Defining capabilities in deployed UK military prehospital emergency care.

The UK military prehospital emergency care (PHEC) operational clinical capability framework must be updated in order that it retains its use as a valid operational planning tool. Specific requirements include accurately defining the PHEC levels and the 'Medical Emergency Response Team' (MERT), while reinforcing PHEC as a specialist area of clinical practice that requires an assured set of competencies at all levels and mandatory clinical currency for vocational providers.A military PHEC review panel was convened by the Defence Consultant Advisor (DCA) for PHEC. Each PHEC level was reviewed and all issues which had, or could have arisen from the existing framework were discussed until agreement between the six members of this panel was established.An updated military PHEC framework has been produced by DCA PHEC, which defines the minimum requirements for each operational PHEC level. These definitions cover all PHEC providers, irrespective of professional background. The mandatory requirement for appropriate clinical exposure for vocational and specialist providers is emphasised. An updated definition of MERT has been agreed.This update provides clarity to the continually evolving domain of UK military PHEC. It sets out the PHEC provider requirements in order to be considered operationally deployable in a PHEC role. There are implications for training, manning and recruitment to meet these requirements, but the processes required to address these are already underway and well described elsewhere.

The Caenorhabditis elegans Shugoshin regulates TAC-1 in cilia.

The conserved Shugoshin (SGO) protein family is essential for mediating proper chromosome segregation from yeast to humans but has also been implicated in diverse roles outside of the nucleus. SGO's roles include inhibiting incorrect spindle attachment in the kinetochore, regulating the spindle assembly checkpoint (SAC), and ensuring centriole cohesion in the centrosome, all functions that involve different microtubule scaffolding structures in the cell. In Caenorhabditis elegans, a species with holocentric chromosomes, SGO-1 is not required for cohesin protection or spindle attachment but appears important for licensing meiotic recombination. Here we provide the first functional evidence that in C. elegans, Shugoshin functions in another extranuclear, microtubule-based structure, the primary cilium. We identify the centrosomal and microtubule-regulating transforming acidic coiled-coil protein, TACC/TAC-1, which also localizes to the basal body, as an SGO-1 binding protein. Genetic analyses indicate that TAC-1 activity must be maintained below a threshold at the ciliary base for correct cilia function, and that SGO-1 likely participates in constraining TAC-1 to the basal body by influencing the function of the transition zone 'ciliary gate'. This research expands our understanding of cellular functions of Shugoshin proteins and contributes to the growing examples of overlap between kinetochore, centrosome and cilia proteomes.

Antithrombotic Therapy and Hematoma Risk during Image-guided Core-Needle Breast Biopsy.

Background For image-guided core-needle breast biopsy (CNBB), it remains unclear whether antithrombotic medication should be withheld because of hematoma risk. Purpose To determine hematoma risk after CNBB in patients receiving antithrombotic medication and to stratify risk by antithrombotic type. Materials and Methods This HIPAA-compliant retrospective study included US-, stereotactic-, or MRI-guided CNBBs performed across six academic and six private practices between April 2019 and April 2021. Patients were instructed to continue antithrombotic medications, forming two groups: antithrombotic and nonantithrombotic. Hematomas were defined as new biopsy-site masses with a diameter of 2 cm or larger on postprocedure mammograms. Hematomas were considered clinically significant if management involved an intervention other than manual compression. Patient age, type of antithrombotic medication, practice type, image guidance modality, needle gauge and type, and outcome of pathologic analysis were recorded. Multivariable logistic regression analysis was used to analyze variables associated with hematomas. Results A total of 3311 biopsies were performed in 2664 patients (median age, 60 years; IQR, 48-70 years; 2658 women). The nonantithrombotic group included 2788 biopsies, and the antithrombotic group included 523 biopsies (328 low-dose aspirin, 73 full-dose antiplatelet drugs, 51 direct oral anticoagulants, 36 warfarin, 32 daily nonsteroidal anti-inflammatory drugs, three heparin or enoxaparin). The antithrombotic group had a higher overall hematoma rate (antithrombotic group: 49 of 523 biopsies [9.4%], nonantithrombotic group: 172 of 2788 biopsies [6.2%]; P = .007), but clinically significant hematoma rates were not different (antithrombotic group: two of 523 biopsies [0.4%], nonantithrombotic group: one of 2788 biopsies [0.04%]; P = .07). At multivariable analysis, age (odds ratio [OR], 1.02; 95% CI: 1.01, 1.03; P < .001), 9-gauge or larger needles (OR, 2.1; 95% CI: 1.28, 3.3; P = .003), and full-dose antiplatelet drugs (OR, 2.5; 95% CI: 1.29, 5.0; P = .007) were associated with higher hematoma rates. US guidance (OR, 0.26; 95% CI: 0.17, 0.40; P < .001) and 10-14-gauge needles (OR, 0.53; 95% CI: 0.36, 0.79; P = .002) were predictive of no hematoma. Conclusion Because clinically significant hematomas were uncommon, withholding antithrombotic medications before core-needle breast biopsy may be unnecessary. Postbiopsy hematomas were associated with full-dose antiplatelet drugs, patient age, and 9-gauge or larger needles. No association was found with other types of antithrombotic medication. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chang and Yoen in this issue.

