Feasibility, safety, and efficacy of early prophylactic donor lymphocyte infusion after T cell-depleted allogeneic stem cell transplantation in acute leukemia patients.

Prophylactic donor lymphocyte infusion (DLI) starting at 6 months after T cell-depleted allogeneic stem cell transplantation (TCD-alloSCT) can introduce a graft-versus-leukemia (GvL) effects with low risk of severe graft-versus-host-disease (GvHD). We established a policy to apply low-dose early DLI at 3 months after alloSCT to prevent early relapse. This study analyzes this strategy retrospectively. Of 220 consecutive acute leukemia patients undergoing TCD-alloSCT, 83 were prospectively classified to have a high relapse risk and 43 were scheduled for early DLI. 95% of these patients received freshly harvested DLI within 2 weeks of the planned date. In patients transplanted with reduced intensity conditioning and an unrelated donor, we found an increased cumulative incidence of GvHD between 3 and 6 months after TCD-alloSCT for patients receiving DLI at 3 months compared to patients who did not receive this DLI (0.42 (95%Confidence Interval (95% CI): 0.14-0.70) vs 0). Treatment success was defined as being alive without relapse or need for systemic immunosuppressive GvHD treatment. The five-year treatment success in patients with acute lymphatic leukemia was comparable between high- and non-high-risk disease (0.55 (95% CI: 0.42-0.74) and 0.59 (95% CI: 0.42-0.84)). It remained lower in high-risk acute myeloid leukemia (AML) (0.29 (95% CI: 0.18-0.46)) than in non-high-risk AML (0.47 (95% CI: 0.42-0.84)) due to an increased relapse rate despite early DLI.

Under which conditions are changes in the treatment of people under involuntary commitment justified during the COVID-19 pandemic? An ethical evaluation of current developments in Germany.

The COVID-19 pandemic poses significant challenges in psychiatric hospitals, particularly in the context of the treatment of people under involuntary commitment. The question arises at various points in the procedure for and process of involuntary commitment whether procedural modifications or further restrictive measures are necessary to minimise the spread of COVID-19 and protect all people involved from infection. In the light of current developments in Germany, this article examines under which conditions changes in the treatment of people under involuntary commitment are ethically justified in view of the COVID-19 pandemic. Among others, we discuss ethical arguments for and against involuntary commitments with reference to COVID-19, the use of different coercive interventions, the introduction of video hearings, an increased use of video surveillance and interventions based on the German Infection Protection Act. We argue that strict hygiene concepts, the provision of sufficient personal protective equipment and frequent testing for COVID-19 should be the central strategies to ensure the best possible protection against infection. Any further restrictions of the liberty of people under involuntary commitment require a sound ethical justification based on the criteria of suitability, necessity and proportionality. A strict compliance with these criteria and the continued oversight by external and independent control mechanisms are important to prevent ethically unjustified restrictions and discrimination against people with the diagnosis of a mental disorder during the COVID-19 pandemic.

High incidence of (ultra)low oesophageal temperatures during cryoballoon pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Low oesophageal temperatures (OTs) during cryoballoon pulmonary vein isolation (PVI) have been associated with complications. This study assessed the incidence of low OT in clinical practice during cryoballoon PVI and verified possible predictive values for low OT. METHODS: Consecutive patients who underwent PVI using the second-generation cryoballoon were retrospectively included. The distance from the oesophagus to the different pulmonary veins (PVs) (OP distance), body mass index (BMI), sex, age, balloon temperature and application time were studied as potential predictors of low OTs. Computed tomography was performed before the procedure to determine the OP distance. OT was measured using an oesophageal temperature probe. Applications were ended prematurely if the OT reached <16 °C. Low and ultralow OT were defined as OT <20 and <16 °C respectively. RESULTS: Two hundred and four patients were included. Low OT was observed in 54 patients (26%) and 27 patients (13%) reached ultralow OTs. OP distance was the only predictor of low OTs after multivariate analysis. A cut-off value of 19 mm showed 96.2% sensitivity and 37.8% specificity in predicting low OTs. No clinically relevant relation was found between low OTs and BMI, age, sex, balloon temperature or application duration. CONCLUSIONS: The incidence of low OT was 26% for cryoballoon PVI. OP distance was the only predictor of low OTs. Since an OP distance <19 mm was present in all patients in at least one PV, we recommend routine OT measurement during PVI cryoballoon therapy to prevent oesophagus-related complications.

