Preliminary study of elastic-tension digital neoprene orthoses for proximal interphalangeal joint flexion contracture.

Flexion contracture of the proximal interphalangeal joint (PIPJ) is one of the most frequent complications in finger trauma. Orthoses are the most widely used method to optimize total end-range time (TERT). No previous studies showed that an elastic tension orthosis could be applied for longer than 12 h. We aimed to demonstrate that the elastic-tension digital neoprene orthosis (ETDNO) can achieve higher TERT and therefore better range of motion than other elastic-tension orthoses (ETO) described in the literature. A prospective study of treatment of PIPJ flexion contracture included 10 PIP joints in 8 patients who met the selection criteria. They were instructed to use the ETDNO for around 23 h per day as far as possible, during a period of 3 weeks. Patients reported a mean TERT of 20.6 h a day. PIPJ contracture improved by a mean Torque Range of Motion (TROM) of 23.5° at 500 g and 22.9° at 800 g of passive extension force during the 3-week treatment. Based on the results of this study, the ETDNO appears to offer a highly effective approach for improving PIPJ flexion contracture, increasing range of motion in extension. ETDNO's efficacy probably lies in the significantly improved comfort and low-profile design, enabling excellent compliance and thus optimizing TERT. LEVEL OF EVIDENCE: Level III.

The earliest known reported occurrence of dentigerous cyst in a six-month-old child.

The earliest reported case of the occurrence of a dentigerous cyst is described; the cyst surrounded an unerupted permanent tooth bud in a 6-month-old infant. Most commonly these lesions present between the second and third decades of life. They rarely occur before 10 years of age and have not been documented prior to 1 year of age. In the case reported here, the treatment instituted was extraction of the adjacent deciduous tooth and enucleation of the cyst along with the permanent molar tooth bud. Clinicians should be aware of the potential for this lesion to occur across a wide range of ages and the importance of prompt diagnosis and treatment to prevent complications and reduce morbidity.

[Group Training of Patients with Chronic Lung Diseases under Outpatient Conditions - Recommendations of the Working Group Lung Sports in Germany and the German Airways League]. / Ambulanter Lungensport und körperliches Training bei Patienten mit Atemwegs- und Lungenkrankheiten.

To improve acceptance and use of physical training by patients with chronic lung diseases, recommendations for performing lung exercises on an outpatient basis in a group setting are given by experts in physical training, sports therapists and pulmonologists. The evidence-based positive effects of physical training were analyzed for asthma , COPD, interstitial lung diseases, cystic fibrosis, lung carcinoma, and pulmonary hypertension. The requirements for lung exercises in outpatient groups as well as compensation by care providers were given on the basis of legal regulations. Furthermore, the main items of the training units as well as supervision by specially trained group leaders in relation to the severity of the underlying lung disease are described. Finally, aspects of safety of the participating patients are discussed, including the prevention of infection with corona-2-virus.

[Recommendations from the German Respiratory Society for Pulmonary Rehabilitation in Patients with COVID-19]. / DGP-Empfehlungen zur pneumologischen Rehabilitation bei COVID-19.

The German Respiratory Society (DGP) has commissioned Assembly 12 "Rehabilitation, Prevention and Tobacco Control" to develop recommendations for the implementation of pulmonary rehabilitation in COVID-19 patients. This position paper is based on the current state of knowledge, which develops daily. This position paper describes the health consequences in COVID-19 as well as the indications for pulmonary rehabilitation. Rehabilitative therapies in COVID-19 are already indicated on the ward or intensive care unit, continue as early pulmonary rehabilitation in the acute hospital and as pulmonary rehabilitation in pulmonary rehabilitation centers. The main focus of this position paper is to propose recommendations for the content-related implementation of a multimodal, interdisciplinary pulmonary rehabilitation in COVID-19 patients.

Complexity of gap junctions between horizontal cells of the carp retina.

