens have demonstrated efficacy with significantly reduced early morbidity and mortality. We examined the safety and efficacy of rituximab-BEAM-CAMPATH as reduced-intensity conditioning for allo-HSCT in follicular lymphomas. Minimal residual disease was assessed by polymerase chain reaction (PCR) for bcl-2/IgH translocations, and chimerism by X,Y-FISH or PCR amplification of short tandem repeat sequences. At a median follow-up of 521 days (371-719), four of five patients were alive and three were in complete molecular remission. Three patients required pre-emptive treatment for CMV reactivation. One succumbed to a perforated viscus and one had slowly progressive disease. A graft-versus-lymphoma effect was demonstrable and quantitative PCR for bcl-2/IgH may allow better accuracy in scheduling post-allograft rituximab and/or donor lymphocyte infusions. Although follow-up is short, reduced-intensity allo-HSCT with BEAM-CAMPATH conditioning appears to be safe, effective in inducing a molecular remission and is potentially curative. Further recruitment and much longer follow-up will be necessary to determine if this impacts favourably upon disease-free and overall survival.