Scalp Block: Tool for Diagnosis in Postoperative Headache of Unknown Origin.

No abstract available

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Role of anesthesia in endovascular stroke therapy.

Purpose of review: Recent randomized clinical trials have demonstrated strong efficacy of endovascular therapy (EVT) for acute ischemic stroke (AIS) from large vessel occlusions; in the USA alone, tens of thousands of patients annually may benefit. The impact of the type of anesthesia used during mechanical thrombectomy on patient outcomes remains controversial. This review discusses the current literature on the effects of anesthesia type on patient outcome following endovascular stroke therapy. Recent findings: EVT is the standard of treatment for intracranial large vessel occlusions. Recent studies show that general anesthesia is associated with negative clinical outcome in AIS patients undergoing EVT. Two of the possible mechanisms of this finding are systolic hypotension and hypocapnia. However, the only published randomized controlled studies to date, sedation vs. intubation for endovascular stroke treatment and anesthesia during stroke showed no difference in short-term clinical outcome between EVT patients treated with general anesthesia and conscious sedation and improved longer-term outcome in the general anesthesia group. Summary: Retrospective reports, and the 2015 American Heart Association/American Stroke Association Guideline (focused update of the 2013 guidelines for the early management of patients with AIS regarding endovascular treatment) based on these reports, are in favor of sedation (conscious sedation) over general anesthesia for endovascular stroke thrombectomy. However, the two randomized controlled prospective studies published provide inconclusive evidence as to the best anesthetic practice for endovascular stroke therapy. More randomized clinical trials are needed to optimize anesthetic patient care in AIS. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Dissecting patterns of preparatory activity in the frontal eye fields during pursuit target selection

We investigated the composition of preparatory activity of frontal eye field (FEF) neurons in monkeys performing a pursuit target selection task. In response to the orthogonal motion of a large and a small reward target, monkeys initiated pursuit biased towards the direction of large reward target motion. FEF neurons exhibited robust preparatory activity preceding movement initiation in this task. Preparatory activity consisted of two components, ramping activity that was constant across target selection conditions and a flat offset in firing rates that signaled the target selection condition. Ramping activity accounted for 50% of the variance in the preparatory activity and was linked most strongly, on a trial-by-trial basis, to pursuit eye movement latency rather than to its direction or gain. The offset in firing rates that discriminated target selection conditions accounted for 25% of the variance in the preparatory activity, and was commensurate with a winner-take-all representation signaling the direction of large reward target motion rather than a representation that matched the parameters of the upcoming movement. These offer new insights into the role the frontal eye fields play in target selection and pursuit control. They show that preparatory activity in the FEF signals more strongly when to move rather than where or how to move, and suggest that structures outside the FEF augment its contributions to the target selection process.

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Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat.

Botulinum toxin (Btx) is used in children with cerebral palsy and other neurological patients to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in the central gain of the stretch reflex circuitry in response to botulinum toxin injection in the triceps surae muscle in rats. Experiments were performed in 21 rats. 8 rats were in a control group and 13 rats were injected with 6 IU of Btx in the left triceps surae muscle. Two weeks after Btx injection larger monosynaptic reflexes (MSR) were recorded from the left (injected) than the right (non-injected) L4 + L5 ventral roots following stimulation of the corresponding dorsal roots. A similar increase on the left side was observed in response to stimulation of descending motor tracts, suggesting that increased excitability of spinal motor neurones may at least partly explain the increased reflexes. However, significant changes were also observed in post-activation depression of the MSR suggesting that plastic changes in transmission from Ia afferent to the motor neurons may also be involved. The data demonstrate that muscle paralysis induced by Btx injection is accompanied by plastic adaptations in the central stretch reflex circuitry, which counteract the antispastic effect of Btx.

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Apple patents discreet 911 dialing technology

When alerted with the technology, responders would receive the phone's location as well as livestream video or audio

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SC EMT, patient hospitalized after ambulance crash

The ambulance was en route to the hospital with a patient at the time of the crash

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IAFC, PulsePoint announce partnership to increase cardiac arrest survival rates

The partnership aims to reinforce the use of a smartphone app to connect nearby CPR-trained citizens and off-duty responders with people in cardiac arrest

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Spinal anaesthesia in neonates and infants: what about the cerebral oxygen saturation?