In the vertebrate retina, horizontal cells (HCs) reveal homologous coupling by gap junctions (gj), which are thought to consist of different connexins (Cx). However, recent studies in mouse, rabbit and zebrafish retina indicate that individual HCs express more than one connexin. To provide further insights into the composition of gj connecting HCs and to determine whether HCs express multiple connexins, we examined the molecular identity and distribution of gj between HCs of the carp retina. We have cloned four carp connexins designated Cx49.5, Cx55.5, Cx52.6 and Cx53.8 with a close relationship to connexins previously reported in HCs of mouse, rabbit and zebrafish, respectively. Using in situ hybridization, Cx49.5 expression was detected in different subpopulations of retinal neurons including HCs, whereas the Cx52.6 transcript was localized exclusively in HCs. Using specific antibodies, Cx55.5 and Cx53.8 were detected on dendrites of all four HC subtypes and axon terminals. Immunoelectron microscopy confirmed the presence of Cx55.5 and Cx53.8 in gap junctions between these processes and Cx55.5 was additionally observed in HC dendrites invaginating cone pedicles, suggesting its participation in the modulation of photoreceptor output in the carp retina. Furthermore, using single-cell RT-PCR, all four connexins were detected in different subtypes of HCs, suggesting overlapping expression patterns. Thus, the composition of gj mediating homologous coupling between subtypes of carp HCs appears to be more complex than expected. Moreover, BLAST searches of the preliminary carp genome, using novel sequences as query, suggest that most of the analyzed connexin genes are duplicated in carp.

Influence of Xe and Kr impurities on x-ray yield from debris-free plasma x-ray sources with an Ar supersonic gas jet irradiated by femtosecond near-infrared-wavelength laser pulses.

Many aspects of physical phenomena occurring when an intense laser pulse with subpicosecond duration and an intensity of 10^{18}-10^{19}W/cm^{2} heats an underdense plasma in a supersonic clustered gas jet are studied to determine the relative contribution of thermal and nonthermal processes to soft- and hard-x-ray emission from debris-free plasmas. Experiments were performed at the University of Nevada, Reno (UNR) Leopard laser operated with a 15-J, 350-fs pulse and different pulse contrasts (10^{7} or 10^{5}). The supersonic linear (elongated) nozzle generated Xe cluster-monomer gas jets as well as jets with Kr-Ar or Xe-Kr-Ar mixtures with densities of 10^{18}-10^{19}cm^{-3}. Prior to laser heating experiments, all jets were probed with optical interferometry and Rayleigh scattering to measure jet density and cluster distribution parameters. The supersonic linear jet provides the capability to study the anisotropy of x-ray yield from laser plasma and also laser beam self-focusing in plasma, which leads to efficient x-ray generation. Plasma diagnostics included x-ray diodes, pinhole cameras, and spectrometers. Jet signatures of x-ray emission from pure Xe gas, as well as from a mixture with Ar and Kr, was found to be very different. The most intense x-ray emission in the 1-9 KeV spectral region was observed from gas mixtures rather than pure Xe. Also, this x-ray emission was strongly anisotropic with respect to the direction of laser beam polarization. Non-local thermodynamic equilibrium (Non-LTE) models have been implemented to analyze the x-ray spectra to determine the plasma temperature and election density. Evidence of electron beam generation in the supersonic jet plasma was found. The influence of the subpicosecond laser pulse contrast (a ratio between the laser peak intensity and pedestal pulse intensity) on the jets' x-ray emission characteristics is discussed. Surprisingly, it was found that the x-ray yield was not sensitive to the prepulse contrast ratio.

Functional hyposplenism after hematopoietic stem cell transplantation.

Functional hyposplenism is associated with chronic GvHD (cGvHD) following hematopoietic stem cell transplantation (HSCT). We hypothesized that hyposplenism measured by pitted red cell counts in cGvHD was transient and related to the severity of disease. We performed a serial, retrospective review of 36 pediatric post-HSCT patients' pit counts at BC Children's Hospital from 2005 to 2013 and compared those counts with the clinical course of patients with late acute GvHD (aGvHD)/cGvHD. Of the 36 patients, 22 had late aGvHD/cGvHD based on National Institutes of Health consensus criteria. Fourteen of 22 GvHD patients had an abnormal pitted red cell count. Ten of 14 abnormal patients had late acute or overlap GvHD syndrome, primarily gastrointestinal disease. A second cohort was prospectively evaluated in a multicenter adult HSCT biomarker trial. We identified 3 out of 10 control patients who had an abnormal pitted red cell count, 3 out of 10 with classic cGvHD and 5 out of 9 patients with overlap syndrome were abnormal. In both the retrospective and prospective studies, hyposplenism was present in patients without late aGvHD/cGvHD suggesting current guidelines regarding antibiotic prophylaxis against encapsulated bacteria after HSCT need to be re-addressed and abnormal pit counts could be used to guide prophylaxis in all HSCT patients.

Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested?

We previously showed that minimal residual disease (MRD) detection pre-hematopoietic cell transplant (HCT) and acute GvHD (aGvHD) independently predicted risk of relapse in pediatric ALL. In this study we further define risk by assessing timing of relapse and the effects of leukemia risk category and post-HCT MRD. By multivariate analysis, pre-HCT MRD <0.1% and aGvHD by day +55 were associated with decreased relapse and improved event-free survival (EFS). Intermediate leukemia risk status predicted decreased relapse, and improved EFS and overall survival (OS). Patients with pre-HCT MRD ⩾0.1% who did not develop aGvHD compared with those with MRD <0.1% who did develop aGvHD had much worse survival (2 years EFS 18% vs 71%; P=0.001, 2 years OS 46 vs 74%; P=0.04). Patients with pre-HCT MRD <0.1% who did not experience aGvHD had higher rates of relapse than those who did develop aGvHD (40% vs 13%; P= 0.008). Post-HCT MRD led to a substantial increase in relapse risk (HR=4.5, P<0.01). Patients at high risk of relapse can be defined after transplant using leukemia risk category, presence of MRD pre or post HCT, and occurrence of aGvHD. An optimal window to initiate intervention to prevent relapse occurs between day +55 and +200 after HCT.

Results in using the Freiburger monosyllabic speech test in noise without and with hearing aids.

The Freiburger Speech Test (FST) has been the gold standard in speech testing by word recognition score in Germany for many years. Recently, it has been demonstrated that for an amount of 104 test-persons there is no significant deviation within the lists. The objective of this study was to determine the percentiles of the distinct measuring situations in quiet and with noise (e.g. applied in hearing aid fitting) and the average benefit using hearing aids. In this prospective study, 623 patients with SNHL and equipped with hearing aids for at least 3 months have been investigated by means of the Freiburger monosyllabic test (FBE) without and with hearing aids and in quiet or with noise (CCITT noise, 65/60 dB signal-noise ratio) in free field conditions at 65 dB to determine the ratio of intelligibility. To investigate the different diagnostic conditions a linear mixed model was applied. The dependent binary variable corresponds to the number of understood syllables. The average age of all subjects was about 72.6 years. The average rate of understanding in the FBE without hearing aids and in quiet was 38.5 %, with hearing aids and in quiet 67.7 %, without hearing aids and with noise 22.4 %, and with hearing aids and with noise 39.8 %. All results were presented with the depending confidence intervals. The extent of hearing loss and the quality of hearing aid fitting can be successfully measured using the FST in quiet and with background noise (CCITT noise). In quiet, an average hearing improving gain of 29.2 % points and with noise a gain of 17.4 % points could be estimated with a successful hearing aid fitting.

New frontiers in pediatric Allo-SCT: novel approaches for children and adolescents with ALL.

Although most children with ALL can be cured by chemotherapy approaches, allogeneic hematopoietic cell transplant (HCT) therapy offers a better chance of cure to selected high-risk patients in first remission and most children who relapse. Although transplant-related mortality has decreased significantly in the past decade, relapse remains high after HCT for ALL; developing strategies to decrease relapse and improve survival are vital. Recent studies have shown that relapse risk can be accurately defined using measurements of minimal residual disease (MRD) both pre- and post-HCT and by knowing whether patients get GVHD in the first 2 months after transplant. With these risk definitions in hand, investigators are now applying novel agents and immunotherapeutic methods in attempt to lower MRD before transplant and modulate the GVL effect after transplant. With powerful new immunological approaches coming on line, the transplant process itself will likely expand to include pre and/or post-HCT interventions aimed at reducing relapse.

Vascular communications between donor and recipient tissues after successful full face transplantation.

The vascular reorganization after facial transplantation has important implications on future surgical planning. The purpose of this study was to evaluate blood flow (BF) after full face transplantation using wide area-detector computed tomography (CT) techniques. Three subjects with severe craniofacial injury who underwent full face transplantation were included. All subjects underwent a single anastomosis bilaterally of the artery and vein, and the recipient tongue was preserved. Before and after surgery, dynamic volume CT studies were analyzed for vascular anatomy and blood perfusion. Postsurgical CT showed extensive vascular reorganization for external carotid artery (ECA) angiosome; collateral flows from vertebral, ascending pharyngeal or maxillary arteries supplied the branches from the recipient ECAs distal to the ligation. While allograft tissue was slightly less perfused when the facial artery was the only donor artery when compared to an ECA-ECA anastomosis (4.4 ± 0.4% vs. 5.7 ± 0.7%), allograft perfusion was higher than the recipient normal neck tissue. BF for the recipient tongue was maintained from contralateral/donor arteries when the lingual artery was sacrificed. Venous drainage was adequate for all subjects, even when the recipient internal jugular vein was anastomosed in end-to-end fashion on one side. In conclusion, dynamic CT identified adequate BF for facial allografts via extensive vascular reorganization.

[Smoking cessation in patients with COPD]. / Tabakentwöhnung bei COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Cigarette smoking is the main cause of COPD. Quitting smoking is thus the most effective treatment strategy and central in COPD prevention. A number of guidelines on prevention, diagnosis, therapy and rehabilitation of COPD have been published. To help implementing and standardizing smoking cessation in COPD a guideline was published 2008 in Germany focusing on this complex issue. The present guideline is an update of the 2008 guideline and has a high grade of evidence (S3 according to the AWMF; Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften). The guideline gives comprehensive and practical information on how to integrate smoking cessation as an central part of COPD therapy.

Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031.

We previously reported preliminary findings that post induction imatinib mesylate (340 mg/m(2)/day), in combination with intensive chemotherapy, resulted in outcomes similar to blood and marrow transplant (BMT) for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1-21 years) with and without allogeneic BMT (N=91). We explore the impacts of additional chromosomal abnormalities and minimal residual disease (MRD) by flow cytometry on outcomes. The 5-year disease-free survival was similar for Cohort 5 patients, treated with chemotherapy plus imatinib (70%±12%, n=28), sibling donor BMT patients (65%±11%, n=21) and unrelated donor BMT patients (59±15%; P=0.60, n=13). Patients with additional cytogenetic abnormalities had worse outcomes (P=0.05). End induction (pre-imatinib) MRD was not prognostic for Cohort 5 or allogeneic BMT patients, although limited by small numbers. The re-induction rate following relapse was similar to other higher-risk ALL groups. Longer-term follow-up confirms our initial observation of substantially good outcomes for children and adolescents with Ph+ ALL treated with imatinib plus intensive chemotherapy with no advantage for allogeneic BMT.

Relationship between pediatric blood and marrow transplant center volume and day +100 mortality: Pediatric Blood and Marrow Transplant Consortium experience.

The number of patients receiving a BMT is currently being used as a factor in the accreditation process in determining whether a center can provide a high-quality BMT. Such criteria particularly impact pediatric BMT centers as most of them perform a relatively small number of BMTs. To determine whether patient volume is a valid marker of pediatric BMT center's capabilities, the Pediatric Blood and Marrow Transplant Consortium (PBMTC) evaluated data from its registry to define the relationship between a pediatric transplant center's patient volume and day +100 mortality. The analyses evaluated 2575 transplants from 60 centers reporting to the PBMTC between the years 2002 and 2004. The volume-outcome relationship was evaluated while adjusting for 46 independent data categories divided between nine variables that were known- or suspected-mortality risk factors. We found no association between transplant center volume and day +100 mortality in several analyses. A calculated intraclass correlation coefficient also indicated that differences in individual transplant center volume contributed to only 1% of the variance in day +100 mortality within the PBMTC. The results of this study suggest that factors other than transplant center volume contribute to variation in day +100 mortality among pediatric patients.

NBN phosphorylation regulates the accumulation of MRN and ATM at sites of DNA double-strand breaks.

In response to ionizing radiation, the MRE11/RAD50/NBN complex re-distributes to the sites of DNA double-strand breaks (DSBs) where each of its individual components is phosphorylated by the serine-threonine kinase, ATM. ATM phosphorylation of NBN is required for the activation of the S-phase checkpoint, but the mechanism whereby these phosphorylation events signal the checkpoint machinery remains unexplained. Here, we describe the use of direct protein transduction of the homing endonuclease, I-PpoI, into human cells to generate site-specific DSBs. Direct transduction of I-PpoI protein results in rapid accumulation and turnover of the endonuclease in live cells, facilitating comparisons across multiple cell lines. We demonstrate the utility of this system by introducing I-PpoI into isogenic cell lines carrying mutations at the ATM phosphorylation sites in NBN and assaying the effects of these mutations on the spatial distribution and temporal accumulation of NBN and ATM at DSBs by chromatin immunoprecipitation, as well as timing and extent of DSB repair. Although the spatial distribution of NBN and ATM recruited to the sites of DSBs was comparable between control cells and those expressing phosphorylation mutants of NBN, the timing of accumulation of NBN and ATM was altered. Serine-to-alanine mutations that blocked phosphorylation resulted in delayed recruitment of both NBN and ATM to DSBs. Serine-to-glutamic acid substitutions that mimicked the phosphorylation event resulted in both increased and prolonged accumulation of both NBN and ATM at DSBs. The repair of DSBs in cells lacking full-length NBN was significantly delayed compared with control cells, whereas blocking phosphorylation of NBN resulted in a more modest delay in repair. These data indicate that following the induction of DSBs, phosphorylation of NBN regulates its accumulation, and that of ATM, at sites of DNA DSB as well as the timing of the repair of these sites.

Anti-CD13 Abs in children with extensive chronic GVHD and their relation to soluble CD13 after allogeneic blood and marrow transplantation from a Children's Oncology Groups Study, ASCT0031.

Our group previously demonstrated a strong association between elevated plasma soluble CD13 enzyme activity and newly diagnosed extensive chronic GVHD (cGVHD) in children. As cytotoxic anti-CD13 Abs have been documented after blood and marrow transplant (BMT) in association with CMV infection and cGVHD, we hypothesized that soluble CD13 contributes to cGVHD pathogenesis by induction of CD13 reactive Abs and that anti-CD13 Abs could be additional biomarkers for newly diagnosed pediatric extensive cGVHD. Using prospectively collected plasma samples from pediatric allogeneic BMT (allo-BMT) subjects with cGVHD and controls without cGVHD enrolled in a large multi-institution Children's Oncology Group cGVHD therapeutic trial, we evaluated whether soluble CD13 correlates with induction of anti-CD13 Abs. We found that CD13 reactive Abs are present in a proportion of patients after allo-BMT, but did not seem to correlate with the presence of soluble CD13. Anti-CD13 Abs also did not meet our criteria as a diagnostic biomarker for cGVHD. These data do not confirm that induction of CD13 reactive Abs is a mechanism for cGVHD in children nor are part of the pathogenesis of cGVHD associated with elevated soluble CD13. The exact role of CD13 in cGVHD remains to be determined.

Intracranial calcification after cord blood neonatal transplantation for krabbe disease.

Infantile-onset Krabbe disease results from a deficiency of the lysosomal enzyme galactocerebrosidase and leads to death from profound central and peripheral demyelination. Neonatal hematopoietic cell transplantation may result in near-normal cognitive development and partial rescue of gross motor development. The long-term course of the disorder for treated patients seems to involve slowly progressive neurological impairment. We describe the detailed 3-year outcomes of this experimental procedure using umbilical cord blood in a prenatally-diagnosed newborn with Krabbe disease. Substantial perivascular calcifications and atrophy of the white matter developed in the first year post-transplantation. Despite persistent neuroradiological and electrophysiological evidence of leukodystrophy, at age 3 years she has had only mildly impaired non-motor development and moderately impaired motor skills. The cause of these severe white matter changes may have been due to ongoing Krabbe disease or to effects of the chemotherapy regimen or to an interaction of these factors. Extended long-term follow-up of children neonatally transplanted for Krabbe disease is needed before the full utility and limitations of neonatal transplantation can be determined.