Active aspiration versus simple compression to remove residual gas from the abdominal cavity after laparoscopic cholecystectomy: a randomized clinical trial.

PURPOSE: After laparoscopic surgical procedures, residual gas in the abdominal cavity can cause post-operative pain, which is commonly located in the shoulder region. Previous studies suggested that post-laparoscopy pain can be prevented by active suctioning of intraabdominal gas at the end of surgery. METHODS: This randomized controlled trial (registered at DRKS 00,023,286) compared active suctioning versus manual compression in their ability to reduce pain after laparoscopic cholecystectomy. Patients scheduled for laparoscopic cholecystectomy were eligible for trial participation. The primary outcome measure was post-operative pain intensity after 12 h. All the patients were examined by MRI scanning to quantify the intraabdominal gas volume after the intervention. RESULTS: As planned, 60 patients were recruited. The two groups (n = 30 each) were very similar at the end of surgery. Active suctioning reduced the amount of residual pneumoperitoneum more than simple compression (median volume 1.5 versus 3.0 ml, p = 0.002). The primary outcome measure, abdominal pain after 12 h, was slightly lower in the intervention group (- 0.5 points, 95% confidence interval + 0.5 to - 1.7), but without reaching statistical significance (p = 0.37). After 12 h, shoulder pain was present in 10 patients in each group (p = 1.0). Independent of group assignment, however, residual gas volume was significantly associated with higher pain intensity. CONCLUSIONS: Active suctioning appears to have only a minor preventive effect on post-laparoscopy pain, probably because evacuation of the pneumoperitoneum remains incomplete in some patients. Other more effective maneuvers for gas removal should be preferred.

Orbital Fingerprint of Topological Fermi Arcs in the Weyl Semimetal TaP.

The monopnictides TaAs and TaP are well-established Weyl semimetals. Yet, a precise assignment of Fermi arcs, accommodating the predicted chiral charge of the bulk Weyl points, has been difficult in these systems, and the topological character of different surface features in the Fermi surface is not fully understood. Here, employing a joint analysis from linear dichroism in angle-resolved photoemission and first-principles calculations, we unveil the orbital texture on the full Fermi surface of TaP(001). We observe pronounced switches in the orbital texture at the projected Weyl nodes, and show how they facilitate a topological classification of the surface band structure. Our findings establish a critical role of the orbital degrees of freedom in mediating the surface-bulk connectivity in Weyl semimetals.

Production Standard and Stability of Compounded Del Nido Cardioplegia Solution.

Background: The del Nido cardioplegia solution (dNCS) was originally developed for pediatric cardiac surgery, being now also used for adult patients. Hospital pharmacies frequently resort to internal dNCS production which has led to an increase in the need for validated parameters for compounding and storage. Objective: This report defines in-house production standards, as well as the stability of dNCS under optimal storage conditions. Methods: All ingredients were sterile and United States Pharmacopeia (USP)/National Formulary (NF) certified. All final bags were quarantined at 4°C for quality control, when 3 of 33 weekly bags were randomly assayed for potassium content. Each lot was only released if all 3 samples were within ±5% of target. Stability testing was performed per USP 797 guidance. Over a 6-month period, 4 different lots and 4 bags from each lot of dNCS were assayed. Each bag was assessed for physical and chemical stability while refrigerated at 4°C, at 35°C in an incubator, and at 70°C under 80% relative humidity. A light exposure arm was also set up at 25°C under 150 lumens. Calibrators of lidocaine, mannitol, and gluconate were freshly prepared and assayed with the samples by Liquid chromatography/Mass spectrometry (LC/MS). Results: Lidocaine concentrations averaged 0.117 mg/mL (95.8% of theoretical) at 4°C for 30 days. At 35°C, they decayed by 67% in 30 days, while at 70°C nearly 50% was lost after the first day. A first-order kinetics was observed with an Arrhenius activation energy of 25 kcal/mol. Degradation products identified under stress conditions were absent in the stable product. Conclusions: The dNCS is stable for at least 30 days under 4°C refrigeration in ethylene vinyl acetate (EVA) bags.

