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Pain management and opioid consumption following outpatient orthopedic surgery may be influenced by several variables, including knowledge of safe opioid use. A prospective randomized study was undertaken to understand the effect of preoperative opioid education on opioid consumption following outpatient orthopedic surgeries. A total of 237 patients undergoing outpatient orthopedic surgeries were prospectively randomized to receive preoperative opioid education or not. Postoperative data collected included the number of pills taken, daily visual analog scale (VAS) pain scores, adverse events, and attitude toward the pain experience. A total of 107 patients were randomized to receive preoperative education and 130 to not receive preoperative education. On average, 27 pills were prescribed to each patient. The preoperative opioid education group consumed significantly fewer opioids (6 pills) when compared with the group not receiving education (12 pills) ( P Orthopedics . 2021;44(2):123–127.]

The genetics of late-onset Alzheimer's disease (AD) is complex due to the heterogeneous nature of the disorder. APOE*4 is the strongest genetic risk factor for AD. Genome-wide association studies have identified more than 30 additional loci, each having relatively small effect size. Known AD loci explain only about 30% of the genetic variance, and thus much of the genetic variance remains unexplained. To identify some of the missing heritability of AD, we analyzed whole-exome sequencing (WES) data focusing on non-APOE*4 carriers from two WES datasets: 720 cases and controls from the University of Pittsburgh and 7,252 cases and controls from the Alzheimer's Disease Sequencing Project. Following separate WES analyses in each dataset, we performed meta-analysis for overlapping markers present in both datasets. Among the four variants reaching the exome-wide significance threshold, three were from known AD loci: APOE/rs7412 (odds ratio (OR) = 0.40; p = 5.46E-24), TOMM40/rs157581 (OR = 1.49; p = 4.04E-07), and TREM2/rs75932628 (OR = 4.00; p = 1.15E-07). The fourth significant variant, rs199533, was from a novel locus on chromosome 17 in the NSF gene (OR = 0.78; p = 2.88E-07). NSF was also significant in the gene-based analysis (p = 1.20E-05). In the GTEx data, NSF/rs199533 is a cis-eQTL for multiple genes in the brain and blood, including NSF that is highly expressed across all brain tissues, including regions that typically show amyloid-β accumulation. Further characterization of genes that are affected by NSF/rs199533 may help to shed light on the roles of these genes in AD etiology.

Objectives To examine the relationship between duration of the cognitive symptoms, from the earliest reported symptom to death, and hippocampal sclerosis (HS) and TAR‐DNA binding protein of 43kDA (TDP‐43) in Alzheimer’s disease (AD) patients. Methods The study was conducted in 359 cognitively impaired patients who met the pathological criteria for AD (NIA‐Reagan intermediate or high). The mean age at onset was 69.5 ± 8.8 years (range 37‐95) and the mean duration of the symptoms was 10.5 ± 4.2 years. The association between symptoms duration and HS and TDP‐43 was examined with logistic regression analyses controlling for age at death, atherosclerosis in the Circle of Willis (CW), cerebral infarcts, gender, baseline Mini Mental State Examination scores, APOE‐4 allele, and presence of Lewy bodies (LB). Results HS was present in 18% (n = 64) and TDP‐43 in 51.5% (n = 185) of the patients. HS and TDP‐43 were more frequent in patients whose symptoms lasted more than 10 years. LBs were present in 72% of the patients with HS and in 64% of the patients with TDP‐43. Age at onset was not associated with TDP‐43 or HS. HS was associated with duration of symptoms and LB, TDP‐43, and atherosclerosis in the CW. TDP‐43 was associated with duration of symptoms, LB, and HS. Interpretation HS and TDP‐43 are present in early and late onset AD. However, their presence is mainly driven by the duration of symptoms and the presence of LB. This suggests that HS and TDP‐43 are part of the later neuropathological changes in AD.

