Variable Clinical Courses of Varicella Zoster Virus Infection-related or Vaccination-related Bone Marrow Failure.

We report 5 children with bone marrow failure (BMF) after primary varicella zoster virus (VZV) infection or VZV vaccination, highlighting the highly variable course. Two patients were treated with intravenous immunoglobulins; one had a slow hematologic recovery, and the other was rescued by allogeneic hematopoietic stem cell transplantation (HSCT). Of the 2 patients treated with immunosuppressive therapy with antithymocyte globulin and cyclosporine, one had a complete response, and the other was transplanted for nonresponse. One patient underwent a primary allograft. All patients are alive. This study demonstrated that VZV-associated BMF is a life-threatening disorder that often requires HSCT.

"Collateral beauty." Experiences and needs of professionals caring for parents continuing pregnancy after a life-limiting prenatal diagnosis: A grounded theory study.

BACKGROUND: Caring for parents continuing pregnancy after learning about a severe life-limiting condition in their unborn is challenging. Most existing studies focus on affected families, whereas research on the subjective experience of care professionals is scarce. AIM: We aimed to (1) explore experiences and needs of involved care professionals, (2) obtain information about existing care structures, and (3) identify requirements for a structured perinatal palliative care program. DESIGN: Grounded Theory study using theoretical sampling. Data was collected by semi-structured interviews and analyzed following the principles of grounded theory coding and situational analysis. SETTING: A total of 18 professionals from 12 different services in Munich and surroundings participated in the study: 8 physicians, 3 midwives, 2 nurses, 1 each pregnancy counselor, grief counselor, chaplain, clinical psychologist, and undertaker. RESULTS: Several organizations provide support for affected parents, but inter-institutional communication is scarce. Due to the lack of a dedicated perinatal palliative care program, professionals make immense and partly unpaid efforts to support concerned parents. Providers experience "collateral beauty" in their work despite all the suffering and grief. This includes the development of a humble attitude and feelings of gratitude toward life, the feeling of having a meaningful task and professional as well as personal growth. Requirements for a structured perinatal palliative care program include: fostering peer support, ensuring regular supervision, and enhancing interdisciplinary exchange. CONCLUSIONS: Perinatal palliative care demands a high level of personal engagement but is experienced as highly rewarding by care professionals.

"More life and more days"-patient and care characteristics in a specialized acute pediatric palliative care inpatient unit.

Only a few acute hospital inpatient units dedicated to pediatric palliative care (PPC) patients exist today. Clinical data on the patients and care provided at specialized acute PPC inpatient units (PPCUs) are scarce. This study aims at describing patient and care characteristics on our PPCU to learn about the complexity and relevance of inpatient PPC. A retrospective chart analysis was performed on the 8-bed PPCU of the Center for Pediatric Palliative Care of the Munich University Hospital, including demographic, clinical, and treatment characteristics (487 consecutive cases; 201 individual patients; 2016-2020). Data were analyzed descriptively; the chi-square test was used for comparisons. Patients' age (1-35.5 years, median: 4.8 years) and length of stay (1-186 days, median 11 days) varied widely. Thirty-eight percent of patients were admitted repeatedly (range 2-20 times). Most patients suffered from neurological diseases (38%) or congenital abnormalities (34%); oncological diseases were rare (7%). Patients' predominant acute symptoms were dyspnea (61%), pain (54%), and gastrointestinal symptoms (46%). Twenty percent of patients suffered from > 6 acute symptoms, 30% had respiratory support incl. invasive ventilation, 71% had a feeding tube, and 40% had full resuscitation code. In 78% of cases, patients were discharged home; 11% died on the unit. CONCLUSION: This study shows the heterogeneity, high symptom burden, and medical complexity of the patients on the PPCU. The high dependency on life-sustaining medical technology points to the parallelism of life-prolonging and palliative treatments that is typical for PPC. Specialized PPCUs need to offer care at the intermediate care level in order to respond to the needs of patients and families. WHAT IS KNOWN: • Pediatric patients in outpatient PPC or hospices present with a variety of clinical syndromes and different levels of complexity and care intensity. • There are many children with life-limiting conditions (LLC) in hospitals, but specialized PPC hospital units for these patients are rare and poorly described. WHAT IS NEW: • Patients on a specialized PPC hospital unit show a high symptom burden and a high level of medical complexity, including dependency on medical technology and frequent full resuscitation code. • The PPC unit is mainly a place for pain and symptom management as well as crisis intervention, and needs to be able to offer treatment at the intermediate care level.

