Remote photobiomodulation targeted at the abdomen or legs provides effective neuroprotection against parkinsonian MPTP insult.

Photobiomodulation (PBM)-the irradiation of tissue with low-intensity light-mitigates neuropathology in rodent models of Parkinson's disease (PD) when targeted at the head ('transcranial PBM'). In humans, however, attenuation of light energy by the scalp and skull necessitates a different approach. We have reported that targeting PBM at the body also protects the brain by a mechanism that spreads from the irradiated tissue ('remote PBM'), although the optimal peripheral tissue target for remote PBM is currently unclear. This study compared the neuroprotective efficacy of remote PBM targeting the abdomen or leg with transcranial PBM, in mouse and non-human primate models of PD. In a pilot study, the neurotoxin MPTP was used to induce PD in non-human primates; PBM (670 nm, 50 mW/cm2 , 6 min/day) of the abdomen (n = 1) was associated with fewer clinical signs and more surviving midbrain dopaminergic cells relative to MPTP-injected non-human primates not treated with PBM. Validation studies in MPTP-injected mice (n = 10 per group) revealed a significant rescue of midbrain dopaminergic cells in mice receiving PBM to the abdomen (~80%, p < .0001) or legs (~80%, p < .0001), with comparable rescue of axonal terminals in the striatum. Strikingly, this degree of neuroprotection was at least as, if not more, pronounced than that achieved with transcranial PBM. These findings confirm that remote PBM provides neuroprotection against MPTP-induced destruction of the key circuitry underlying PD, with both the abdomen and legs serving as viable remote targets. This should provide the impetus for a comprehensive investigation of remote PBM-induced neuroprotection in other models of PD and, ultimately, human patients.

Editorial Commentary: For Single-Bundle Anterior Cruciate Ligament Reconstruction, Graft Fixation Should Be Performed at a Medium Tension in Full Extension: Multiple Bundle Reconstruction May Require a Different Strategy.

Successful anterior cruciate ligament reconstruction requires a multifaceted approach to replicate normal knee anatomy and biomechanics. Graft tensioning force and the angle at which this tension is applied intraoperatively are factors under the surgeon's control. The literature suggests the best tensioning strategy for single bundle reconstructions is at medium tension in full extension, while tensioning multiple bundles is best done at 20° at lower overall tension. Graft tensioning should be individualized with attention paid to graft choice and fixation. Generally, stiffer grafts are thought to require additional force to create the same amount of lengthening. For example, bone-patellar tendon-bone grafts tend to be stiffer than quadrupled hamstring grafts and the native anterior cruciate ligament. Hamstring grafts also are thought to exhibit greater stress relaxation over time, thus elongating and potentially causing increased laxity over time. Pretensioning may eliminate some postoperative graft creep, typically more of an issue with hamstring grafts.

The Majority of Patients Aged 40 and Older Having Allograft Anterior Cruciate Ligament Reconstruction Achieve a Patient Acceptable Symptomatic State.

PURPOSE: To evaluate patient satisfaction, retear rates, and patient-reported outcomes (PROs) in patients aged 40 and older undergoing allograft anterior cruciate ligament reconstruction (ACLR). The secondary goal was to compare these parameters between groups of patients with intact versus failed grafts, and to evaluate these in relation to a historically reported International Knee Documentation Committee (IKDC) patient-acceptable symptoms state (PASS) score. METHODS: Records of patients aged 40 and older who underwent ACLR between 2005 and 2016 at a single institution with a minimum 2-year follow-up were retrospectively reviewed. Patient-reported satisfaction, outcome scores, and failure rates were analyzed. The rate of achieving a previously defined IKDC PASS score based on younger cohorts was reported, and an updated PASS threshold for older patients was calculated. RESULTS: 201 patients were included with a mean age of 48.6 years (range: 40-68) and mean follow-up of 6.2 years (range: 2.8-11.2). 182 (90.5%) patients reported satisfaction following surgery. 16 (8.0%) patients experienced failure of their ACLR, 10 of which underwent revision ACLR. The median IKDC score in the intact ACLR group was 86.2, compared to 66.7 in the failure group (P < .001). In total, 134 (72.4%) patients in the intact group achieved the historical PASS score of 75.9 on IKDC compared to only 4 (25%) in the failure group (χ2 = 15.396, P < .001). An updated IKDC PASS threshold for older cohorts was calculated to be 66.7. CONCLUSION: Patients aged 40 and older who underwent allograft ACLR had an 8.0% failure rate at a mean follow-up of 6 years. Graft failure in patients aged 40 and older was associated with worse PROs. The majority of patients achieved the historically reported IKDC PASS threshold. Additionally, an updated age-appropriate IKDC PASS score of 66.7 was calculated to aid in future ACLR studies assessing older patients. STUDY DESIGN: Level IV.