Periacetabular osteotomy through the pararectus approach: technical feasibility and control of fragment mobility by a validated surgical navigation system in a cadaver experiment.

PURPOSE: The pararectus approach has been validated for managing acetabular fractures. We hypothesised it might be an alternative approach for performing periacetabular osteotomy (PAO). METHODS: Using four cadaver specimens, we randomly performed PAO through either the pararectus or a modified Smith-Petersen (SP) approach. We assessed technical feasibility and safety. Furthermore, we controlled fragment mobility using a surgical navigation system and compared mobility between approaches. The navigation system's accuracy was tested by cross-examination with validated preoperative planning software. RESULTS: The pararectus approach is technically feasible, allowing for adequate exposure, safe osteotomies and excellent control of structures at risk. Fragment mobility is equal to that achieved through the SP approach. Validation of these measurements yielded a mean difference of less <1 mm without statistical significance. CONCLUSION: Experimental data suggests the pararectus approach might be an alternative approach for performing PAO. Clinical validation is necessary to confirm these promising preliminary results.

Reduced intensity versus myeloablative conditioning for MDS: long-term results of an EBMT phase III study (RICMAC).

Short-term outcome of myeloablative (MAC) and reduced intensity (RIC) conditioning in the prospective randomized international EBMT RICMAC study in patients with myelodyplastic syndrome (MDS) was comparable but longer follow up is lacking. Patients with MDS aged 18-65 years were randomized to receive MAC (N = 64) with busulfan/cyclophosphamide or RIC (n = 65) with busulfan/fludarabine followed by stem cell transplantation -(HCT) from HLA matched or mismatched donor. After a median follow-up of 6.2 (0.4-12.5) years, 10-year OS and RFS were 54.0% and 43.9% for RIC and 44.4% and 44.2% for MAC (p = 0.15 and p = 0.78), respectively. Since the first report, 6 patients died on NRM, 4 after RIC, and 2 after MAC. Similarly, 8 patients relapsed (4 in each arm), increasing the number of relapsed patients to 28. The second HCT was performed in 18 pts, 8 in the MAC, and 10 in the RIC arm. In a multivariate analysis, ECOG status and chemotherapy prior to HCT were independent risk factors for OS and RFS, ECOG and low cytogenetic risk for NRM and chemotherapy prior to HCT for RI. Patients with low cytogenetic risk had better OS [p = 0.002], RFS [p = 0.02], and NRM (p = 0.015) after RIC as compared to MAC.

SAM-Competitive EZH2-Inhibitors Induce Platinum Resistance by EZH2-Independent Induction of ABC-Transporters.

T-cell lymphomas are heterogeneous and rare lymphatic malignancies with unfavorable prognosis. Consequently, new therapeutic strategies are needed. The enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 and responsible for lysine 27 trimethylation of histone 3. EZH2 is overexpressed in several tumor entities including T-cell neoplasms leading to epigenetic and consecutive oncogenic dysregulation. Thus, pharmacological EZH2 inhibition is a promising target and its clinical evaluation in T-cell lymphomas shows favorable results. We have investigated EZH2 expression in two cohorts of T-cell lymphomas by mRNA-profiling and immunohistochemistry, both revealing overexpression to have a negative impact on patients' prognosis. Furthermore, we have evaluated EZH2 inhibition in a panel of leukemia and lymphoma cell lines with a focus on T-cell lymphomas characterized for canonical EZH2 signaling components. The cell lines were treated with the inhibitors GSK126 or EPZ6438 that inhibit EZH2 specifically by competitive binding at the S-adenosylmethionine (SAM) binding site in combination with the common second-line chemotherapeutic oxaliplatin. The change in cytotoxic effects under pharmacological EZH2 inhibition was evaluated revealing a drastic increase in oxaliplatin resistance after 72 h and longer periods of combinational incubation. This outcome was independent of cell type but associated to reduced intracellular platinum. Pharmacological EZH2 inhibition revealed increased expression in SRE binding proteins, SREBP1/2 and ATP binding cassette subfamily G transporters ABCG1/2. The latter are associated with chemotherapy resistance due to increased platinum efflux. Knockdown experiments revealed that this was independent of the EZH2 functional state. The EZH2 inhibition effect on oxaliplatin resistance and efflux was reduced by additional inhibition of the regulated target proteins. In conclusion, pharmacological EZH2 inhibition is not suitable in combination with the common chemotherapeutic oxaliplatin in T-cell lymphomas revealing an EZH2-independent off-target effect.

