Innovation in surgical trauma care education: assessment of a Panamerican Trauma Society online surgical skills course hosted by the Spanish Surgical Association.

PURPOSE: Incorporating surgical skills education in trauma care is essential for young surgeons and surgical trainees. This study describes an innovative e-learning course for teaching trauma care surgical skills in an international cooperative setting. Furthermore, it aims to offer valuable insights on enhancing e-learning practices. METHODS: The Panamerican Trauma Society and the Spanish Surgical Association have joined forces to launch an online course focusing on advanced trauma care surgical skills. This report provides an in-depth examination of the project and scrutinizes participant feedback through a post-course survey. The survey thoroughly evaluates their satisfaction level, the usefulness of the course content, and their view on its clinical relevance. RESULTS: Three hundred eighty-two surgeons from 16 countries completed an online course. Three hundred seventy-nine of them responded to the post-course survey. The mean age was 36, with 64% females and 36% males. The course consisted of 9.9 h of academic content, including 5 h of video lectures and 4.9 h of live discussions. Ninety-seven percent of the participants were practicing general and acute care surgeons, and only 2% were exclusively dedicated to trauma surgery. Sixty-one percent of participants highly valued real-time interaction with faculty, and 95% believed their trauma surgical skills would improve. Additionally, 93% of the participants were satisfied or very satisfied with the e-learning experience. CONCLUSIONS: The use of video-based instructional materials has revolutionized surgical education. With online courses in trauma surgery, surgeons can now improve their skills and better prepare themselves to handle severe trauma cases. This innovative approach to surgical education has proven to be very effective and can potentially enhance patients' quality of care.

Inflammation on the Waiting List Is a Risk Factor for New-Onset Prediabetes and Post-Transplant Diabetes Mellitus: A Prospective Study.

INTRODUCTION: Inflammation is a risk factor for diabetes in the general population. The role of inflammation in prediabetes or post-transplant diabetes mellitus (PTDM) is not clear. We evaluated the association between inflammatory markers in patients on the waiting list for renal transplantation and the onset of prediabetes and PTDM 12 months after transplantation. METHODS: This is a post hoc analysis of a prospective study that included nondiabetic patients on the waiting list for kidney transplantation who underwent an oral glucose tolerance test (OGTT) and were followed up to 12 months after transplantation. At this time, those patients without PTDM underwent another OGTT. At pre-transplantation, five cytokines: TNFα, IL6, IL1ß, CRP, MCP1 were determined. The association between inflammation and prediabetes/PTDM was evaluated using multiple regression models. RESULTS: 110 patients on the waiting list were enrolled: 74 had normal glucose metabolism and 36 had prediabetes or occult diabetes. At 12 months, 53 patients had normal glucose metabolism, 25 prediabetes, and 32 PTDM. In multiple regression analysis, pre-transplant inflammation was not a risk factor for prediabetes or PTDM. This was attributed to the high interrelation between obesity, prediabetes, and inflammation: about 75% of the cases had these conditions. In a sub-analysis, we analyzed only patients without prediabetes and occult diabetes on the waiting list and found that TNFα levels and BMI at pre-transplantation were independently associated with the onset of prediabetes or PTDM 1 year after transplantation. CONCLUSIONS: Pre-transplant inflammation and BMI are risk factors for prediabetes and PTDM in patients without glucose metabolism alterations.

Treatment of early borderline lesions in low immunological risk kidney transplant patients: a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study.

BACKGROUND: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. METHODS: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. DISCUSSION: This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. TRIAL REGISTRATION: clinicaltrials.gov : NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1 . Protocol Version 2 of 21 January 2022. SPONSOR: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org .

Reconfigurable Magnonic Crystals Based on Imprinted Magnetization Textures in Hard and Soft Dipolar-Coupled Bilayers.

Reconfigurable magnetization textures offer control of spin waves with promising properties for future low-power beyond-CMOS systems. However, materials with perpendicular magnetic anisotropy (PMA) suitable for stable magnetization-texture formation are characterized by high damping, which limits their applicability in magnonic devices. Here, we propose to overcome this limitation by using hybrid structures, i.e., a PMA layer magnetostatically coupled to a low-damping soft ferromagnetic film. We experimentally show that a periodic stripe-domain texture from a PMA layer is imprinted upon the soft layer and induces a nonreciprocal dispersion relation of the spin waves confined to the low-damping film. Moreover, an asymmetric bandgap features the spin-wave band diagram, which is a clear demonstration of collective spin-wave dynamics, a property characteristic for magnonic crystals with broken time-reversal symmetry. The composite character of the hybrid structure allows for stabilization of two magnetic states at remanence, with parallel and antiparallel orientation of net magnetization in hard and soft layers. The states can be switched using a low external magnetic field; therefore, the proposed system obtains an additional functionality of state reconfigurability. This study offers a link between reconfigurable magnetization textures and low-damping spin-wave dynamics, providing an opportunity to create miniaturized, programmable, and energy-efficient signal processing devices operating at high frequencies.