Abstract

Background. Spinal Anaesthesia (SA) has been firmly established as an efficient and safe technique, with minimal cardio-respiratory disturbance when administered in the neonatal period. Our objective was to assess the haemodynamic consequences of SA in infants, particularly its impact on cerebral perfusion using near-infrared spectroscopy (NIRS)-based cerebral oximetry (rSc_O2).Methods. All infants up to 60 weeks' postmenstrual age, whether formerly preterm or not, and undergoing spinal anaesthesia, were enrolled. Haemodynamic data records, rSc_O2 and mean arterial blood pressure (MAP), were prospectively collected before SA (T0) and every five min for 30 min (T30) after the puncture. Compared with baseline measures, any changes of > 10% in rSc_O2 and of > 20% in MAP were considered clinically significant. Relative variations of data between T0 and T30 were analysed.Results. Data of 103 infants were analysed. The mean relative changes in rSc_O2 were −2.25% (97.5% CI [−3.97; −0.5]) at T15, and 0.11% (97.5% CI [−1.67; 1.90]) at T30. No significant variation of rSc_O2 was recorded. The mean changes in MAP were respectively −13.94% (97.5% CI [−17.74; −10.14]) at T15 and −20.27% (97.5% CI [−24,25; −16.29]) at T30. MAP decrease was statistically and clinically significant 30 min after SA. No correlation between changes in MAP and rSc_O2 was found. The subgroup analysis did not reveal any effect of added intrathecal clonidine or preterm birth history on these results.Conclusions. In neonate and infants, SA did not cause clinically significant variation in cerebral oxygen saturation. Despite a significant decrease in MAP, cerebral auto-regulation seems to remain effective in neonates and not altered by spinal anaesthesia.

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Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial

Abstract

Background: Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. We hypothesized that early fibrinogen replacement, guided by viscoelastometric testing, reduces blood product usage and bleed size.Methods: Women with PPH 1000–1500 ml were enrolled. If Fibtem A5 was ≤15 mm and bleeding continued, subjects were randomized to fibrinogen concentrate or placebo. The primary outcome compared the number of units of red blood cells, plasma, cryoprecipitate and platelets transfused.Results: Of 663 women enrolled 55 were randomized. The adjusted incidence rate ratio (IRR) (95% CI) for the number of allogeneic units transfused in the fibrinogen group compared with placebo was 0.72 (0.3–1.7), P=0.45. In pre-specified subgroup analyses, subjects who had a Fibtem A5 ≤12 mm at the time of randomization and who received fibrinogen concentrate received a median (25th–75th centile) of 1 (0–4.5) unit of allogeneic blood products and had an additional 300 (100–350) ml blood loss whereas those who received placebo also received 3 (0–6) units of allogeneic blood products and had 700 (200–1550) ml additional blood loss; these differences were not statistically significantly different. There was one thrombotic event in each group.Conclusions: Infusion of fibrinogen concentrate triggered by Fibtem A5 ≤15 mm did not improve outcomes in PPH. Pre-specified subgroup analyses suggest that fibrinogen replacement is not required if the Fibtem A5 is > 12 mm or Clauss fibrinogen >2 g litre⁻¹, but an effect below these levels cannot be excluded. The raised fibrinogen at term appears to be a physiological buffer rather than required for haemostasis.Trial registration: ISRCTN46295339 (http://ift.tt/2uIJ5tt, last accessed 5 July 2017), EudraCT 2012-005511-11 (http://ift.tt/2vjagIm, last accessed 5 July 2017).

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Sevoflurane activates hippocampal CA3 kainate receptors (Gluk2) to induce hyperactivity during induction and recovery in a mouse model

Abstract

Background: In addition to general anaesthetic effects, sevoflurane can also induce hyperactive behaviours during induction and recovery, which may contribute to neurotoxicity; however, the mechanism of such effects is unclear. Volatile anaesthetics including isoflurane have been found to activate the kainate (GluK2) receptor. We developed a novel mouse model and further explored the involvement of kainate (GluK2) receptors in sevoflurane-induced hyperactivity.Methods: Maximal speed, mean speed, total movement distance and resting percentage of C57BL/6 mice were quantitatively measured using behavioural tracking software before and after sevoflurane anaesthesia. Age dependence of this model was also analysed and sevoflurane-induced hyperactivity was evaluated after intracerebral injection of the GluK2 receptor blocker NS-102. Neurones from the hippocampal CA3 region were used to undertake in vitro electrophysiological measurement of kainate currents and miniature excitatory postsynaptic potential (mEPSP).Results: Sevoflurane induced significant hyperactivities in mice under sevoflurane 1% anaesthesia and during the recovery period, characterized as increased movement speed and total distance. The hyperactivity was significantly increased in young mice compared with adults (P<0.01) and pre-injection of NS-102 significantly prevented this sevoflurane-induced hyperactivity. In electrophysiological experiments, sevoflurane significantly increased the frequency of mEPSP at low concentrations and evoked kainate currents at high concentrations.Conclusions: We developed a behavioural model in mice that enabled characterization of sevoflurane-induced hyperactivity. The kainate (GluK2) receptor antagonist attenuated these sevoflurane-induced hyperactivities in vivo, suggesting that kainate receptors might be the underlying therapeutic targets for sevoflurane-induced hyperactivities in general anaesthesia.

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Randomized trial of near-infrared spectroscopy for personalized optimization of cerebral tissue oxygenation during cardiac surgery

Abstract

Background. We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys.Methods. In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery.Results. The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 (n=98 patient-specific algorithm; n=106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups.Conclusions. These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery.Clinical trial registration.http://ift.tt/HkCGY7, ISRCTN 23557269.

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Predicting successful supraclavicular brachial plexus block using pulse oximeter perfusion index

Abstract

Background. Supraclavicular nerve block is a popular approach for anaesthesia for upper limb surgeries. Conventional methods for evaluation of block success are time consuming and need patient cooperation. The aim of this study was to evaluate whether the perfusion index (PI) can be used to predict and provide a cut-off value for ultrasound-guided supraclavicular nerve block success.Methods. The study included 77 patients undergoing elective orthopaedic procedures under ultrasound-guided supraclavicular nerve block. After local anaesthetic injection, sensory block success was assessed every 3 min by pinprick, and motor block success was assessed every 5 min by the ability to flex the elbow and the hand against resistance. The PI was recorded at baseline and at 10, 20, and 30 min after anaesthetic injection in both blocked and non-blocked limbs. The PI ratio was calculated as the PI after 10 min divided by the PI at the baseline. Receiver operating characteristic curves were constructed for the accuracy of the PI in detection of block success.Results. The PI was higher in the blocked limb at all time points, and this was paralleled by a higher PI ratio compared with the unblocked limb. Both the PI and the PI ratio at 10 min after injection showed a sensitivity and specificity of 100% for block success at cut-off values of 3.3 and 1.4, respectively.Conclusions. The PI is a useful tool for evaluation of successful supraclavicular nerve block. A PI ratio of > 1.4 is a good predictor for block success.

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Lower-body negative pressure decreases noninvasively measured intracranial pressure and internal jugular vein cross-sectional area during head-down tilt

Long-term spaceflight induces a near visual acuity change in ~50% of astronauts. In some crew members, postflight cerebrospinal fluid (CSF) opening pressures by lumbar puncture are as high as 20.9 mmHg; these members demonstrated optic disc edema. CSF communicates through the cochlear aqueduct to affect perilymphatic pressure and tympanic membrane motion. We hypothesized that 50 mmHg of lower-body negative pressure (LBNP) during 15° head-down tilt (HDT) would mitigate elevations in internal jugular vein cross-sectional area (IJV CSA) and intracranial pressure (ICP). Fifteen healthy adult volunteers were positioned in sitting (5 min), supine (5 min), 15° HDT (5 min), and 15° HDT with LBNP (10 min) postures for data collection. Evoked tympanic membrane displacements (TMD) quantified ICP noninvasively. IJV CSA was measured using standard ultrasound techniques. ICP and IJV CSA increased significantly from the seated upright to the 15° HDT posture (P < 0.05), and LBNP mitigated these increases. LBNP at 25 mmHg reduced ICP during HDT (TMD of 322.13 ± 419.17 nl) to 232.38 ± 445.85 nl, and at 50 mmHg ICP was reduced further to TMD of 199.76 ± 429.69 nl. In addition, 50 mmHg LBNP significantly reduced IJV CSA (1.50 ± 0.33 cm²) during 15° HDT to 0.83 ± 0.42 cm². LBNP counteracts the headward fluid shift elevation of ICP and IJV CSA experienced during microgravity as simulated by15° HDT. These data provide quantitative evidence that LBNP shifts cephalic fluid to the lower body, reducing IJV CSA and ICP.