Neuromuscular choristoma-associated desmoid-type fibromatosis: Establishing a nerve territory concept.

INTRODUCTION: Desmoid-type fibromatosis (DTF) frequently arises in patients with neuromuscular choristoma (NMC). We hypothesize that NMC-associated DTF occurs in soft tissues innervated by the NMC-affected nerve, and arises from CTNNB1-mutated (myo) fibroblasts within or directly adjacent to the NMC. MATERIALS AND METHODS: A retrospective review of patients treated at our institution was performed for patients with biopsy-confirmed diagnosis of NMC-DTF. Clinical presentation, physical examination, electrodiagnostic findings and radiological features (MR and FDG PET/CT images for each NMC-DTF) and pathologic re-review of available materials were analyzed. A literature review was also performed. RESULTS: Eight patients from our institution met the inclusion criteria. All patients presented with neuropathic symptoms and soft tissue or bone changes in the nerve territory innervated by the NMC. All MR images (N=8 cases) showed the characteristic features of NMC, and also showed direct contact between unifocal (N=5) or multifocal (N=3) DTF(s) and the NMC-affected nerve NMC. FDG PET/CT (N=2 cases) showed diffuse, increased FDG uptake along the entire affected nerve segment, contiguous with the FDG-avid DTF. In all cases, the DTFs arose in the soft tissues of the NMC-affected nerve's territory. No patient developed DTF at any other anatomic site. CONCLUSIONS: These data demonstrate that NMC-DTF arises solely within the NMC-affected nerve territory, and has direct contact with the NMC itself. Based on all these findings and the multifocality of NMC in several cases, we recommend imaging and surveillance of the entire NMC-affected nerve (from spine to distal extremity) to identify clinically-occult DTF in patients with NMC.

The Emerging Role of Percutaneous Thermal Ablation in the Treatment of Thoracic Malignancies: A Review.

Thoracic malignancies pose a significant public health burden in the United States, with primary lung cancer accounting for nearly 25% of cancer deaths each year. Percutaneous thermal ablation (PTA) for the treatment of lung cancer has evolved from a novel oncologic strategy in the 1970s, to a limited therapeutic option in select patients through the early 2000s, into its current rapidly expanding role as an adjunct therapy, or even standalone treatment, for a diverse group of thoracic malignancies in patients with both localized and disseminated disease. Radiofrequency ablation (RFA) benefits from the largest clinical dataset and greater user experience, but its utility has been limited by a suboptimal heating mechanism in the setting of poor thermal conductive properties within the lung. As the limitations of RFA have come into sharper focus, microwave ablation (MWA) has emerged as a potentially superior ablation technique due to its ease of use and improved heating profile, allowing for larger ablation zones with reduced treatment times. Cryoablation shares many of the technical features of MWA, while targeting cancer cells via pressurized argon gas to induce cryodestruction of target tissue. In clinical practice, the need for at least two cryoprobes and prolonged freeze-thaw protocols adds to procedural time and complexity. To date, there is considerable evidence supporting the safety, tolerability, and efficacy of these minimally invasive modalities, which have been shown to be cost effective and can often be performed on an outpatient basis. Clinical outcomes continue to improve as more data is acquired for each modality, enabling clinicians to refine patient selection and tailor follow-up protocols to better reflect expected post-procedural imaging findings and potential complications. At present, combined multi-modality therapy is an exciting area of active investigation, particularly in cryoablation due to an apparent synergism with established immunotherapies. Recent data suggests PTA may also be useful in more aggressive malignancies, such as advanced NSCLC and small cell lung cancer. Looking forward, PTA remains well positioned to be a valuable therapeutic option in the treatment of patients with lung cancer.

Microwave Ablation in the Liver: An Update.

