Coexistence of antithrombin deficiency and suspected inferior vena cava atresia in an adolescent and his mother - case report and clinical implications.

BACKGROUND: Antithrombin deficiency (ATD) is an autosomal dominant thrombophilia presenting with varying phenotypes. In pediatric patients with ATD, thrombosis typically develops during the neonatal period or adolescence. However, to date there are no consistent recommendations on the therapeutic management of children with ATD. Inferior vena cava atresia (IVCA) belongs to a range of congenital or acquired vena cava malformations and is described as an independent risk factor for thrombosis. The present case report explores two cases of combined ATD and IVCA in an adolescent and his mother. CASE PRESENTATION: A 14-year-old male presented with extensive deep venous thromboses (DVTs) of both lower extremities as well as an IVCA. The patient had previously been diagnosed with an asymptomatic ATD without therapeutic consequences at that time. His mother was suffering from an ATD and had herself just been diagnosed with IVCA, too. The DVTs in the adolescent were treated by systemic anticoagulation and catheter-directed local thrombolysis causing favourable results. Yet, despite adequate oral anticoagulation the DVTs in both lower extremities reoccurred within 1 week after the patient was discharged from hospital. This time, thrombolysis could not be fully achieved. Surprisingly, probing and stenting of the IVCA was achieved, indicating an acquired IVCA which could have occurred after undetected thrombosis in early childhood. Genetic analyses showed the same mutation causing ATD in both son and mother: heterozygote missense mutation c.248 T > C, p.(Leu83Pro), within the heparin binding domain of antithrombin. This mutation was never reported in mutation databases before. CONCLUSIONS: To our knowledge this is the first case report discussing combined ATD and IVCA in two family members. Since ATDs present with clinical heterogeneity, taking a thorough family history is crucial for the anticipation of possible complications in affected children and decisions on targeted diagnostics and therapeutic interventions. Affected families must be educated on risk factors and clinical signs of thrombosis and need an immediate diagnostic workup in case of clinical symptoms. IVCA in patients with ATD could occur due to thrombotic occlusion at a very early age. Therefore, in case of family members with IVCA and ATD ultrasound screening in newborns should be considered.

Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

Quantitative electroencephalography supports diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy.

Long-term treatment of multiple sclerosis with natalizumab (NTZ) carries the risk of a devastating complication in the form of an encephalopathy caused by a reactivation of a latent John Cunningham virus infection (progressive multifocal leucoencephalopathy, PML). Early diagnosis is associated with considerably better prognosis. Quantitative EEG as an objective, rater-independent technique provides high sensitivity (88%) and specificity (82%) for the diagnosis of NTZ-PML. Combination of diagnostic modalities addressing static morphological (brain MRI) as well as functional (EEG) pathologic changes may improve risk management programmes.

The Non-Langerhans Cell Histiocytoses (Rare Histiocytoses) - Clinical Aspects and Therapeutic Approaches.

Rare histiocytoses, also called non-Langerhans cell histiocytoses, include all proliferative disorders of histiocytes, macrophages and dendritic cells that are not classified as Langerhans cell histiocytosis (LCH) and do not belong to the hemophagocytic lymphohistiocytosis (HLH) group of diseases. Thus, the term includes numerous benign or malignant, localized or systemic, adult or pediatric diseases. The classification of the histiocytic disorders has been revised several times. Here, we follow the classification recently published by Jean Francois Emile and an international expert panel, defining subgroups of histiocytoses described as L-Group, C-Group, M-Group, R-Group, and H-Group, which stands for LCH-like, cutaneous or mucocutaneous, malignant, Rosai-Dorfman-Disease like and HLH like. Some of the diseases have an excellent prognosis after resection or even disappear spontanously, others progress rapidly, requiring intensive systemic therapies. The malignant non-Langerhans cell histiocytoses in general have a poor prognosis, here, complex chemotherapy protocols are usually applied, with inconsistant results. An interesting perspective in non-malignant rare histiocytoses might be small molecular inhibitors, in particular BRAF inhibitors, since BRAF mutations have been found in some subtypes of non-Langerhans cell histiocytoses. By prospective and retrospective collection of experiences in a new registry (the "International Rare Histiocytic Disorders Registry", IRHDR), knowledge about these rare diseases might hopefully be improved.

The German national registry for primary immunodeficiencies (PID).

In 2009, a federally funded clinical and research consortium (PID-NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID.

Group therapy for patients with psychogenic nonepileptic seizures: a pilot study.

Great advances have been made in the diagnosis of people with psychogenic nonepileptic seizures (PNES) since the advent of video/EEG monitoring. However, treatment options for this population have lagged significantly. This pilot study was undertaken to evaluate whether group therapy done with a psychodynamic focus would offer a useful intervention. Twelve patients entered the study and seven completed at least 75% of the 32 weekly sessions. The Beck Depression Inventory and the Global Severity Index of the Symptom Checklist-90 showed improvement as well as an overall decrease in PNES frequency. The data suggest that group therapy focusing on interpersonal issues may benefit patients with PNES.

Late response to radiochemotherapy in pediatric glioblastoma: report on two patients treated according to HIT-GBM protocols.

High-grade gliomas in children are rare and the best treatment is undetermined. The German language group study HIT-GBM compares various induction protocols for subsequent patient cohorts. Currently, cisplatinum, etoposide, ifosfamide, and vincristine are given simultaneously with extended-field radiotherapy. Imaging is done 3 weeks after to define treatment response, followed by 6-weekly controls during consolidation with lomustine, vincristine, and prednisone. The authors report on 2 patients with incompletely resected glioblastoma multiforme in which response was lacking 3 weeks after radiochemotherapy but became evident 12 weeks later. This suggests that later time points are required to assess induction protocol response.

Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.

BACKGROUND: Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control. METHODS: Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population. RESULTS: Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition. CONCLUSION: Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

Decreased sensitivity of drug-resistant cells towards T cell cytotoxicity.

Killing of target cells by cytotoxic T cells is mediated by induction of apoptosis requiring functional death pathways. Kill is mediated either by the CD95 or the perforin/granzyme pathway. We found that SH-EP neuroblastoma cells are preferentially killed via CD95, while in the T leukemia cell line CEM CD95 and perforin/granzyme are involved. In both types of cell lines, cells resistant to CD95- and drug-induced apoptosis are crossresistant to cytotoxic T cell kill. Resistant cells show decreased apoptosis and deficient activation of caspases indicated by decreased cleavage of the prototype caspase substrate PARP. Preincubation with the caspase inhibitor zVAD-fmk strongly decreased LAK cell kill in sensitive cells. Although parental CEM cells could be sensitized for LAK kill by preincubation with doxorubicin, resistance could not be reverted in doxorubicin or CD95 resistant CEM cells. These data demonstrate the crossresistance in induction of apoptosis by different cytotoxic regimens in tumor cells and may have implications for the immunotherapy of tumors in which apoptosis resistance was induced by previous chemotherapy.

Predictors of posttraumatic stress symptoms among survivors of the Oakland/Berkeley, Calif., firestorm.

OBJECTIVE: The purpose of this study was to examine factors predicting the development of posttraumatic stress symptoms after a traumatic event, the 1991 Oakland/Berkeley firestorm. The major predictive factors of interest were dissociative, anxiety, and loss of personal autonomy symptoms reported in the immediate aftermath of the fire; contact with the fire; and life stressors before and after the fire. METHOD: Subjects were recruited from several sources so that they would vary in their extent of contact with the fire. Of 187 participants who completed self-report measures about their experiences in the aftermath of the firestorm, 154 completed a follow-up assessment. Of these 154 subjects, 97% completed the follow-up questionnaires 7-9 months after the fire. The questionnaires included measures of posttraumatic stress and life events since the fire. RESULTS: Dissociative and loss of personal autonomy symptoms experienced in the fire's immediate aftermath, as well as stressful life experiences occurring later, significantly predicted posttraumatic stress symptoms measured 7-9 months after the firestorm by a civilian version of the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder and the Impact of Event Scale. Dissociative symptoms more strongly predicted posttraumatic symptoms than did anxiety and loss of personal autonomy symptoms. Intrusive thinking differs from other kinds of posttraumatic symptoms in being related directly to the trauma and previous stressful life events. CONCLUSIONS: These findings suggest that dissociative symptoms experienced in the immediate aftermath of a traumatic experience and subsequent stressful experiences are indicative of risk for the later development of posttraumatic stress symptoms. Such measures may be useful as screening procedures for identifying those most likely to need clinical care to help them work through their reactions to the traumatic event and to subsequent stressful experiences.

Acute stress disorder as a predictor of posttraumatic stress symptoms.

OBJECTIVE: Using the DSM-IV diagnostic criteria for acute stress disorder, the authors examined whether the acute psychological effects of being a bystander to violence involving mass shootings in an office building predicted later posttraumatic stress symptoms. METHOD: The participants in this study were 36 employees working in an office building where a gunman shot 14 persons (eight fatally). The acute stress symptoms were assessed within 8 days of the event, and posttraumatic stress symptoms of 32 employees were assessed 7 to 10 months later. RESULTS: According to the Stanford Acute Stress Reaction Questionnaire, 12 (33%) of the employees met criteria for the diagnosis of acute stress disorder. Acute stress symptoms were found to be an excellent predictor of the subjects' posttraumatic stress symptoms 7-10 months after the traumatic event. CONCLUSIONS: These results suggest not only that being a bystander to violence is highly stressful in the short run, but that acute stress reactions to such an event further predict later posttraumatic stress symptoms.

Long-term remission of APL with a second allogeneic BMT after CNS relapse following HLA-identical allogeneic BMT.

Second allogeneic bone marrow transplantation (BMT) for AML relapsing after an initial BMT has a poor prognosis, with a probability of a 2-y disease-free survival below 30 per cent, caused both by treatment-related mortality (TRM) and high relapse rate. While TRM is most likely due to heavy pretreatment, AML relapse after BMT may be due to resistant disease or to a poor graft-versus-leukaemia (GvL) effect of the transplant. The degree of GvL may depend on individual donor/recipient immunoreactivity. In most published cases of second allogeneic BMT, both transplants were performed from the same donor. Here, we describe a patient who was first transplanted for acute promyelocytic leukaemia (APL) (AML FAB M3v) from his HLA-identical brother and received intensive immunotherapy including donor lymphocytes and IL2. He remained free from GvHD >I degrees, but developed CNS relapse. After a second BMT from another HLA-identical brother, he spontaneously developed GvHD III degrees, and has now been disease free for nearly 3 years. In this patient, long-term remission of AML relapsing after BMT was achieved by combining remission induction using an individual chemotherapy protocol with a second BMT from an alternative matched related donor and transient GvHD III degrees, which probably conferred a GVL effect.

Successful HLA-identical bone marrow transplantation in a patient with PNP deficiency using busulfan and fludarabine for conditioning.

PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurological symptomatology including ataxia, developmental delay and spasticity. Patients usually die in the first or second decade of life due to recurrent infections. The only curative treatment is bone marrow transplantation (BMT). We describe a 22-month-old girl who underwent BMT from her HLA-identical brother. Conditioning consisted of busulfan and fludarabine only, resulting in low toxicity and prompt engraftment. At 18 months after BMT, the girl has developed normal immunological functions, and her neurological status has improved.

Coping styles associated with psychological adjustment to advanced breast cancer.

The aim of this study was to determine whether psychological adjustment to advanced breast cancer was positively associated with expressing emotion and adopting a fighting spirit and negatively associated with denial and fatalism. Total mood disturbance on the Profile of Mood States was used as the measure of psychological adjustment. The Courtauld Emotional Control Scale measured emotional expression, and the Mental Adjustment to Cancer measured fighting spirit, denial, and fatalism. The sample included 101 women with a diagnosis of metastatic or recurrent breast cancer. Fighting spirit and emotional expressiveness were found to be associated with better adjustment. No association was found between mood disturbance and denial or fatalism. Because this was a cross-sectional study, no conclusions regarding a causal relationship between adjustment and emotional expressiveness or adjustment and fighting spirit were possible.

Traumatic stress, life events, and emotional support in women with metastatic breast cancer: cancer-related traumatic stress symptoms associated with past and current stressors.

This study examined levels of intrusion and avoidance symptoms and their relationships to past life stress, current emotional support, disease-related variables, and age in 125 women with metastatic breast cancer. The results indicate that a sizable proportion of these women experienced clinically significant levels of intrusion and avoidance symptoms related to their cancer, particularly those with both more stressful past life events and higher current levels of aversive emotional support. Additionally, both types of symptoms were associated with shorter time since recurrence, and avoidance symptoms were associated with smaller emotional support networks. These results indicate that metastatic breast cancer is an emotionally traumatic event for a significant proportion of women, particularly those with past life stressors and unsupportive social environments.

Revictimization and information processing in women survivors of childhood sexual abuse.

This study examined the effect of sexual revictimization on information processing of trauma-related stimuli in a sample of child sexual abuse (CSA) survivors diagnosed with posttraumatic stress disorder (PTSD). Fifty-one treatment-seeking women participated in this study. Participants completed the Sexual Experiences Survey regarding sexual revictimization in the last 6 months and performed a modified emotional Stroop task in which they named the colors of neutral words (e.g., apple), general threat words (e.g., malignant and death), and sexual/victimization words (e.g., penis and abuser). As predicted, the revictimized participants (n = 16) took significantly longer to color-name sexual/victimization words than did the nonrevictimized participants. These results suggest that revictimization serves to prime preexisting "trauma" memory networks, thereby amplifying the impact of childhood sexual trauma on selective attention toward trauma-related stimuli.

Representations of self in women sexually abused in childhood.

OBJECTIVE: This exploratory study examined the self representations of 27 women sexually abused in childhood and their association with symptomatology. METHOD: Twenty-seven self-identified female survivors of childhood sexual abuse completed the Trauma Symptom Checklist-40, Beck Depression Inventory, State-Trait Anxiety Inventory and a measure designed to elicit subjects' self-generated descriptors of selves. RESULTS: Discrepancies in views of current self when compared to ideal or future selves were positively correlated with all symptom measures. Discrepancies in representations of current self compared to views of who they were when they were with their perpetrator were negatively correlated with trait anxiety. Self integration, as defined in this study, was negatively correlated with symptoms. CONCLUSIONS: This study suggests that cognitive representations of self are an important indicator of adjustment in survivors of childhood sexual abuse.

Trauma and dissociation.

The stress associated with experiencing or witnessing physical trauma can cause abrupt and marked alterations in mental state, including anxiety and transient dissociative symptoms. Intense manifestations of this pattern of response to trauma are described in a new diagnostic category proposed for DSM-IV: acute stress disorder. Severe dissociative symptoms may predict subsequent posttraumatic stress disorder. Persons who experience a series of traumatic events may be especially vulnerable to a variety of dissociative states, including amnesia, fugue, depersonalization, and multiple personality disorder. Treatment for these symptoms emphasizes strengthening supportive interpersonal relationships and developing insight that reduces psychological pain by integrating the trauma into a meaningful, less self-blaming perspective.

[Laparoscopic inguinal herniorrhaphy in children--experiences in a primary medical care center]. / Die laparoskopische herniorrhaphie des leistenbruches im kindesalter--erfahrungen in einem krankenhaus der grund--und regelversorgung.

AIM: Children undergoing laparoscopic herniorrhaphy may benefit from a minimally invasive access and the possible exploration of the contralateral groin. In this prospective feasibility study, the experiences and results after introduction of this method in a tertiary referral medical center are reported. METHODS: 50 laparoscopic herniorrhaphies were performed in 44 children (32 boys and 12 girls, range: 17 months-11 years) with open inner inguinal rings between January 2001 and March 2007. In 6 children (13.6 %) an additional contralateral open inner inguinal ring was detected. Laparoscopic access was obtained with a 5-mm laparoscope which was inserted transumbilically and two 2-mm needle holders were inserted through the inferolateral abdominal wall. The open inner inguinal rings were closed in 8 children using a resorbable Z-suture and in 36 children using a monofilamentous non-absorbable suture. Follow-up examinations included records of intra- and postoperative complications, recurrence rate and economic aspects. RESULTS: No intra- or perioperative complications occurred. Median operation time was 19 minutes. 43 / 44 operations were carried on an outpatient basis. Average material costs were about 20 Euro without any difference from the open access. During 36 months the follow-up rate was 91 %. Two children who had previously received an absorbable suture suffered from a recurring groin hernia within the first 6 months. CONCLUSION: Laparoscopic herniorrhaphy in children represents a safe and effective surgical method that can be recommended for tertiary referral medical centers with training facilities and experience in minimally invasive surgery.