Reliability of International Classification of Disease-9 Versus International Classification of Disease-10 Coding for Proximal Femur Fractures at a Level 1 Trauma Center.

INTRODUCTION: The Centers for Medicare & Medicaid services proposed that transitioning from the 9th to the 10th revision of the International Classification of Disease (ICD) would provide better data for research. This study sought to determine the reliability of ICD-10 compared with ICD-9 for proximal femur fractures. METHODS: Available imaging studies from 196 consecutively treated proximal femur fractures were retrospectively reviewed and assigned ICD codes by three physicians. Intercoder reliability (ICR) was calculated. Collectively, the physicians agreed on what should be the correct codes for each fracture, and this was compared with coding found in the medical and billing records. RESULTS: No significant difference was observed in ICR for both ICD-9 and ICD-10 exact coding, which were both unreliable. Less specific coding improved ICR. ICD-9 general coding was better than ICD-10. Electronic medical record coding was unreliable. Billing codes were also unreliable, yet ICD-10 was better than ICD-9. DISCUSSION: ICD-9 and ICD-10 lack reliability in coding proximal femur fractures. ICD-10 results in data that are no more reliable than those found with ICD-9. LEVEL OF EVIDENCE: Level I diagnostic.

Synthetic bone: Design by additive manufacturing.

A broad range of synthetic trabecular-like metallic lattices are 3D printed, to study the extra design freedom conferred by this new manufacturing process. The aim is to propose new conceptual types of implant structures for superior bio-mechanical matching and osseo-integration: synthetic bone. The target designs are 3D printed in Ti-6Al-4V alloy using a laser-bed process. Systematic evaluation is then carried out: (i) their accuracy is characterised at high spatial resolution using computed X-ray tomography, to assess manufacturing robustness with respect to the original geometrical design intent and (ii) the mechanical properties - stiffness and strength - are experimentally measured, evaluated, and compared. Finally, this new knowledge is synthesised in a conceptual framework to allow the construction of so-called implant design maps, to define the processing conditions of bone tailored substitutes, with focus on spine fusion devices. The design criteria emphasise the bone stiffness-matching, preferred range of pore structure for bone in-growth, manufacturability of the device and choice of inherent materials properties which are needed for durable implants. Examples of the use of such maps are given with focus on spine fusion devices, emphasising the stiffness-matching, osseo-integration properties and choice of inherent materials properties which are needed for durable implants. STATEMENT OF SIGNIFICANCE: We present a conceptual bio-engineering design methodology for new biomedical lattices produced by additive manufacturing, which addresses some of the critical points in currently existing porous implant materials. Amongst others: (i) feasibility and accuracy of manufacturing, (ii) design to the elastic properties of bone, and (iii) sensible pores sizes for osseointegration. This has inspired new and novel geometrical latticed designs which aim at improving the properties of intervertebral fusion devices. In their fundamental form, these structures are here fabricated and tested. When integrated into medical devices, these concepts could offer superior medical outcomes.

The effect of induction with propofol or ketamine and diazepam on quality of anaesthetic recovery in dogs.