Domain Wall Automotion in Three-Dimensional Magnetic Helical Interconnectors.

The fundamental limits currently faced by traditional computing devices necessitate the exploration of ways to store, compute, and transmit information going beyond the current CMOS-based technologies. Here, we propose a three-dimensional (3D) magnetic interconnector that exploits geometry-driven automotion of domain walls (DWs), for the transfer of magnetic information between functional magnetic planes. By combining state-of-the-art 3D nanoprinting and standard physical vapor deposition, we prototype 3D helical DW conduits. We observe the automotion of DWs by imaging their magnetic state under different field sequences using X-ray microscopy, observing a robust unidirectional motion of DWs from the bottom to the top of the spirals. From experiments and micromagnetic simulations, we determine that the large thickness gradients present in the structure are the main mechanism for 3D DW automotion. We obtain direct evidence of how this tailorable magnetic energy gradient is imprinted in the devices, and how it competes with pinning effects that are due to local changes in the energy landscape. Our work also predicts how this effect could lead to high DW velocities, reaching the Walker limit during automotion. This work demonstrates a possible mechanism for efficient transfer of magnetic information in three dimensions.

Two-Step Resist Deposition of E-Beam Patterned Thick Py Nanostructures for X-ray Microscopy.

Patterned elements of permalloy (Py) with a thickness as large as 300 nm have been defined by electron beam lithography on X-ray-transparent 50 nm thick membranes in order to characterize their magnetic structure via Magnetic Transmission X-ray Microscopy (MTXM). To avoid the situation where the fragility of the membranes causes them to break during the lithography process, it has been found that the spin coating of the resist must be applied in two steps. The MTXM results show that our samples have a central domain wall, as well as other types of domain walls, if the nanostructures are wide enough.

Implementation and Uptake of Rural Lung Cancer Screening.

OBJECTIVE: Given the higher rates of tobacco use along with increased mortality specific to lung cancer in rural settings, low-dose CT (LDCT)-based lung cancer screening could be particularly beneficial to such populations. However, limited radiology facilities and increased geographical distance, combined with lower income and education along with reduced patient engagement, present heightened barriers to screening initiation and adherence. METHODS: In collaboration with community leaders and stakeholders, we developed and implemented a community-based lung cancer screening program, including telephone-based navigation and tobacco cessation counseling support, serving 18 North Texas counties. Funding was available to support clinical services costs where needed. We collected data on LDCT referrals, orders, and completion. RESULTS: To raise awareness for lung cancer screening, we leveraged our established collaborative network of more than 700 community partners. In the first year of operation, 107 medical providers referred 570 patients for lung cancer screening, of whom 488 (86%) were eligible for LDCT. The most common reasons for ineligibility were age (43%) and insufficient tobacco history (20%). Of 381 ordered LDCTs, 334 (88%) were completed. Among screened patients, 61% were current smokers and 36% had insurance coverage for the procedure. The program cost per patient was $430. DISCUSSION: Implementation, uptake, and completion of LDCT-based lung cancer screening is feasible in rural settings. Community outreach, health promotion, and algorithm-based navigation may support such efforts. Given low lung cancer screening rates nationally and heightened lung cancer risk in rural populations, similar programs in other regions may be particularly impactful.

Estimated GFR Slope in Kidney Transplant Patients: When the Error Is Random.

