Role Of Transplantation Research Articles

Role of autologous bone marrow transplant in multiple myeloma

The treatment of newly diagnosed multiple myeloma has evolved rapidly over the recent years. In younger patients, autologous stem cell transplantation (ASCT) is still considered the standard of care, but the availability of new effective drugs with novel mechanisms of action in the last decade has resulted in a new scenario that has caused the role of transplantation itself to be currently undergoing scrutiny. Maintaining the response of first-line therapy is an important objective in multiple myeloma, where despite intensive therapy followed by ASCT the majority of patients will relapse. In this field, the recent results of different consolidation and maintenance therapies after transplant are very encouraging. These strategies have come to stay and will play an essential role in the next future to improve the prognosis of young patients with newly diagnosed multiple myeloma. Finally, new conditioning regimens will also be tested in the forthcoming years in an attempt to further improve posttransplant responses. Multiple myeloma ASCT must be integrated within a more global therapeutic approach including new and more effective induction, consolidation, and maintenance approaches. Efforts aimed in the development of more effective and less toxic preparative regimens to further augment disease control are also warranted.

BAFF and BAFF-R Levels Are Associated With Risk of Long-Term Kidney Graft Dysfunction and Development of Donor-Specific Antibodies

There are lines of evidence that B cells may play a role in transplantation. B cell activating factor, BAFF, is a homotrimer that has been shown to play a role in B cell survival, maturation and activation. To date, little is known of the role of BAFF and its receptors in transplantation. We analyzed the level of BAFF mRNA and its soluble protein, as well as transcripts coding for its receptors, BAFF-R, TACI and BCMA, in the blood of 143 patients with stable kidney transplant function 5 years or more posttransplantation. Three endpoints were analyzed: the time to renal dysfunction, the time to appearance of anti-HLA antibodies and the time to development of donor-specific antibodies. We established threshold values for BAFF and BAFF-R and showed that (1) stable patients with high BAFF-R levels had a higher risk of developing graft dysfunction, (2) patients with lower levels of BAFF transcripts or a higher level of soluble BAFF had a significantly higher risk of developing donor-specific antibodies. These data suggest that BAFF constitutes a risk factor for renal graft dysfunction and development of donor-specific antibodies. They also suggest that agents targeting BAFF-R interactions may offer new therapeutic opportunities in transplantation.

Immunoregulatory properties of rapamycin-conditioned monocyte-derived dendritic cells and their role in transplantation.

In efforts to minimize the chronic administration of immunosuppression (IS) drugs in transplantation and autoimmune disease, various cell-based tolerogenic therapies, including the use of regulatory or tolerogenic dendritic cells (tolDC) have been developed. These DC-based therapies aim to harness the inherent immunoregulatory potential of these professional antigen-presenting cells. In this short review, we describe both the demonstrated tolerogenic properties, and current limitations of rapamycin-conditioned DC (RAPA-DC). RAPA-DC are generated through inhibition of the integrative kinase mammalian target of rapamycin (mTOR) by the immunosuppressive macrolide rapamycin during propagation of monocyte-derived DC. Consistent with the characteristics of tolDC, murine RAPA-DC display resistance to phenotypic maturation induced by pro-inflammatory stimuli; exhibit the ability to migrate to secondary lymphoid tissue (important for ‘cross-presentation’ of antigen to T cells), and enrich for naturally-occurring CD4+ regulatory T cells. In rodent models, delivery of recipient-derived RAPA-DC pulsed with donor antigen prior to organ transplantation can prolong allogeneic heart-graft survival indefinitely, especially when combined with a short course of IS. These encouraging data support ongoing efforts to develop RAPA-DC for clinical testing. When compared to murine RAPA-DC however, human RAPA-DC have proven only partially resistant to maturation triggered by pro-inflammatory cytokines, and display heterogeneity in their impact on effector T-cell expansion and function. In total, the evidence suggests the need for more in-depth studies to better understand the mechanisms by which mTOR controls human DC function. These studies may facilitate the development of RAPA-DC therapy alone or together with agents that preserve/enhance their tolerogenic properties as clinical immunoregulatory vectors.

