Regional Anesthesia in the Austere Environment: Lessons Learned from Current Out-of-Hospital Practice.

INTRODUCTION: Pain management for trauma in the extreme environment is vital for both casualty comfort and aiding safe extrication. However, adequate pain management in a resource-limited environment can be challenging and is often limited. We conducted a scoping review of the use of regional anesthesia in the prehospital environment, evaluating which regional anesthetic procedure was performed for various indications, their efficacy, and the type of healthcare provider delivering the anesthetic. METHODS: A PRISMA-guided systematic literature review was conducted of Medline, Embase, and Cochrane databases for studies reporting the use of regional anesthesia in the prehospital environment published before June 30, 2022. RESULTS: Thirty studies met the criteria and were included in the review. The most common types of regional anesthesia were fascia-iliaca compartment block (n = 317, from 12 studies) and femoral nerve block (n = 210, from 8 studies), along with various other blocks for a range of indications. These blocks had good efficacy and a low-risk profile and could be delivered by a wide range of healthcare providers. CONCLUSIONS: Regional anesthesia is an effective and non-resource-heavy pain management tool in prehospital environments, which may be applicable to austere settings. It can cover a wide range of injuries and can avoid systemic complications for casualties that may already be challenging to manage in out-of-hospital settings. Additionally, regional anesthesia can be effectively delivered by a wide range of providers. This review provides a holistic summary of pain management using regional anesthesia in the prehospital environment, with a discussion on its potential use in more extreme settings.

Perioperative Dietary Restriction of Carbohydrates in the Management of Blood Glucose Levels in Patients Undergoing Total Knee Replacement.

BACKGROUND: Approximately 75% of the US population over 65 years has prediabetes or diabetes. Despite current evidence for the efficacy of carbohydrate restriction in managing blood glucose, this practice has not been implemented as part of routine perioperative blood sugar management. We hypothesize that a carbohydrate reduced hospital diet (CRD) of 135 g/d may improve blood sugar levels following total knee arthroplasty (TKA) compared to a non-carbohydrate reduced hospital diet (NCRD). METHODS: We randomized non-insulin-dependent prediabetic and diabetic patients undergoing TKA to either an NCRD or a CRD. Sixty-four patients were enrolled in the study and 2 were excluded, leading to 62 patients in the final analysis. The NCRD group included 14 females (47%) and 16 males (53%), with mean age of 68.5 years (±6.3 years). The CRD group included 16 females (50%) and 16 males (50%), with mean age of 68.0 years (±8.0 years). For hemoglobin A1C, the NCRD group had mean 5.8% (±0.6%) and the CRD group had mean 5.7% (±0.8%). For body mass index, the NCRD group had mean 29.3 kg/m2 (±6.3 kg/m2) and the CRD group 32.7 kg/m2 (±5.0 kg/m2). The primary outcome measure was mean blood glucose. RESULTS: Mean blood sugar values during hospital stay were significantly lower in the CRD group with 121.5 mg/dL (±17.1 mg/dL) compared to the NCRD group 141.2 mg/dL (±31.3 mg/dL, P = .0031). CONCLUSION: Blood sugar levels after surgery can be significantly reduced with a CRD. Further research is necessary to study the effect of reduced blood sugar levels on complications and infection rates following TKA surgery. LEVEL OF EVIDENCE: I.

Intraoperative Ketamine in Total Knee Arthroplasty Does Not Decrease Pain and Narcotic Consumption: A Prospective Randomized Controlled Trial.

BACKGROUND: Multiple studies have demonstrated that ketamine, a glutamate receptor blocker, may decrease postoperative pain in abdominal and orthopedic surgeries. However, its role with spinal anesthesia and total knee arthroplasty (TKA) remains unknown. The purpose of this study is to determine the efficacy of subanesthetic dosing of ketamine during TKA on postoperative pain and narcotic consumption. METHODS: In this prospective, randomized, double-blinded clinical trial, we enrolled 91 patients undergoing primary TKA with spinal anesthesia in a single institution from 2017 to 2018. Patients were randomized to receive intraoperative ketamine infusion at a rate of 6 mcg/kg/min for 75 minutes or a saline placebo. All patients received spinal anesthesia and otherwise identical surgical approaches, pain management, and rehabilitation protocols. Patient-reported visual analog pain scores were calculated preoperatively, postoperative days (POD) 0-7, and 2 weeks. Narcotic consumption was evaluated on POD 0 and 1. RESULTS: There was no difference in average pain between ketamine and placebo at all time points except for at PODs 1 (45 vs 56, P = .041) and 4 (39 vs 49, P = .040). For least pain experienced, patients administered with ketamine experienced a reduction in pain only at POD 4 (22 vs 35, P = .011). There was no difference in maximum pain cohorts at all time points of the study or in-hospital morphine equivalents between the 2 cohorts. CONCLUSION: As part of multimodal pain management protocol, intraoperative ketamine does not result in a clinically significant improvement in pain and narcotic consumption following TKA.