Visualizing social support in home pediatric palliative care using network maps.

BACKGROUND: Home care of children with life-limiting diseases is extremely challenging for parents/family caregivers and their social environment. In order to gain new insights into the perspective of family caregivers, we employed digital Network Maps for the first time in the field of pediatric palliative care. AIM: To examine whether the use of Network Maps helps to identify and visualize significant members of the social support system and the quality of the relationship, as well as the main areas of life that are experienced as being supportive by each individual. DESIGN: The design was an integrated mixed methods study. Creation of Network Maps was assessed in conjunction with qualitative interviews. In addition, participants gave an oral feedback on the Network Maps themselves. SETTING/PARTICIPANTS: Parents of patients supported by a Specialized Home Pediatric Palliative Care team were eligible for inclusion. Forty-five parents were enrolled in the study. RESULTS: All mothers and fathers were able to generate their individual Network Map without problems. The composition of the support systems differed greatly, even between members of the same family. Parents named on average 11 supporting actors, mainly family members and health care professionals. Some relationships were perceived as helpful and stressful at the same time. CONCLUSION: Network Maps appear to be an appropriate tool for the collection, reconstruction, and assessment of the current support situation of parents of dying children. Further studies should examine the usefulness of Network Maps for the understanding of the caregivers' support needs and for the development of psychosocial interventional strategies by pediatric palliative care teams.

Identifying key elements for paediatric advance care planning with parents, healthcare providers and stakeholders: A qualitative study.

BACKGROUND: Although international guidelines recommend discussions about goals of care and treatment options for children with severe and life-limiting conditions, there are still few structured models of paediatric advance care planning. AIM: The study aimed at identifying key components of paediatric advance care planning through direct discussions with all involved parties. DESIGN: The study had a qualitative design with a participatory approach. Participants constituted an advisory board and took part in two transdisciplinary workshops. Data were collected in discussion and dialogue groups and analysed using content analysis. SETTING/PARTICIPANTS: We included bereaved parents, health care providers and stakeholders of care networks. RESULTS: Key elements were discussions, documentation, implementation, timing and participation of children and adolescents. Parents engage in discussions with facilitators and persons of trust to reach a decision. Documentation constitutes the focus of professionals, who endorse brief recommendations for procedures in case of emergencies, supplemented by larger advance directives. Implementation hindrances include emotional barriers of stakeholders, disagreements between parents and professionals and difficulties with emergency services. Discussion timing should take into account parental readiness. The intervention should be repeated at regular intervals, considering emerging needs and increasing awareness of families over time. Involving children and adolescents in advance care planning remains a challenge. CONCLUSION: A paediatric advance care planning intervention should take into account potential pitfalls and barriers including issues related to timing, potential conflicts between parents and professionals, ambiguity towards written advance directives, the role of non-medical carers for paediatric advance care planning implementation, the need to involve the child and the necessity of an iterative process.

Allogeneic hematopoietic cell transplantation in Farber disease.

BACKGROUND: Farber disease (FD) is a rare, lysosomal storage disorder caused by deficient acid ceramidase activity. FD has long been considered a fatal disorder with death in the first three decades of life resulting either from respiratory insufficiency as a consequence of airway involvement or from progressive neurodegeneration because of nervous system involvement. Peripheral symptoms associated with FD, including inflammatory joint disease, have been described to improve relatively rapidly after hematopoietic cell transplantation (HCT). AIMS: To evaluate the disease-specific status and limitations in the long-term follow-up after HCT, investigate genotype/phenotype correlations and the benefit of allogeneic HCT in FD patients with nervous system involvement. PATIENTS AND METHODS: Transplant- and disease-related information of ten FD patients was obtained by using a questionnaire, physicians' letters and additional telephone surveys. ASAH1 gene mutations were identified to search for genotype/phenotype correlations. RESULTS: After mainly busulfan-based preparative regimens, all patients engrafted with one late graft loss. The inflammatory symptoms resolved completely in all patients. Abnormal neurologic findings were present pre-transplant in 4/10 patients, post-transplant in 6/10 patients. Mutational analyses revealed new mutations in the ASAH1 gene and a broad diversity of phenotypes without a genotype/phenotype correlation. With a median follow-up of 10.4 years, overall survival was 80% with two transplant-related deaths. CONCLUSION: Allogeneic HCT leads to complete and persistent resolution of the inflammatory aspects in FD patients. It appears to have no beneficial effect on progression of nervous system involvement. New mutations in the acid ceramidase gene were identified. A genotype/phenotype correlation could not be established.