Background: To determine the prevalence of prosthetic joint infections (PJIs) after elective clean hand surgery in order to determine whether prophylactic antibiotics are warranted in patients who have previously undergone total joint arthroplasty (TJA). Methods: All patients undergoing elective clean hand surgery between 2012 and 2018 were retrospectively cross-referenced with patients who had previously undergone a TJA at the same urban academic medical center. Inclusion criteria were any patients who underwent clean hand surgery during the study period who were an adult between the ages of 30 and 90, had a previous TJA, and did not have a previous history of a PJI. All charts were reviewed to collect data on patient demographics, co-morbidities, the type of TJA and hand surgery performed, whether prophylactic antibiotics were used prior to the hand surgery, and whether a PJI occurred within 3 months of the hand surgery. Results: Total of 331 patients (181 females and 150 males) were identified over the 6-year period that met inclusion criteria. In total, 13% of the patients received prophylactic antibiotics prior to their hand surgery and 87% had not. Only 1 case of a PJI occurred within 3 months of a hand surgery. No relationship was identified between the PJI and the hand surgery, nor the need for preoperative antibiotic prophylaxis. Conclusions: Incidence of PJI after clean hand surgery is very low. We do not recommend the routine use of antibiotic prophylaxis in patients undergoing clean elective hand surgery with a history of prior TJA in order to prophylax against a PJI.

Background: Alzheimer’s disease (AD) is a complex disease influenced by the environment and genetics; however, much of the genetic component remains unaccounted for. Objective: The purpose of this work was to use genome-wide association analyses to detect genetic associations with incident AD in a sample of older adults aged 75 and above. Methods: We performed a genome-wide association study (GWAS) on genome-wide genotyped and imputed data (14,072,053 variants) on the Gingko Evaluation of Memory (GEM) study sample consisting of 424 incident dementia (mean age = 84.46±3.91) and 2,206 non-demented (mean age = 84.55±3.23) subjects. Results: The established association of APOE*4 carriers with AD was confirmed in this community-based sample of older subjects (odds ratio (OR) = 2.22; p = 9.36E-14) and was stronger in females (OR = 2.72; p = 1.74E-10) than in males (OR = 1.88; p = 2.43E-05). We observed a novel genome-wide significant (GWS) locus on chromosome 12 near ncRNA LOC105369711/rs148377161 (OR = 3.31; p = 1.66E-08). In addition, sex-stratified analyses identified two novel associations in males: one near ncRNA LOC729987/rs140076909 on chromosome 1 (OR = 4.51; p = 3.72E-08) and the other approaching GWS near ncRNA LOC105375138/rs117803234 on chromosome 7 (OR = 3.76; p = 6.93E-08). Conclusion: The use of community-based samples of older individuals and incident dementia as a phenotype may be a helpful approach for the identification of novel genes for AD, which may not be detected in standard case-control studies. Replication of these signals and further studies of these regions and genes will help to provide a clearer picture for their role in AD.

Pyogenic flexor tenosynovitis (PFT)is a potentially devastating closed-space infection of the flexor tendon sheath of the hand that can result in considerable morbidity. Management of PFT, regardless of the pathogen, includes prompt administration of empirical intravenous antibiotics and often surgical treatment. However, currently, there is no standardized treatment algorithm for PFT in regards to the need for, timing, or type of surgical treatment. Many utilize a combination of surgical decompression and sheath irrigation. However, despite prompt treatment, and regardless of the protocol used, complication rates can be high, leading to impaired function and even amputation of the affected digit. Further research is needed to elucidate the role of local antibiotics and corticosteroids in treating this condition and potentially preventing the morbid outcomes that are currently seen. This paper reviews the background, microbiology, and treatment options and controversies surrounding PFT.

Background Compromised sleep is a known phenomenon with compressive neuropathies such as carpal tunnel syndrome. However, the prevalence of sleep disturbance with cubital tunnel syndrome (CuTS) and the effect on sleep after ulnar nerve decompression are not well understood. We hypothesized that CuTS results in sleep disturbances and that decompression surgery would result in improvement in overall sleep quality. Methods Consecutive patients with electrodiagnostic-proven CuTS indicated for decompression were prospectively enrolled. Demographic data, McGowan grade, electrodiagnostic (electromyography) severity, visual analog scale pain score, the 11-item version of the Disabilities of the Arm, Shoulder and Hand questionnaire, and the Insomnia Severity Index scale data were collected preoperatively and at 2 weeks and 3 months postoperatively. Results There were 145 patients enrolled, with 97% available at 2 weeks and 72% available at the final 3-month follow-up. Surgical decompression procedures consisted of 102 in situ releases and 43 transpositions. The average preoperative Insomnia Severity Index score for the entire cohort was 10.7, above the threshold for a diagnosis of insomnia, which subsequently improved to 4.1 by final follow-up postoperatively, consistent with resolution of the insomnia. There was no difference in the extent of sleep improvement between in situ decompression and transposition. Similarly, electromyography severity and McGowan grade also did not appear to significantly affect the extent of sleep improvement. Conclusion CuTS decompression surgery, irrespective of surgical type and preoperative severity, resulted in improvement in sleep by the 3 month postoperative visit.

