Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations.

Anti-N-methyl-D-aspartate receptor-associated encephalitis (NMDARE) is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction. The mechanism of pathogenesis remains incompletely understood, but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways. Young adults are most frequently affected; the median age at diagnosis is 21 years. There is a strong female predilection with a female sex predominance of 4:1. NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma. However, NMDARE has also been described in patients with small cell lung cancer, clear cell renal carcinoma, and other benign and malignant neoplasms. Diagnosis is based on correlation of the clinical presentation, electroencephalography, laboratory studies, and imaging. Computed tomography, positron emission tomography, and magnetic resonance imaging are essential to identify an underlying tumor, exclude clinicopathologic mimics, and predict the likelihood of long-term functional impairment. Nuclear imaging may be of value for prognostication and to assess the response to therapy. Treatment may involve high-dose corticosteroids, intravenous immunoglobulin, and plasma exchange. Herein, we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria, treatment regimens, and proposed pathogenetic mechanisms.

Fascial plane approach to anesthetizing the radial, median, and ulnar nerves: an educational review.

Brachial plexus block provides effective anesthesia and analgesia for upper extremity surgery but requires injection of large anesthetic volumes near major vascular structures. Moreover, the extensive motor and sensory loss produced by plexus block often exceeds the neural distribution needed for corresponding surgical procedures.High-resolution ultrasound facilitates selective nerve blocks at nearly every level of the upper extremity. We present fascial plane injection techniques for selective radial, median, and ulnar nerve blocks. These techniques can be used to match sensory distribution with specific surgical procedures. They are performed using low anesthetic volumes and without proximity to nerves or vascular structures. In this article, fresh cadaver dissections with corresponding ultrasound images are used to demonstrate stepwise fascial plane techniques for the radial, median, and ulnar nerves. These techniques are performed using familiar anatomic landmarks.Practical applications of these techniques are demonstrated for commonly performed procedures of the upper extremity. Corresponding injection volumes with duration of postoperative analgesia are presented. Selected injections are described for both surgical anesthesia and postoperative analgesia.Selective fascial plane injections can provide surgical anesthesia and postoperative analgesia in settings that might otherwise require much larger volumes of local anesthetic. These selective nerve blocks can match sensory loss with the anatomic pain distribution in each patient. Reliable techniques for selective nerve blocks of the upper extremity can expand the capabilities for ultrasound-guided regional anesthesia.

Early-onset pancreatic cancer: a review of molecular mechanisms, management, and survival.

OBJECTIVES: Early-onset pancreatic cancer (EOPC) - defined as pancreatic cancer diagnosed before the age of 50 years - is associated with a poor prognosis as compared to later-onset pancreatic cancer (LOPC). Emerging evidence suggests that EOPC may exhibit a genetic signature and tumor biology that is distinct from that of LOPC. We review genetic mutations that are more prevalent in EOPC relative to LOPC and discuss the potential impact of these mutations on treatment and survival. MATERIALS AND METHODS: Using PubMed and Medline, the following terms were searched and relevant citations assessed: "early onset pancreatic cancer," "late onset pancreatic cancer," "pancreatic cancer," "pancreatic cancer genes," and "pancreatic cancer targeted therapy." RESULTS: Mutations in CDKN2, FOXC2, and SMAD4 are significantly more common in EOPC as compared to LOPC. In addition, limited data suggest that PI3KCA mutations are more frequently observed in EOPC as compared to LOPC. KRAS mutations are relatively rare in EOPC. CONCLUSIONS: Genetic mutations associated with EOPC are distinct from those of LOPC. The preponderance of the evidence suggest that poor outcomes in EOPC are related both to advanced stage of presentation and unique tumor biology. The molecular and genetic features of EOPC warrant further investigation in order to optimize management.

Factors Affecting Inpatient Mortality and Length of Stay in Nonmetastatic Colorectal Cancer: Insights from the National Inpatient Sample.

OBJECTIVE: The objective of this study was to assess the effect of opioid use and other factors on inpatient length of stay (LOS) and mortality among patients hospitalized with nonmetastatic colorectal cancer (NMCRC). MATERIALS AND METHODS: We analyzed discharge encounters collected from the 2016 to 2017 National Inpatient Sample (NIS) to evaluate the effect of long-term opioid use (90 d or longer) and cancer-related complications on LOS and mortality among hospitalized patients with NMCRC. RESULTS: A total of 94,535 patients with NMCRC were included in the analysis. Long-term opioid users had a shorter average LOS and reduced inpatient mortality as compared with nonopioid users (5.97±5.75 vs. 6.66±6.92 d, P<0.01; and adjusted odds ratio=0.72, 95% confidence interval: 0.56-0.93, respectively). Factors that significantly increased both LOS and mortality included infection, venous thromboembolism, and chemotherapy-induced neutropenia; the average LOS was 2.7, 2.6, and 0.7 days longer, and the adjusted odds ratio for risk of inpatient mortality was 3.7, 1.2, and 1.2, respectively (P<0.05), for patients admitted with these cancer-related complications. CONCLUSIONS: Long-term opioid use is associated with decreased LOS and inpatient mortality among patients with NMCRC. Individuals admitted for cancer-related complications face a longer LOS and increased mortality as compared with those admitted without these morbidities.

Second primary malignancies in patients with melanoma in situ: Insights from the surveillance, epidemiology, and end results program.

BACKGROUND: Melanoma in situ (MIS) is among the most frequently diagnosed cancers in the United States. Emerging data suggest that MIS is associated with an increased risk of developing a second primary malignancy (SPM). OBJECTIVES: To determine trends in MIS-associated SPMs and identify MIS-specific features that increase SPM risk. METHODS: In this retrospective population-based study, we identified 90,075 patients who were diagnosed with MIS between 1973 and 2015 from the Surveillance, Epidemiology, and End Results database. The risk of developing an SPM among these individuals was compared to individuals without a diagnosis of MIS. The risk of developing an SPM among patients with a diagnosis of MIS was also increased over time. RESULTS: Patients with a diagnosis of MIS had an increased relative risk (RR) of developing an SPM as compared to the general population with an identical age, sex, race, and follow-up period. The RR of a metachronous malignancy in MIS patients also increased over time, as follows: 1.16 (95 % CI: 1.07-1.26), 1.19 (95 % CI: 1.14-1.23), 1.30 (95 % CI: 1.27-1.33), and 1.52 (95 % CI: 1.49-1.56) in 1973-1982, 1983-1992, 1993-2002, and 2003-2015, respectively (P < 0.05). In addition, there was a direct correlation between the number of MIS lesions and SPM risk; ≥1, ≥2, and ≥3 tumors portended a 1.5-2, 2-3, and 4-5-fold increased risk of developing an SPM, respectively. CONCLUSIONS: MIS is associated with an increased risk of developing an SPM and therefore individuals with a history of MIS may benefit from close medical surveillance.

Sociodemographic Characteristics as Predictors of Outcomes in Hepatocellular Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Race, gender, insurance status, and income play important roles in predicting health care outcomes. However, the impact of these factors has yet to be fully elucidated in the setting of hepatocellular carcinoma (HCC). METHODS: We designed a retrospective cohort study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program to identify patients diagnosed with resectable HCC (N = 28,518). Demographic factors of interest included race (Asian/Pacific Islander [API], African American [AA], Native American/Alaska Native [NA], or White [WH]) and gender (male [M] or female [F]). Insurance classifications included those having Medicare/Private Insurance [ME/PI], Medicaid [MAID], or No Insurance [NI]. Median household income was estimated for all diagnosed with HCC. Endpoints included: (1) overall survival; (2) likelihood of receiving a recommendation for surgery; and (3) specific surgical intervention performed. Multivariate multinomial logistic regression for relative risk ratio (RRR) and Cox regression models were used to identify pertinent associations. RESULTS: Race, gender, insurance status, and income had statistically significant effects on the likelihood of surgical recommendation and overall survival. API were more likely to receive a recommendation for hepatic resection (RRR = 1.45; 95% CI: 1.31-1.61; Reference Race: AA) and exhibited prolonged overall survival (HR = 0.77; 95% CI: 0.73-0.82; Reference Race: AA) as compared to members of any other ethnic group; there was no difference in these endpoints between AA, NA, or WH individuals. Gender also had a significant effect on survival: Females exhibited superior overall survival (HR = 0.89; 95% CI: 0.85-0.93; Reference Gender: M) as compared to males. Patients who had ME/PI were more likely than those with MAID or NI to receive a surgical recommendation. ME/PI was also associated with superior overall survival. Conclusions: Race, gender, insurance status, and income have measurable effects on HCC management and outcomes. The underlying causes of these disparities warrant further investigation.

Patient outcomes in myeloproliferative neoplasm-related thrombosis: Insights from the National Inpatient Sample.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (MPNs) - polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) - often present with thrombosis. We aimed to determine the inpatient mortality, cost of care, and length-of-stay among individuals with Philadelphia-negative MPNs who had arterial or venous thrombosis associated with admission versus those who were admitted for non-thrombosis-related events. METHODS: Using ICD-10M coding, we identified 7,128,770 patients from the National Inpatient Sample (NIS) database who were hospitalized in 2016. 31,302 patients had a diagnosis of a Philadelphia-negative MPN. Mortality, length-of-stay, and cost of care were compared between patients who had thrombosis included among the top three diagnoses and those who were admitted for other reasons. Chi-squared test for categorical variables and t-test for continuous variables were used to compare baseline characteristics. Final multivariable models were constructed to determine predictors of outcomes. RESULTS: Inpatient mortality was significantly higher among individuals with Philadelphia-negative MPN who had thrombosis associated with admission as compared to those who were hospitalized for other reasons (5.7% versus 3.1%, P < 0.001). Unadjusted cost of care was also significantly higher for patients with thrombosis as compared to those without thrombosis ($25,539.06 versus $19,002.72 USD, respectively, P < 0.001). Length-of-stay was longer among the former group as compared to the latter (8.26 versus 7.95 days, P = 0.0963). However, this finding did not reach statistical significance. CONCLUSIONS: Hospitalization for MPN-related thrombotic events is associated with excess inpatient mortality and higher cost of care. However, thrombosis has no statistically significant effect on length-of-stay among this population. The underlying causes of mortality and cost disparities among patients with MPN-associated thrombosis warrant further investigation.

Management of hypertension in COVID-19.

The ACE2 receptor plays a central role in severe acute respiratory syndrome coronavirus 2 host cell entry and propagation. It has therefore been postulated that angiotensin converting enzyme inhibitors and angiotensin receptor blockers may upregulate ACE2 expression and thus increase susceptibility to infection. We suggest that alternative anti-hypertensive agents should be preferred among individuals who may be exposed to this increasingly common and potentially lethal virus.

Predicting cost of inhalational anesthesia at low fresh gas flows: impact of a new generation carbon dioxide absorbent.

It is well known that low fresh gas flows result in lower cost of inhalational agents. A new generation of carbon dioxide absorbents allows low flow anesthesia with all anesthetics but these new compounds are more expensive. This study examines the cost of inhalational anesthesia at different fresh gas flows combined with the cost of absorbent. The cost of sevoflurane and desflurane is lower at low fresh gas flows. Paradoxically the cost of isoflurane is cheaper at 2 L/min than at lower fresh gas flows due to increased cost of carbon dioxide absorbent. Therefore low fresh gas flows should be used when feasible with sevoflurane and desflurane, but higher fresh gas flows up to 2 L/min may be more economical with isoflurane during maintenance phase of anesthesia.

True Cost of Operating Room Time: Implications for an Orthopaedic Trauma Service.

OBJECTIVE: To derive an accurate estimate of the operating cost per minute for an orthopaedic trauma room. STUDY DESIGN: Retrospective economic analysis. SETTING: Level II Trauma Center. INTERVENTION: Hospital cost-accounting system query. MAIN OUTCOME MEASUREMENTS: Direct fixed costs, direct variable costs, and hospital overhead. RESULTS: Operating room per minute costs include direct variable costs of $2.77, direct fixed costs of $2.47, and hospital overhead costs of $10.97. Total per minute costs amounted to $16.21. This does not include professional fees of anesthesiology or surgeons or the costs of soft goods or implants. CONCLUSIONS: This is the first published study to document the true per minute cost of an orthopaedic trauma operating room. Such information is valuable when defining the value of a dedicated operating room, negotiating employment contracts, defining call stipends, and brokering capital purchases for the orthopaedic trauma service. LEVEL OF EVIDENCE: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Persistent Left Superior Vena Cava (PLSVC) with a Connection to the Azygos System: Case Report and Clinical Implications.

Persistent left superior vena cava (PLSVC) is a rare anatomic variant that has a significant effect on the structure of the heart and venous system with clinical implications that are far-reaching. The presence of this variant is relevant to central venous catheter insertion, cardioverter-defibrillator placement, coronary artery bypass grafting, and numerous other medical procedures. In this report, we describe a rare case of PLSVC with a connection to the azygos system; notably, the vast majority of PLSVCs connect to the coronary sinus. We also discuss the anatomic and anesthetic considerations for individuals with this uncommon variant.

Cost Savings Opportunities in Perioperative Management of the Patients With Orthopaedic Trauma.

Considerable opportunities for cost savings exist surrounding the perioperative management of patients with orthopaedic fracture and trauma. Scientific evidence is available to support each potential cost savings measure. Much of these data had been documented for years but has never been adhered to, resulting in millions of dollars in unnecessary testing and treatment. Careful attention to preoperative laboratory testing can save huge amounts of money and expedite medical clearance for injured patients. The use of a dedicated orthopaedic trauma operating room has been shown to improve resource utilization, decrease costs, and surgical complications. A variety of anesthetic techniques and agents can reduce operative time, recovery room time, and hospital lengths of stay. Strict adherence to blood utilization protocols, appropriate deep venous thrombosis prophylaxis, and multimodal postoperative pain control with oversight from dedicated hip fracture hospitalists is critical to cost containment. Careful attention to postoperative disposition to acute care and management of postoperative testing and radiographs can also be another area of cost containment. Institutional protocols must be created and followed by a team of orthopaedic surgeons, hospitalists, and anesthesiologists to significantly impact the costs associated with care of patient with orthopaedic trauma and fracture.

The Clinical and Economic Impact of Generic Locking Plate Utilization at a Level II Trauma Center.

OBJECTIVES: In today's climate of cost containment and fiscal responsibility, generic implant alternatives represent an interesting area of untapped resources. As patents have expired on many commonly used trauma implants, generic alternatives have recently become available from a variety of sources. The purpose of this study was to examine the clinical and economic impact of a cost containment program using high quality, generic orthopaedic locking plates. The implants available for study were anatomically precontoured plates for the clavicle, proximal humerus, distal radius, proximal tibia, distal tibia, and distal fibula. DESIGN: Retrospective review. SETTING: Level II Trauma center. PATIENTS: 828 adult patients with operatively managed clavicle, proximal humerus, distal radius, proximal tibia, tibial pilon, and ankle fractures. INTERVENTION: Operative treatment with conventional or generic implants. RESULTS: The 414 patients treated with generic implants were compared with 414 patients treated with conventional implants. There were no significant differences in age, sex, presence of diabetes, smoking history or fracture type between the generic and conventional groups. No difference in operative time, estimated blood loss or intraoperative complication rate was observed. No increase in postoperative infection rate, hardware failure, hardware loosening, malunion, nonunion or need for hardware removal was noted. Overall, our hospital realized a 56% reduction in implant costs, an average savings of $1197 per case, and a total savings of $458,080 for the study period. CONCLUSIONS: Use of generic orthopaedic implants has been successful at our institution, providing equivalent clinical outcomes while significantly reducing implant expenditures. Based on our data, the use of generic implants has the potential to markedly reduce operative costs as long as quality products are used. LEVEL OF EVIDENCE: Therapeutic Level III.

Hurt, tired and queasy: Specific variants in the ATPase domain of the TRAP1 mitochondrial chaperone are associated with common, chronic "functional" symptomatology including pain, fatigue and gastrointestinal dysmotility.

Functional disorders are common conditions with a substantial impact on a patients' wellbeing, and can be diagnostically elusive. There are bidirectional associations between functional disorders and mitochondrial dysfunction. In this study, provided clinical information and the exon sequence of the TRAP1 mitochondrial chaperone were retrospectively reviewed with a focus on the functional categories of chronic pain, fatigue and gastrointestinal dysmotility. Very-highly conserved TRAP1 variants were identified in 73 of 930 unrelated patients. Functional symptomatology is strongly associated with specific variants in the ATPase binding pocket. In particular, the combined presence of all three functional categories is strongly associated with p.Ile253Val (OR 7.5, P = 0.0001) and with two other interacting variants (OR 18, P = 0.0005). Considering a 1-2% combined variant prevalence and high odds ratios, these variants may be an important factor in the etiology of functional symptomatology.