Routine Postoperative Laboratory Tests Are Unnecessary After Partial Knee Arthroplasty.

BACKGROUND: While partial knee arthroplasty (PKA) is increasingly performed on an outpatient basis, many surgeons still admit patients overnight and obtain laboratory studies on the first postoperative day. The purpose of this study was to investigate the utility and cost effectiveness of routine postoperative laboratory studies after PKA. METHODS: This is a retrospective review of 322 consecutive unilateral or bilateral simultaneous PKAs (unicompartmental, patellofemoral, and modular bicompartmental knee arthroplasty) performed by a single surgeon. There were 408 complete blood counts and basic metabolic panels ordered. RESULTS: Despite a large number of laboratory studies ordered and abnormalities detected, there was a 1.6% rate of laboratory-associated interventions (for either hypokalemia or hyperglycemia in 5 patients) and no red blood cell transfusions. Hospital charges associated with laboratory studies totaled $85,413. There were no 90-day postoperative hospital readmissions or emergency department evaluations related to abnormal postoperative laboratory values. CONCLUSION: With an increasing emphasis placed on cost containment, the low rate of laboratory-associated interventions after PKA suggests that routinely obtaining laboratory studies are neither necessary nor cost effective.

High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications.

We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and African-Americans (34.2%), was analyzed for CNVs in a single study using a uniform array platform and computational process. We have catalogued and characterized 54,462 individual CNVs, 77.8% of which were identified in multiple unrelated individuals. These nonunique CNVs mapped to 3272 distinct regions of genomic variation spanning 5.9% of the genome; 51.5% of these were previously unreported, and >85% are rare. Our annotation and analysis confirmed and extended previously reported correlations between CNVs and several genomic features such as repetitive DNA elements, segmental duplications, and genes. We demonstrate the utility of this data set in distinguishing CNVs with pathologic significance from normal variants. Together, this analysis and annotation provides a useful resource to assist with the assessment of CNVs in the contexts of human variation, disease susceptibility, and clinical molecular diagnostics.

Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease.

BACKGROUND & AIMS: Recently an association was shown between the single nucleotide polymorphism (SNP), rs11209026, within the interleukin-23 receptor (IL23R) locus and Crohn's disease (CD) as a consequence of a genome-wide association study of this disease in adults. We examined the effects of this and other previously reported SNPs at this locus with respect to CD in children. METHODS: By using data from our ongoing genome-wide association study in our cohort of 142 pediatric CD patients and 281 matched controls, we investigated the association of the previously reported SNPs at the IL23R locus with the childhood form of this disease. RESULTS: By using the Fisher exact test, the minor allele frequency of rs11209026 in the patients was 1.75%, whereas it was 6.61% in the controls, yielding a protective odds ratio (OR) of 0.25 (95% confidence interval, 0.10-0.65; 1-sided P = 9.2 x 10(-4)). Furthermore, of all the SNPs previously reported, rs11209026 was associated the most strongly. A subsequent family based association test (which is more resistant to population stratification) with 65 sets of trios derived from our initial patient cohort yielded significant association with rs11209026 in a transmission disequilibrium test (1-sided P = .0017). In contrast, no association was detected to the caspase-recruitment domain 15 gene for the inflammatory bowel disease phenotype. CONCLUSIONS: The OR of the IL23R variant in our pediatric study is highly comparable with that reported previously in a non-Jewish adult inflammatory bowel disease case-control cohort (OR, 0.26). As such, variants in the IL23R gene confer a similar magnitude of risk of CD to children as for their adult counterparts.

Infections in anterior cruciate ligament reconstruction.

CONTEXT: Anterior cruciate ligament (ACL) reconstruction is a safe, common, and effective method of restoring stability to the knee after injury, but evolving techniques of reconstruction carry inherent risk. Infection after ACL reconstruction, while rare, carries a high morbidity, potentially resulting in a poor clinical outcome. EVIDENCE ACQUISITION: Data were obtained from previously published peer-reviewed literature through a search of the entire PubMed database (up to December 2012) as well as from textbook chapters. RESULTS: Treatment with culture-specific antibiotics and debridement with graft retention is recommended as initial treatment, but with persistent infection, consideration should be given to graft removal. Graft type likely has no effect on infection rates. CONCLUSION: The early diagnosis of infection and appropriate treatment are necessary to avoid the complications of articular cartilage damage and arthrofibrosis.

Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.

Recently a modest, but consistently, replicated association was demonstrated between obesity and the single-nucleotide polymorphism (SNP), rs17782313, 3' of the MC4R locus as a consequence of a meta-analysis of genome-wide association (GWA) studies of the disease in white populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European-American (EA) obese children (BMI > or =95th percentile) and 3,960 EA controls (BMI <95th percentile), as well as 1,008 African-American (AA) obese children and 2,715 AA controls. rs571312, rs10871777, and rs476828 (perfect surrogates for rs17782313) yielded odds ratios in the EA cohort of 1.142 (P = 0.045), 1.137 (P = 0.054), and 1.145 (P = 0.042); however, there was no significant association with these SNPs in the AA cohort. When investigating all 30 SNPs present on the Illumina BeadChip at this locus, again there was no evidence for association in AA cases when correcting for the number of tests employed. As such, variants 3' to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in white children as to their adult white counterparts but this observation did not extend to AAs.

The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI.

The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. A number of genetic determinants of adult BMI have already been established through genome-wide association (GWA) studies. In this study, we examined 25 single-nucleotide polymorphisms (SNPs) corresponding to 13 previously reported genomic loci in 6,078 children with measures of BMI. Fifteen of these SNPs yielded at least nominally significant association to BMI, representing nine different loci including INSIG2, FTO, MC4R, TMEM18, GNPDA2, NEGR1, BDNF, KCTD15, and 1q25. Other loci revealed no evidence for association, namely at MTCH2, SH2B1, 12q13, and 3q27. For the 15 associated variants, the genotype score explained 1.12% of the total variation for BMI z-score. We conclude that among 13 loci that have been reported to associate with adult BMI, at least nine also contribute to the determination of BMI in childhood as demonstrated by their associations in our pediatric cohort.

Association of the BANK 1 R61H variant with systemic lupus erythematosus in Americans of European and African ancestry.

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs10516487, within the B-cell gene BANK1 and systemic lupus erythematosus (SLE) as a consequence of a genome wide association study of this disease in European and Argentinean populations. In a bid for replication, we examined the effects of the R61H non-synonymous variant with respect to SLE in our genotyped American cohorts of European and African ancestry. Utilizing data from our ongoing genome-wide association study in our cohort of 178 Caucasian SLE cases and 1808 Caucasian population-based controls plus 148 African American (AA) SLE cases and 1894 AA population-based controls we investigated the association of the previously described non-synonymous SNP at the BANK1 locus with the disease in the two ethnicities separately. Using a Fisher's exact test, the minor allele frequency (MAF) of rs10516487 in the Caucasian cases was 22.6% while it was 31.2% in Caucasian controls, yielding a protective odds ratio (OR) of 0.64 (95% CI 0.49-0.85; one-sided p = 7.07 × 10(-4)). Furthermore, the MAF of rs10516487 in the AA cases was 18.7% while it was 23.3% in AA controls, yielding a protective OR of 0.75 (95% CI 0.55-1.034; one-sided p = 0.039). The OR of the BANK1 variant in our study cohorts is highly comparable with that reported previously in a South American/European SLE case-control cohort (OR = 0.72). As such, R61H in the BANK1 gene confers a similar magnitude of SLE protection, not only in European Americans, but also in African Americans.

Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes.

OBJECTIVE: Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes, a common multifactorial disease with a strong genetic component. To fully utilize the GWA data that we had obtained by genotyping 563 type 1 diabetes probands and 1,146 control subjects, as well as 483 case subject-parent trios, using the Illumina HumanHap550 BeadChip, we designed a full stage 2 study to capture other possible association signals. RESEARCH DESIGN AND METHODS: From our existing datasets, we selected 982 markers with P < 0.05 in both GWA cohorts. Genotyping these in an independent set of 636 nuclear families with 974 affected offspring revealed 75 markers that also had P < 0.05 in this third cohort. Among these, six single nucleotide polymorphisms in five novel loci also had P < 0.05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) plus 1,673 control subjects. RESULTS: Two markers (rs9976767 and rs3757247) remained significant after adjusting for the number of tests in this last cohort; they reside in UBASH3A (OR 1.16; combined P = 2.33 x 10(-8)) and BACH2 (1.13; combined P = 1.25 x 10(-6)). CONCLUSIONS: Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity.

Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP.

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050-1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.

A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study.

OBJECTIVE: In stage 1 of our genome-wide association (GWA) study for type 1 diabetes, one locus at 16p13 was detected (P = 1.03 x 10(-10)) and confirmed in two additional cohorts. Here we describe the results of testing, in these additional cohorts, 23 loci that were next in rank of statistical significance. RESEARCH DESIGN AND METHODS: Two independent cohorts were studied. The Type 1 Diabetes Genetics Consortium replication cohort consisted of 549 families with at least one child diagnosed with diabetes (946 total affected) and DNA from both parents. The Canadian replication cohort consisted of 364 nuclear family trios with one type 1 diabetes-affected offspring and two parents (1,092 individuals). RESULTS: One locus at 12q13, with the highest statistical significance among the 23, was confirmed. It involves type 1 diabetes association with the minor allele of rs1701704 (P = 9.13 x 10(-10), OR 1.25 [95% CI 1.12-1.40]). CONCLUSIONS: We have discovered a type 1 diabetes locus at 12q13 that is replicated in an independent cohort of type 1 diabetic patients and confers a type 1 diabetes risk comparable with that of the 16p13 locus we recently reported. These two loci are identical to two loci identified by the whole-genome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach.

Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 x 10(-8) and 6.95 x 10(-8), respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 x 10(-8); OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.