Hepatocellular carcinoma (HCC) and secondary hepatic malignancies, most often arising from colorectal cancer, are a leading cause of morbidity and cancer-related deaths worldwide. In lieu of first-line surgical resection, which is precluded in more than 75% of cases due to underlying comorbid conditions or locally advanced disease, several minimally-invasive transarterial and thermal ablation procedures have emerged as safe and effective alternative therapies in select patients. Among the thermal ablative techniques, microwave ablation (MWA) has become the preferred treatment modality because of its operational convenience and superior heating profile, allowing for larger ablation zones and reduced treatment times while maintaining high technical success rates. To date, MWA has been demonstrated to provide equivalent, and in some cases improved, clinical outcomes compared to radiofrequency ablation (RFA) in patients with inoperable HCC or oligometastatic disease. Active areas of investigation include the comparison of MWA and transarterial therapies, such as transarterial chemoembolization (TACE), as well as combined multimodality therapies. Here we review the emerging topic of MWA for the treatment of hepatic malignancies by examining staging and treatment strategies, available technologies, procedural protocol and technique, and clinical outcomes.

Avoidance of scapular winging while approaching tumors of the middle scalene region.

BACKGROUND: Large tumors arising from the middle scalene region can displace the middle scalene muscle and distort regional anatomy, placing nerves at risk. Understanding the surgical anatomy of these nerves is key to approaching pathology of the middle scalene muscle and avoiding damage to the dorsal scapular, long thoracic, and spinal accessory nerves, each of which can cause scapular winging and associated morbidity if injured. METHODS: IRB approval was obtained for this study, allowing cases with relevant pathology to be reviewed and presented to highlight the relevant surgical technique. Anatomical depictions were created to correlate intraoperative images with known anatomical relationships. RESULTS: Key to this approach is consideration of the regional anatomy in a standard supraclavicular approach, the superficial plane, containing the anterior scalene muscle and brachial plexus, and the oblique plane containing the middle scalene muscle, long thoracic, spinal accessory, and dorsal scapular nerves. Identification and mobilization of each of these structures prior to lesion removal can not only provide likely boundaries of the tumor, but also allow for protection of the nerves to avoid injury that may lead to scapular winging with associated morbidity and functional impairment of the upper extremity. CONCLUSIONS: Lesions of the middle scalene region often split two important anatomical planes, the superficial and deep, creating an advantageous surgical corridor through an anterolateral approach. Through early identification of known anatomy, these two planes can be developed, and a safe approach to the lesion of the middle scalene region can be exploited.

Editorial Commentary: Second-Generation Microfracture-We Are Only As Strong As Our Weakest Link.

Injuries to the articular cartilage of the knee are increasingly common, especially in athletes. The operative management of these focal chondral lesions continues to be a regenerative challenge. The microfracture (MFx) procedure has become a first-line arthroscopic treatment method for small, symptomatic chondral lesions, and it frequently serves as the standard technique against which other cartilage repair procedures are compared. Over time, outcome studies have defined the weaknesses and limitations of first-generation MFx. The second iteration of MFx seeks to optimize regeneration using the trilogy of cells, scaffolds, and growth factors. As surgeons, we are only as strong as our weakest link.

How to Manage Cartilage Injuries?

Although small cartilage injuries are commonly found in knee arthroscopy procedures, significant chondral and osteochondral injuries are relatively infrequent. Incidence of cartilage injury rises when considering traumatic origin, especially when approaching significant ligamentous or meniscal pathology. Options for restoration span the gamut from benign neglect to open procedures that restore both cartilage and subchondral bone. The best choice of procedure largely depends on lesion size, depth, and location. Smaller lesions isolated to cartilage <2 cm2 can be treated with marrow stimulation techniques such as microfracture with or without biologic options (bone marrow aspirate concentrate or platelet-rich plasma with or without cartilage precursors or scaffolds). Microfracture alone in larger lesions has been reported to be less durable and it is therefore not recommended for larger lesions. Smaller lesions <2 cm2 that include a subchondral injury can be treated with osteochondral autograft implantation, in which a core of cartilage and bone is transferred from a relative non-weightbearing surface to the lesion. Larger osteochondral lesions >2 cm2 are better treated with osteochondral allograft transplantation, where osteochondral cores from a size-matched, fresh cadaver are matched to the patient's lesion. This option may require multiple cores to be placed in a "snowman" pattern; however, recent literature demonstrated that a single plug might produce better outcomes. Alternatively, for large chondral-only lesions, a resurfacing procedure may be chosen that may include biologic options. Autologous chondrocyte implantation (ACI), currently in its third iteration (matrix ACI [MACI]), is an excellent choice with good long-term durability. In addition, MACI may be used for chondral lesions in the patellofemoral joint where matching the native joint topology may be more difficult. If the patient has an underlying bone marrow lesion but an intact cartilage cap that appears healthy on arthroscopic examination, one may consider a core decompression and injection with biologics such as BMAC and bony scaffold with fibrin glue (also known as bioplasty). It is also critical that the surgeon address any concomitant knee pathology that would compromise cartilage restoration. This includes addressing malalignment with distal femoral, proximal tibial, or tibial tubercle osteotomy, significant meniscal deficiency with meniscal transplant, and any instability from lack of cruciate or collateral ligaments with ligament reconstruction.

Targeted fascicular biopsy in a patient with prostate cancer.

Patients who present with a history of cancer and the new onset of lumbosacral or peripheral neuropathy should be evaluated for the potential of metastasis. Targeted fascicular biopsy can be useful to diagnose atypical lesions within peripheral nerves in patients with major or progressive neurological deficits. In this video, the authors demonstrate the technique of targeted fascicular biopsy of the sciatic nerve in a 63-year-old man with a history of prostate cancer. The video can be found here: https://youtu.be/PTOX9XxNBDU .

Intraoperative intravenous fluorescein as an adjunct during surgery for peroneal intraneural ganglion cysts.

The intraoperative use of intravenous fluorescein is presented in a case of peroneal intraneural ganglion cyst. When illuminated with the operative microscope and yellow filter, this fluorophore provided excellent visualization of the abnormal cystic peroneal nerve and its articular branch connection. The articular (synovial) theory for the pathogenesis of intraneural cysts is further supported by this pattern of fluorescence. Further, our report presents a novel use of fluorescein in peripheral nerve surgery.

Extensive perineural spread of an intrapelvic sciatic malignant peripheral nerve sheath tumor: a case report.

Perineural spread has been described in multiple neoplasms of neural and non-neural origin. The peripheral nervous system may represent a highway by which tumors can spread throughout the body. Malignant peripheral nerve sheath tumor (MPNST) is a neoplasm arising from peripheral nerves with high rates of local recurrence and distant metastases, leading to a poor 5-year overall survival. In many cases, the optimal treatment involves wide en bloc excision with negative margins as well as chemotherapy and radiation. Even in cases of negative surgical margins, recurrence rates are high, suggesting possible skip lesions or very distant infiltration along the involved nerve. We report a case of high-grade MPNST of the sciatic nerve with post-mortem dissection and histopathologic characterization of perineural spread of microscopic disease to sites significantly proximal and distal to areas with evidence of gross disease, which may help to explain the high rates of local and distal recurrence in MPNST.

Accessory neuropathy after sternotomy: Clinico-anatomical correlation supporting an inflammatory cause.

Inflammatory etiologies are becoming increasingly recognized as explanations of some neuropathies, especially those occurring in the perioperative period. Although "brachial neuritis" is known to affect extraplexal nerves, accessory nerve palsy following median sternotomy has been attributed to stretch on the nerve. To better elucidate stretch as a potential cause, a cadaveric study was performed. Two patients who developed accessory nerve palsy following median sternotomy are presented to illustrate features consistent with the diagnosis of a perioperative inflammatory neuropathy. Five adult unembalmed cadavers underwent exposure of the bilateral accessory nerves in the posterior cervical triangle. A median sternotomy was performed and self-retaining retractors positioned. With the head in neutral, left rotation and right rotation, retractors were opened as during surgery while observing and recording any accessory nerve movements. The self-retaining sternal retractors were fully opened to a mean inter-blade distance of 13 cm. Regardless of head position, from the initial retractor click to maximal opening there was no gross movement of the accessory nerve on the left or right sides. Opening self-retaining sternal retractors does not appear to stretch the accessory nerve in the posterior cervical triangle. Based on our clinical experience and cadaveric results, we believe that inflammatory conditions, (i.e., idiopathic brachial plexitis) can involve the accessory nerve, and might be triggered by surgical procedures. Clin. Anat. 31:417-421, 2018. © 2017 Wiley Periodicals, Inc.

Near-infrared light is neuroprotective in a monkey model of Parkinson disease.

OBJECTIVE: To examine whether near-infrared light (NIr) treatment reduces clinical signs and/or offers neuroprotection in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson disease. METHODS: We implanted an optical fiber device that delivered NIr (670 nm) to the midbrain of macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.5-2.1mg/kg) were made over a 5- to 7-day period, during which time the NIr device was turned on. This was then followed by a 3-week survival period. Monkeys were evaluated clinically (eg, posture, bradykinesia) and behaviorally (open field test), and their brains were processed for immunohistochemistry and stereology. RESULTS: All monkeys in the MPTP group developed severe clinical and behavioral impairment (mean clinical scores = 21-34; n = 11). By contrast, the MPTP-NIr group developed much less clinical and behavioral impairment (n = 9); some monkeys developed moderate clinical signs (mean scores = 11-15; n = 3), whereas the majority--quite remarkably--developed few clinical signs (mean scores = 1-6; n = 6). The monkeys that developed moderate clinical signs had hematic fluid in their optical fibers at postmortem, presumably limiting NIr exposure and overall clinical improvement. NIr was not toxic to brain tissue and offered neuroprotection to dopaminergic cells and their terminations against MPTP insult, particularly in animals that developed few clinical signs. INTERPRETATION: Our findings indicate NIr to be an effective therapeutic agent in a primate model of the disease and create the template for translation into clinical trials.

Widespread brain transcriptome alterations underlie the neuroprotective actions of dietary saffron.

Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for 2, 5 or 10 days before administration of the parkinsonian neurotoxin MPTP (50 mg/kg). Five days of saffron pre-conditioning provided the greatest benefit against MPTP-induced neuropathology, significantly mitigating both loss of functional dopaminergic cells in the substantia nigra pars compacta (p < 0.01) and abnormal neuronal activity in the caudate-putamen complex (p < 0.0001). RNA microarray analysis of the brain transcriptome of mice pre-conditioned with saffron for 5 days revealed differential expression of 424 genes. Bioinformatics analysis identified enrichment of molecular pathways (e.g. adherens junction, TNFR1 and Fas signaling) and expression changes in candidate genes (Cyr61, Gpx8, Ndufs4, and Nos1ap) with known neuroprotective actions. The apparent biphasic nature of the dose-response relationship between saffron and measures of neuroprotection, together with the stress-inducible nature of many of the up-regulated genes and pathways, lend credence to the idea that saffron, like various other phytochemicals, is a hormetic stimulus, with functions beyond its strong antioxidant capacity. These findings provide impetus for a more comprehensive evaluation of saffron as a neuroprotective intervention.

Neuroprotective effect of Myo/Nog cells in the stressed retina.

Myo/Nog cells are essential for eye development in the chick embryo and respond to injury in adult tissues. These cells express mRNA for the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein (BMP) inhibitor Noggin and the cell surface protein recognized by the G8 monoclonal antibody (mAb). In this study, we determined that Myo/Nog cells are present in low numbers in the retina of the mouse eye. G8-positive Myo/Nog cells were distinguished from neuronal, Müller and microglial cells that were identified with antibodies to calretinin, Chx10, glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1, respectively. In the neonatal retina, the number of Myo/Nog cells increased in parallel with cell death induced by transient exposure to hyperoxia. In this model of retinopathy of prematurity, depletion of Myo/Nog cells by intravitreal injection of the G8 mAb and complement increased cell death. These findings demonstrate that Myo/Nog cells are a distinct population of cells, not previously described in the retina, which increases in response to retinal damage and mitigate hypoxia-induced cell death.

Near-infrared light (670 nm) reduces MPTP-induced parkinsonism within a broad therapeutic time window.

We have shown previously that near-infrared light (NIr), when applied at the same time as a parkinsonian insult (e.g. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP), reduces behavioural deficits and offers neuroprotection. Here, we explored whether the timing of NIr intervention-either before, at the same time or after the MPTP insult-was important. Mice received MPTP injections (total of 50 mg/kg) and, at various stages in relation to these injections, extracranial application of NIr. Locomotor activity was tested with an open-field test, and brains were processed for immunohistochemistry. Our results showed that regardless of when NIr was applied in relation to MPTP insult, behavioural impairment was reduced by a similar magnitude. The beneficial effect of NIr was fast-acting (within minutes) and long-lasting (for several days). There were more dopaminergic cells in the NIr-treated MPTP groups than in the MPTP group; there was no clear indication that a particular combination of NIr treatment and MPTP injection resulted in a higher cell number. In summary, irrespective of whether it was applied before, at the same time as or after MPTP insult, NIr reduced both behavioural and structural measures of damage by a similar magnitude. There was a broad therapeutic time window of NIr application in relation to the stage of toxic insult, and the NIr was fast-acting and long-lasting.