[An infant with vesicles on the arm]. / Een zuigeling met blaasjes op de arm.

A 9-month-old infant presentedwithvesicles on the arm in theeighthcervicaldermatomesinceseveraldays. PCR analysis of thefluid of thevesiclesrevealedthepresence of the varicella zoster virus (VZV). It turned out thatthe infant had been in contact withthis virus at theage of 5 months; bythenthechild was protectedbymaternal VZV-antibodies, whichprevented adequate development of immunityagainstthe virus. Therefore, herpes zoster coulddevelop a few months later.

To prescribe, or not to prescribe: decision making in HIV-1 post-exposure prophylaxis.

OBJECTIVES: We investigated the trend in usage of post-exposure prophylaxis (PEP) after HIV-1 risk exposure and evaluated PEP prescription decision making of physicians according to guidelines. METHODS: All PEP consultations from January 2014 to December 2016 in patients presenting at the University Hospital of Cologne (Germany) were retrospectively analysed. HIV risk contacts included sexual and occupational exposure. The European AIDS Clinical Society (EACS) Guidelines for HIV PEP (version 9.0, 2017) were used for assessment. RESULTS: A total of 649 patients presented at the emergency department (ED) or the clinic for infectious diseases (IDC) for PEP consultations. A continuous increase in the number of PEP requests was recorded: 189 in 2014, 208 in 2015 and 252 in 2016. PEP consultations in men who have sex with men (MSM) showed a remarkable increase in 2016 (2014, n = 96; 2015, n = 101; 2016, n = 152). Decisions taken by physicians with a specialization in infectious diseases (n = 547) included 61 (11%) guideline-discordant prescriptions [2014: 14% (n = 22); 2015: 9% (n = 16); 2016: 11% (n = 23)]. Among these, sexual exposure accounted for 45 (74%) cases, including 15 cases of nonconsensual sex, while occupational exposure accounted for 14 (23%) cases and other exposure two cases (3%). The main reason for guideline-discordant PEP prescriptions was emotional stress of the patient (n = 37/61). CONCLUSIONS: PEP prescriptions are increasing and decision making is influenced by patients' emotional stress, but PEP prescriptions should be strictly administered according to risk assessment.

Use of three-dimensional computed tomography overlay for real-time cryoballoon ablation in atrial fibrillation reduces radiation dose and contrast dye.

AIMS: Cryoballoon pulmonary vein (PV) isolation in patients with atrial fibrillation has proven to be effective in short-term and long-term follow-up. To visualise the PV anatomy, pre-ablation contrast pulmonary venography is commonly performed. Three-dimensional (3D) computed tomography (CT) overlay is a new technique creating a live 3D image of the left atrium by integrating a previously obtained CT scan during fluoroscopy. To evaluate the benefits of 3D CT overlay during cryoballoon ablation, we studied the use of 3D CT overlay versus contrast pulmonary venography in a randomised fashion in patients with paroxysmal atrial fibrillation undergoing cryoballoon PV isolation. METHODS AND RESULTS: Between October 2012 and June 2013, 30 patients accepted for PV isolation were randomised to cryoballoon PV isolation using either 3D CT overlay or contrast pulmonary venography. All patients underwent a pre-procedural cardiac CT for evaluation of the anatomy of the left atrium (LA) and the PVs. In the 3D CT overlay group, a 3D reconstruction of the LA and PVs was made. An overlay of the CT reconstruction was then projected over live fluoroscopy. Patients in the contrast pulmonary venography group received significantly more contrast agent (77.1 ± 21.2 cc vs 40.1 ± 17.6 cc, p < 0.001) and radiation (43.0 ± 21.9 Gy.cm2 vs 28.41 ± 11.7 Gy.cm2, p = 0.04) than subjects in the 3D CT overlay group. There was no difference in total procedure time, fluoroscopy time and the amount of cryoapplications between the two groups. CONCLUSION: The use of 3D CT overlay decreases radiation and contrast dye exposure and can assist in guiding cryoballoon-based PV isolation.