BACKGROUND: The evaluation of renal function changes over time is crucial in day-to-day renal transplant care, and the slope of renal function is a major outcome in clinical trials. Little is known about the reliability of estimated glomerular filtration rate (eGFR) in reflecting real glomerular filtration rate (GFR) changes. METHODS: We analyzed the variability of eGFR slope by 63 equations in estimating measured GFR (mGFR) changes in 110 renal transplant patients. The agreement between eGFR and mGFR slopes was evaluated by the concordance correlation coefficient and the limits of agreement. Patients were grouped based on mGFR slope in rapid GFR loss: faster than -3 mL/min/y; stable renal function: -3 to +3 mL/min/y; and improvement in GFR: higher than +3 mL/min/y. RESULTS: Concordance correlation coefficient averaged 0.36 and limits of agreement ±10 mL/min/y, indicating very poor agreement between eGFR and mGFR slopes. The eGFR slope classified patients into the same group of mGFR slope only in 25% of the cases. In about two-thirds of patients, the eGFR slope was either markedly faster or slower than the mGFR slope. In half of these cases, the discrepancy between mGFR and eGFR slopes was ≥50%. CONCLUSIONS: Formulas are neither accurate nor precise in reflecting real GFR decline in renal transplant patients, making them unreliable for clinical practice and trials.

Complex free-space magnetic field textures induced by three-dimensional magnetic nanostructures.

The design of complex, competing effects in magnetic systems-be it via the introduction of nonlinear interactions1-4, or the patterning of three-dimensional geometries5,6-is an emerging route to achieve new functionalities. In particular, through the design of three-dimensional geometries and curvature, intrastructure properties such as anisotropy and chirality, both geometry-induced and intrinsic, can be directly controlled, leading to a host of new physics and functionalities, such as three-dimensional chiral spin states7, ultrafast chiral domain wall dynamics8-10 and spin textures with new spin topologies7,11. Here, we advance beyond the control of intrastructure properties in three dimensions and tailor the magnetostatic coupling of neighbouring magnetic structures, an interstructure property that allows us to generate complex textures in the magnetic stray field. For this, we harness direct write nanofabrication techniques, creating intertwined nanomagnetic cobalt double helices, where curvature, torsion, chirality and magnetic coupling are jointly exploited. By reconstructing the three-dimensional vectorial magnetic state of the double helices with soft-X-ray magnetic laminography12,13, we identify the presence of a regular array of highly coupled locked domain wall pairs in neighbouring helices. Micromagnetic simulations reveal that the magnetization configuration leads to the formation of an array of complex textures in the magnetic induction, consisting of vortices in the magnetization and antivortices in free space, which together form an effective B field cross-tie wall14. The design and creation of complex three-dimensional magnetic field nanotextures opens new possibilities for smart materials15, unconventional computing2,16, particle trapping17,18 and magnetic imaging19.

Optimizing a Protocol to Assess Immune Responses after SARS-CoV-2 Vaccination in Kidney-Transplanted Patients: In Vivo DTH Cutaneous Test as the Initial Screening Method.

Previously, the delayed-type hypersensitivity (DTH) cutaneous test with the spike protein of SARS-CoV-2 has been shown to be a simple in vivo method to measure T-cell functionality after natural infection and in vaccinated individuals. METHODS: Twenty-five kidney-transplanted recipients were immunized with two doses of the mRNA-based Pfizer-BioNTech COVID19 vaccine three weeks apart. Cell-immune response (CIR) was evaluated ten weeks later using an in vivo DTH skin test and in vitro with an interferon gamma release assay (IGRA). Humoral Immune Response (HIR) was determined by the measurement of specific IgG anti-S1 SARS-CoV-2. RESULTS: Ten weeks after the second dose of the vaccine, 23 out of 25 transplanted patients had a positive DTH skin test, while in vitro CIR was considered positive in 20 patients. Unspecific stimulation was positive in all 25 patients, showing no T-cell defect. Seven out of twenty-five patients had a negative specific anti-spike IgG. CIR was positive in all immune-competent control patients. CONCLUSIONS: DTH is a useful, simple, and cheaper tool that can be used to assess cellular immune response, with an excellent correlation with the in vitro CIR. CIR assessment after vaccination in these immunocompromised patients is an excellent complement to HIR-based methods. This skin test could be used if classical in vitro methods cannot be applied.

AutoMeKin2021: An open-source program for automated reaction discovery.

AutoMeKin2021 is an updated version of tsscds2018, a program for the automated discovery of reaction mechanisms (J. Comput. Chem. 2018, 39, 1922). This release features a number of new capabilities: rare-event molecular dynamics simulations to enhance reaction discovery, extension of the original search algorithm to study van der Waals complexes, use of chemical knowledge, a new search algorithm based on bond-order time series analysis, statistics of the chemical reaction networks, a web application to submit jobs, and other features. The source code, manual, installation instructions and the website link are available at: https://rxnkin.usc.es/index.php/AutoMeKin.