OBJECTIVE: To evaluate the quality of recovery in dogs undergoing elective orthopaedic surgery induced with either propofol or a combination of ketamine and diazepam. MATERIALS AND METHODS: Sixty client-owned dogs undergoing single-limb elective orthopaedic procedures were enrolled. Dogs were randomly assigned to receive induction with propofol (4 mg/kg) (group P) or ketamine (5 mg/kg) with diazepam (0.25 mg/kg) (group KD) to which all scorers were blinded. The recovery monitoring period lasted for 1 hour following extubation. The recovery period was video-recorded for blinded scoring at a later time. Scoring for quality of recovery was carried out using three different systems (lower numbers=better quality): a simple descriptive scale (1 to 5), a visual analogue scale (0 to 10 cm) and a numeric rating scale (0 to 10). Videos were reviewed by three ACVAA board-certified anaesthesiologist raters. RESULTS: Five dogs were deemed to be ineligible. The mean (±SD) duration of anaesthesia was 260.4 ±57.84 minutes in group KD and 261.1 ±51.83 minutes in group P. There was no difference between groups for time to extubation, head lift or sternal recumbency. The number of dogs having a recovery that was scored overall as bad (mean simple descriptive scale > 4, mean visual analogue scale or numeric rating scale > 5) was not different between groups. Dogs in group KD had significantly lower scores than group P dogs (simple descriptive scale P=0.01, numeric rating scale P=0.03, visual analogue scale P=0.03). CLINICAL SIGNIFICANCE: Induction with ketamine and diazepam resulted in a smoother recovery from anaesthesia than induction with propofol.

The Red Kangaroo pericardium as a material source for the manufacture of percutaneous heart valves.

BACKGROUND: The kangaroo pericardium might be considered to be a good candidate material for use in the manufacture of the leaflets of percutaneous heart valves based upon the unique lifestyle. The diet consists of herbs, forbs and strubs. The kangaroo pericardium holds an undulated structure of collagen. MATERIAL AND METHOD: A Red Kangaroo was obtained after a traffic fatality and the pericardium was dissected. Four compasses were cut from four different sites: auricular (AUR), atrial (ATR), sternoperitoneal (SPL) and phrenopericardial (PPL). They were investigated by means of scanning electron microscopy, light microscopy and transmission electron microscopy. RESULTS: All the samples showed dense and wavy collagen bundles without vascularisation from both the epicardium and the parietal pericardium. The AUR and the ATR were 150±25µm thick whereas the SPL and the PPL were thinner at 120±20µm. The surface of the epicardium was smooth and glistening. The filaments of collagen were well individualized without any aggregation, but the banding was poorly defined and somewhat blurry. CONCLUSION: This detailed morphological analysis of the kangaroo pericardium illustrated a surface resistant to thrombosis and physical characteristics resistant to fatigue. The morphological characteristics of the kangaroo pericardium indicate that it represents an outstanding alternative to the current sources e.g., bovine and porcine. However, procurement of tissues from the wild raises supply and sanitary issues. Health concerns based upon sanitary uncertainty and reliability of supply of wild animals remain real problems.

Prevalence of HIV Viral Load Suppression Among Psychiatric Inpatients with Comorbid Substance Use Disorders.

A consistently suppressed viral load enables HIV (+) patients to live longer, healthier lives and reduces the probability of transmitting the virus. Since the prevalence of HIV is four times higher among those with psychiatric disorders than in the general population, it is likely that this group would also have greater difficulty remaining in care and achieving viral suppression. A secondary data analysis utilizing screening data from the Preventing AIDS Through Health (PATH) for Triples (PFT) Study were examined to assess HIV load suppression among 254 psychiatric inpatients with comorbid substance use disorders in Philadelphia. Viral load results from the past 12 months were obtained from medical records for 63 inpatients identified as HIV (+). The sample was predominately African American (76%), male (56%), and the average age was 43 years. Psychiatric disorders included depression (64%), schizophrenia (21%), and bipolar disorder (13%) with patients reporting use of alcohol (73%), cocaine (64%), cannabis (29%) and opioids (16%) prior to admission. Among this high risk sample of HIV (+) patients, about one-half (52%) achieved viral suppression, with recent opioid users six times more likely to have a detectable viral load than non-opioid users (OR 6.0; CI 1.1-31.7, p = .035). The 52% viral load suppression rate among psychiatric inpatient was higher than expected, given that the CDC's national suppression rate among those diagnosed with HIV in the general population is 58%. However, individuals with mental illness and substance use disorders require constant surveillance, monitoring, and supportive services to achieve viral suppression. Many of those who were virally suppressed were engaged in Philadelphia's extensive treatment network, whereas those who were detectable and enrolled in the PFT intervention were often homeless with unstable psychiatric symptoms and current substance use disorders, particularly opioid abuse.

Continuous flow hygroscopicity-resolved relaxed eddy accumulation (Hy-Res REA) method of measuring size-resolved sodium chloride particle fluxes.

