Reading a preoperative CT scan to guide complex abdominal wall reconstructive surgery.

Computed tomography (CT) scanning is the imaging modality of choice when planning the overall management and operative approach to complex abdominal wall hernias. Despite its availability and well-recognised benefits there are no guidelines or recommendations regarding how best to read or report such scans for this application. In this paper we aim to outline an approach to interpreting preoperative CT scans in abdominal wall reconstruction (AWR). This approach breaks up the interpretive process into 4 steps-concentrating on the hernia or hernias, any complicating features of the hernia(s), the surrounding soft tissues and the abdominopelvic cavity as a whole-and was developed as a distillation of the authors' collective experience. We describe the key features that should be looked for at each of the four steps and the rationale for their inclusion.

Small bowel obstruction caused by a fibrotic bow-string appendix: a consequence of non-operative management of acute appendicitis.

A 73-year-old woman presented with small bowel obstruction that failed to settle with conservative management. Over the previous 2 years she had presented twice with computed tomography scan-proven acute appendicitis with localised perforation of the appendix tip. In view of medical comorbidities, she was treated non-operatively with clinical and radiological resolution on each occasion, but on the third presentation laparoscopy was undertaken for non-resolving small bowel obstruction and the non-inflamed appendix itself was identified as a fibrous band causing compression of the distal ileum and complete small bowel obstruction. Following division and appendicectomy, the patient made an uneventful recovery. This case illustrates the potential consequence of repeated appendiceal inflammation and non-operative management and may be seen increasingly as this approach is widely adopted during the COVID-19 pandemic.

Supporting the development of the research and clinical trials therapeutic radiographers workforce: The RaCTTR survey.

INTRODUCTION: The Research and Clinical Trials Therapeutic Radiographers network is a College of Radiographers Specialist Interest Group. It was established to develop and facilitate a support network for therapeutic radiographers working in roles which involve the delivery of radiotherapy clinical trials. Its establishment highlighted the challenges faced by therapeutic radiographers employed in these roles. Consequently, the authors sought to formally capture the working landscape of this subsection of the radiographic workforce, aiming to ascertain any potential barriers to professional development and the increase of clinical trials activity by 15% mandated by NHS England. METHODS: A Qualtrics survey was designed, pilot tested and distributed to the sixty-two radiotherapy departments across England and the devolved nations. Departments were questioned on the size, structure and the scope of practice of their radiotherapy research and clinical trials team members. FINDINGS: Thirty-nine complete responses were received, providing a response rate of 62%, with each region of the UK represented in the survey. The findings demonstrated issues related to the number of posts affecting capacity, contract status jeopardising the security and effectiveness of their role and the activities specific to research and clinical trials being 'bolted on' to existing roles. Although advanced practice was being undertaken by around a third of this workforce the findings established several barriers including individual/teams' capacity and a perceived lack of support for therapeutic radiographers to progress in clinical trials roles. CONCLUSION: The findings illustrate several important implications which if not addressed may not only hinder UK radiotherapy departments to achieve the national increase of 15% of clinical trial activity over the next three years but also restrict the growth in size and scope of professional practice of the workforce. IMPLICATIONS FOR PRACTICE: The research and clinical trials workforce need to adopt a collaborative approach to profile raising and establish a standardised professional scope of practice to support growth and recognition of their role.

The College of Radiographers Research Strategy for the next five years.

This article outlines the updated College of Radiographers (CoR) Research Strategy. This new research strategy will shape the approach to research from the radiography profession over the next five years. This will apply to all the profession and is aspirational and future thinking. The updated research strategy is the fifth research strategy presented by the CoR. Over the last five years, there have been considerable developments within healthcare and healthcare research. As this article is being written we are still in the middle of a global pandemic (Covid-19) which has influenced all our lives. However, despite the challenges of the last year, we are in a stronger position as a profession with more radiographers working towards and gaining masters and doctoral level qualifications. There are more radiographers working in clinical academic roles and there has been further development of radiographers coordinating and delivering research as well as becoming research leaders. This updated research strategy supports the radiography profession in delivering research-based practice over the next five years offering a framework within which radiographers can develop.

Pamidronate reduces bone loss after allogeneic stem cell transplantation.