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Aim Complement-fixing (CF) HLA antibodies (Ab) play an important role in transplantation because they can initiate inflammatory processes within the graft that lead to rejection. The Luminex Ig-binding assay (LUM-Ig) is now the principal method for HLA Ab testing. The C1q-binding assasy (LUM-C1q) can distinguish between CF and non-CF Abs. We show here evidence that the differential reactivity of CF HLA Ab depends on the structural composition of epitope (Ep)-carrying alleles (Al). Methods Human cytotoxic class I Ep-specific monoclonal antibodies (mAb) were tested in LUM-Ig and LUM-C1q (OneLambda). Results were compared to CDC reactivity with informative cells from the 13th International Workshop. Results Two reactivity patterns were observed. For some mAb, Ep-carrying Al reacted similarly in all assays. But certain mAb reacted with more Al in LUM-Ig than in LUM-C1q and CDC. Reactivity was analyzed with HLAMatchmaker, incorporating the concept that eplets are essential parts of structural Eps which can contact the 6 Complementarity Determining Regions (CDRs) of Ab. The data show that LUM-Ig mAb are specific for eplets but that LUM-C1q and CDC reactivity require an additional polymorphic amino acid configuration on eplet-carrying Al. Conclusions The findings must be viewed in context of formation of an antigen-Ab complex resulting in release of free energy necessary to stabilize binding and to induce conformational change in the Fc part of the Ab structure to expose the C1q receptor, the first step of Complement activation. The CF properties of HLA Ab require not only specific recognition of an eplet but also depend on interactions of other CDRs with critical amino acid configurations within the structural Ep. Eplet-carrying Al that lack such critical configurations will bind with Ab but the amount of free energy is insufficient to expose the C1q-binding site and there is no CF. This concept is important to our understanding whether or not CF donor-specific HLA Ab can initiate Ab-mediated rejection.

Invited Commentary

Plastic bronchitis after Fontan completion is a known but difficult complication to treat. The onset usually denotes a failing Fontan, although Griffiths and colleagues [1Griffiths E.R. Kaza A.K. Wyler von Ballmoos M.C. et al.Evaluating failing Fontans for heart transplantation: predictors of death.Ann Thorac Surg. 2009; 88: 558-564Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar] had shown the occurrence of plastic bronchitis in the group of Fontan with preserved ventricular function as opposed to those who have failed ventricular pump. There is also a close relation to other exudative complications, such as protein-losing enteropathy, and denotes a failing protoplasm not tolerating this Fontan connection resulting in exudative lesions [2Siulvilairat S. Cabalka A.K. Cetta F. Grogan M. Hagler D.J. O'Leary P.W. Protein-losing enteropathy after the Fontan operation: associations and predictors of clinical outcome.Congent Heart Dis. 2008; 3: 262-268Crossref PubMed Scopus (40) Google Scholar]. Grutter and colleagues [3Grutter G. Di Carlo D. Gandolfo F. et al.Plastic bronchitis after extracardiac Fontan operation.Ann Thorac Surg. 2012; 94: 860-864Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar] presented their experience with plastic bronchitis in four patients. Although the group is small, all of them went through almost a similar course of events with chylothorax and requirement of coil embolization for collaterals, and all of them had preserved ventricular function. They had attempted various medical measures to treat the intractable plastic bronchitis with success in two of them, with both waiting to have transplantation. The other two died because of either the condition itself or complications in the process of managing it. I congratulate the authors for an excellent commentary on this condition, covering various pathogenetic mechanism and treatment options available. As mentioned in the article, casts of plastic bronchitis can be of two types, and acellular casts are common in failing Fontan patients. It is rare to see cellular elements unless there is associated bronchial anomaly, although all patients in this study group had mixed casts and two of them had bronchopulmonary disease in the form of malacia or obstructive airway disease. Whether this could have helped in the resolution of cast formation on medical management is difficult to ascertain, but one has to be careful in interpreting these, as quite often patients with extensive cast formation would also have significant impact on pulmonary function resulting in cellular exudates. Attempts have been made to clear the casts by instrumentation with mixed results. Intractable casts in the airway is difficult to manage, and authors have rightly sequenced various medical management including aerosols, pulmonary vasodilators, and tissue plasminogen activators [4Nayar S. Parmar R. Kulkarni S. Cherian K.M. Treatment of plastic bronchitis.Ann Thorac Surg. 2007; 83: 1884-1886Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar]. Fenestration of Fontan circulation has a definitive role in reducing the incidence of exudative lesions but its efficacy in reducing the cast formation after its onset is a matter of debate. Role of transplantation after the onset of plastic bronchitis offers again mixed results in terms of resolution of further cast formation [5Gamba A. Merlo M. Fiocchi R. et al.Heart transplantation in patients with previous Fontan operations.J Thorac Cardiovasc Surg. 2004; 127: 555-562Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar], although one would expect otherwise. Plastic Bronchitis After Extracardiac Fontan OperationThe Annals of Thoracic SurgeryVol. 94Issue 3PreviewWe discuss 4 cases of plastic bronchitis (PB) after Fontan procedure observed at our Institution, with the aim to identify an effective treatment and possible factors favoring the onset of PB. Plastic bronchitis is an uncommon disease characterized by recurrent formation of large pale bronchial casts obstructing the tracheobronchial tree. The treatment includes inhaled or systemic steroids, aerosolized mucolytics, bronchoscopic lavage, direct bronchoscopic extraction and, in few reports, aerosolized fibrinolytic and pulmonary vasodilators. Full-Text PDF