The accurate representation of aerosols in climate models requires direct ambient measurement of the size- and composition-dependent particle production fluxes. Here, we present the design, testing, and analysis of data collected through the first instrument capable of measuring hygroscopicity-based, size-resolved particle fluxes using a continuous-flow Hygroscopicity-Resolved Relaxed Eddy Accumulation (Hy-Res REA) technique. The Hy-Res REA system used in this study includes a 3D sonic anemometer, two fast-response solenoid valves, two condensation particle counters, a scanning mobility particle sizer, and a hygroscopicity tandem differential mobility analyzer. The different components of the instrument were tested inside the US Environmental Protection Agency's Aerosol Test Facility for sodium chloride and ammonium sulfate particle fluxes. The new REA system design does not require particle accumulation, and therefore avoids the diffusional wall losses associated with long residence times of particles inside the air collectors of traditional REA devices. A linear relationship was found between the sodium chloride particle fluxes measured by eddy covariance and REA techniques. The particle detection limit of the Hy-Res REA flux system is estimated to be ~3 × 105 m-2 s-1. The estimated sodium chloride particle classification limit, for the mixture of sodium chloride and ammonium sulfate particles of comparable concentrations, is ~6 × 106 m-2 s-1.

Increasing Obesity Prevalence in the United States End-Stage Renal Disease Population.

Background: Among ESRD patients, obesity may improve dialysis-survival but decreases likelihood of transplantation, and as such, obesity prevalence may directly affect growth of the dialysis population. Objective: The objective of this study was to assess BMI trends in the ESRD population as compared to the general population. Materials and Methods: Incident adult ESRD patients were identified from the United States Renal Data System from 01/01/1995-12/31/2010 (n=1,458,350). Data from the Behavioral Risk Factor Surveillance System (n=4,303,471) represented the US population. Trends in BMI, obesity classes I (BMI of 30-34.9), II (BMI of 35-39.9), and III (BMI ≥ 40), were examined by year of dialysis initiation. Trends in BMI slope were compared between the ESRD and US populations using linear regression. Results: Mean BMI of ESRD patients in 1995 was 25.2 as compared to 29.4 in 2010, a 16.7% increase, while the US population's mean BMI increased from 25.3 to 27.2, a 7.5% increase. BMI increase among the ESRD population was significantly more rapid than among the US population (ß: 0.16, 95% CI: 0.14-0.18, p<0.001). Conclusions and Recommendations: Mean BMI among the ESRD population is increasing more rapidly than the US population. Given decreased access to kidney transplantation among ESRD patients with obesity, future research should be directed at controlling healthcare expenditures by identifying strategies to address the obesity epidemic among the US ESRD population.

Impact of Protease Inhibitor-Based Anti-Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients.

Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p = 0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.

Spinal cord ability ruler: an interval scale to measure volitional performance after spinal cord injury.

STUDY DESIGN: Retrospective statistical analysis of database. OBJECTIVE: Spinal cord injury (SCI) clinical trials are challenged to enroll participants, and early trial outcomes have often been equivocal. We hypothesized that a specifically designed novel true linear interval-scaled outcome measure targeted to simultaneously track a broad range of SCI will enable more inclusive enrollment of participants and valid comparisons of functional changes after SCI. METHODS: To define a single SCI measurement framework, we used items from existing measures. To evaluate linearity and validity of the measure, we used rigorous psychometric Rasch analysis on two data sets from over 2500 traumatic SCI participants (all levels and severities of SCI) within the EMSCI (European Multicenter study about SCI) database. RESULTS: Volitional performance was found to be the unidimensional construct that would detect and track a treatment effect from a central nervous system-directed therapeutic. Along with early evidence for voluntary neurological control of upper-extremity muscle contractions, volitional performance is best described by goal-directed activities of daily living that are increasingly difficult to re-acquire when activity within more caudal spinal segments is required. Validity of the Spinal Cord Ability Ruler (SCAR) as a linear interval construct was confirmed with Rasch analysis. All measurement items were properly ordered, as well as being precise and stable across clinically relevant groups. Only 5/24 items had some misfit. Targeting was excellent over time after SCI, with few gaps and only modest floor and ceiling effects (3% each). CONCLUSIONS: SCAR is a quantitative linear measure of volitional performance across an inclusive range of tetraplegic and paraplegic SCI.

Increased Mortality and Graft Loss With Kidney Retransplantation Among Human Immunodeficiency Virus (HIV)-Infected Recipients.