Near-infrared light treatment reduces astrogliosis in MPTP-treated monkeys.

We have reported previously that intracranial application of near-infrared light (NIr) reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether NIr reduces the gliosis in this animal model. Sections of midbrain (containing the substantia nigra pars compacta; SNc) and striatum were processed for glial fibrillary acidic protein (to label astrocytes; GFAP) and ionised calcium-binding adaptor molecule 1 (to label microglia; IBA1) immunohistochemistry. Cell counts were undertaken using stereology, and cell body sizes were measured using ImageJ. Our results showed that NIr treatment reduced dramatically (~75 %) MPTP-induced astrogliosis in both the SNc and striatum. Among microglia, however, NIr had a more limited impact in both nuclei; although there was a reduction in overall cell size, there were no changes in the number of microglia in the MPTP-treated monkeys after NIr treatment. In summary, we showed that NIr treatment influenced the glial response, particularly that of the astrocytes, in our monkey MPTP model of Parkinson's disease. Our findings raise the possibility of glial cells as a future therapeutic target using NIr.

The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice.

We have used the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model to explore whether (i) the neuroprotective effect of near infrared light (NIr) treatment in the SNc is dose-dependent and (ii) the relationship between tyrosine hydroxylase (TH)+ terminal density and glial cells in the caudate-putamen complex (CPu). Mice received MPTP injections (50 mg/kg) and 2 J/cm2 NIr dose with either 2 d or 7 d survival period. In another series, with a longer 14 d survival period, mice had a stronger MPTP regime (100 mg/kg) and either 2 J/cm2 or 4 J/cm2 NIr dose. Brains were processed for routine immunohistochemistry and cell counts were made using stereology. Our findings were that in the 2 d series, no change in SNc TH+ cell number was evident after any treatment. In the 7 d series however, MPTP insult resulted in ∼45% reduction in TH+ cell number; after NIr (2 J/cm2) treatment, many cells were protected from the toxic insult. In the 14 d series, MPTP induced a similar reduction in TH+ cell number. NIr mitigated the loss of TH+ cells, but only at the higher dose of 4 J/cm2; the lower dose of 2 J/cm2 had no neuroprotective effect in this series. The higher dose of NIr, unlike the lower dose, also mitigated the MPTP- induced increase in CPu astrocytes after 14 d; these changes were independent of TH+ terminal density, of which, did not vary across the different experimental groups. In summary, we showed that neuroprotection by NIr irradiation in MPTP-treated mice was dose-dependent; with increasing MPTP toxicity, higher doses of NIr were required to protect cells and reduce astrogliosis.

How Drug Shortages Affect Clinical Care: The Case of the Surgical Anesthetic Propofol.

BACKGROUND: Periodic drug shortages have become a reality in clinical practice. In 2010, in the context of a nationwide drug shortage, our hospital experienced an abrupt 3-month shortage of the surgical anesthetic propofol. The purpose of this retrospective study was to survey the clinical impact of the abrupt propofol shortage at our hospital and to survey for any change in perioperative mortality. METHODS: A retrospective before-and-after analysis, comparing May through July 2010 (group A, prior to the propofol shortage) to August through October 2010 (group B, during the propofol shortage). RESULTS: In May through July 2010, before the propofol shortage, a majority of patients (80%) received propofol (group A, n = 2,830). In August through October 2010, during the propofol shortage, a majority of patients (81%) received etomidate (group B, n = 3,066). We observed that net usage of etomidate increased by more than 600% in our hospital. Baseline health characteristics and type of surgery were similar between groups A and B. Thirty-day and 2-year mortality were similar between groups A and B. The reported causes and frequency of mortality in groups A and B were also similar. CONCLUSION: The propofol shortage led to an increased usage of etomidate by more than 600%. In spite of that, we did not detect an increase in mortality associated with the increased use of etomidate during a 3-month propofol shortage.