BACKGROUND: Rapid bone loss occurs from the proximal femur after allogeneic stem cell transplantation (alloSCT). OBJECTIVE: The objective of the study was to evaluate effects of high-dose pamidronate therapy on bone loss (BMD) after alloSCT. DESIGN: This was a randomized, multicenter, open-label, 12-month prospective study of iv pamidronate (90 mg/month) beginning before conditioning vs. no pamidronate. All 116 patients also received calcitriol (0.25 microg/d) and calcium (1000 mg/d), which were continued for another year. MAIN OUTCOME MEASURES: Primary objectives were to compare changes in BMD 12 months after alloSCT at the femoral neck, lumbar spine, and total hip between the treatment arms and assess influences of glucocorticoid and cyclosporin therapy on these changes. RESULTS: Pamidronate reduced bone loss at the spine, femoral neck, and total hip by 5.6, 7.7, and 4.9% (all P < or = 0.003), respectively, at 12 months. However, BMD of the femoral neck and total hip was still 2.8 and 3.5% lower than baseline, respectively (P < 0.05) with pamidronate. Only differences at the total hip remained significant between the two groups at 24 months. Benefits were restricted to patients receiving an average daily prednisolone dose greater than 10 mg and cyclosporin therapy for more than 5 months within the first 6 months of alloSCT. CONCLUSIONS: Pamidronate markedly reduced but did not completely prevent postallogeneic bone marrow transplantation bone loss. BMD benefits were greatest in patients on higher doses of immunosuppressive therapy, but most were lost 12 months after stopping pamidronate. Studies of more potent bisphosphonates or anabolic therapy with PTH after alloSCT are warranted with the aim of durable maintenance of bone mass.

A phase I dose-escalation study of etoposide continuous infusion added to busulphan/cyclophosphamide as conditioning prior to autologous or allogeneic stem cell transplantation.

Relapse of the primary disease remains the predominant cause of death following bone marrow transplantation for high-risk haematological malignancies. Improved supportive care and patient selection have resulted significant improvements in toxicity with standard conditioning regimens. Further dose intensification to reduce the risk of relapse may therefore be feasible. We determined the maximal tolerated dose (MTD) of a 5-day continuous infusion (CI) of etoposide when added to oral busulphan 16 mg/kg and intravenous cyclophosphamide 120 mg/kg (Bu/Cy) as conditioning in 44 autograft and 18 allograft recipients at high risk of relapse. The major toxicity of escalating doses of etoposide was oral and gastro-intestinal mucositis, reflected by a statistically significant increase in the requirement for total parenteral nutrition in both autografts and allograft recipients. Time to neutrophil and platelet recovery, opiate analgesia requirements, and duration of hospitalization were not affected by etoposide dose escalation. The MTD in autograft recipients was 300 mg/m(2)/day (1500 mg/m(2) total dose), and 100 mg/m(2)/day (500 mg/m(2) total dose) for allograft recipients. Mucositis and hepatotoxicity were more frequent in allograft recipients, suggesting that methotrexate may have contributed to the lower tolerable dose in these patients. As a consequence, further dose escalation may not be possible in heavily pre-treated patients undergoing allogeneic transplantation. Conversely, high dose CI etoposide can be added with relative safety to Bu/Cy in autograft recipients.

Fresh frozen plasma: a solution to heparin resistance during cardiopulmonary bypass.

The reasons for the highly variable response of patients to heparin remain incompletely understood. Empirical maintenance of the activated clotting time (ACT) at levels of 400 to 480 seconds appears to be safe for cardiopulmonary bypass (CPB). For patients with ACT responses lower than predicted for initial heparin doses, titration with additional heparin has been customary. In 44 patients undergoing cardiopulmonary bypass, 20 patients were identified as having initial ACTs of 300 seconds or less after receiving 300 units per kilogram of heparin. In 11 of them, ACTs were titrated to 400 to 480 seconds with additional heparin. Nine were given 2 units of fresh frozen plasma shortly after institution of CPB. In this group, there was significant augmentation of the ACT immediately after infusion of plasma. No differences in total heparin dosages given during CPB were found between 24 control patients with initially acceptable ACTs and the group receiving fresh frozen plasma. In contrast, more heparin was necessary in the patients with a low ACT titrated with heparin alone. Data also indicated that protamine sulfate requirements were substantially lower after administration of plasma than were those in either the control or the heparin-titrated, low ACT group. Fresh frozen plasma appears to "normalize" the heparin-ACT dose-response curve in heparin-resistant patients and to lessen total heparin requirements during CPB.

CsA 2-h concentration correlates best with area under the concentration-time curve after allo-SCT compared with trough CsA.

The relationship between CsA levels and area under the curve (AUC) in allo-SCT recipients, and the effect of age, concomitant use of steroid and MDR-1 polymorphism on this relationship remain largely unexplored. Steady-state CsA blood concentrations at time 0 (C0), 1 (C1), 1.5 (C1.5), 2 (C2), 3 (C3), 4 (C4), 6 (C6), 8 (C8) and 12 (C12) h post oral CsA dose were taken from 27 consenting allo-SCT recipients (receiving myeloablative or non-myeloablative conditioning) at D(15)-D(25) (all participants) and D(40)-D(80) (participants with myeloablative conditioning). The CsA AUC(0-4h), AUC(0-8h) and AUC(0-12h) were determined using trapezoidal rule, and the relationships between AUCs and CsA concentrations at various time points were examined. Poor correlation was observed between C0 and AUC(0-4h) (r(2)=0.15), AUC(0-8h) (r(2)=0.21) and AUC(0-12h) (r(2)=0.53). C2 was better correlated with AUC(0-4h) (r(2)=0.88), AUC(0-8h) (r(2)=0.76) and AUC(0-12h) (r(2)=0.83). The aforementioned factors did not influence the observed relationship. CsA levels taken at 2 h post oral CsA administration may represent the optimal time point for monitoring the biological effects of calcineurin inhibitors in allo-SCT recipients.