Doubts and strategies in the treatment of follicular lymphoma

In the past 5 years,the treatment paradigm for patients with follicular lymphoma(FL) has undergone significant changes,with the development of effective new agents that are now being used in the upfront,maintenance,and relapsed/refractory settings.Although these new therapies have led to improvements in patient outcomes,numerous questions remain regarding their optimal use in the treatment of the disease.In this article,the questions related to the timing of therapy for asymptomatic patients,strategies for treating advanced and relapsed/refractory disease,the safety and efficacy of rituximab maintenance and the evolving role of transplantation in the era of novel agents were responded.The latest data from clinical trials of investigational agents that are showing promise in FL were also discussed. Key words: Lymphoma, follicular; , Asymptomtic diseases; Recurrence; Rituximab; Stem cell transplantation; maintenance treatment

Stem Cell Transplantation for Multiple Myeloma: Who, When, and What Type?

Early randomized trials of high-dose chemotherapy with autologous stem cell rescue showed improved progression-free survival (PFS) over conventional chemotherapy. However, in the era of novel agents for myeloma in conjunction with the evolution of hematopoietic stem cell transplantation, many new questions arise. First, how can novel agents be incorporated into the transplant paradigm? Given the efficacy of new induction regimens, should transplant be delayed until relapse? Also, in the era of individualized medicine, chronologic age alone should not drive decisions regarding transplantation. Therefore, the feasibility and role of transplantation in older patients with myeloma is being studied. The controversy of transplant type (i.e., autologous compared with reduced intensity allogeneic transplant) remains unresolved. Several large international trials have demonstrated conflicting results in regard to an overall survival (OS) benefit with the allogeneic approach. The role of allogeneic transplant remains under study especially in the high-risk population, which has high relapse rates with traditional autologous approaches. Future directions to reduce relapse include post-transplantation consolidation and maintenance therapy with either approved agents or new agents and immunotherapy, either vaccine based or natural killer (NK) and T-cell based.

Current opinion on the role of resection and liver transplantation for hepatocellular cancer

Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide with rising incidence in developed countries. The best treatment options with curative intent for patients with HCC are liver resection or transplantation, although the role of hepatic ablative therapies has also been recognized. Surgical resection has emerged as the primary treatment in carefully selected patients of HCC. With the advances in surgical and radiological techniques, the perioperative mortality has been reduced to less than 5 % depending on the extent of resection and hepatic reserve. The role of liver transplantation (LT) as the mainstay of treatment for the majority of patients with HCC has evolved in the last few decades. Historically, the Milan criteria have been considered the gold standard for selecting patients; more expanded selection criteria to include those with more advanced tumors have been implemented in recent years. Living donor liver transplantation (LDLT) has emerged as a way to expand the donor pool and has influenced the role of transplantation for HCC, especially in communities with little access to cadaveric transplantation. Salvage transplantation is an alternative option as it allows a window for the biologically less favorable lesions to declare tumor behavior. Salvage transplantation also decreases the burden on transplant resources. Sirolimus, a novel immunosuppressant drug with anti-tumor effect, may have a role in limiting the severity of recurrent disease after transplantation for HCC, and play an important role in the future management of transplant recipients. This article examines the literature on current status of management of HCC.