Compared to men, women are disproportionally affected by Alzheimer's disease (AD) and have an accelerated trajectory of cognitive decline and disease progression. Neurobiological factors underlying gender differences in AD remain unclear. This study investigated brain beta-amyloid (Aβ)-related neural system differences in cognitively normal older men and women (N = 61; 41 females, 65–93 years old). We found that men and women showed different associations between Aβ load and hippocampal functional connectivity. During associative memory encoding, in men greater Aβ burden was accompanied by greater hippocampus-prefrontal connectivity (i.e., more synchronized activities), whereas in women hippocampal connectivity did not vary by Aβ burden. For resting-state data, the interaction of gender × Aβ on hippocampal connectivity did not survive multiple comparison in the whole-brain analyses. In the region of interest–based analyses, resting-state hippocampal-prefrontal connectivity was positively correlated with Aβ load in men and was negatively correlated with Aβ load in women. The observed Aβ-related neural differences may explain the accelerated trajectory of cognitive decline and AD progression in women.

The clinical diagnosis of Alzheimer's disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect Aβ peptides Aβ42 and Aβ40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search for biofluid biomarkers, other than in CSF, and the development of biomarker assays have accelerated significantly and now represent the fastest-growing field in AD research. The goal of this study was to determine the differential enrichment of noncoding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EV) of AD patients and Cognitively Normal controls (NC). Using RNA-seq, we profiled four significant classes of ncRNAs: miRNAs, snoRNAs, tRNAs, and piRNAs. We report a significant enrichment of SNORDs – a group of snoRNAs, in AD samples compared to NC. To verify the differential enrichment of two clusters of SNORDs – SNORD115 and SNORD116, localized on human chromosome 15q11-q13, we used plasma samples of an independent group of AD patients and NC. We applied ddPCR technique and identified SNORD115 and SNORD116 with a high discriminatory power to differentiate AD samples from NC. The results of our study present evidence that AD is associated with changes in the enrichment of SNORDs, transcribed from imprinted genomic loci, in plasma EV and provide a rationale to further explore the validity of those SNORDs as plasma biomarkers of AD.

Background: African American/Black adults have a disproportionate incidence of Alzheimer’s disease (AD) and are underrepresented in biomarker discovery efforts. Objective: This study aimed to identify potential diagnostic biomarkers for AD using a combination of proteomics and machine learning approaches in a cohort that included African American/Black adults. Methods: We conducted a discovery-based plasma proteomics study on plasma samples (N = 113) obtained from clinically diagnosed AD and cognitively normal adults that were self-reported African American/Black or non-Hispanic White. Sets of differentially-expressed proteins were then classified using a support vector machine (SVM) to identify biomarker candidates. Results: In total, 740 proteins were identified of which, 25 differentially-expressed proteins in AD came from comparisons within a single racial and ethnic background group. Six proteins were differentially-expressed in AD regardless of racial and ethnic background. Supervised classification by SVM yielded an area under the curve (AUC) of 0.91 and accuracy of 86%for differentiating AD in samples from non-Hispanic White adults when trained with differentially-expressed proteins unique to that group. However, the same model yielded an AUC of 0.49 and accuracy of 47%for differentiating AD in samples from African American/Black adults. Other covariates such as age, APOE4 status, sex, and years of education were found to improve the model mostly in the samples from non-Hispanic White adults for classifying AD. Conclusion: These results demonstrate the importance of study designs in AD biomarker discovery, which must include diverse racial and ethnic groups such as African American/Black adults to develop effective biomarkers.

