ApoE Mimetic Peptides as Therapy for Traumatic Brain Injury.

The lack of targeted therapies for traumatic brain injury (TBI) remains a compelling clinical unmet need. Although knowledge of the pathophysiologic cascades involved in TBI has expanded rapidly, the development of novel pharmacological therapies has remained largely stagnant. Difficulties in creating animal models that recapitulate the different facets of clinical TBI pathology and flaws in the design of clinical trials have contributed to the ongoing failures in neuroprotective drug development. Furthermore, multiple pathophysiological mechanisms initiated early after TBI that progress in the subacute and chronic setting may limit the potential of traditional approaches that target a specific cellular pathway for acute therapeutic intervention. We describe a reverse translational approach that focuses on translating endogenous mechanisms known to influence outcomes after TBI to develop druggable targets. In particular, numerous clinical observations have demonstrated an association between apolipoprotein E (apoE) polymorphism and functional recovery after brain injury. ApoE has been shown to mitigate the response to acute brain injury by exerting immunomodulatory properties that reduce secondary tissue injury as well as protecting neurons from excitotoxicity. CN-105 represents an apoE mimetic peptide that can effectively penetrate the CNS compartment and retains the neuroprotective properties of the intact protein.

Neuroprotection and Therapeutic Implications of Creatine Supplementation for Brain Injury Complications.

Creatine supplementation has not been researched for Traumatic Brain Injury (TBI) extensively, but studies suggest potential as a neuroprotective agent and potential treatment for brain-injury complications. Patients suffering from TBI experience mitochondrial dysfunction, neuropsychological burden, and deficits in cognitive performance due to malperformance of brain creatine levels, diminished brain Adenosine Triphosphate (ATP) levels, glutamate toxicity, and oxidative stress. In this systemic review, the current available research is reviewed to examine the effects of creatine on common sequalae of TBI within children, adolescents, and mice. Past and present data still lacks the knowledge of creatine supplementation for the adult population and military members during TBI. PubMed was searched for studies which assessed the correlation between creatine supplementation of TBI complications. The search strategy yielded 40 results, of which 15 articles were included in this systemic review. The results of the review supported an apparent understanding creatine does offer an obvious benefit to patients suffering from TBI and post-injury complications under specific guidelines. Time and dose dependent metabolic alterations seem to be only exceptionally prevalent when given as a prophylaxis or if given acutely. Results are only clinically significant after a month of supplementation. Although patients may need many therapeutic treatments to recover from TBI, especially in acute resuscitation, creatine shows superior efficacy as a neuroprotective agent in battling the chronic manifestations which lead to oxidative stress and cognitive function post brain injury.

Urgent-start peritoneal dialysis: Association with outcomes.

The majority of end-stage kidney disease (ESKD) patients start dialysis without adequate pre-dialysis planning. Of these patients, the vast majority initiate in-centre haemodialysis using a central venous catheter (ICHD-CVC). A minority utilise urgent-start peritoneal dialysis (USPD), whereby a peritoneal dialysis catheter is placed and used for dialysis without the usual 2-4-week waiting period. In this multicentre, retrospective study of adult patients initiating dialysis during 2018, we compared outcomes among patients utilising these two dialysis initiation routes. Patients who initiated dialysis via ICHD-CVC were matched 1:1 to patients who utilised USPD on the basis of aetiology of ESKD, race, diabetes status and insurance type. Hospitalisation and mortality were evaluated from dialysis initiation through the first of death, transplant, loss to follow-up or study end (30 June 2019). Outcomes were compared using models adjusted for age and sex. A total of 717 USPD patients were matched to ICHD-CVC patients. During follow-up, USPD patients were hospitalised at a rate of 1.21 admissions/patient-year (pt-yr) versus 1.51 admissions/pt-yr for ICHD-CVC. This corresponded to a 24% lower rate of hospitalisation among USPD patients (adjusted incidence rate ratio 0.76, 95% confidence interval [CI] 0.65-0.88). Mortality rates were 0.08 and 0.11 deaths/pt-yr among USPD patients and ICHD-CVC patients, respectively (adjusted hazard ratio 0.84, 95% CI 0.62, 1.15). These findings suggest that more widespread adoption of USPD may be beneficial among patients with limited pre-dialysis planning.

Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury.

The treatment of traumatic brain injury (TBI) in military populations is hindered by underreporting and underdiagnosis. Clinical symptoms and outcomes may be mitigated with an effective pre-injury prophylaxis. This study evaluates whether CN-105, a 5-amino acid apolipoprotein E (ApoE) mimetic peptide previously shown to modify the post-traumatic neuroinflammatory response, would maintain its neuroprotective effects if administered prior to closed-head injury in a clinically relevant murine model. CN-105 was synthesized by Polypeptide Inc. (San Diego, CA) and administered to C57-BL/6 mice intravenously (IV) and/or by intraperitoneal (IP) injection at various time points prior to injury while vehicle treated animals received IV and/or IP normal saline. Animals were randomized following injury and behavioral observations were conducted by investigators blinded to treatment. Vestibulomotor function was assessed using an automated Rotarod (Ugo Basile, Comerio, Italy), and hippocampal microglial activation was assessed using F4/80 immunohistochemical staining in treated and untreated mice 7 days post-TBI. Separate, in vivo assessments of the pharmacokinetics was performed in healthy CD-1. IV CN-105 administered prior to head injury improved vestibulomotor function compared to vehicle control-treated animals. CN-105 co-administered by IP and IV dosing 6 h prior to injury also improved vestibulomotor function up to 28 days following injury. Microglia counted in CN-105 treated specimens were significantly fewer (P = 0.03) than in vehicle specimens. CN-105 improves functional outcomes and reduces hippocampal microglial activation when administered prior to injury and could be adapted as a pre-injury prophylaxis for soldiers at high risk for TBI.

Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector-Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients.

BACKGROUND: Studies have demonstrated that mRNA-based SARS-CoV-2 vaccines are highly effective among patients on dialysis. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness relative to other vaccines, such those on the basis of adenovirus technologies. METHODS: In this retrospective study, we compared the clinical effectiveness of adenovirus vector-based Ad26.COV2.S (Janssen/Johnson & Johnson) to mRNA-based BNT162b2 (Pfizer/BioNTech) in a contemporary cohort of patients on dialysis. Patients who received a first BNT162b2 dose were matched 1:1 to Ad26.COV2.S recipients on the basis of date of first vaccine receipt, US state of residence, site of dialysis care (in-center versus home), history of COVID-19, and propensity score. The primary outcome was the comparative rate of COVID-19 diagnoses starting in the 7th week postvaccination. In a subset of consented patients who received Ad26.COV2.S, blood samples were collected ≥28 days after vaccination and anti-SARS-CoV-2 immunoglobulin G antibodies were measured. RESULTS: A total of 2572 matched pairs of patients qualified for analysis. Cumulative incidence rates of COVID-19 did not differ for BNT162b2 versus Ad26.COV2.S. No differences were observed in peri-COVID-19 hospitalizations and deaths among patients receiving BNT162b2 versus Ad26.COV2.S, who were diagnosed with COVID-19 during the at-risk period. Results were similar when excluding patients with a history of COVID-19, in subgroup analyses restricted to patients who completed the two-dose BNT162b2 regimen, and in patients receiving in-center hemodialysis. SARS-CoV-2 antibodies were detected in 59.4% of 244 patients who received Ad26.COV2.S. CONCLUSIONS: In a large real-world cohort of patients on dialysis, no difference was detected in clinical effectiveness of BNT162b2 and Ad26.COV2.S over the first 6 months postvaccination, despite an inconsistent antibody response to the latter.

23.4% Hypertonic Saline: A Tactical Option for the Management of Severe Traumatic Brain Injury With Impending or Ongoing Herniation.

There are limited options available to the combat medic for management of traumatic brain injury (TBI) with impending or ongoing herniation. Current pararescue and Tactical Combat Casualty Care (TCCC) guidelines prescribe a bolus of 3% or 5% hypertonic saline. However, this fluid bears a tactical burden of weight (~570g) and pack volume (~500cm3). Thus, 23.4% hypertonic saline is an attractive option, because it has a lighter weight (80g) and pack volume (55cm3), and it provides a similar osmotic load per dose. Current literature supports the use of 23.4% hypertonic saline in the management of acute TBI, and evidence indicates that it is safe to administer via peripheral and intraosseous cannulas. Current combat medic TBI treatment algorithms should be updated to include the use of 23.4% hypertonic saline as an alternative to 3% and 5% solutions, given its effectiveness and tactical advantages.

Impact of Rescheduling a Missed Hemodialysis Treatment on Clinical Outcomes.

RATIONALE & OBJECTIVE: Among patients treated with in-center hemodialysis (HD), missed treatments are associated with higher subsequent rates of hospitalization and other adverse outcomes compared with attending treatment. The objective of this study was to determine whether and to what degree attending a rescheduled treatment on the day following a missed treatment ameliorates these risks. STUDY DESIGN: Retrospective, observational. SETTING & PARTICIPANTS: Included patients were those who were, as of any of 12 index dates during 2014, adult Medicare beneficiaries treated with in-center HD (vintage ≥ 90 days) on a Monday/Wednesday/Friday schedule. EXPOSURE: Treatment attendance on the index date and the subsequent day. OUTCOMES: Hospital admissions, emergency department visits, mortality, blood pressure, and anemia measures, considered during the 7- and 30-day periods following exposure. ANALYTICAL APPROACH: In parallel analyses, patients who missed or rescheduled treatment were each matched (1:5) to patients who attended treatment on the index date on the basis of index day of week and propensity score. Within the matched cohorts, outcomes were compared across exposures using repeated-measures generalized linear models. RESULTS: Compared with attending treatment (N = 19,260), a missed treatment (N = 3,852) was associated with a 2.09-fold higher rate of hospitalization in the subsequent 7 days; a rescheduled treatment (N = 2,128) was associated with a 1.68-fold higher rate of hospitalization than attending (N = 10,640). Compared with attending treatment, hospitalization rates were 1.39- and 1.28-fold higher among patients who missed and rescheduled treatment, respectively, during the 30-day outcome period. Emergency department visits followed a similar pattern of associations as hospitalization. No statistically significant associations were observed with respect to mortality for either missed or rescheduled treatments compared with attending treatment. LIMITATIONS: Possible influence of unmeasured confounding; unknown generalizability to patients with non-Medicare insurance. CONCLUSIONS: Attending a rescheduled in-center HD treatment attenuates but does not fully mitigate the adverse effects of a missed treatment.

Beyond the burn: Studies on the physiological effects of flamethrowers during World War II.

Flamethrowers are widely considered one of warfare's most controversial weapons and are capable of inflicting gruesome physical injuries and intense psychological trauma. Despite being the last of the major combatants in World War II (WWII) to develop them, the United States military quickly became the most frequent and adept operator of portable flamethrowers. This gave the U.S. military ample opportunity to observe the effects of flamethrowers on enemy soldiers. However, while most people in modern times would consider immolation by flamethrower to be an unnecessarily painful and inhumane way to inflict casualties, immolation was, at one point during World War II (WWII), referred to as "mercy killing" by the U.S. Chemical Warfare Service (CWS). This mischaracterization arose from a series of first-hand accounts describing what were believed to be quick, painless, and unmarred deaths, as well as from a poor and incomplete understanding of flamethrower lethality. As a result, indirect mechanisms such as hypoxia and carbon monoxide poisoning were generally absent from accounts of the flamethrower's fatal effects. It was not until several years after flamethrowers were introduced to the frontlines that the CWS and National Defense Research Committee (NDRC) conducted a series of tests to better understand the physiological and toxicological effects of flamethrowers. This article examines how the initial absence of scientific data on the physiologic effects of flamethrowers led to an inaccurate understanding of their lethality, and bizarre claims that one of history's most horrific instruments of war was considered one of the more "humane" weapons on the battlefield.

The Prehospital Evaluation and Care of Moderate/Severe TBI in the Austere Environment.

Increased resource constraints secondary to a smaller medical footprint, prolonged evacuation times, or overwhelming casualty volumes all increase the challenges of effective management of traumatic brain injury (TBI) in the austere environment. Prehospital providers are responsible for the battlefield recognition and initial management of TBI. As such, targeted education is critical to efficient injury recognition, promoting both provider readiness and improved patient outcomes. When austere conditions limit or prevent definitive treatment, a comprehensive understanding of TBI pathophysiology can help inform acute care and enhance prevention of secondary brain injury. Field deployable, noninvasive TBI assessment and monitoring devices are urgently needed and are currently undergoing clinical evaluation. Evidence shows that the assessment, monitoring, and treatment in the first few hours and days after injury should focus on the preservation of cerebral perfusion and oxygenation. For cases where medical management is inadequate (eg, evidence of an enlarging intracranial hematoma), guidelines have been developed for the performance of cranial surgery by nonneurosurgeons. TBI management in the austere environment will continue to be a challenge, but research focused on improving evidence-based monitoring and therapeutic interventions can help to mitigate some of these challenges and improve patient outcomes.

Safety and efficacy of heparin during dialysis in the context of systemic anticoagulant and antiplatelet medications.

Heparin is widely used to prevent coagulation during hemodialysis. Although systemic anticoagulants and antiplatelet agents are commonly prescribed in the hemodialysis population, the safety and efficacy of heparin in the presence of these medications is unclear. This retrospective cohort study considered adult hemodialysis patients treated in the United States (August 2015-July 2017). For each month, patients were ascribed a three-part exposure status (heparin use, anticoagulant use, antiplatelet agent use) based on electronic health records. Outcomes included anemia measures, peri-treatment bleeding and clotting, and hospitalization for gastrointestinal (GI) bleeding. Within systemic medication exposure categories, associations of heparin use were examined using adjusted generalized linear, negative binomial, or Poisson models. Across all systemic medication exposures, heparin use was associated with lower erythropoiesis stimulating agent (ESA) dose, higher hemoglobin levels, and lower monthly intravenous (IV) iron dose; lower rates of clotting during treatment and hospitalization for GI bleeding; and similar rates of peri-treatment bleeding. Associations with respect to ESA, IV iron, hemoglobin, and clotting were approximately twofold more potent in the absence of a systemic anticoagulant; the presence of an antiplatelet agent had little impact. Neither medication type influenced associations between heparin use and peri-treatment or GI bleeding. These results suggest that heparin use is safe and effective in the presence and absence of systemic anticoagulants and antiplatelet agents. Clinical judgment must be applied to assess bleeding risk in individual patients; however, the decision to withhold heparin should not solely be based upon the concurrent use of anticoagulant or antiplatet agents.

The Impact of Midodrine on Outcomes in Patients with Intradialytic Hypotension.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of hemodialysis, and is associated with significant morbidity and mortality. Off-label use of the alpha-1 andrenergic receptor agonist midodrine to reduce the frequency and severity of IDH is common. However, limited data exist to support this practice. This study sought to examine real-world efficacy of midodrine with respect to relevant clinical and hemodynamic outcomes. METHODS: Here, we compared a variety of clinical and hemodynamic outcomes among adult patients who were prescribed midodrine (n = 1,046) and matched controls (n = 2,037), all of whom were receiving in-center hemodialysis treatment at dialysis facilities in the United States (July 2015 - September 2016). Mortality, all-cause hospitalization, cardiovascular hospitalization, and hemodynamic outcomes were considered from the month following the initiation of midodrine (or corresponding month for controls) until censoring for discontinuation of dialysis, transplant, loss to follow-up, or study end (September 30, 2016). Rate outcomes were compared using Poisson models and quantitative outcomes using linear mixed models; all models were adjusted for imbalanced patient characteristics. RESULTS: Compared to non-use, midodrine use was associated with higher rates of death (adjusted incidence rate ratio 1.37, 95% CI 1.15-1.62), all-cause hospitalization (1.31, 1.19-1.43) and cardiovascular hospitalization (1.41, 1.17-1.71). During follow-up, midodrine use tended to be associated with lower pre-dialysis systolic blood pressure (SBP), lower nadir SBP, greater fall in SBP during dialysis, and a greater proportion of treatments affected by IDH. CONCLUSION: Although residual confounding may have influenced the results, the associations observed here are not consistent with a potent beneficial effect of midodrine with respect to either clinical or hemodynamic outcomes.

Hepatitis C virus infection in patients with end-stage renal disease.

Chronic hepatitis C virus (HCV) infection is a major global health problem affecting 3-5 million people in the United States and over 100 million worldwide. Chronic HCV infection, which can lead to cirrhosis and hepatocellular carcinoma, also results in numerous other complications, including impairment of renal function. Because HCV is most often transmitted via parenteral exposure to blood or blood products, patients with end-stage renal disease (ESRD) treated with hemodialysis are at particular risk for infection. Historically, the medications available to treat HCV infection in these patients had significant side effects and were not particularly effective in generating a sustained virologic response. Since 2011, a number of direct-acting antiviral therapies have emerged that can lead to virological cure in the vast majority of patients, with low pill burden and few side effects. Here, we describe the biology and pathophysiology of HCV infection, and summarize current information on new therapies, with a particular focus on their application in patients with chronic kidney disease including ESRD.

Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream Infection.