Excellent outcomes have been demonstrated in primary human immunodeficiency virus (HIV)-positive (HIV+) kidney transplant recipients, but a subset will lose their graft and seek retransplantation (re-KT). To date, no study has examined outcomes among HIV+ re-KT recipients. We studied risk for death and graft loss among 4149 (22 HIV+ vs. 4127 HIV-negative [HIV-]) adult re-KT recipients reported to the Scientific Registry of Transplant Recipients (SRTR) (2004-2013). Compared to HIV- re-KT recipients, HIV+ re-KT recipients were more commonly African American (63.6% vs. 26.7%, p < 0.001), infected with hepatitis C (31.8% vs. 5.0%, p < 0.001) and had longer median time on dialysis (4.8 years vs. 2.1 years, p = 0.02). There were no significant differences in length of time between the primary and re-KT events by HIV status (1.5 years vs. 1.4 years, p = 0.52). HIV+ re-KT recipients experienced a 3.11-fold increased risk of death (adjusted hazard ratio [aHR]: 3.11, 95% confidence interval [CI]: 1.82-5.34, p < 0.001) and a 1.96-fold increased risk of graft loss (aHR: 1.96, 95% CI: 1.14-3.36, p = 0.01) compared to HIV- re-KT recipients. Re-KT among HIV+ recipients was associated with increased risk for mortality and graft loss. Future research is needed to determine if a survival benefit is achieved with re-KT in this vulnerable population.

Increased microvascular permeability in mice lacking Epac1 (Rapgef3).

AIM: Maintenance of the blood and extracellular volume requires tight control of endothelial macromolecule permeability, which is regulated by cAMP signalling. This study probes the role of the cAMP mediators rap guanine nucleotide exchange factor 3 and 4 (Epac1 and Epac2) for in vivo control of microvascular macromolecule permeability under basal conditions. METHODS: Epac1-/- and Epac2-/- C57BL/6J mice were produced and compared with wild-type mice for transvascular flux of radio-labelled albumin in skin, adipose tissue, intestine, heart and skeletal muscle. The transvascular leakage was also studied by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using the MRI contrast agent Gadomer-17 as probe. RESULTS: Epac1-/- mice had constitutively increased transvascular macromolecule transport, indicating Epac1-dependent restriction of baseline permeability. In addition, Epac1-/- mice showed little or no enhancement of vascular permeability in response to atrial natriuretic peptide (ANP), whether probed with labelled albumin or Gadomer-17. Epac2-/- and wild-type mice had similar basal and ANP-stimulated clearances. Ultrastructure analysis revealed that Epac1-/- microvascular interendothelial junctions had constitutively less junctional complex. CONCLUSION: Epac1 exerts a tonic inhibition of in vivo basal microvascular permeability. The loss of this tonic action increases baseline permeability, presumably by reducing the interendothelial permeability resistance. Part of the action of ANP to increase permeability in wild-type microvessels may involve inhibition of the basal Epac1-dependent activity.

Unexplained spikes in lamotrigine serum concentration: nonlinear elimination?

OBJECTIVES: The objective of this study was to evaluate possible nonlinear lamotrigine (LTG) pharmacokinetics at elevated concentration. LTG is reported to have linear kinetics, so that elimination rate is linearly proportional to blood concentration and a change in dose is accompanied by a proportionate change in serum concentration. We encountered patients in whom LTG serum concentration increased dramatically in response to minor or no change in LTG dose. We studied this phenomenon in patients with LTG toxicity in one clinic. MATERIALS AND METHODS: Using electronic medical records from 1997 to 2014, we identified patients who developed clinical LTG toxicity with LTG serum concentrations >20 mg/l, after tolerating lamotrigine at lower serum concentrations. We reviewed LTG dose change and other changes that preceded the episode of toxicity. RESULTS: Twenty-two patients had at least one episode of LTG toxicity with levels higher than 20 mg/l (of 922 patients with available levels). The peak serum concentration varied from 21.1 to 40.3 mg/l (mean 28.7). The increase in level was explained in three patients (post-delivery in one, addition of valproate in two). In the 18 others, the increase was not explained or it was disproportionate to an increase in LTG dose. CONCLUSIONS: Spikes in LTG levels and associated clinical toxicity may occur unexpectedly, suggesting that elimination kinetics may be nonlinear in some individuals at serum concentrations in the upper range. Measurement and close monitoring of LTG levels is warranted for new symptoms that could be consistent with lamotrigine toxicity, particularly when the baseline serum concentration has been >10 mg/l.

Systematic review of clinical practice guidelines in kidney transplantation.