Optimization of home treatment in haemophilia: effects of transmural support by a haemophilia nurse on adherence and quality of life.

BACKGROUND: Transmural support by a haemophilia nurse may improve treatment and may empower parents and patients. AIM: To measure the effect of structured home visits by a haemophilia nurse in (parents of) patient on aspects of prophylactic home treatment. METHODS: A multicentre intervention study in two paediatric haemophilia treatment centres was performed. Primary outcome measures were: adherence to prescribed treatment, health-related quality of life and behavioural scores. Secondary outcome measures were: total clotting factor consumption, self-efficacy and number of joint bleeds. RESULTS: Over a period of 22 months (median, IQR 21-23), four to seven home visits in 46 patients (mean age 9.4 ± 4.2 years) were made. No difference in adherence to prescribed treatment was seen after the home visits when compared to baseline measurements. Both the Child Health Questionnaire (CHQ) scales on 'Role functioning - Emotional/Behavioural' (P = 0.02, d = 0.53) and 'Parental Time Impact' (P = 0.04, d = 0.33) were reduced after intervention. The disease-specific Haemo-QoL questionnaire showed improvement in domains: 'Family' (P = 0.04, d = -0.14), 'Friends' (P = 0.03, d = -0.29) and 'Perceived support' (P = 0.03, d = -0.37). Significant improvement was observed with regard to domain 'Communication' of the VERITAS-Pro scale (P = 0.03, d = -0.28). CONCLUSIONS: After a period of transmural care by a haemophilia nurse, significant but small positive effects were demonstrated with regard to communication and increase of perceived support between parents and haemophilia treatment centre. No improvement was observed in other outcome measures.

Prognostic pre-transplant factors in myelodysplastic syndromes primarily treated by high dose allogeneic hematopoietic stem cell transplantation: a retrospective study of the MDS subcommittee of the CMWP of the EBMT.

Many pre-transplant factors are known to influence the outcome of allogeneic stem cell transplantation (SCT) treatment in myelodysplastic syndromes (MDS). However, patient cohorts are often heterogeneous by disease stage and treatment modalities, which complicates interpretation of the results. This study aimed to obtain a homogeneous patient cohort by including only de novo MDS patients who received upfront allogeneic SCT after standard high dose myelo-ablative conditioning. The effect of pre-transplant factors such as age, disease stage, transfusions, iron parameters and comorbidity on overall survival (OS), non-relapse mortality (NRM), and relapse incidence (RI) was evaluated in 201 patients. In this cohort, characterized by low comorbidity and a short interval between diagnosis and transplantation, NRM was the most determinant factor for survival after SCT (47 % after 2-year follow-up). WHO classification and transfusion burden were the only modalities with a significant impact on overall survival after SCT. Estimated hazard ratios (HR) showed a strongly increased risk of death, NRM and RI, in patients with a high transfusion-burden (HR 1.99; P = 0.006, HR of 1.89; P = 0.03 and HR 2.67; P = 0.03). The HR's for ferritin level and comorbidity were not significantly increased.

Atypical polycystic ovary syndrome--a genetic analysis.

BACKGROUND/AIMS: Although polycystic ovary syndrome (PCOS) is a common endocrinopathy the pathogenesis is not entirely understood. Typically, high androgen levels are associated with increased virilization. We report 2 rare groups of patients with either unexpectedly high testosterone levels despite low virilization as well as patients with low testosterone levels despite high grade of virilization. One possibility for the atypical PCOS may be based on an altered androgen receptor (AR) signaling. METHODS: 6 patients and when available the parents were included in this study. Alterations of the metaphase chromosomes by GTG staining, the length of both the trinucleotide CAG- and GGC-repeats of the androgen receptor (AR) gene was determined by PCR, further the entire AR gene was sequenced and analyzed. RESULTS: The GTG banding revealed no chromosomal alterations and the range of CAG- and GGC-repeat lengths are within the normal range. Interestingly, by sequencing of the entire AR gene few genetic mutations were identified. CONCLUSION: The detected mutations do not alter the AR protein sequence but they change the codon usage towards less frequent codons that potentially may alter AR protein levels and androgen signaling. In addition to this, we postulate also other causes for manifestation of atypical PCOS, which may include AR-coregulators or epigenetic alterations. To our knowledge this is the first report of combining chromosomal analysis of PCOS patients with full sequencing of the human AR gene and linking codon usage to PCOS.

Prognostic value of microvolt T-wave alternans in a real-world ICD population. Twente ICD Cohort Studie (TICS).

INTRODUCTION: Survival benefit from ICD implantation is relatively low in primary prevention patients. Better patient selection is important to maintain maximum survival benefit while reducing the number of unnecessary implants. Microvolt T-wave alternans (MTWA) is a promising risk marker. In this study, we aimed to evaluate the predictive value of MTWA in ICD patients. METHODS AND RESULTS: This study was a substudy of the Twente ICD Cohort Study (TICS). Patients with ischaemic or non-ischaemic left ventricular dysfunction who received an ICD following current ESC guidelines were eligible for inclusion. Exercise-MTWA was performed and classified as non-negative or negative. The primary endpoint was the composite of mortality and appropriate shock therapy. Analysis was performed in 134 patients (81 % male, mean age 62 years, mean ejection fraction 26.5 %). MTWA was non-negative in 64 %. There was no relation between non-negative MTWA testing and mortality and/or appropriate shock therapy (all p-values >0.15). Due to clinical conditions, 24 % were ineligible for testing. These patients experienced the highest risk for mortality (p < 0.01). CONCLUSION: Non-negative MTWA testing did not predict mortality and/or appropriate shock therapy. Furthermore, MTWA testing is not feasible in a large percentage of patients. These ineligible patients experience the highest risk for mortality.

Optimisation of cardiac resynchronization therapy in clinical practice during exercise.

AIMS: Although cardiac resynchronisation therapy (CRT) is an established treatment to improve cardiac function, a significant amount of patients do not experience noticeable improvement in their cardiac function. Optimal timing of the delay between atrial and ventricular pacing pulses (AV delay) is of major importance for effective CRT treatment and this optimum may differ between resting and exercise conditions. In this study the feasibility of haemodynamic measurements by the non-invasive finger plethysmographic method (Nexfin) was used to optimise the AV delay during exercise. METHODS AND RESULTS: Thirty-one patients implanted with a CRT device in the last 4 years participated in the study. During rest and in exercise, stroke volume (SV) was measured using the Nexfin device for several AV delays. The optimal AV delay at rest and in exercise was determined using the least squares estimates (LSE) method. Optimisation created a clinically significant improvement in SV of 10 %. The relation between HR and the optimal AV delay was patient dependent. CONCLUSION: A potential increase in SV of 10 % can be achieved using Nexfin for optimisation of AV delay during exercise. A considerable number of patients showed benefit with lengthening of the AV delay during exercise.

[Variety of the radial forearm phalloplasty with respect to urethral construction - a review]. / Varianten des Radialispenoids im Hinblick auf die Harnröhrenkonstruktion- Übersichtsarbeit.

SUMMARY: The radial forearm flap is an established procedure for phalloplasty. 3 different methods concerning flap design and urethral construction are reported in the literature. METHODS: A literature review between the years 1993 and 2012 was performed. The purpose of the review was an analysis of the different techniques of the radial forearm flap with respect to urethral construction in forming a phallus in female to male transsexual patients. Urological and flap specific complications were assed and compared between the methods. RESULTS: 9 studies with 714 patients were included into the analysis. One stage procedures for phalloplasty were performed in the majority of cases in 665 patients (93%). Among these 530 patients (74.2%) received a Chang design phallic construction. A 2 stage procedure with a prelaminated urethra was conducted in 49 patients (7%) and reported in 3 studies. CONCLUSION: The results show a higher rate of urological complications for the technique with urethra prefabrication so far. However, this technique presents with a lower incidence of partial flap loss and smaller donor sites compared to the Chang design phalloplasty. No conclusions can be drawn for the Gottlieb design penile construction because only few and incomplete data are available in the literature.

Incidence and predictors of phantom shocks in implantable cardioverter defibrillator recipients.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are designed to deliver shocks or antitachycardia pacing (ATP) in the event of ventricular arrhythmias. During follow-up, some ICD recipients experience the sensation of ICD discharge in the absence of an actual discharge (phantom shock). The aim of this study was to evaluate the incidence and predictors of phantom shocks in ICD recipients. METHODS: Medical records of 629 consecutive patients with ischaemic or dilated cardiomyopathy and prior ICD implantation were studied. RESULTS: With a median follow-up of 35 months, phantom shocks were reported by 5.1 % of ICD recipients (5.7 % in the primary prevention group and 3.7 % for the secondary prevention group; p=NS). In the combined group of primary and secondary prevention, there were no significant predictors of the occurrence of phantom shocks. However, in the primary prevention group, phantom shocks were related to a history of atrial fibrillation (p=0.03) and NYHA class

The group medical appointment (GMA) in haemophilia and von Willebrand's disease: a new development in outpatient paediatric care.

The Group Medical Appointment (GMA) is a novel consultation form in which patients undergo individual consultations in each other's presence. To compare participants' experiences with GMA and Individual Medical Appointments (IMA), the usual standard of care, our team recently implemented the GMA for children aged 0-18 years with haemophilia or von Willebrand's disease. Participants' experiences with GMA were measured using a standardized QUOTE-questionnaire. Of 100 addressed families, 53 participated in GMA. Of these 53 families, 38 parents (72%) and 14 adolescents (82%) filled in the questionnaire about the GMA. Patients not on prophylaxis were defined as less experienced and patients on prophylaxis, as experienced. Although parents were satisfied with both GMA and IMA (median score 8.0 vs. 9.0 of 10), a significant difference was demonstrated between less experienced and experienced parents. After GMA, less experienced parents were significantly more satisfied (median score 8.0 vs. 5.0; P-value 0.006), felt more social support (82% vs. 30%; P-value 0.005) and reported additional learning effects with regard to disease and treatment (64% vs. 0%; P-value <0.001) than experienced parents. None of the less experienced parents reported privacy problems during GMA compared with 40% of experienced parents. In adolescents an identical trend was reported. Sixty-six per cent of parents would join a GMA in the future and 87% would recommend a GMA to others. The GMA is a valuable addition in haemophilia and von Willebrand care, especially for less experienced patients. It leads to improved satisfaction, social support and improved information.

Continuation of vitamin K antagonists as acceptable anticoagulation regimen in patients undergoing pulmonary vein isolation.

BACKGROUND: Recent studies have demonstrated that radiofrequency isolation of the pulmonary veins (PVI) is an effective treatment for symptomatic atrial fibrillation. Based on these positive results, non- pharmacological therapy has been incorporated in the guidelines for drug refractory atrial fibrillation, resulting in an increased popularity. The prevention of thromboembolic complications remains an important issue. METHODS: In January 2010, we adopted an anticoagulation strategy based on continuation of vitamin K antagonists (VKAs) and selective use of transoesophageal echocardiogram (TEE). We retrospectively analysed the results of this strategy in all patients referred for PVI treatment. VKAs were started for all patients 2 months prior to treatment. Discontinuation of oral anticoagulation was considered 3 months after treatment based on thromboembolic and bleeding risk profile. Bleeding and thromboembolic complications were registered during outpatient clinic follow-up up until 3 months. RESULTS: We performed 151 PVI procedures from January 2010 to March 2011. All patients were seen 6 weeks after discharge. No transient ischaemic accidents or ischaemic cerebrovascular incidents occurred pre-, peri- or postprocedure. Four (2.7%) procedures were complicated by tamponade requiring pericardiocentesis. CONCLUSIONS: Our data support the increasing evidence for continuation of periprocedural administration of VKAs complemented by a selective TEE approach as a safe therapy for thromboembolic complications.