Perinatal Palliative Care: A qualitative study evaluating the perspectives of pregnancy counselors.

BACKGROUND: A prenatal diagnosis of a life-limiting disease raises complex ethical, emotional, and medical issues. Studies suggest that 40%-85% of parents decide to continue the pregnancy if given the option of Perinatal Palliative Care. However, structured Perinatal Palliative Care programs are missing in many European countries. In Germany, parents have the right to free psychosocial support from pregnancy counseling services after the prenatal diagnosis of a life-limiting disease. AIM: We aimed to investigate whether German professional pregnancy counselors perceive the need for structured Perinatal Palliative Care and if so, how it should be conceived. DESIGN: This is a qualitative interview study with purposeful sampling. The interviews were analyzed with the coding method of Saldaña. SETTING/PARTICIPANTS: A total of 10 professionals from three different pregnancy counseling services participated in the study. RESULTS: The main topics raised by the professionals were as follows: (1) counseling and parental support during the decision-making process; (2) fragmented or missing support infrastructure for parents; and (3) challenges, hesitations, and barriers, particularly from the different stakeholders, regarding a Perinatal Palliative Care framework. They highlighted the importance of the integration of Perinatal Palliative Care in existing structures, a multi-professional approach, continuous coordination of care and education for all healthcare providers involved. CONCLUSION: A structured Perinatal Palliative Care program is considered as necessary by the pregnancy counselors. Future research should focus on (1) needs reported by concerned parents; (2) attitude and role of all healthcare providers involved; (3) strategies to include stakeholders in the development of Perinatal Palliative Care networks; and (4) outcome parameters for evaluation of Perinatal Palliative Care frameworks.

"Hope for the best, prepare for the worst": A qualitative interview study on parents' needs and fears in pediatric advance care planning.

BACKGROUND: Pediatric advance care planning is advocated by healthcare providers because it may increase the chance that patient and/or parent wishes are respected and thus improve end-of-life care. However, since end-of-life decisions for children are particularly difficult and charged with emotions, physicians are often afraid of addressing pediatric advance care planning. AIM: We aimed to investigate parents' views and needs regarding pediatric advance care planning. DESIGN: We performed a qualitative interview study with parents of children who had died from a severe illness. The interviews were analyzed by descriptive and evaluation coding according to Saldaña. SETTING/PARTICIPANTS: We conducted semi-structured interviews with 11 parents of 9 children. Maximum variation was sought regarding the child's illness, age at death, care setting, and parent gender. RESULTS: Parents find it difficult to engage in pediatric advance care planning but consider it important. They argue for a sensitive, individualized, and gradual approach. Hope and quality of life issues are primary. Parents have many non-medical concerns that they want to discuss. Written advance directives are considered less important, but medical emergency plans are viewed as necessary in particular cases. Continuity of care and information should be improved through regular pediatric advance care planning meetings with the various care providers. Parents emphasize the importance of a continuous contact person to facilitate pediatric advance care planning. CONCLUSION: Despite a need for pediatric advance care planning, it is perceived as challenging. Needs-adjusted content and process and continuity of communication should be a main focus in pediatric advance care planning. Future research should focus on strategies that facilitate parent engagement in pediatric advance care planning to increase the benefit for the families.

Medical indication regarding life-sustaining treatment for children: Focus groups with clinicians.

BACKGROUND: Decisions about medical indication are a relevant problem in pediatrics. Difficulties arise from the high prognostic uncertainty, the decisional incapacity of many children, the importance of the family, and conflicts with parents. The objectivity of judgments about medical indication has been questioned. Yet, little is known about the factors pediatricians actually include in their decisions. AIM: Our aims were to investigate which factors pediatricians apply in deciding about medical indication, and how they manage conflicts with parents. DESIGN: We performed a qualitative focus group study with experienced pediatricians. The transcripts were subjected to qualitative content analysis. SETTING/PARTICIPANTS: We conducted three focus groups with pediatricians from different specialties caring for severely ill children/adolescents. They discussed life-sustaining treatment in two case scenarios that varied according to diagnosis, age, and gender. RESULTS: The decisions about medical indication were based on considerations relating to the individual patient, to the family, and to other patients. Individual patient factors included clinical aspects and benefit-burden considerations. Physicians' individual views and feelings influenced their decision-making. Different factors were applied or weighed differently in the two cases. In case of conflict with parents, physicians preferred solutions aimed at establishing consensus. CONCLUSION: The pediatricians defined medical indication on a case-by-case basis and were influenced by emotional reasoning. In contrast to prevailing ethico-legal principles, they included the interests of other persons in their decisions. Decision-making strategies should incorporate explicit discussions of social aspects and physicians' feelings to improve the transparency of the decision-making process and reduce bias.