Fabrication of a 3D Nanomagnetic Circuit with Multi-Layered Materials for Applications in Spintronics.

Three-dimensional (3D) spintronic devices are attracting significant research interest due to their potential for both fundamental studies and computing applications. However, their implementations face great challenges regarding not only the fabrication of 3D nanomagnets with high quality materials, but also their integration into 2D microelectronic circuits. In this study, we developed a new fabrication process to facilitate the efficient integration of both non-planar 3D geometries and high-quality multi-layered magnetic materials to prototype 3D spintronic devices, as a first step to investigate new physical effects in such systems. Specifically, we exploited 3D nanoprinting, physical vapour deposition and lithographic techniques to realise a 3D nanomagnetic circuit based on a nanobridge geometry, coated with high quality Ta/CoFeB/Ta layers. The successful establishment of this 3D circuit was verified through magnetotransport measurements in combination with micromagnetic simulations and finite element modelling. This fabrication process provides new capabilities for the realisation of a greater variety of 3D nanomagnetic circuits, which will facilitate the understanding and exploitation of 3D spintronic systems.

Non-Planar Geometrical Effects on the Magnetoelectrical Signal in a Three-Dimensional Nanomagnetic Circuit.

Expanding nanomagnetism and spintronics into three dimensions (3D) offers great opportunities for both fundamental and technological studies. However, probing the influence of complex 3D geometries on magnetoelectrical phenomena poses important experimental and theoretical challenges. In this work, we investigate the magnetoelectrical signals of a ferromagnetic 3D nanodevice integrated into a microelectronic circuit using direct-write nanofabrication. Due to the 3D vectorial nature of both electrical current and magnetization, a complex superposition of several magnetoelectrical effects takes place. By performing electrical measurements under the application of 3D magnetic fields, in combination with macrospin simulations and finite element modeling, we disentangle the superimposed effects, finding how a 3D geometry leads to unusual angular dependences of well-known magnetotransport effects such as the anomalous Hall effect. Crucially, our analysis also reveals a strong role of the noncollinear demagnetizing fields intrinsic to 3D nanostructures, which results in an angular dependent magnon magnetoresistance contributing strongly to the total magnetoelectrical signal. These findings are key to the understanding of 3D spintronic systems and underpin further fundamental and device-based studies.

Creation and observation of Hopfions in magnetic multilayer systems.

Among topological solitons, magnetic skyrmions are two-dimensional particle-like objects with a continuous winding of the magnetization, and magnetic Hopfions are three-dimensional objects that can be formed from a closed loop of twisted skyrmion strings. Theoretical models suggest that magnetic Hopfions can be stabilized in frustrated or chiral magnetic systems, and target skymions can be transformed into Hopfions by adapting their perpendicular magnetic anisotropy, but their experimental verification has been elusive so far. Here, we present an experimental study of magnetic Hopfions that are created in Ir/Co/Pt multilayers shaped into nanoscale disks, known to host target skyrmions. To characterize three-dimensional spin textures that distinguish Hopfions from target skyrmions magnetic images are recorded with surface-sensitive X-ray photoemission electron microscopy and bulk-sensitive soft X-ray transmission microscopy using element-specific X-ray magnetic circular dichroism effects as magnetic contrast. These results could stimulate further investigations of Hopfions and their potential application in three-dimensional spintronics devices.

Artificial Double-Helix for Geometrical Control of Magnetic Chirality.

Chirality plays a major role in nature, from particle physics to DNA, and its control is much sought-after due to the scientific and technological opportunities it unlocks. For magnetic materials, chiral interactions between spins promote the formation of sophisticated swirling magnetic states such as skyrmions, with rich topological properties and great potential for future technologies. Currently, chiral magnetism requires either a restricted group of natural materials or synthetic thin-film systems that exploit interfacial effects. Here, using state-of-the-art nanofabrication and magnetic X-ray microscopy, we demonstrate the imprinting of complex chiral spin states via three-dimensional geometric effects at the nanoscale. By balancing dipolar and exchange interactions in an artificial ferromagnetic double-helix nanostructure, we create magnetic domains and domain walls with a well-defined spin chirality, determined solely by the chiral geometry. We further demonstrate the ability to create confined 3D spin textures and topological defects by locally interfacing geometries of opposite chirality. The ability to create chiral spin textures via 3D nanopatterning alone enables exquisite control over the properties and location of complex topological magnetic states, of great importance for the development of future metamaterials and devices in which chirality provides enhanced functionality.