A prospective multicenter trial of peripheral blood stem cell sibling allografts for acute myeloid leukemia in first complete remission using fludarabine-cyclophosphamide reduced intensity conditioning.

The role of allogeneic transplantation in patients with de novo acute myeloid leukemia in first complete remission (AML-CR1) is controversial. Aiming to preserve a graft-versus-leukemia effect, but minimize morbidity and mortality from conditioning-related toxicity and graft-versus-host disease (GVHD), we conducted a prospective multicenter study of reduced-intensity conditioning (RIC) as preparation for peripheral blood stem cell sibling allografts in patients with intermediate or poor risk AML-CR1. Conditioning consisted of fludarabine 125 mg/m(2) and cyclophosphamide 120 mg/kg. Thirty-four patients were transplanted with a median age of 45 years; 85% had intermediate risk cytogenetics. Early toxicity was minimal. The overall incidence of grade II-IV acute GVHD was low (21%), but the 3 patients (9%) who developed grade IV GVHD died. Donor T cell chimerism was rapid and generally complete, but complete myeloid chimerism was delayed. Thirteen patients (38%) relapsed, 12 within a year of transplant. The estimated disease-free survival (DFS) and overall survival at 2 years was 56% (95% confidence interval [CI] 39%-71%) and 68% (95% CI 50%-81%), respectively. The incidence of extensive chronic GVHD (cGVHD) was low (24% of surviving patients at 12 months) and most survivors had an excellent performance status. These observations justify a prospective comparison of RIC versus myeloablative conditioning allografts for AML-CR1.

Autografting followed by rituximab for chemosensitive mantle cell lymphoma: a pilot study and literature review.

Mantle cell lymphoma (MCL) is rarely cured with either conventional-dose chemotherapy or autografting. Recent evidence suggests that anti-CD20 monoclonal antibody therapy (rituximab) in combination with chemotherapy may improve the response rate. We report a pilot study of autografting using busulfan-melphalan conditioning followed by rituximab in 9 patients (median age 52 years) with chemosensitive MCL. Rituximab was given for 4 doses of 375 mg/m(2) between 4 and 10 weeks post-transplant. Three of 5 patients autografted after induction therapy remain alive in clinical and molecular complete remission at 33-50 months post-transplant. Only 1 of 4 patients autografted after relapse remains in complete remission. Two of the 3 patients with persistent marrow molecular positivity post-autograft became negative after rituximab therapy. Molecular negativity was first observed in 2 patients only after rituximab therapy. Overall, 2 patients have relapsed and the remaining 3 died of late-onset respiratory failure, probably reflecting infection and/or aggressive conditioning in an older patient population. These preliminary results, together with a review of the literature, suggest that the combination of autografting and rituximab may lead to durable molecular remissions in patients with chemosensitive MCL. Further studies are required to clarify whether the administration of rituximab: (1) is optimal pre- or post-autograft and (2) impacts on the incidence of infection and idiopathic pneumonitis in this context.

A comparative study of several antibiotic formulations using a design based on a combination of balanced incomplete blocks and Latin squares.

A practical application of an experimental design, suitable for the comparison of several treatments, and based on combining balanced incomplete blocks and Latin squares balanced for carryover effects, is presented in the context of comparing a number of paediatric antibiotic formulations for taste, smell and colour. The recommended designs originally suggested by Patterson, have the advantage of balanced incomplete blocks, in that a single trial may be used to compare a larger number of treatments than may reasonably be given to any individual subject. In addition, the incorporation of suitably chosen Latin squares allows for assessment of any effect of order of presentation of the treatments and for any simple first-order carryover effect of one treatment into the following treatment period. Inclusion of such effects in the overall analysis could result in the reduction of bias in the comparisons of the treatments.

Cladribine followed by autologous stem-cell transplantation in progressive multiple sclerosis.

We studied the safety of autologous peripheral blood stem-cell transplantation (PBSCT) in four patients with progressive multiple sclerosis. Clinical and magnetic resonance imaging outcomes were secondary end-points. Cladribine administration preceded filgrastim-primed PBSC collection, aiming for lymphocyte depletion. Conditioning was with antithymocyte globulin and cyclophosphamide. The procedure was well tolerated, but without obvious clinical benefit. The study was terminated when other therapeutic options with lower morbidity became available.