Listening to parents: The role of symptom perception in pediatric palliative home care.

OBJECTIVE: This study analyzes symptom perception by parents and healthcare professionals and the quality of symptom management in a pediatric palliative home care setting and identifies which factors contribute to a high quality of palliative and end-of-life care for children. METHODS: In this retrospective, cross-sectional study, parents were surveyed at the earliest three months after their child's death. All children were cared for by a specialized home pediatric palliative care team that provides a 24/7 medical on-call service. Questionnaires assessed symptom prevalence and intensity during the child's last month of life as perceived by parents, symptom perception, and treatment by medical staff. The responses were correlated with essential palliative care outcome measures (e.g., satisfaction with the care provided, quality-of-life of affected children and parents, and peacefulness of the dying phase). RESULTS: Thirty-eight parent dyads participated (return rate 84%; 35% oncological disorders). According to parental report, dyspnea (61%) and pain (58%) were the dominant symptoms with an overall high symptom load (83%). Pain, agitation, and seizures could be treated more successfully than other symptoms. Successful symptom perception was achieved in most cases and predicted the quality of symptom treatment (R 2, 0.612). Concordant assessment of symptom severity between parents and healthcare professionals (HCPs) improved the satisfaction with the care provided (p = 0.037) as well as the parental quality-of-life (p = 0.041). Even in cases with unsuccessful symptom control, parents were very satisfied with the SHPPC team's care (median 10; numeric rating scale 0-10) and rated the child's death as highly peaceful (median 9). Significance of the results: The quality and the concordance of symptom perception between parents and HCPs essentially influence parental quality-of-life as well as parental satisfaction and constitute a predictive factor for the quality of symptom treatment and palliative care.

Pediatric advance care planning from the perspective of health care professionals: a qualitative interview study.

BACKGROUND: Pediatric advance care planning differs from the adult setting in several aspects, including patients' diagnoses, minor age, and questionable capacity to consent. So far, research has largely neglected the professionals' perspective. AIM: We aimed to investigate the attitudes and needs of health care professionals with regard to pediatric advance care planning. DESIGN: This is a qualitative interview study with experts in pediatric end-of-life care. A qualitative content analysis was performed. SETTING/PARTICIPANTS: We conducted 17 semi-structured interviews with health care professionals caring for severely ill children/adolescents, from different professions, care settings, and institutions. RESULTS: Perceived problems with pediatric advance care planning relate to professionals' discomfort and uncertainty regarding end-of-life decisions and advance directives. Conflicts may arise between physicians and non-medical care providers because both avoid taking responsibility for treatment limitations according to a minor's advance directive. Nevertheless, pediatric advance care planning is perceived as helpful by providing an action plan for everyone and ensuring that patient/parent wishes are respected. Important requirements for pediatric advance care planning were identified as follows: repeated discussions and shared decision-making with the family, a qualified facilitator who ensures continuity throughout the whole process, multi-professional conferences, as well as professional education on advance care planning. CONCLUSION: Despite a perceived need for pediatric advance care planning, several barriers to its implementation were identified. The results remain to be verified in a larger cohort of health care professionals. Future research should focus on developing and testing strategies for overcoming the existing barriers.

Hematopoietic stem cell transplantation in children and young adults with secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia.

Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.9 years (range, 1.2 to 13.0 years). At a median age of 13.1 years (range, 4.4 to 26.7 years), patients underwent HSCT with bone marrow (n = 6) or peripheral blood stem cell (n = 11) grafts from HLA-matched sibling donors (n = 2), mismatched family donors (n = 2), or unrelated donors (n = 13). Monosomy 7 was detected in 13 patients. The preparative regimen consisted of busulfan, cyclophosphamide, and melphalan in 11 patients and other agents in 6 patients. All patients achieved neutrophil engraftment. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and that of chronic GVHD was 70%. Relapse occurred in 1 patient. The major cause of death was transplant-related complication (n = 9). Overall survival and event-free survival at 5 years after HSCT were both 41%. In summary, this study indicates that HSCT is a curative therapy for some patients with sMDS/sAML after aplastic anemia. Future efforts should focus on reducing transplantation-related mortality.