EVALUATION OF IMMUNE FUNCTION IN TWO POPULATIONS OF GREEN SEA TURTLES (CHELONIA MYDAS) IN A DEGRADED VERSUS A NONDEGRADED HABITAT.

There is a strong correlation between degraded marine habitats and the prevalence of diseases such as green turtle fibropapillomatosis (GTFP) in coastal populations. In GTFP, small to large tumors grow on the turtle's soft tissues and shell, while internal nodules may also occur. The disease primarily affects juvenile green sea turtles (Chelonia mydas) that reside in nearshore waters. As a link has been shown between environmental pollution and immune suppression in a variety of animals, the objective of our research was to compare innate and adaptive immune responsiveness in green sea turtles from a severely degraded and a more pristine habitat, which differ greatly in rates of GTFP. We quantified phagocytosis by flow cytometry and performed in vitro stimulation analysis to measure activity of both the innate and adaptive immune systems in wild-caught Florida green turtles. Sea turtles from the degraded environment, both with and without visible cutaneous tumors, exhibited significantly reduced phagocytosis and stimulation indices than did those from the less polluted environment. Our results suggest that environmental factors may contribute to the development of GTFP and thus can impact the health of sea turtle populations.

Forensic-Psychiatric Risk Evaluations: Perspectives of Forensic Psychiatric Experts and Older Incarcerated Persons From Switzerland.

Background: Forensic-psychiatric risk assessments of persons in prisons aim to provide treatment for their mental health disorders to prevent risk of recidivism. Based on the outcomes of such evaluations, it is decided, for instance, whether the person can be released or be assigned to further treatment with or without privileges. A negative evaluation would mean that the assessed person must remain in prison or in a forensic institution until his or her mental health has improved to live safely in the community. This paper highlights the process of forensic-psychiatric evaluations and the challenges faced by the two parties directly involved in this process in Switzerland. Methods: Data for this manuscript are gathered using semi-structured one-to-one interviews. The study participants included a purposive sample of 41 older incarcerated persons under measures (i.e., mandated by court order to psychotherapeutic and psychiatric treatment), and 23 expert participants working in Swiss prisons or forensic institutions. We analyzed data using thematic analysis. Results: Study findings within four themes are reported. First we describe the standards and procedures that expert participants use to carry out adequate risk assessments and conditions under which they refuse to perform such assessments. Thereafter, we present expert participants' concerns associated with predictive risk assessments and highlight the need to be cautious in drawing conclusion from them. We then reveal older incarcerated participants' reports on the inconsistencies with the forensic expertise and their belief that these reports tend to be negative toward them. The final theme concerns older participants' experiences of how these evaluations negatively impact their lives and their perspectives of a different future. Conclusion: The study findings about forensic-psychiatric risk assessments point to the need for a clearer communication on how these evaluations take place and how decisions are taken based on them. As incarceration under measures denotes the necessity to continue therapy and reduce dangerousness, it is important that accused person understands his or her real progress, feel that the decisions are objective and justified, and are aware of the progress needed to achieve the goal of eventual release. Such clarity will not only be valuable for those under measures, but also the justice system.

Histological evidence for the existence of germ cell tumor cells showing embryonal carcinoma morphology but lacking OCT4 expression and cisplatin sensitivity.

The biological basis for manifestation of chemotherapy resistance in metastatic testicular germ cell tumors (GCT) remains obscure and is of particular clinical interest. In nonseminomatous GCT (NSGCT) the pluripotent embryonal carcinoma (EC) cells are the precursors of the manifold differentiated structures but also drive the malignant growth. They are known to be hypersensitive towards DNA-damaging agents and to express the embryonal transcription factor OCT4. We recently characterized EC cells that lack OCT4 expression and show cisplatin resistance. In the present, immunohistochemical study we analyzed the composition of NSGCT with the focus on such OCT4-negative EC cells using a NSGCT xenograft model as well as patient-derived NSGCT samples. In the xenograft model, the cisplatin-sensitive cell line H12.1 gives rise to xenografts where EC structures are mainly composed of OCT4-positive cells, whereas xenografts from the resistant cell line 1411HP exclusively comprise OCT4-negative EC areas. We found that post-chemotherapy residual metastatic tumors of patients can be comprised of exclusively OCT4-negative EC, whereas the matched testicular primary tumor harbors OCT4-positive EC. Thorough histological analyses revealed a few examples of such OCT4-negative EC cells also in the testicular primary tumor as well as in xenografts from the cisplatin-sensitive NSGCT-cell line. For these cells we propose an identity as early extraembryonal progenitor cells directly derived from OCT4-expressing EC cells. This challenges the use of the term EC cell. The data also support our hypothesis that malignant growth of resistant NSGCT may be driven by this cell type.

An official American thoracic society statement: position statement on ATS activities for the promotion of respiratory and sleep/wake health and the care of the critically ill in the United States.

BACKGROUND: The 1997 American Thoracic Society (ATS) statement "A Framework for Health Care Policy in the United States" outlined core principles for the Society's activities in the public health arena. In the succeeding 10 years, profound changes have taken place in the United States health care environment. In addition, the 2005 publication of the Society's Vision highlighted some differences between the original Statement and our current priorities. Therefore, the Health Policy Committee embarked on a re-analysis and re-statement of the Society's attitudes and strategies with respect to health and public policy. This Statement reflects the findings of the Committee. PURPOSE: To outline the key aspects of an internal ATS strategy for the promotion of respiratory and sleep/wake health and the care of the critically ill in the United States. METHODS: Committee discussion and consensus-building occurred both before and after individual members performed literature searches and drafted sections of the document. Comments were solicited on the draft document from ATS committee and assembly chairs and the Executive Committee, resulting in substantive revisions of the final document. RESULTS: Specific strategies are suggested for the ATS in the arenas of research, training and education, patient care, and advocacy so as to enhance the delivery of health care in the fields of respiratory medicine, sleep medicine, and critical care. CONCLUSIONS: The American Thoracic Society's Mission, Core Principles, and Vision provide clear guidance for the formulation of specific strategies that will serve to promote improved respiratory health and care of the critically ill in the United States.

Allonymous science: the politics of placing and shifting credit in public-private nutrition research.

Ideally, guidelines reflect an accepted position with respect to matters of concern, ranging from clinical practices to researcher behaviour. Upon close reading, authorship guidelines reserve authorship attribution to individuals fully or almost fully embedded in particular studies, including design or execution as well as significant involvement in the writing process. These requirements prescribe an organisation of scientific work in which this embedding is specifically enabled. Drawing from interviews with nutrition scientists at universities and in the food industry, we demonstrate that the organisation of research labour can deviate significantly from such prescriptions. The organisation of labour, regardless of its content, then, has consequences for who qualifies as an author. The fact that fewer food industry employees qualify is actively used by the food industry to manage the credibility and ownership of their knowledge claims as allonymous science: the attribution of science assisted by authorship guidelines blind to all but one organisational frame.

Standardized Definitions of Bleeding After Transbronchial Lung Biopsy: A Delphi Consensus Statement From the Nashville Working Group.