NEW & NOTEWORTHY The current study provides new evidence that 25 or 50 mmHg of lower body negative pressure reduces jugular venous pooling and intracranial pressure during simulated microgravity. Therefore, spaceflight countermeasures that sequester fluid to the lower body may mitigate cephalic venous congestion and vision impairment.

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Influence of maximal fat oxidation on long-term weight loss maintenance in humans

Impaired maximal fat oxidation has been linked to obesity and weight regain after weight loss. The aim was to investigate the relationship between maximal fat oxidation (MFO) and long-term weight loss maintenance. Eighty subjects [means (SD): age, 36(13) yrs; BMI, 38(1) kg/m²] were recruited from a total of 2,420 former participants of an 11- to 12-wk lifestyle intervention. Three groups were established based on percent weight loss at follow-up [5.3(3.3) yr]: clinical weight loss maintenance (CWL), >10% weight loss; moderate weight loss (MWL), 1–10% weight loss; and weight regain (WR). Body composition (dual X-ray absorptiometry) and fat oxidation (indirect calorimetry) during incremental exercise were measured at follow-up. Blood and a muscle biopsy were sampled. At follow-up, a U-shaped parabolic relationship between MFO and percent weight loss was observed (r = 0.448; P < 0.001). Overall differences between CWL, MWL, and WR were observed in MFO (mean [95% confidence interval], in g/min, respectively: 0.46 [0.41–0.52]; 0.32 [0.27–0.38]; 0.45 [0.38–0.51]; P = 0.002), maximal oxygen uptake (Vo_2max, in ml·min^–1·FFM^–1, respectively; 49 [46–51]; 43 [40–47]; 41 [39–44]; P = 0.007), HAD-activity (in µmol·g^–1·min^–1, respectively: 123 [113–133]; 104 [91–118]; 97 [88–105]; P < 0.001), muscle protein content of CD36 (in AU, respectively: 1.1 [1.0–1.2]; 0.9 [0.8–1.0]; 0.9 [0.8–0.9]; P = 0.008) and FABPpm (in AU, respectively, 1.0 [0.8–1.2]; 0.7 [0.5–0.8]; 0.7 [0.5–0.9]; P = 0.008), body fat (in %, respectively: 33 [29–38]; 42 [38–46]; 52 [49–55]; P < 0.001), and plasma triglycerides (in mM, respectively: 0.8 [0.7–1.0]; 1.3 [0.9–1.7]; 1.6 [1.0–2.1]; P = 0.013). CWL and WR both had higher MFO compared with MWL, but based on different mechanisms. CWL displayed higher Vo_2max and intramuscular capacity for fat oxidation, whereas abundance of lipids at whole-body level and in plasma was higher in WR.

NEW & NOTEWORTHY Impaired maximal fat oxidation has been linked to obesity and weight regain after weight loss. Noteworthy, maximal fat oxidation was equally high after clinical weight loss maintenance and weight regain compared with moderate weight loss. A high maximal fat oxidation after clinical weight loss maintenance was related to higher maximal oxygen updake, content of key proteins involved in transport of lipids across the plasma membrane and β-oxidation. In contrast, a high maximal fat oxidation after weight regain was related to higher availability of lipids, i.e., general adiposity and plasma concentration of triglycerides.

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Obesity-induced discrepancy between contractile and metabolic phenotypes in slow- and fast-twitch skeletal muscles of female obese Zucker rats

A clear picture of skeletal muscle adaptations to obesity and related comorbidities remains elusive. This study describes fiber-type characteristics (size, proportions, and oxidative enzyme activity) in two typical hindlimb muscles with opposite structure and function in an animal model of genetic obesity. Lesser fiber diameter, fiber-type composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of muscle fiber types were assessed in slow (soleus)- and fast (tibialis cranialis)-twitch muscles of obese Zucker rats and compared with age (16 wk)- and sex (females)-matched lean Zucker rats (n = 16/group). Muscle mass and lesser fiber diameter were lower in both muscle types of obese compared with lean animals even though body weights were increased in the obese cohort. A faster fiber-type phenotype also occurred in slow- and fast-twitch muscles of obese rats compared with lean rats. These adaptations were accompanied by a significant increment in histochemical succinic dehydrogenase activity of slow-twitch fibers in the soleus muscle and fast-twitch fiber types in the tibialis cranialis muscle. Obesity significantly increased plasma levels of proinflammatory cytokines but did not significantly affect protein levels of peroxisome proliferator-activated receptors PPAR or PGC1α in either muscle. These data demonstrate that, in female Zucker rats, obesity induces a reduction of muscle mass in which skeletal muscles show a diminished fiber size and a faster and more oxidative phenotype. It was noteworthy that this discrepancy in muscle's contractile and metabolic features was of comparable nature and extent in muscles with different fiber-type composition and antagonist functions.

NEW & NOTEWORTHY This study demonstrates a discrepancy between morphological (reduced muscle mass), contractile (shift toward a faster phenotype), and metabolic (increased mitochondrial oxidative enzyme activity) characteristics in skeletal muscles of female Zucker fatty rats. It is noteworthy that this inconsistency was comparable (in nature and extent) in muscles with different structure and function.

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Surgical Anti-Reflux Options Beyond Fundoplication

Abstract

Purpose of Review

This paper provides an overview of current and future surgical interventions available for the management of gastroesophageal reflux disease (GERD) beyond the well established and recognized fundoplication. Review the current indications and outcomes of these surgical procedures.

Recent Findings

Fundoplication has been a cornerstone of the surgical management of GERD. However, other effective surgical options exist and can be considered based on prior interventions as well as patient, anatomical or other factors. These options are intended to address some of the shortcomings or potential complications of fundoplication such as symptom recurrence, dysphagia, or gas bloating, for example.

Summary

Alternative procedures to fundoplication include magnetic sphincter augmentation, electrical stimulation and Roux-en-Y gastric bypass. The indication for surgical management remains failure of or inability to tolerate medical therapy.

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A tribute to Prof. Dr. Najet Belhadj

Publication date: June 2017
Source:Arab Journal of Gastroenterology, Volume 18, Issue 2





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Editorial Board

Publication date: June 2017
Source:Arab Journal of Gastroenterology, Volume 18, Issue 2





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Drug use and phylogenetic clustering of hepatitis C virus infection among people who use drugs in Vancouver, Canada: A latent class analysis approach

Journal of Viral Hepatitis

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New York attorney general says will sue over Obamacare repeal

Reuters Health News

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Diagnostic reliability of pediatric appendicitis score, ultrasound and low-dose computed tomography scan in children with suspected acute appendicitis

Therapeutics and Clinical Risk Management

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Ovarian cancer screening: harms still outweigh benefits, USPSTF says

Reuters Health News

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Relationship between uric acid and dehydration in children with gastroenteritis

Pediatrics International

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Vasectomy does not raise prostate cancer risk: study

Reuters Health News

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Association between nonalcoholic fatty liver disease and peripheral artery disease in patients with type 2 diabetes

Internal Medicine Journal

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Risk of postoperative complications among inflammatory bowel disease patients treated preoperatively with vedolizumab

The American Journal of Gastroenterology

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Long term effects: Galectin-1 and specific immunotherapy for allergic responses in the intestine

Allergy

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Innovative and collaborative approach to improve community access to hepatitis C therapy

The Journal for Nurse Practitioners

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Novel risk stratification for metachronous recurrence after curative endoscopic submucosal dissection for early gastric cancer

Gastrointestinal Endoscopy

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Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B carriers

Alimentary Pharmacology and Therapeutics

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Artificial sweeteners may not be risk free

Reuters Health News

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Risk of severe acute liver injury among patients with brain cancer treated with temozolomide: A nested case-control study using the healthcore integrated research database

Journal of Neuro-Oncology

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Botulinum toxin A as an adjunct to abdominal wall reconstruction for incisional hernia