Objective. Copy number variation (CNV) is a structural variation in the human genome that has been associated with multiple clinical phenotypes. B cells are important components of rheumatoid arthritis- (RA-) mediated immune response; hence, CNV in the regulators of B cells (such as VPREB1) can influence RA susceptibility. In this study, we aimed to explore the association of CNV in the VPREB1 gene with RA susceptibility in the Pakistani population. Methods. A total of 1,106 subjects (616 RA cases, 490 healthy controls) were selected from three rheumatology centers in Pakistan. VPREB1 CNV was determined using the TaqMan® CN assay (Hs02879734_cn, Applied Biosystems, Foster City, CA, USA), and CNV was estimated by using CopyCaller® (version 2.1; Applied Biosystems, USA) software. Odds ratio (OR) was calculated by logistic regression with sex and age as covariates in R. Results. A significant association between >2 VPREB1 CNV and RA risk was observed with an OR of 3.92 (95% CI: 1.27 - 12.12; p=0.01746) in the total sample. Whereas p=0.00381). Conclusion. CNV>2 of VPREB1 is a risk factor for RA in the total Pakistani population, while CNV<2 is protective in women.

Genome-wide association studies (GWAS) have identified multiple type 2 diabetes (T2D) loci, mostly among populations of European descent. There is a high prevalence of T2D among Pakistanis. Both genetic and environmental factors may be responsible for this high prevalence. In order to understand the shared genetic basis of T2D among Pakistanis and Europeans, we examined 77 genome-wide significant variants previously implicated among European populations. We genotyped 77 single-nucleotide polymorphisms (SNPs) by iPLEX® Gold or TaqMan® assays in a case-control sample of 1,683 individuals. Association analysis was performed using logistic regression. A total of 16 SNPs (TCF7L2/rs7903146, GLIS3/rs7041847, CHCHD9/rs13292136, PLEKHA1/rs2292626, FTO/rs9936385, CDKAL1/rs7756992, KCNJ11/rs5215, LOC105372155/rs12970134, KCNQ1/rs163182, CTRB1/rs7202877, ST6GAL1/rs16861329, ADAMTS9-AS2/rs6795735, LOC105370275/rs1359790, C5orf67/rs459193, ZBED3-AS1/rs6878122 and UBE2E2/rs7612463) showed statistically significant associations after controlling for the false discovery rate. While KCNQ1/rs163182 and ZBED3-AS1/rs6878122 showed opposite allelic effects, the remaining significant SNPs had the same allelic effects as reported previously. Our data indicate that a selected number of T2D loci previously identified among populations of European descent also affect the risk of T2D in the Pakistani population.

A true understanding of the distribution and functional correlates of Alzheimer’s disease pathology in dementia-free older adults requires a population-based perspective. Here we report initial findings from a sample of 102 cognitively unimpaired participants (average age 77.2 years, 54.9% women, 13.7% APOE*4 carriers) recruited for neuroimaging from a larger representative population-based cohort participating in an ongoing longitudinal study of aging, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT). All participants scored

Background Incidence of dementia increases exponentially with age; little is known about its risk factors in the ninth and 10th decades of life. We identified predictors of dementia with onset after age 85 years in a longitudinal population-based cohort. Methods On the basis of annual assessments, incident cases of dementia were defined as those newly receiving Clinical Dementia Rating (CDR) ≥1. We used a machine learning method, Markov modeling with hybrid density-based and partition-based clustering, to identify variables associated with subsequent incident dementia. Results Of 1439 participants, 641 reached age 85 years during 10 years of follow-up and 45 of these became incident dementia cases. Using hybrid density-based and partition-based, among those aged 85+ years, probability of incident dementia was associated with worse self-rated health, more prescription drugs, subjective memory complaints, heart disease, cardiac arrhythmia, thyroid disease, arthritis, reported hypertension, higher systolic and diastolic blood pressure, and hearing impairment. In the subgroup aged 85 to 89 years, risk of dementia was also associated with depression symptoms, not currently smoking, and lacking confidantes. Conclusions An atheoretical machine learning method revealed several factors associated with increased probability of dementia after age 85 years in a population-based cohort. If independently validated in other cohorts, these findings could help identify the oldest-old at the highest risk of dementia.

Genome-wide association studies (GWAS) of coronary artery disease (CAD) have revealed multiple genetic risk loci. We assessed the association of 47 genome-wide significant single-nucleotide polymorphisms (SNPs) at 43 CAD loci with coronary stenosis in a Pakistani sample comprising 663 clinically ascertained and angiographically confirmed cases. Genotypes were determined using the iPLEX Gold technology. All statistical analyses were performed using R software. Linkage disequilibrium (LD) between significant SNPs was determined using SNAP web portal, and functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases. Genotyping comparison was made between cases with severe stenosis (≥70%) and mild/minimal stenosis (PLG/rs4252120 (p=0.0078), KIAA1462/rs2505083 (p=0.005), and SLC22A3/rs2048327 (p=0.045) and two with recessive models SORT1/rs602633 (p=0.005) and UBE2Z/rs46522 (p=0.03). PLG/rs4252120 was in LD with two functional PLG variants (rs4252126 and rs4252135), each with a RegulomeDB score of 1f. Likewise, KIAA1462/rs2505083 was in LD with a functional SNP, KIAA1462/rs3739998, having a RegulomeDB score of 2b. In the GTEx database, KIAA1462/rs2505083, SLC22A3/rs2048327, SORT1/rs602633, and UBE2Z/rs46522 SNPs were found to be expression quantitative trait loci (eQTLs) in CAD-associated tissues. In conclusion, five genome-wide significant SNPs previously reported in European GWAS were replicated in the Pakistani sample. Further association studies on larger non-European populations are needed to understand the worldwide genetic architecture of CAD.

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease. The interaction of genetic and environmental factors is likely necessary for RA. Among potential genetic factors, many major histocompatibility complex (MHC) and non-MHC variants may be involved in RA susceptibility. CTLA4 is involved in the regulation of T-cell response during an immune reaction, and multiple CTLA4 single nucleotide polymorphisms (SNPs) have been associated with numerous autoimmune diseases, including RA. To our knowledge, the genetic association of CTLA4 with RA risk has not been examined previously in the Pakistani population. In this study, we sequenced the entire CTLA4 gene and flanking regions in 95 Pakistani RA cases followed the screening of identified variants in Study 1 sample consisting of 350 RA cases and controls. Four common significant variants identified in Study 1 sample were further examined in a larger Study 2 replication sample comprising 1,678 independent RA cases and controls. We report significant associations of three variants from the combined analysis: rs3087243 (OR = 1.26, p = 4.47E-03), rs5742909 (OR = 1.78, p = 4.60E-03), and rs11571319 (OR = 1.48, p = 6.64E-03); the latter is a novel association in the Pakistani sample.

Common variants in the hepatic lipase (LIPC) gene have been shown to be associated with plasma lipid levels; however, the distribution and functional features of rare and regulatoryLIPCvariants contributing to the extreme lipid phenotypes are not well known. This study was aimed to catalogueLIPCvariants by resequencing the entireLIPCgene in 95 non-Hispanic Whites (NHWs) and 95 African blacks (ABs) with extreme HDL-C levels followed byin silicofunctional analyses. A total of 412 variants, including 43 novel variants were identified; 56 were unique to NHWs and 234 were unique to ABs. Seventy-eight variants in NHWs and 89 variants in ABs were present either in high HDL-C group or low HDL-C group. Two non-synonymous variants (p.S289F, p.T405M), found in NHWs with high HDL-C group were predicted to have damaging effect on LIPC protein by SIFT, MT2 and PP2. We also found several non-coding variants that possibly reside in the circRNA and lncRNA binding sites and may have regulatory potential, as identified in rSNPbase and RegulomeDB databases. Our results shed light on the regulatory nature of rare and non-codingLIPCvariants as well as suggest their important contributions in affecting the extreme HDL-C phenotypes.

Rheumatoid arthritis (RA) is a complex and multifactorial autoimmune disorder with the involvement of multiple genetic and environmental factors. Genome-wide association studies (GWAS) have identified more than 50 RA genetic loci in European populations. Given the anticipated overlap of RA-relevant genes and pathways across different ethnic groups, we sought to replicate 58 GWAS-implicated SNPs reported in Europeans in Pakistani subjects. 1,959 unrelated subjects comprising 1,222 RA cases and 737 controls were collected from three rheumatology facilities in Pakistan. Genotyping was performed using iPLEX or TaqMan® methods. A total of 50 SNPs were included in the final association analysis after excluding those that failed assay design/run or postrun QC analysis. Fourteen SNPs (LINC00824/rs1516971, PADI4/rs2240336, CEP57/rs4409785, CTLA4/rs3087243, STAT4/rs13426947, HLA-B/MICA/rs2596565, C5orf30/rs26232, CCL21/rs951005, GATA3/rs2275806, VPS37C/rs595158, HLA-DRB1/rs660895, EOMES/rs3806624, SPRED2/rs934734, and RUNX1/rs9979383) were replicated in our Pakistani sample at false discovery rate (FDR) of p values ranging from 4.73E-06 to 3.48E-02. Our results indicate that several RA susceptibility loci are shared between Pakistani and European populations, supporting the role of common genes/pathways.