A noninvasive postoperative clinical score to identify patients at risk for postoperative pulmonary complications: the Air-Test Score.

BACKGROUND: Postoperative pulmonary complications (PPCs) negatively affect morbidity, healthcare costs and postsurgical survival. Preoperative and intraoperative peripheral oxyhemoglobin saturation (SpO2) levels are independent risk factors for postoperative pulmonary complications (PPCs). The air-test assesses the value of SpO2 while breathing room-air. We aimed at building a clinical score that includes the air-test for predicting the risk for PPCs. METHODS: This is a development and validation study in patients -randomly divided into two cohorts- from a large randomized clinical trial (iPROVE) that enrolled 964 intermediate-to-high risk patients scheduled for abdominal surgery. Arterial oxygenation was assessed on room-air in the preoperative period (preoperative air-test) and 3h after admission to the postoperative care unit (postoperative air-test). The air-test was defined as positive or negative if SpO2 was ≤96% or >96%, respectively. Positive air-tests were stratified into weak (93-96%) or strong (<93%). The primary outcome was a composite of moderate-to-severe PPCs during the first seven postoperative days. RESULTS: A total of 902 patients were included in the final analysis (542 in the development cohort and 360 in the validation cohort). Regression analysis identified five independent risk factors for PPC: age, type of surgery, pre- and postoperative air-test, and atelectasis. The area under the receiver operating characteristic curve (AUC) was 0.79 (95% CI: 0.75-0.82) when including these five independent predictors. We built a simplified score termed "air-test score" by using only the pre- and postoperative SpO2, resulting in an AUC of 0.72 (95% CI: 0.67-0.76) for the derivation and 0.72 (95% CI: 0.66-0.78) for the validation cohort, respectively. The air-test score stratified patients into four levels of risk, with PPCs ranging from <15% to >75%. CONCLUSIONS: The simple, non-invasive and inexpensive bedside air-test score, evaluating pre- and postoperatively SpO2 measured on room-air, helps to predict the risk for PPCs.

Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial.

BACKGROUND: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. METHODS: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. RESULTS: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. CONCLUSIONS: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. CLINICAL TRIAL REGISTRATION: NCT02776046.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.

AFFINImeter: A software to analyze molecular recognition processes from experimental data.

The comprehension of molecular recognition phenomena demands the understanding of the energetic and kinetic processes involved. General equations valid for the thermodynamic analysis of any observable that is assessed as a function of the concentration of the involved compounds are described, together with their implementation in the AFFINImeter software. Here, a maximum of three different molecular species that can interact with each other to form an enormous variety of supramolecular complexes are considered. The corrections currently employed to take into account the effects of dilution, volume displacement, concentration errors and those due to external factors, especially in the case of ITC measurements, are included. The methods used to fit the model parameters to the experimental data, and to generate the uncertainties are described in detail. A simulation tool and the so called kinITC analysis to get kinetic information from calorimetric experiments are also presented. An example of how to take advantage of the AFFINImeter software for the global multi-temperature analysis of a system exhibiting cooperative 1:2 interactions is presented and the results are compared with data previously published. Some useful recommendations for the analysis of experiments aimed at studying molecular interactions are provided.

Randomized Controlled Trial Assessing the Impact of Tacrolimus Versus Cyclosporine on the Incidence of Posttransplant Diabetes Mellitus.

INTRODUCTION: Despite the high incidence of posttransplant diabetes mellitus (PTDM) among high-risk recipients, no studies have investigated its prevention by immunosuppression optimization. METHODS: We conducted an open-label, multicenter, randomized trial testing whether a tacrolimus-based immunosuppression and rapid steroid withdrawal (SW) within 1 week (Tac-SW) or cyclosporine A (CsA) with steroid minimization (SM) (CsA-SM), decreased the incidence of PTDM compared with tacrolimus with SM (Tac-SM). All arms received basiliximab and mycophenolate mofetil. High risk was defined by age >60 or >45 years plus metabolic criteria based on body mass index, triglycerides, and high-density lipoprotein-cholesterol levels. The primary endpoint was the incidence of PTDM after 12 months. RESULTS: The study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac-SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac-SM, and 9.7% for CsA-SM (relative risk [RR] Tac-SW vs. CsA-SM 3.9 [1.2-12.4; P = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [0.8-8.9; P = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (P = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence P = 0.04). Graft and patient survival, and graft function were similar among arms. CONCLUSION: In high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence.