Successful liver transplantation from deceased donors with active COVID-19 infections with undetectable SARS-CoV-2 in donor liver and aorta.

BACKGROUND: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had unprecedented effects on society and modern healthcare. In liver transplantation, uncertainty regarding the safety of performing transplants during the early stage of the pandemic resulted in increased waitlist mortality. Additionally, concerns about disease transmission led to avoidance of deceased donors with COVID-19 infections. Several successful case reports describing incidental transplant of organs from donors with COVID-19 infections or intentional transplant of such donors into recipients with current or prior COVID-19 infections prompted the transplant community to re-evaluate that position. While excellent short-term results have been published, little is known about use of donors with active infections and the extent of COVID-19 organ involvement, which may affect long term outcomes. METHODS: We report the successful transplantation of three livers from deceased donors with active COVID-19 infections. Donor liver and aortic tissues were evaluated by sensitive molecular testing for SARS-CoV-2 RNA via in situ hybridization and real-time quantitative reverse transcription PCR. RESULTS: Postoperatively, all patients had excellent allograft function, without clinical or molecular evidence of SARS-CoV-2 transmission in donor tissues. CONCLUSION: This evidence supports the use of liver donors with active COVID-19 infections.

Noninvasive Risk Stratification for Nonalcoholic Fatty Liver Disease Among Living Liver Donor Candidates: A Proposed Algorithm.

To reduce waitlist mortality, living donor liver transplantation (LDLT) has increased over the past decade in the United States, but not at a rate sufficient to completely mitigate organ shortage. As a result, there are ongoing efforts to expand the living liver donor pool. Simultaneously, the prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population has increased, which has significant implications on the pool of potential living liver donors. As such, a clinical assessment algorithm that exhaustively evaluates for NAFLD and fibrosis is critical to the safe expansion of LDLT. An ideal algorithm would employ safe and noninvasive methods, relying on liver biopsy only when necessary. While exclusion of NAFLD and fibrosis by noninvasive means is widely studied within the general population, there are no well-accepted guidelines for evaluation of living donors using these modalities. Here we review the current literature regarding noninvasive NALFD and fibrosis evaluation and propose a potential algorithm to apply these modalities for the selection of living liver donors.

Steroid-sparing maintenance immunosuppression is safe and effective after simultaneous liver-kidney transplantation.

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.

Innovative approach to the difficult ventricular shunt using pleural access device for maintenance drainage: case report.

Patients with complex medical problems and multiple failed ventricular shunts require continued innovation for hydrocephalus management. The authors report the case of a 4-year-old boy with refractory hydrocephalus and secondary reduced ability to absorb CSF in both the pleural and peritoneal cavities following renal transplantation. A novel management approach was devised with split shunting to pleural and peritoneal targets as well as prophylactic pleural port placement to provide a method for minimally invasive thoracentesis should symptomatic pleural effusions develop. Fluid was successfully aspirated via the pleural port with relief of symptoms over a period of 16 months without complication. The authors demonstrate that a previously undescribed approach to distal shunting can prevent neurological sequelae of shunt failure and permit noninvasive maintenance drainage for patients in whom symptomatic pleural effusion is a recurrent complication.

Delayed Graft Function in Simultaneous Liver Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF) is associated with inferior posttransplant outcomes in kidney transplantation. Given these adverse outcomes, we sought to determine the incidence, unique risk factors, and posttransplant outcomes for simultaneous liver kidney (SLK) transplant recipients developing DGF. METHODS: We studied 6214 adult SLK recipients from March 2002 to February 2017 using the Scientific Registry of Transplant Recipients. We determined associations between risk factors and DGF using Poisson multivariate regression and between DGF and graft failure and mortality using Cox proportional hazard analysis. RESULTS: The overall rate of DGF was 21.8%. Risk factors for DGF in the hepatitis C virus (HCV)-negative recipient population included pretransplant dialysis (adjusted incident rate ratio [aIRR] 3.26, P = 0.004), donor body mass index (aIRR 1.25 per 5 kg/m, P = 0.01), and transplantation with a donation after circulatory death (aIRR 5.38, P = 0.001) or imported donor organ (regional share aIRR 1.69, P = 0.03; national share aIRR 4.82, P < 0.001). DGF was associated with a 2.6-fold increase in kidney graft failure (adjusted hazard ratio [aHR] 2.63, P < 0.001), 1.6-fold increase in liver graft failure (aHR 1.62, P < 0.001), and 1.6-fold increase in mortality (aHR 1.62, P < 0.001). CONCLUSIONS: In HCV-negative SLK recipients, recipient pretransplant dialysis and components of kidney graft quality comprise significant risk factors for DGF. Regardless of HCV status, DGF is associated with inferior posttransplant outcomes. Understanding these risk factors during clinical decision-making may improve prevention of DGF and may represent an opportunity to improve posttransplant outcomes.

Liver Transplantation for Severe Alcoholic Hepatitis, Updated Lessons from the World's Largest Series.

BACKGROUND: Six-month sobriety before transplantation for alcoholic liver disease is typically required but poorly supported by data. We initiated a pilot program after a report of liver transplantation for severe alcoholic hepatitis (SAH) in which the 6-month rule was waived. We previously reported early outcomes; we now provide longer follow-up in the largest cohort of early liver transplantation for SAH in the literature to date. STUDY DESIGN: Forty-six carefully selected patients with SAH underwent liver transplantation from October 2012 through July 2017; none had been abstinent for 6 months. We also examined 34 patients with alcoholic cirrhosis who received liver transplants under standard protocols with at least 6 months sobriety. We identified patient characteristics and primary outcomes of patient and graft survival, as well as alcohol recidivism. Secondary outcomes included post-transplantation infection, malignancy, and rejection. RESULTS: Compared with patients with alcoholic cirrhosis, SAH patients were younger and with shorter drinking history and higher Model for End-Stage Liver Disease scores at listing and at transplantation. Of these patients, 46% received preoperative steroids; all were nonresponders by Lille score. At a median follow-up time of 532 days (interquartile range 281 to 998 days), there were no significant differences between groups by log-rank testing of Kaplan-Meier estimates for patient and graft survival or alcohol recidivism. CONCLUSIONS: In the largest cohort of patients reported, outcomes after liver transplantation for SAH had excellent 1-year outcomes, similar to those seen in patients who received transplants with 6 months of sobriety. Recidivism was similar in the 2 groups. Early liver transplantation for SAH represents life-saving therapy for patients with otherwise high mortality, calling into question the utility of the 6-month rule in predicting outcomes in patients receiving transplants for alcoholic liver disease.

A Randomized, Controlled Trial of Mirror Therapy for Upper Extremity Phantom Limb Pain in Male Amputees.

OBJECTIVE: Phantom limb pain (PLP) is prevalent in patients post-amputation and is difficult to treat. We assessed the efficacy of mirror therapy in relieving PLP in unilateral, upper extremity male amputees. METHODS: Fifteen participants from Walter Reed and Brooke Army Medical Centers were randomly assigned to one of two groups: mirror therapy (n = 9) or control (n = 6, covered mirror or mental visualization therapy). Participants were asked to perform 15 min of their assigned therapy daily for 5 days/week for 4 weeks. The primary outcome was pain as measured using a 100-mm Visual Analog Scale. RESULTS: Subjects in the mirror therapy group had a significant decrease in pain scores, from a mean of 44.1 (SD = 17.0) to 27.5 (SD = 17.2) mm (p = 0.002). In addition, there was a significant decrease in daily time experiencing pain, from a mean of 1,022 (SD = 673) to 448 (SD = 565) minutes (p = 0.003). By contrast, the control group had neither diminished pain (p = 0.65) nor decreased overall time experiencing pain (p = 0.49). A pain decrement response seen by the 10th treatment session was predictive of final efficacy. CONCLUSION: These results confirm that mirror therapy is an effective therapy for PLP in unilateral, upper extremity male amputees, reducing both severity and duration of daily episodes. REGISTRATION: NCT0030144 ClinicalTrials.gov.

A modified Kampala trauma score (KTS) effectively predicts mortality in trauma patients.

BACKGROUND: Mortality prediction in trauma patients has relied upon injury severity scoring tools focused on anatomical injury. This study sought to examine whether an injury severity scoring system which includes physiologic data performs as well as anatomic injury scores in mortality prediction. METHODS: Using data collected from 18 Level I trauma centers and 51 non-trauma center hospitals in the US, anatomy based injury severity scores (ISS), new injury severity scores (NISS) were calculated as were scores based on a modified version of the physiology-based Kampala trauma score (KTS). Because pre-hospital intubation, when required, is standard of care in the US, a modified KTS was calculated excluding respiratory rate. The predictive ability of the modified KTS for mortality was compared with the ISS and NISS using receiver operating characteristic (ROC) curves. RESULTS: A total of 4716 individuals were eligible for study. Each of the three scores was a statistically significant predictor of mortality. In this sample, the modified KTS significantly outperformed the ISS (AUC=0.83, 95% CI 0.81-0.84 vs. 0.77, 95% CI 0.76-0.79, respectively) and demonstrated similar predictive ability compared to the NISS (AUC=0.83, 95% CI 0.81-0.84 vs. 0.82, 95% CI 0.80-0.83, respectively). CONCLUSIONS: The modified KTS may represent a useful tool for assessing trauma mortality risk in real time, as well as in administrative data where physiologic measures are available. Further research is warranted and these findings suggest that the collection of physiologic measures in large databases may improve outcome prediction.

Observation of limb movements reduces phantom limb pain in bilateral amputees.

BACKGROUND: Mirror therapy has been demonstrated to reduce phantom limb pain (PLP) experienced by unilateral limb amputees. Research suggests that the visual feedback of observing a limb moving in the mirror is critical for therapeutic efficacy. OBJECTIVE: Since mirror therapy is not an option for bilateral lower limb amputees, the purpose of this study was to determine if direct observation of another person's limbs could be used to relieve PLP. METHODS: We randomly assigned 20 bilateral lower limb amputees with PLP to visual observation (n = 11) or mental visualization (n = 9) treatment. Treatment consisted of seven discrete movements which were mimicked by the amputee's phantom limbs moving while visually observing the experimenter's limbs moving, or closing the eyes while visualizing and attempting the movements with their phantom limbs, respectively. Participants performed movements for 20 min daily for 1 month. Response to therapy was measured using a 100-mm visual analog scale (VAS) and the McGill Short-Form Pain Questionnaire (SF-MPQ). RESULTS: Direct visual observation significantly reduced PLP in both legs (P < 0.05). Amputees assigned to the mental visualization condition did not show a significant reduction in PLP. INTERPRETATION: Direct visual observation therapy is an inexpensive and effective treatment for PLP that is accessible to bilateral lower limb amputees.

Is the Kampala trauma score an effective predictor of mortality in low-resource settings? A comparison of multiple trauma severity scores.

BACKGROUND: In the developed world, multiple injury severity scores have been used for trauma patient evaluation and study. However, few studies have supported the effectiveness of different trauma scoring methods in the developing world. The Kampala Trauma Score (KTS) was developed for use in resource-limited settings and has been shown to be a robust predictor of death. This study evaluates the ability of KTS to predict the mortality of trauma patients compared to other trauma scoring systems. METHODS: Data were collected on injured patients presenting to Central Hospital of Yaoundé, Cameroon from April 15 to October 15, 2009. The KTS, Injury Severity Score, Revised Trauma Score, Glasgow Coma Scale, and Trauma Injury Severity Score were calculated for each patient. Scores were evaluated as predictors of mortality using logistic regression models. Areas under receiver operating characteristic (ROC) curves were compared. RESULTS: Altogether, 2855 patients were evaluated with a mortality rate of 6 per 1000. Each score analyzed was a statistically significant predictor of mortality. The area under the ROC for KTS as a predictor of mortality was 0.7748 (95% CI 0.6285-0.9212). There were no statistically significant pairwise differences between ROC areas of KTS and other scores. Similar results were found when the analysis was limited to severe injuries. CONCLUSIONS: This comparison of KTS to other trauma scores supports the adoption of KTS for injury surveillance and triage in resource-limited settings. We show that the KTS is as effective as other scoring systems for predicting patient mortality.

Use of a virtual integrated environment in prosthetic limb development and phantom limb pain.

Patients face two major difficulties following limb loss: phantom limb pain (PLP) in the residual limb and limited functionality in the prosthetic limb. Many studies have focused on decreasing PLP with mirror therapy, yet few have examined the same visual ameliorating effect with a virtual or prosthetic limb. Our study addresses the following key questions: (1) does PLP decrease through observation of a 3D limb in a virtual integration environment (VIE) and (2) can consistent surface electromyography (sEMG) signals from the VIE drive an advanced modular prosthetic limb (MPL)? Recorded signals from the residual limb were correlated to the desired motion of the phantom limb, and changes in PLP were scored during each VIE session. Preliminary results show an overall reduction in PLP and a trend toward improvement in signal-to-motion accuracy over time. These signals allowed MPL users to perform a wide range of hand motions.

Using a virtual integration environment in treating phantom limb pain.

The Revolutionizing Prosthetics 2009 program conducted by the Defense Advanced Research Projects Agency (DARPA) has resulted in a Virtual Integration Environment (VIE) that provides a common development platform for researchers and clinicians that design, model and build prosthetic limbs and then integrate and test them with patients. One clinical need that arose during the VIE development was a feature to easily create and model animations that represent patient activities of daily living (ADLs) and simultaneously capture real-time surface EMG activity from the residual limb corresponding to the ADLs. An application of this feature is being made by the Walter Reed Military Amputee Research Program (MARP) where they are utilizing the VIE to investigate methods of reducing upper extremity amputee phantom limb pain (PLP).

The road to recovery and rehabilitation for injured service members with limb loss: a focus on Iraq and Afghanistan.

Amputation of an extremity due to traumatic injury or a vascular occlusive disease is a life-altering event that occurs when limb salvage is not possible. While an amputation is viewed as a life saving procedure clinically, limb deficiency may result in an immediate loss in social, physical and financial well-being for the patient. Military personnel returning from Operation Enduring Freedom and Operation Iraqi Freedom face unique challenges due to short residual limbs, unplanned amputations, high incidences of multiple limb loss, and accustomed activity levels prior to an amputation. The primary rehabilitation goal for these individuals is to provide them with an expedited recovery and progressive reintroduction into the civilian or active duty population. It is the purpose of this review to discuss the most frequent rehabilitation hardships service members endure following combat related trauma and future of prosthetic limb technology.

Phantom limb pain: theories and therapies.

BACKGROUND AND OBJECTIVE: Since the beginning of the conflicts in Iraq and Afghanistan, there has been a dramatic increase in the number of military service members with single and multiple-limb amputations. Phantom limb pain (PLP) frequently develops in these individuals. As a result, identifying the best methods to treat PLP is critical. The review highlights areas of inquiry related to phantom pain, with a focus on PLP. REVIEW SUMMARY: This review discusses phantom sensations and phantom pain that arise after amputation of a body part, and summarizes the differences between the 2 conditions. Characteristics of PLP are also discussed, including the onset, duration, and location of PLP. Theories explaining the etiology and presence of PLP are reviewed, along with the numerous treatment options reported in the published data for such pain, including the use of mirrors for treating pain. We conclude with a description of one military hospital's experiences with PLP. CONCLUSIONS: Although more research has been done in previous years, this review identifies the need for continuing investigations. The etiology of PLP needs to be determined through more vigorous investigation, and a focus must be placed on defining treatment options in addition to mirror therapy that will improve the quality of life of those who suffer from this condition.

Physiological and psychological fatigue in extreme conditions: the military example.

The extreme conditions causing fatigue in military service members in combat and combat training deserve special consideration. The collective effects of severe exertion, limited caloric intake, and sleep deprivation, combined with the inherent stressors of combat, lead to both physiological and psychological fatigue that may significantly impair performance. Studies of combat training have revealed a myriad of endocrine, cognitive, and neurological changes that occur as a result of exposure to extreme conditions. Further contributory effects of multiple military deployments, post-traumatic stress disorder, and traumatic brain injury may also influence both the susceptibility to and expression of fatigue states. Further research is needed to explore these effects to enhance military readiness and performance as well as prevent injuries.

High incidence of 'synaesthesia for pain' in amputees.

Synaesthesia for pain is a phenomenon where a person experiences pain when observing or imagining another in pain. Anecdotal reports of this type of experience have most commonly occurred in individuals who have lost a limb. Distinct from phantom pain, synaesthesia for pain is triggered specifically in response to pain in another. Here, we provide the first preliminary investigation into synaesthesia for pain in amputees to determine the incidence and characteristics of this intriguing phenomenon. Self-referring amputees (n=74) answered questions on synaesthesia for pain within a broader survey of phantom pain. Of the participants, 16.2% reported that observing or imagining pain in another person triggers their phantom pain. Further understanding of synaesthesia for pain may provide a greater insight to abnormal empathic function in clinical populations as well as therapeutic intervention for at risk groups.

Incorporation of another person's limb into body image relieves phantom limb pain: a case study.

Phantom limb phenomena are well characterized, but the underlying mechanisms remain unclear. Here we report a patient who relieves his phantom sensations and pain, experienced as itching and cramping, through scratching or massaging his prosthesis or the leg of another person. This pain relief occurs only when phantom limb sensations are present. We hypothesize that symptom relief results from incorporation of the foreign limb into the patient's body image, mediated by the sensory mirror neuron system, relieving pain by restoring concordance between sensory systems.

Mild traumatic brain injury update.

Traumatic brain injury (TBI) is a prevalent condition throughout the civilian and military populations. Although TBI can be classified as mild, moderate, or severe, most TBIs are considered mild. Understanding the pathophysiologic mechanism(s) of mild TBI through basic science and clinical cohort studies is an area of active research. While it is well understood that most people recover from a mild TBI with minimal treatment, some patients experience long-term consequences that require rehabilitation and specialized care. Common characteristics of brain injury include loss of consciousness (LOC), posttraumatic amnesia (PTA), and postconcussion syndrome (PCS). The development of LOC, PTA, and PCS greatly depends on the nature of the injury, and the degrees to which they develop are not necessarily consistent with symptom presentation. In recent years, sports concussions have become an area of increased research and public interest in the civilian population; similarly, blast TBI has gained attention in the military. Depending on the nature of the injury, different outcomes may result in the two populations. Consequently, treatments for mild TBI are rather diverse, and early intervention is the key to maximizing outcomes following a TBI. These topics and more will be discussed throughout this article.