Risk of skin cancer and other malignancies in kidney,liver, heart and lung transplant recipients 1970 to 2008—A Swedish population‐based study

Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population‐based studies have quantified and compared cancer risks according to graft type and with long‐term follow‐up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow‐up of 93,432 person‐years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIR_{cancer excl SCC} 2.4 (95% CI, 2.2–2.5); SIR_SCC 121 (95% CI, 116–127). Cancer risks were most increased among heart and/or lung recipients SIR_{cancer excl SCC} 3.3 (95% CI, 2.8–4.0); SIR_SCC 198 (95% CI, 174–224), followed by kidney SIR_{cancer excl SCC} 2.3 (95% CI, 2.1–2.4); SIR_SCC 121 (95% CI, 116–127) and liver recipients SIR_{cancer excl SCC} 2.3 (95% CI, 1.9–2.8); SIR_SCC 32 (95% CI, 24–42). During follow‐up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post‐transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.     

Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR)

Background

Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance.

Methods

Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009–2018) were retrospectively analyzed.

Results

Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively.

Conclusion

Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.     

Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation

m-TOR inhibitors (e.g. sirolimus) are well-tolerated immunosuppressants used in renal transplantation for prophylaxis of organ rejection, and are associated with long-term graft survival. Early use of sirolimus is often advocated by clinicians, but this may be associated with a number of side-effects including impaired wound-healing, lymphoceles and delayed graft function. As transplant clinicians with experience in the use of sirolimus, we believe such side-effects can be limited by tailored clinical management. We present recommendations based on published literature and our clinical experience. Furthermore, guidance is provided on sirolimus use during surgery, both at transplantation and for subsequent operations.     

Methodological considerations for linked blood donor‐component‐recipient analyses in transfusion medicine research

In recent years, there has been a concerted effort to improve our understanding of the quality and effectiveness of transfused blood components. The expanding use of large datasets built from electronic health records allows the investigation of potential benefits or adverse outcomes associated with transfusion therapy. Together with information regarding blood donor demographics and component collection and manufacturing, these datasets permit evaluation of associations between donor or component factors and transfusion recipient outcomes. Large linked 'vein‐to‐vein' datasets provide the power to study exposures relevant to transfusion efficacy and safety, many of which would not otherwise be amenable to study for practical or sample size reasons. Analyses of these large donor‐component‐recipient datasets allow for characterization of the populations under study and provide an evidence base for future clinical studies. Knowledge generated from linked analyses has the potential to change the way donors are selected and how components are processed, stored and allocated. However, unrecognized confounding and biased statistical methods continue to be limitations in the study of transfusion exposures and patient outcomes. Given these challenges, results of observational studies of blood donor demographics, storage age and transfusion practice have been conflicting. This review summarizes statistical and methodological challenges in analyses of linked blood donor, component and transfusion recipient outcomes.     

Antibody prevalence and titer to norovirus (genogroup II) correlate with secretor (FUT2) but not with ABO phenotype or Lewis (FUT3) genotype

BACKGROUND: Histo-blood group antigens and secretor status have been associated with susceptibility to Norovirus infections, which suggests that antibody prevalence and titer might correlate with these phenotypes. METHODS: Plasma samples (n = 105) from Swedish blood donors that had been genotyped for secretor (FUT2) and Lewis (Le; FUT3) genotypes and phenotyped for ABO and Le blood groups were analyzed for immunoglobulin G antibody prevalence and titers to norovirus genogroup (GG) II.4. RESULTS: The results showed that nonsecretors (se4128se428) and Lea+b- individuals not only had significantly lower antibody titers than did secretors (P < .0001) and Lea-b+ individuals (P < .0002) but were also significantly more often antibody negative (P < .05). Antibody titers in secretors were not significantly different between individuals of different Le (FUT3) genotypes or different ABO phenotypes. CONCLUSIONS: Nonsecretors and Lea+b- individuals are significantly less prone to be infected with GGII noroviruses. This new information extends previous knowledge and supports the hypothesis that nonsecretors are relatively but not absolutely resistant to norovirus infections.     

Aminooxyacetic acid induced accumulation of GABA in the rat brain

The effect of aminooxyacetic acid (AOAA, 90 mg/kg i.v.) on bicuculline, picrotoxin and 3-mercaptopropionic acid (3-MPA) induced convulsions and on GABA concentrations in cerebellum, whole brain and a synaptosomal fraction of whole brain was investigated. At various intervals after AOAA the rats were either injected with one of the convulsive drugs or sacrificed for analysis of the GABA concentration. AOAA caused a rapid initial (0-30 min) and a later slower increase of GABA in cerebellum and whole brain. In the synaptosomal fraction the GABA accumulation was delayed and less pronounced when compared to the whole brain. The bicuculline induced convulsions were markedly potentiated during the first hour but completely blocked from 2-6 h after AOAA. Picrotoxin showed a somewhat different pattern to bicuculline in the interactions with AOAA. The initial strong potentiation was not observed but the later phase of protection was present. In the interactions with 3-MPA, the effect of AOAA was always protective. The time to onset of convulsions was gradually increased during the first 30 min after AOAA. This protective effect remained practically unchanged up to 6 h after AOAA. However, once started, the convulsions were generally of the same duration and intensity. The results can be interpreted as GABA accumulating after AOAA stimulates GABA receptors to a degree more or less proportional to the whole brain GABA concentration and further that GABA synthetized in neurons is liberated, stimulates inhibitory bicuculline sensitive (predominant) and excitatory bicuculline insensitive receptors and is captured to a large extent by non-neuronal cells.     

PAIN VARIATIONS DURING CANCER TREATMENT IN CHILDREN: A Descriptive Survey

Structured interviews were conducted with 66 children and their families to investigate how the experience of pain varied during cancer treatment. At diagnosis, 49% experienced cancer-related pain. Intense pain was more common at the beginning of treatment when it was often believed that pain treatment could be better. Procedure- and treatment-related pain were the major problems initially. Procedural pain gradually decreased, but treatment-related pain was constant and dominating. For some procedures pain was rated highest initially, lower during the second period, and higher again during the final part of treatment. Pain intensity measurement was seldom performed, and parents increasingly considered themselves better judges of their child's pain than professionals. Increased knowledge about pain and pain treatment in children with cancer, where most pain is iatrogenic, will help us to meet the needs and demands of children and parents, and to reduce pain to a minimum.