Background Hand surgery under local anesthesia only has been used more frequently in recent years. The purpose of this study was to compare perioperative time and cost for carpal tunnel release performed under local anesthesia ("wide-awake local anesthesia no tourniquet," or WALANT) only to carpal tunnel release performed under intravenous sedation. Methods A retrospective comparison of intraoperative (operating room) surgical time and postoperative (postanesthesia care unit) time for consecutive carpal tunnel release procedures performed under both intravenous sedation and wide-awake local anesthesia was undertaken. All operations were performed by the same surgeon using the same mini-open surgical technique. A cost analysis was performed by means of standardized anesthesia billing based on base units, time, and conversion rates. Results There were no significant differences between the two groups in terms of total operative time, 28 minutes in the intravenous sedation group versus 26 minutes in the wide-awake local anesthesia group. Postanesthesia care unit times were significantly longer in the intravenous sedation group (84 minutes) compared to the wide-awake local anesthesia group (7 minutes). Depending on conversion rates used, a total of $139 to $432 was saved in each case performed with wide-awake local anesthesia by not using anesthesia services. In addition, a range of $1320 to $1613 was saved for the full episode of care, including anesthesia costs, operating room time, and postanesthesia care unit time for each patient undergoing wide-awake local anesthesia carpal tunnel release. Conclusion Carpal tunnel release surgery performed with the wide-awake local anesthesia technique offers significant reduction in cost for use of anesthesia and postanesthesia care unit resources.

Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer’s disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using 11C-labeled Pittsburgh Compound-B (PiB)-PET imaging followed by meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype. The APOE region showed the most significant association where several SNPs surpassed the genome-wide significant threshold, with APOE*4 being most significant (P-meta = 9.09E-30; β = 0.18). Interestingly, after conditioning on APOE*4, 14 SNPs remained significant at P APOE region that were not in linkage disequilibrium with APOE*4. Outside the APOE region, the meta-analysis revealed 15 non-APOE loci with P P-meta = 4.87E-07) and 3 (P-meta = 9.69E-07). Functional analyses of these SNPs indicate their potential relevance with AD pathogenesis. Top 15 non-APOE SNPs along with APOE*4 explained 25–35% of the amyloid variance in different datasets, of which 14–17% was explained by APOE*4 alone. In conclusion, we have identified novel signals in APOE and non-APOE regions that affect amyloid deposition in the brain. Our data also highlights the presence of yet to be discovered variants that may be responsible for the unexplained genetic variance of amyloid deposition.

Unstable fracture-dislocations of the elbow, and in particular the "terrible triad" injury consisting of an elbow dislocation with a fracture of the radial head and coronoid, are complex injuries that can be plagued and complicated by persistent instability. Acute and chronic instability is a difficult problem and is best managed early by avoidance and restoration of stability. A number of treatment options have been proposed to manage acute postfixation instability of the elbow joint. Traditional stabilization options include immobilization with splinting or casting, cross-articular pinning, and external fixation (hinged or static), followed by early physical therapy. However, each of these approaches can still yield persistent elbow instability. We are proposing a new technique of acute but temporary bridge plate stabilization of the elbow joint to protect the concentrically reduced elbow joint following repair of all injured structures to restore stability followed by staged removal and the delayed initiation of therapy.