Central venous catheters (CVCs) contribute disproportionately to bloodstream infection (BSI) and, by extension, to infection-related hospitalization, mortality, and health care costs in patients undergoing dialysis. Recent product advancements may reduce BSIs, but a sufficiently powered comparative-effectiveness study is needed to facilitate evidence-based patient care decisions. In a 13-month, prospective, cluster-randomized, open-label trial, we compared BSI rates in facilities using ClearGuard HD antimicrobial barrier caps (ClearGuard group) with those in facilities using Tego hemodialysis connectors plus Curos disinfecting caps (Tego+Curos group). Forty DaVita dialysis facilities in the United States were pair-matched by BSI rate, number of patients using CVCs, and geographic location, and then cluster randomized 1:1. We enrolled all adult patients undergoing dialysis with CVCs at these facilities, except those allergic to heparin or chlorhexidine. Overall, 1671 patients participated in the study, accruing >183,000 CVC-days. The study outcome was positive blood culture (PBC) rate as an indicator of BSI rate. We calculated results at the cluster level and adjusted for the facility cluster effect. During a 3-month run-in period immediately before study interventions, the groups had similar BSI rates (P=0.8). During the 13-month intervention period that immediately followed, the ClearGuard group had a BSI rate significantly lower than that of the Tego+Curos group (0.28 versus 0.75 PBCs per 1000 CVC-days, respectively; P=0.001). No device-related adverse events were reported. In conclusion, compared with Tego connectors plus Curos caps, ClearGuard HD antimicrobial barrier caps significantly lowered the rate of catheter-related BSIs in patients undergoing hemodialysis using CVCs, representing an important advancement in hemodialysis patient care.

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

BACKGROUND: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. METHODS: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. RESULTS: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. CONCLUSIONS: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD.

Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose: an analysis of the randomized FIND-CKD trial.

BACKGROUND: Preclinical studies demonstrate renal proximal tubular injury after administration of some intravenous iron preparations but clinical data on renal effects of intravenous iron are sparse. METHODS: FIND-CKD was a 56-week, randomized, open-label, multicenter study in which patients with non-dialysis dependent chronic kidney disease (ND-CKD), anemia and iron deficiency without erythropoiesis-stimulating agent therapy received intravenous ferric carboxymaltose (FCM), targeting either higher (400-600 µg/L) or lower (100-200 µg/L) ferritin values, or oral iron. RESULTS: Mean (SD) eGFR at baseline was 34.9 (11.3), 32.8 (10.8) and 34.2 (12.3) mL/min/1.73 m2 in the high ferritin FCM (n = 97), low ferritin FCM (n = 89) and oral iron (n = 167) groups, respectively. Corresponding values at month 12 were 35.6 (13.8), 32.1 (12.7) and 33.4 (14.5) mL/min/1.73 m2. The pre-specified endpoint of mean (SE) change in eGFR from baseline to month 12 was +0.7 (0.9) mL/min/1.73 m2 with high ferritin FCM (p = 0.15 versus oral iron), -0.9 (0.9) mL/min/1.73 m2 with low ferritin FCM (p = 0.99 versus oral iron) and -0.9 (0.7) mL/min/1.73 m2 with oral iron. No significant association was detected between quartiles of FCM dose, change in ferritin or change in TSAT versus change in eGFR. Dialysis initiation was similar between groups. Renal adverse events were rare, with no indication of between-group differences. CONCLUSION: Intravenous FCM at doses that maintained ferritin levels of 100-200 µg/L or 400-600 µg/L did not negatively impact renal function (eGFR) in patients with ND-CKD over 12 months versus oral iron, and eGFR remained stable. These findings show no evidence of renal toxicity following intravenous FCM over a 1-year period. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00994318 (first registration 12 October 2009).

Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model.

Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.

Lower Extremity Compartment Syndrome From Prolonged Limb Compression and Immobilization During an Airborne Operation.

Acute compartment syndrome (ACS) involving the leg can occur in association with various traumatic and nontraumatic conditions, and it can have serious longterm consequences when unrecognized or untreated. Nontraumatic causes of ACS, such as those associated with cases of prolonged immobilization and/or extremity compression, can be easily overlooked, and several cases of ACS occurring with prolonged surgical positioning can be found in the literature. We present the case of a 19-year-old Army paratrooper who developed acute anterior and lateral compartment syndrome of the lower extremity after being immobilized in an aircraft for hours with several hundred pounds of equipment compressing his lower extremities. To our knowledge, this is the first documented case of ACS occurring as a result of prejump conditions. It demonstrates a potentially serious complication that could result in medical separation and/or permanent disability of the service member. ACS of the extremity should be considered in any Soldier who is required to bear heavy loads, is immobilized for several hours at a time, and complains of symptoms such as extremity pain, numbness, and weakness.

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial.

Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600µg/L) or lower (100-200µg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.