What Is the Role of Transplantation for Indolent Lymphoma?

Despite advances in chemoimmunotherapy, indolent B-cell non-Hodgkin lymphomas (B-NHLs) are generally not considered curable with this approach. Much attention has been paid to the prospect of hematopoietic cell transplantation (HCT) as a way to improve long-term outcomes for this group of diseases. Autologous (auto) HCT provides intensive conditioning therapy followed by rescue of hematopoiesis, and this has been shown in randomized studies to prolong survival compared with more standard chemotherapy, albeit with increased short-term toxicity and the potential for higher rates of secondary malignancies. Allogeneic (allo) HCT can provide anticancer effects beyond the conditioning therapy through the immune-mediated graft-versus-lymphoma (GVL) effect. It can be administered following myeloablative (MA) conditioning or reduced-intensity (RI) regimens aimed at sufficiently suppressing the patient's immune system to allow engraftment of donor hematopoiesis. However, this same potentially curative alloreactivity of the engrafted immune system can lead to graft-versus-host disease (GVHD), a significant cause of morbidity and mortality following allo HCT. This article will discuss the current role of both auto HCT and allo HCT in the management of indolent lymphoma as well as the relative risks and benefits of each approach such that the reader can place this in context of the multitude of options available for patients with indolent B-NHL.

Low median fluorescence intensity could be a nonsafety concept of immunologic risk evaluation in patients with shared molecular eplets in kidney transplantation

Human leukocyte antigen (HLA) antibodies are usually "epitope" and not "antigen" specific. This work presents an interesting case concerning Luminex median fluorescence intensity (MFI) levels in antibodies considered low risk (<1,000), but producing humoral rejection. These low-titer antibodies could play an important role in transplantation. A 42-year-old woman was retransplanted with a deceased donor with negative complement-dependent cytotoxicity cross-matching. Our patient was pretransplant (PrT) sensitized to HLA antigens (single antigens (SA) = 31%) for 1 previous transplant. Thus, the formerly detected sensitized antigens were A32, A30, A31, cross-reacting group 5C, and DQ3 with a MFI(max) ≈ 4,127. In the posttransplantation period (PTP), the patient exhibited important instability in renal function and we detected an increased SA percentage (61%) with MFI(max) = 15,029 (A*32) with other antigens (detected with a low PrT MFI [<1,000]) as anti-A*03 (MFI(max) = 13,301) and anti-A*11 (MFI(max) = 13,714) specificities. Anti-A*03 was a donor-specific antibody (DSA). Renal biopsy was compatible with humoral rejection. The patient was pulsed with methylprednisolone, plasmapheresis, and intravenous immunoglobulin without improvement. Thus, we added anti-CD20 and the initial clinical response was highly favorable. Biopsies resulted in suggestive rejection reversion. MFI A*03 DSA decreased to 6,908 and later to MFI(max) = 5,505. After a 6-month PTP, the patient is well with MFI(max) = 3,124. It was possible to define exactly the potential immunizing epitope eplets whose recognition determined the specific antibody production. A*32:01, A*30:01, A*31:01 (detected PrT), A*11:01, and A*03:01 (detected PTP) alleles have several shared eplets (62QE, 70AQS, and 76VGT), with 62QE being the only eplet present on all alleles. In conclusion, low MFI levels in antibodies considered low risk could be important in posttransplant humoral rejection, although the patient's renal function can be restored. Thus, specific shared eplets should always be investigated with respect to previous transplant mismatches.