BACKGROUND: Clinical practice guidelines (CPGs) are widely used to inform the development of protocols for clinical management. Previous work has demonstrated that the quality of CPGs varies widely. This systematic review aimed to determine the quality of CPGs in kidney transplantation in the UK. METHODS: CPGs in kidney transplantation published between 2010 and 2017 were identified through searches of MEDLINE, NHS NICE Evidence, and websites of relevant UK societies. Using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool, three appraisers rated the quality of CPGs across six domains, the overall quality of each CPG, and whether it should be recommended for future use. Domain scores were calculated, and inter-rater reliability using the intraclass correlation coefficient (ICC) was reported. RESULTS: Thirteen CPGs met the inclusion criteria. The domain 'clarity of presentation' scored highest, followed closely by 'scope and purpose'. The poorest scoring domains were 'applicability' and 'editorial independence'. Editorial independence also had the widest range of scores. Of the 13 CPGs, one was not recommended for future use, seven were recommended for use with modifications, and five for future use with no need for modification. Mean overall CPG quality was 5 (range 3-6) of a maximum score of 7, and mean inter-rater reliability was substantial with an ICC of 0·71. CONCLUSION: UK CPGs scored satisfactorily, although with wide variation in how well each domain scored both within and across CPGs. The quality of UK CPGs can still be improved.

Dosing Eculizumab for Antibody-Mediated Rejection in Kidney Transplantation: A Case Report.

Severe antibody-mediated rejection (AMR) of a blood type-incompatible (ABOi) living donor kidney transplantation (LDKT) can lead to graft failure, and aggressive therapies, such as the anticomplement antibody eculizumab, are often used to rescue the affected graft. Eculizumab therapy can be crippling financially. Current literature suggests a wide variation in the amount and timing of eculizumab given as rescue therapy in the setting of AMR. Herein we describe a limited-eculizumab regimen in the setting of severe AMR that is both clinically and cost effective. Treatment included escalation in plasmapheresis and intravenous immunoglobulin (PP/IVIg) and eculizumab. Eculizumab therapy was discontinued at the first sign of clinical improvement (2-fold decrease in anti-ABO titer and stabilization of serum creatinine). The current standard of care is to redose eculizumab after any PP treatment, and, in some series, continue with maintenance eculizumab doses. In these 2 cases, discontinuing eculizumab therapy upon observed clinical improvement saved 6 unnecessary doses at a cost of $90,000. Both patients have more than 1 year of follow-up and functioning allografts. Although this is a small and limited study, we suggest that a dosing regimen of eculizumab similar to that presented here may be effective in rescuing a graft following AMR while simultaneously limiting cost.

Identification of Optimal Donor-Recipient Combinations Among Human Immunodeficiency Virus (HIV)-Positive Kidney Transplant Recipients.

For some patient subgroups, human immunodeficiency virus (HIV) infection has been associated with worse outcomes after kidney transplantation (KT); potentially modifiable factors may be responsible. The study goal was to identify factors that predict a higher risk of graft loss among HIV-positive KT recipients compared with a similar transplant among HIV-negative recipients. In this study, 82 762 deceased donor KT recipients (HIV positive: 526; HIV negative: 82 236) reported to the Scientific Registry of Transplant Recipients (SRTR) (2001-2013) were studied by interaction term analysis. Compared to HIV-negative recipients, the hepatitis C virus (HCV) amplified risk 2.72-fold among HIV-positive KT recipients (adjusted hazard ratio [aHR]: 2.72, 95% confidence interval [CI]: 1.75-4.22, p < 0.001). Forty-three percent of the excess risk was attributable to the interaction between HIV and HCV (attributable proportion of risk due to the interaction [AP]: 0.43, 95% CI: 0.23-0.63, p = 0.02). Among HIV-positive recipients with more than three HLA mismatches (MMs), risk was amplified 1.80-fold compared to HIV-negative (aHR: 1.80, 95% CI: 1.31-2.47, p < 0.001); 42% of the excess risk was attributable to the interaction between HIV and more than three HLA MMs (AP: 0.42, 95% CI: 0.24-0.60, p = 0.01). High-HIV-risk (HIV-positive/HCV-positive HLAwith more than three MMs) recipients had a 3.86-fold increased risk compared to low-HIV-risk (HIV-positive/HCV-negative HLA with three or fewer MMs)) recipients (aHR: 3.86, 95% CI: 2.37-6.30, p < 0.001). Avoidance of more than three HLA MMs in HIV-positive KT recipients, particularly among coinfected patients, may mitigate the increased risk of graft loss associated with HIV infection.