Plastic and Reconstructive Surgery - Global Open

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Ten-day quadruple therapy comprising proton pump inhibitor, bismuth, tetracycline, and levofloxacin is more effective than standard levofloxacin triple therapy in the second-line treatment of helicobacter pylori infection: a randomized controlled trial

The American Journal of Gastroenterology

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Lactobacillus reuteri DSM 17938 and a placebo both significantly reduced symptoms in children with functional abdominal pain

Acta Pediatrica

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Early growth in children with coeliac disease: A cohort study

Archives of Diseases in Childhood

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Incidence, predictive factors, and impacts of acute kidney injury in cirrhotic patients hospitalized for cellulitis

Liver International

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Prophylactic therapy of cyclic vomiting syndrome in children: Comparison of amitriptyline and cyproheptadine: A randomized clinical trial

The American Journal of Gastroenterology

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Infant Positioning, Baby Gear Use, and Cranial Asymmetry

Abstract

Objectives This study aimed to identify predictors of cranial asymmetry. We hypothesize that among infants diagnosed with cranial asymmetry in the sampled region, there is an association between exposure to more time in baby gear and less awake time in prone and side-lying than in infants who do not present with this condition. Methods The study employed a cross sectional survey of caregivers of typically developing infants and infants diagnosed with cranial asymmetry. Results A mutivariable model reveals that caregivers of children who are diagnosed with cranial asymmetry report their children spending significantly less time in prone play than those children without a diagnosis of cranial asymmetry. Side-lying and time spent in baby gear did not attain statistical significance. Conclusions for Practice Occupational therapists, physical therapists, pediatricians, nurses and other health care professionals must provide parents with early education about the importance of varying positions and prone play in infancy and address fears and concerns that may serve as barriers to providing prone playtime.

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Moral Distress in Rehabilitation

About a dozen years ago, I took the lead on surveying clinical and nonclinical staff members at the Rehabilitation Institute of Chicago (now the Shirley Ryan AbilityLab) about their perceived moral distress [1]. My colleagues and I asked, "We are interested in learning about the issues that create a sense of moral distress in your daily professional life. What types of situations are troubling for you because of your beliefs about what is right and wrong? What is troubling to you because of conflicts of values?" The results were published in this Journal in 2009 and for many years the data guided the priorities and focus of our ethics initiatives.

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Spanish Translated Abstracts

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Table of Contents

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Copyright Page

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Information for Authors

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Editorial Board

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Academy News – July PM&R

As the primary medical society for the specialty of PM&R, your Academy is focused on moving the specialty and you forward. Academy membership supports initiatives to assist our members with:

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Immune Checkpoint Inhibitors in Organ Transplant Patients.

Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant. Excluding these patients was deliberate due to concern that immune checkpoint inhibitor therapy could lead to graft rejection. The PD-1 and CTLA-4 pathways are essential to downregulate our immune system in the setting of T-cell activation to prevent autoimmunity. Furthermore, both pathways are implicated in transplanted organ tolerance and modulation of the pathways may inadvertently lead to peripheral transplant rejection. Currently, there are no guidelines for the treatment of patients with immune checkpoint inhibitors in the setting of a prior organ transplant. Thus far, there are only 10 reported cases of patients in the literature who were treated in this setting. Two additional cases are reported herein, including 1 patient with a prior cardiac transplant receiving nivolumab for non-small cell lung cancer. Of the 12 cases, 4 patients experienced organ rejection. From these observations, the authors hypothesize factors that affect safety and of this treatment modality in this patient population. These factors include the integral role of the PD-1 pathway compared with the CTLA-4 pathway in organ acceptance, sequential implementation of different immune checkpoint inhibitor classes, length of time with a transplant before therapy, strength of immunosuppressive agents to prevent organ transplant rejection, and immunogenicity of the particular organ grafted. Although limited cases have been reported, there are circumstances in which immune checkpoint inhibitors have been used in the setting of organ transplantation without resulting in organ rejection. A thorough discussion with the patient of the potential risks, including graft rejection, and benefits of this therapy is necessary before beginning this treatment. More research is needed to explore the safety and efficacy of immune checkpoint inhibitors in the setting of organ transplantation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

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