Activity and thermostability increase of xylanase following transplantation with modules sub-divided from hyper-thermophilic CBM9_1-2

Transplantation is useful for elucidating the functions of structural modules and for engineering enzyme properties. Unexpectedly, transplanting a hyper-thermophilic carbohydrate-binding module, CBM9_1-2, into the mesophilic Aspergillus niger GH11 xylanase (Xyn) slightly decreased the thermal inactivation half-life of Xyn. This effect was further investigated by dividing the CBM9_1-2 module into two smaller parts, C1 and C2, which were transplanted into Xyn to create the chimeras Xyn-C1 and Xyn-C2. Both chimeras exhibited higher catalytic activities on xylan than native Xyn. Xyn-C2 exhibited higher binding affinities for both oat spelt and birch wood xylans, and its thermal inactivation half-life (69.3min) was 4 or 5 times longer than that of Xyn (17.6min), Xyn-C1 (13.4min), and the original chimera containing CBM9_1-2 (13.8min). In contrast, Xyn-C1 exhibited higher binding affinity for oat spelt xylan, but not for birch wood xylan. Through this rational engineering of the fungal xylanase, the C2 sub-module was shown to have a different thermostabilizing effect than the C1 sub-module. The different functions of the smaller parts of a large module can play pivotal roles in transplantation.

Subretinal Implantation of Electrospun, Short Nanowire, and Smooth Poly(ε-caprolactone) Scaffolds to the Subretinal Space of Porcine Eyes

Biodegradable scaffolds play an important adjunct role in transplantation of retinal progenitor cells (RPCs) to the subretinal space. Poly(ε-Caprolactone) (PCL) scaffolds with different modifications were subretinally implanted in 28 porcine eyes and evaluated by multifocal electroretinography (mfERG) and histology after 6 weeks of observation. PCL Short Nanowire, PCL Electrospun, and PCL Smooth scaffolds were well tolerated in the subretinal space in pigs and caused no inflammation and limited tissue disruption. PCL Short Nanowire had an average rate of preserved overlying outer retina 17% higher than PCL Electrospun and 25% higher than PCL Smooth. Furthermore, PCL Short Nanowire was found to have the most suitable degree of stiffness for surgical delivery to the subretinal space. The membrane-induced photoreceptor damage could be shown on mfERG, but the reductions in P1 amplitude were only significant for the PCL Smooth. We conclude that of the tested scaffolds, PCL Short Nanowire is the best candidate for subretinal implantation.

Liver transplantation in the management of unresectable hepatoblastoma in children

Complete surgical resection is essential to long-term survival in children with hepatoblastoma. We present the guidelines from the Children's Oncology Group (COG), liver tumor study group of the Societe Internationale Oncologie Pediatrique (SIOPEL), and German Pediatric Oncology Group (GPOH) for early referral of children with potentially unresectable hepatoblastoma to a specialty center with expertise in extreme resection and liver transplantation. Patients who will become candidates for liver transplantation should receive chemotherapy following the same protocols as for children undergoing a partial hepatectomy. The Pediatric Liver Unresectable Tumor Observatory (PLUTO) is an international prospective database established to collect data and make future recommendations on controversial issues regarding the use of transplant in hepatoblastoma including: 1) What is the optimal treatment of multifocal tumors. 2) What is the role of extreme resection vs. liver transplant in patients with major venous involvement. 3) What is the role of transplant in patients who present with lung metastasis. 3) Should patients with tumor relapse be offered a rescue transplant. 4) What is the role of pre- and post- transplant chemotherapy.

Liver transplantation in the management of unresectable hepatoblastoma in children

Complete surgical resection is essential to long-term survival in children with hepatoblastoma. We present the guidelines from the Children's Oncology Group (COG), liver tumor study group of the Societe Internationale Oncologie Pediatrique (SIOPEL), and German Pediatric Oncology Group (GPOH) for early referral of children with potentially unresectable hepatoblastoma to a specialty center with expertise in extreme resection and liver transplantation. Patients who will become candidates for liver transplantation should receive chemotherapy following the same protocols as for children undergoing a partial hepatectomy. The Pediatric Liver Unresectable Tumor Observatory (PLUTO) is an international prospective database established to collect data and make future recommendations on controversial issues regarding the use of transplant in hepatoblastoma including: 1) What is the optimal treatment of multifocal tumors. 2) What is the role of extreme resection vs. liver transplant in patients with major venous involvement. 3) What is the role of transplant in patients who present with lung metastasis. 3) Should patients with tumor relapse be offered a rescue transplant. 4) What is the role of pre- and post- transplant chemotherapy.

Hematopoietic stem cell transplantation for severe congenital neutropenia

Hematopoietic stem cell transplantation (HCT) is the only curative option for patients with severe congenital neutropenia (SCN). Transplant success is dependent on identifying at-risk patients and proceeding to transplant before the development of severe infections or malignant transformation. This review focuses on recent advancements in risk stratification of SCN patients, indications for HCT, and review of published transplant studies. Patients with poor neutrophil response despite high doses of granulocyte colony-stimulating factor (G-CSF) are at greatest risk for malignant transformation. Other studies demonstrate elevated risk with mutations in the G-CSF receptor gene and a specific mutation in the ELANE gene. These patients are at high-risk of sepsis or leukemia development and should proceed to transplant with best available donor. As recent published studies demonstrate, HCT is highly successful in patients without leukemia and, therefore, may be considered in selected low-risk patients given the life-long risk of malignancy and infection. The decision whether to proceed to HCT in healthy patients maintained on G-CSF is difficult. As transplant-related mortality continues to decrease, the role of transplant in SCN is likely to expand to more patients.

Stem Cell Transplantation in Inherited Metabolic Disorders

Allogeneic HSCT is performed for a small number of inborn errors of metabolism (IEM). Over the last years, transplantation outcomes have improved in this group of patients as the factors that predicted for poor transplantation outcomes were understood and addressed. The role of transplantation and its potential benefit for an individual patient with a certain IEM is therefore now much better defined. In parallel with improvements in transplantation techniques, other therapies such as pharmacological enzyme replacement therapy (ERT), substrate inhibition, and gene therapy have been developed and are increasingly available to clinicians and their patients. This review covers the following areas: (1) the scientific principles that underpin transplantation in IEM; (2) the variables of the transplantation process itself that predict for successful outcome in terms of engrafted survival after HSCT; (3) the reasons that some apparently phenotypically similar disorders might respond very differently to transplantation therapy; (4) the factors that currently influence the response of a particular patient with a particular disease to allogeneic transplantation, and how these factors might be manipulated in the future to further improve transplantation outcomes in different metabolic illnesses; and (5) how other therapeutic modalities, including ERT, gene therapy, and substrate reduction therapy, might complement and compete with HSCT in the coming years.

Burkitt lymphoma in adults

The diagnosis of Burkitt Lymphoma (BL) and B-cell lymphomas unclassifiable with features intermediate between Diffuse Large B-cell Lymphoma and BL (BLU) in adults remains problematic even with immunophenotyping and MYC gene analysis. Gene expression profiling may improve categorization but is not routinely available. BL and its variants should be treated with specific regimens incorporating intensive courses of chemotherapy with fractionated alkylating agents and cell cycle phase-specific agents that readily cross the blood brain barrier. Subsequent courses should be given as soon as haematological recovery occurs, with the whole course completed within a few months. A number of regimens have been developed that encompass these principles but there have been no comparative randomized trials. The results from several studies suggest that the addition of rituximab is highly efficacious and this may be particularly valuable in older patients. It is usual to employ 'risk-adapted' strategies in the treatment of BL but these must be continually re-evaluated, and 'response-adapted' approaches should be explored. The role of transplantation is limited and largely confined to autologous transplants in patients who only achieve a partial response on front-line therapy or who have a chemosensitive relapse. Further advances will be greatly facilitated by randomized trials, which will require international collaboration.