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood.

Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090).

Anti-leukaemic activity of a novel haploidentical-transplantation approach employing unmanipulated bone marrow followed by CD6-depleted peripheral blood stem cells in children with refractory/relapsed acute leukaemia.

The treatment outcome of children with refractory acute leukaemia or relapse post-stem cell transplantation is dismal. We report 10 children (non-remission n = 7) who underwent a new haploidentical transplant approach utilizing unmanipulated bone marrow followed by CD6-depleted peripheral blood stem cells. Nine patients had successful engraftment and no evidence of leukaemia. Acute and chronic graft-versus-host-disease was observed in five and three patients, respectively; two patients died of treatment-related toxicity. Seven patients relapsed after 7 (range 3-34) months, however two patients are alive at 6·5 and 7·0 years. This approach provides anti-leukaemic activity even in heavily pre-treated children but long-term disease control requires further intervention.

Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

BACKGROUND: Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. METHODS: In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. FINDINGS: Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. INTERPRETATION: Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. FUNDING: Gentium SpA, European Group for Blood and Marrow Transplantation.

Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria.

AIMS: To evaluate the reproducibility and reliability of the histomorphological criteria differentiating severe aplastic anaemia (SAA) and hypoplastic refractory cytopenia of childhood (RCC), the most frequently acquired hypocellular bone marrow conditions of childhood. METHODS AND RESULTS: We performed a double-blind interobserver study of 100 different cases of SAA and RCC among seven haematopathologists of the European Working Group of MDS in Childhood (EWOG-MDS) and the German SAA study. Cases with foci of typical myelodysplastic syndrome (MDS) morphology, such as patchy erythropoiesis with defective maturation, in an otherwise highly hypocellular or adipocytic bone marrow were classified as having RCC. Bone marrow samples without a patchy distribution, few scattered myeloid cells or haematopoietic aplasia were diagnosed as SAA. In only four of 100 cases did the reference pathologists not reach agreement regarding classification as SAA or RCC. The kappa index was 0.79. CONCLUSIONS: Our results show that the vast majority of SAA and RCC cases can be reliably differentiated by morphological means alone. A clear differentiation between SAA and RCC at presentation is mandatory for optimizing therapy strategies, and might be responsible for the fact that, in the German childhood SAA study, the probability of developing clonal disease after immunosuppressive therapy has dropped to 3%.

CD34+ gene expression profiling of individual children with very severe aplastic anemia indicates a pathogenic role of integrin receptors and the proapoptotic death ligand TRAIL.

UNLABELLED: BACKGROUND Very severe aplastic anemia is characterized by a hypoplastic bone marrow due to destruction of CD34(+) stem cells by autoreactive T cells. Investigation of the pathomechanism by patient-specific gene expression analysis of the attacked stem cells has previously been impractical because of the scarcity of these cells at diagnosis. DESIGN AND METHODS: Employing unbiased RNA amplification, patient-specific gene expression profiling was carried out for CD34(+) cells from patients newly diagnosed with very severe aplastic anemia (n=13), refractory anemia (n=8) and healthy controls (n=10). These data were compared to profiles of myelodysplastic disease (n=55), including refractory anemia (n=18). To identify possible targets of autoimmune attack, presence of autoreactive antibodies was tested in pre-therapeutic sera of patients with very severe aplastic anemia (n=19). RESULTS: CD34(+) gene expression profiling distinguished between healthy controls, children with aplastic or refractory anemia and clonal disease. Interferon stimulated genes such as the apoptosis inducing death ligand TRAIL were strongly up-regulated in CD34(+) cells of patients with aplastic anemia, in particular in patients responding to immunosuppressive treatment. In contrast, mRNA expression of integrin GPVI and the integrin complexes GPIa/IIa, GPIIb/IIIa, GPIB/GPIX/GPV was significantly down-regulated and corresponding antibodies were detected in 7 of 11 profiled patients and in 11 of 19 aplastic anemia patients. CONCLUSIONS As a potential diagnostic tool, patient-specific gene expression profiling of CD34(+) stem cells made it possible to make the difficult differential diagnosis of most patients with aplastic and refractory anemia. Profiling indicated a prognostic correlation of TRAIL expression and patient benefit from immunosuppressive therapy. Downregulation of integrin expression and concurrent presence of autoreactive anti-integrin-antibodies suggested a previously unrecognized pathological role of integrins in aplastic anemia.