BACKGROUND: Transbronchial lung biopsies are commonly performed for a variety of indications. Although generally well tolerated, complications such as bleeding do occur. Description of bleeding severity is crucial both clinically and in research trials; to date, there is no validated scale that is widely accepted for this purpose. Can a simple, reproducible tool for categorizing the severity of bleeding after transbronchial biopsy be created? METHODS: Using the modified Delphi method, an international group of bronchoscopists sought to create a new scale tailored to assess bleeding severity among patients undergoing flexible bronchoscopy with transbronchial lung biopsies. Cessation criteria were specified a priori and included reaching > 80% consensus among the experts or three rounds, whichever occurred first. RESULTS: Thirty-six expert bronchoscopists from eight countries, both in academic and community practice settings, participated in the creation of the scale. After the live meeting, two iterations were made. The second and final scale was vetted by all 36 participants, with a weighted average of 4.47/5; 53% were satisfied, and 47% were very satisfied. The panel reached a consensus and proposes the Nashville Bleeding Scale. CONCLUSIONS: The use of a simplified airway bleeding scale that can be applied at bedside is an important, necessary tool for categorizing the severity of bleeding. Uniformity in reporting clinically significant airway bleeding during bronchoscopic procedures will improve the quality of the information derived and could lead to standardization of management. In addition to transbronchial biopsies, this scale could also be applied to other bronchoscopic procedures, such as endobronchial biopsy or endobronchial ultrasound-guided needle aspiration.

A robust and accurate two-stage approach for automatic recovery of distal locking holes in computer-assisted intramedullary nailing of femoral shaft fractures.

It has been recognized that one of the most difficult steps in intramedullary nailing of femoral shaft fractures is the distal locking - the insertion of distal transverse interlocking screws, for which it is necessary to know the positions and orientations of the distal locking holes (DLHs) of the intramedullary nail (IMN). This paper presents a robust and accurate approach for solving this problem based on two calibrated and registered fluoroscopic images. The problem is formulated as a two-stage model-based optimal fitting process. The first stage, nail detection, automatically estimates the axis of the distal part of the IMN (DP-IMN) by iteratively fitting a cylindrical model to the images. The second stage, pose recovery, resolves the translations and the rotations of the DLHs around the estimated axis by iteratively fitting the geometrical models of the DLHs to the images. An iterative best matched projection point (IBMPP) algorithm is combined with random sample strategies to effectively and robustly solve the fitting problems in both stages. We designed and conducted comprehensive experiments to validate the robustness and the accuracy of the present approach. Our in vitro experiments show on average less than 14 s execution time on a Linux machine, a mean angular error of 0.48 degrees (std = 0.21 degrees ), and a mean translational error of 0.09 mm (std = 0.041 mm). We conclude that the present approach is fast, robust, and accurate for distal locking applications.

Effect of anoxia on the electroretinogram of three anoxia-tolerant vertebrates.

To survive anoxia, neural ATP levels have to be defended. Reducing electrical activity, which accounts for 50% or more of neural energy consumption, should be beneficial for anoxic survival. The retina is a hypoxia sensitive part of the central nervous system. Here, we quantify the in vivo retinal light response (electroretinogram; ERG) in three vertebrates that exhibit varying degrees of anoxia tolerance: freshwater turtle (Trachemys scripta), epaulette shark (Hemiscyllium ocellatum) and leopard frog (Rana pipiens). A virtually total suppression of ERG in anoxia, probably resulting in functional blindness, has previously been seen in the extremely anoxia-tolerant crucian carp (Carassius carassius). Surprisingly, the equally anoxia-tolerant turtle, which strongly depresses brain and whole-body metabolism during anoxia, exhibited a relatively modest anoxic reduction in ERG: the combined amplitude of turtle ERG waves was reduced by approximately 50% after 2 h. In contrast, the shark b-wave amplitude practically disappeared after 30 min of severe hypoxia, and the frog b-wave was decreased by approximately 75% after 40 min in anoxia. The specific A(1) adenosine receptor antagonist CPT significantly delayed the suppression of turtle ERG, while the hypoxic shark ERG was unaffected by the non-specific adenosine receptor antagonist aminophylline, suggesting adenosinergic involvement in turtle but not in shark.

Augmented reality endoscopic system (ARES): preliminary results.

OBJECTIVES: During endoscopic surgery, it is difficult to ascertain the anatomical landmarks once the anatomy is fiddled with or if the operating area is filled with blood. An augmented reality system will enhance the endoscopic view and further enable surgeons to view hidden critical structures or the results of preoperative planning. METHOD: The skull and endoscope are fixed with optical markers that are used as dynamic reference bases for tracking. A small optical tracking device, the easyTrack 200, which is connected to a computer, calculates the positions of the markers. The endoscope is calibrated and registered for augmenting its video with a 3D model. Images of a black and white checkerboard pattern, with 2.5 mm sized squares, are used for calibration with a Matlab based calibration toolbox. Standard modalities of overlay have been developed, including a CT viewer displaying it as an overlay in the endoscopic video stream, and a 3D viewer to render 3D models of preoperatively segmented structures. The accuracy of the augmented reality system was assessed on a plastic skull. RESULTS: The accuracy is calculated by looking at the difference in pixels of several contours in both a real and an overlay image, obtaining a mean of 3-4 pixels that correspond to sub-millimeter accuracy (pixel to mm ratio calculated previously). Mean error was consistently 1-2 [+/- 0.3] mm. CONCLUSIONS: A novel augmented reality system for endoscopic surgery is presented. Highlighting hidden structures or CT overlays in the endoscope will give more information in difficult situations and enhance the operation quality.

Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT.

Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT.

Cytogenetics detects infiltrations of a primary cutaneous acute myeloid leukemia to the kidney.

Extramedullary manifestations of acute myeloid leukemia (AML) are rare and commonly involve one tissue. We report of a cutaneous acute myelomonocytic leukemia infiltrating the kidney next to the skin. A 61-year-old female patient with complex karyotype cutaneous AML FAB M4 underwent abdominal computed tomography scans. A lesion in her left kidney appeared suspicious of renal carcinoma as confirmed by histology. However, fluorescence in situ hybridization cytogenetics revealed a chromosome 11q23 abnormality in the nephrectomy specimen, which also appeared in the leukemic blasts of skin and bone marrow. Closer histomorphologic workup revealed an infiltration of the kidney with leukemia. This case report illustrates how modern diagnostic procedures can help to reveal rare sites of disease.

Predictive sensor based x-ray calibration using a physical model.

Many computer assisted surgery systems are based on intraoperative x-ray images. To achieve reliable and accurate results these images have to be calibrated concerning geometric distortions, which can be distinguished between constant distortions and distortions caused by magnetic fields. Instead of using an intraoperative calibration phantom that has to be visible within each image resulting in overlaying markers, the presented approach directly takes advantage of the physical background of the distortions. Based on a computed physical model of an image intensifier and a magnetic field sensor, an online compensation of distortions can be achieved without the need of an intraoperative calibration phantom. The model has to be adapted once to each specific image intensifier through calibration, which is based on an optimization algorithm systematically altering the physical model parameters, until a minimal error is reached. Once calibrated, the model is able to predict the distortions caused by the measured magnetic field vector and build an appropriate dewarping function. The time needed for model calibration is not yet optimized and takes up to 4 h on a 3 GHz CPU. In contrast, the time needed for distortion correction is less than 1 s and therefore absolutely acceptable for intraoperative use. First evaluations showed that by using the model based dewarping algorithm the distortions of an XRII with a 21 cm FOV could be significantly reduced. The model was able to predict and compensate distortions by approximately 80% to a remaining error of 0.45 mm (max) (0.19 mm rms).