Time-Motion Analysis of Research Nurse Activities in a Lung Transplant Home Monitoring Study

The emergence and subsequent integration of new technologies precipitate changes in roles and work lives of nurses. The nurses' work with home monitoring technologies within a spirometry-based program that transmits pulmonary function data after lung transplantation has characteristics that are distinct from other types of direct patient care. Nurses' changing roles in such programs after transplantation have not been well described. To describe a time-motion study of 2 research nurses in the context of a home-spirometry study to monitor patients' pulmonary status after lung transplantation. A detailed list of research nurses' 67 routine work-related activities was developed and validated to monitor and record activities of research home monitoring nurses. Two weeks of observations were completed; recordings of a second observer established reliability of observations. In 48.8 hours of observation, 610 tasks related to monitoring of 45 patients were recorded. Task time ranged from brief seconds (eg, data review) to 39 minutes (eg, clinic visits). Between-observer intraclass correlation (r = 0.96) reflected high agreement in observations of the duration of activities. Agreement for category of activity was strong (kappa = 0.82), with high levels of agreement (96%). Computer tasks were the most frequent (118 tasks/week) and most time-intensive activities. Nurses' face-to-face interactions with health professionals were equally time intensive (both 267 minutes/week), but not as frequent. Data review tasks were the second most frequent (49/week), although less time-intensive (47 minutes/week). Findings reveal patterns of effort and time expenditure in nurses' evolving roles in home monitoring of the health status of patients after lung transplantation. These findings highlight the centrality and importance of well-developed data management, computer skills, and interprofessional communication skills of nurses who perform responsibilities in this emerging role in transplantation. Efforts to streamline computerized information access, as through integrated information systems, and methods to enhance efficiency in connecting with patients in the clinic may free up time for nurses to engage in other activities of direct benefit to patients. Strategies to supplement face-to-face meetings among professionals with electronic modalities may reduce the time spent meeting, while maintaining or enhancing communication.

Time-motion analysis of research nurse activities in a lung transplant home monitoring study

The emergence and subsequent integration of new technologies precipitate changes in roles and work lives of nurses. The nurses' work with home monitoring technologies within a spirometry-based program that transmits pulmonary function data after lung transplantation has characteristics that are distinct from other types of direct patient care. Nurses' changing roles in such programs after transplantation have not been well described. To describe a time-motion study of 2 research nurses in the context of a home-spirometry study to monitor patients' pulmonary status after lung transplantation. A detailed list of research nurses' 67 routine work-related activities was developed and validated to monitor and record activities of research home monitoring nurses. Two weeks of observations were completed; recordings of a second observer established reliability of observations. In 48.8 hours of observation, 610 tasks related to monitoring of 45 patients were recorded. Task time ranged from brief seconds (eg, data review) to 39 minutes (eg, clinic visits). Between-observer intraclass correlation (r = 0.96) reflected high agreement in observations of the duration of activities. Agreement for category of activity was strong (kappa = 0.82), with high levels of agreement (96%). Computer tasks were the most frequent (118 tasks/week) and most time-intensive activities. Nurses' face-to-face interactions with health professionals were equally time intensive (both 267 minutes/week), but not as frequent. Data review tasks were the second most frequent (49/week), although less time-intensive (47 minutes/week). Findings reveal patterns of effort and time expenditure in nurses' evolving roles in home monitoring of the health status of patients after lung transplantation. These findings highlight the centrality and importance of well-developed data management, computer skills, and interprofessional communication skills of nurses who perform responsibilities in this emerging role in transplantation. Efforts to streamline computerized information access, as through integrated information systems, and methods to enhance efficiency in connecting with patients in the clinic may free up time for nurses to engage in other activities of direct benefit to patients. Strategies to supplement face-to-face meetings among professionals with electronic modalities may reduce the time spent meeting, while maintaining or enhancing communication.

Treatment of multiple myeloma.

The treatment of multiple myeloma has changed dramatically in the past decade. The increase in the number of active agents has generated numerous possible drug combinations that can be used in the first-line and relapsed settings. As a result, there is considerable confusion about the choice of regimens for initial therapy, role of transplantation in the era of new drugs, end points for therapy, and the role of maintenance therapy. A hotly debated area is whether treatment approaches should achieve cure or disease control, which impacts greatly on the treatment strategy employed. This article provides an update on the treatment of multiple myeloma, with a focus on recent advances, newly diagnosed disease, role of transplantation and maintenance therapy. A synthesized approach to the treatment of myeloma is presented, along with a discussion of key paradigms that need to be challenged.