The Path Is Made by Walking-Mapping the Healthcare Pathways of Parents Continuing Pregnancy after a Severe Life-Limiting Fetal Diagnosis: A Qualitative Interview Study.

In Germany, research on experiences and care pathways of parents continuing pregnancy after a life-limiting fetal diagnosis is scarce. There are several recommendations but few structured programs. We aimed to explore experiences and needs of parents, reconstruct their care pathways, and identify requirements for a perinatal palliative care program. We conducted semi-structured interviews with 11 mothers and 9 fathers and analyzed data using the Saldaña's Coding Method. Codes were organized in templates to reconstruct care pathways. Pathways started with a suspicious finding prompting a referral to prenatal diagnostics. Parents experienced severe emotional distress during prenatal diagnostics due to scarce information, insensitiveness, and a perceived pressure towards abortion. As a result, they overlooked referrals to psychosocial counseling, generating a care gap. Most parents reached the decision to continue pregnancy without professional support. They then chose a trusted midwife or gynecologist as main caregiver during pregnancy. There were no regular referrals to palliative care, which mainly became relevant when the child survived. Our data indicate that a perinatal palliative care program requires early and comprehensive information, sensitivity, and a non-directive approach. Already existing support services need to be identified and connected through structured pathways, with a particular focus on midwives.

How to Open the Door: A Qualitative, Observational Study on Initiating Advance Care Discussions with Parents in Pediatric Palliative Care.

Context: Advance care discussions (ACD) between health care professionals (HCPs) and parents of children with a life-limiting disease are a core element of successful pediatric advance care planning (pACP). Yet, they are perceived as a challenging situation for all participants. Objectives: Our goal was to investigate the first step of ACD and identify its challenges and helpful communication strategies to develop a conversation guide for initiating the pACP process and structure the conversational opening. Methods: We performed a participant observation of 11 initial ACD and 24 interviews with 13 HCPs and 20 parents of 11 children cared for by 3 different palliative care teams in southern Germany. Qualitative data collection was supplemented by a questionnaire. Content analysis and conversation analysis were used for evaluation. Results: Parents and HCPs start the process with different expectations, which can lead to misunderstandings and confusion. HCPs gain parental cooperation when they express the purpose of the meeting clearly and early, provide structure and guidance, and give parents time to talk about their experiences and feelings. Addressing dying and death is hard for both sides and requires a sensitive approach. Conclusions: Initiating ACD is extremely challenging for all participants. HCPs and parents should clarify expectations and aims at the beginning of the conversation. Future research should focus on how HCPs can be trained for this task and how the right timing for introducing ACD to families can be identified. Clinical Trial Registration number 049-12.

Participatory Development of a Modular Advance Care Planning Program in Pediatric Palliative Care (MAPPS).

CONTEXT: Decision-making in pediatric palliative care concerns mainly children without decision-making capacity. It has to balance the child's best interests, parental responsibility and the impact on the family system. OBJECTIVES: Advance care planning (ACP) supports decision making about future medical care. A consistent pediatric approach is still missing. This study aimed at developing a pediatric ACP program (pedACP) meeting specific needs of children, parents and professionals. METHODS: Bereaved parents of children with life-limiting conditions and professionals involved in pedACP participated. Employing the technique of constellation analysis, they collaboratively assigned content, actors, tools and warning notes about pedACP along a timeline. The researchers analyzed, systematized and translated these results into a pedACP program draft, which was revised by the participants. RESULTS: The participants' overall focus was on the children's quality of life and an individualized interdisciplinary communication process along the disease trajectory. The program was conceptualized in modular design with fixed modules at the beginning (to build a trustful relationship and frame the process) and at the end (to summarize results and prepare implementation). The main discussions are structured in flexible modules (About the child, Emergencies, Disease-specific scenarios and End of life care). General themes cover timing, communication, engaging children and structural issues. The participants appreciated the program's comprehensiveness and flexibility. CONCLUSION: Parents and professionals combined their perspectives on reflecting goals of care and the complexity of pedACP. They perceived the resulting modular program as suitable for meeting the individual needs of patients, families and professional stakeholders.