Purpose The value of electrodiagnostic (EDX) study grades as a prognostic indicator of clinical results after carpal tunnel release (CTR) remains controversial. In this study, we tested the primary null hypothesis that symptom relief after CTR would not differ based on EDX grade. Secondarily, we evaluated the degree of symptomatic and functional postoperative improvement relative to preoperative EDX grade. Methods We prospectively evaluated 199 consecutive patients with 256 hands after CTR confirmed with EDX. Data were collected before surgery and patients were observed at 2 weeks and 3 months after surgery. There were 20 hands with mild, 126 with moderate, and 110 with severe involvement in the preoperative EDX. Demographic, EDX grade (mild, moderate, or severe); surgical parameters; Quick –Disabilities of the Arm, Shoulder, and Hand questionnaire; symptom severity scale, functional status scale, pain catastrophizing scale, and visual analog scale data were collected and analyzed. Results There was significant improvement in Quick –Disabilities of the Arm, Shoulder, and Hand, symptom severity scale, and functional status scale scores from the preoperative to 2-week and 3-month postoperative visits in all categories of EDX grade. There was no significant difference in the extent of recovery by the 2-week and 3-month visits relative to EDX grade. Catastrophic thinking did not have a significant effect on any of the 3 groups. Pain decreased dramatically at 2 weeks after surgery but there was no additional significant difference in visual analog scale scores between the 2-week and 3-month postoperative visits. Postoperative pain improvement occurred regardless of EDX grade. There were no major complications or reoperations in any group. Conclusions Carpal tunnel release demonstrated consistently significant improvement in outcomes regardless of EDX grade at initial and final follow-up. The extent of postoperative improvement after CTR overall was also not statistically different between groups with differing EDX severity. Older patients with severe CTS achieved more modest gains. Type of study/level of evidence Prognostic II.

BACKGROUND This study evaluated outcomes and complications with endoscopic carpal tunnel release performed with local anesthesia only versus local anesthesia with sedation. The authors hypothesized that patient outcomes and satisfaction would be equivalent in both groups irrespective of anesthesia type. METHODS One hundred fifty-four consecutive patients undergoing endoscopic carpal tunnel release with local anesthesia either with or without sedation were prospectively enrolled in a study of satisfaction and outcomes. Patients were surveyed preoperatively and at 2 weeks and 3 months postoperatively to evaluate satisfaction, symptoms, complications, and disability using the 11-question Disabilities of the Arm, Shoulder, and Hand questionnaire survey; the Levine-Katz carpal tunnel survey; and a customized Likert scale. RESULTS The hypothesis was upheld. Patients reported high levels of satisfaction (96 percent in the local anesthesia group and 93 percent in the local anesthesia with sedation group at 3 weeks). Disability, pain, and symptom scores did not differ significantly between groups at either postoperative time point. After surgery, patients in the sedation group recalled more mean preoperative anxiety (four of 10 versus 2.03 of 10 at 3 months). If they were to undergo surgery again, patients in the sedation group were likely to desire either sedation (68 percent) or general anesthesia (29 percent), whereas patients in the local anesthesia-only group were likely to wish for similar local-only anesthesia (78 percent). There were no reoperations or epinephrine-related complications in either group. CONCLUSIONS Patients undergoing endoscopic carpal tunnel release with the local anesthesia or local anesthesia plus sedation experience similar levels of satisfaction and outcomes. Both methods of anesthesia provide excellent results and allow surgeons and patients to choose freely between the two anesthetic techniques.

Background: Surgical educators are increasingly exploring surgical simulation and other nonclinical teaching adjuncts in the education of trainees. The simulators range from purpose-built machines to inexpensive smartphone or tablet-based applications (apps). This study evaluates a free surgery module from one such app, Touch Surgery, in an effort to evaluate its validity and usefulness in training for hand surgery procedures across varied levels of surgical experience. Methods: Participants were divided into 3 cohorts: fellowship-trained hand surgeons, orthopedic surgery residents, and medical students. Participants were trained in the use of the Touch Surgery app. Each participant completed the Carpal Tunnel Release module 3 times, and participants’ score was recorded for each trial. Participants also completed a customized Likert survey regarding their opinions on the usefulness and accuracy of the app. Statistical analysis using a 2-tailed t test and analysis of variance was performed to evaluate for performance within and between cohorts. Results: All cohorts performed better on average with each subsequent simulation attempt. For all attempts, the experts outperformed the novice and intermediate participants, while the intermediate cohort outperformed the novice cohort. Novice users consistently gave the app better scores for usefulness as a training tool, and demonstrated more willingness to use the product. Conclusions: The study confirms app validity and usefulness by demonstrating that every cohort’s simulator performance improved with consecutive use, and participants with higher levels of training performed better. Also, user confidence in this app’s veracity and utility increased with lower levels of training experience.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is the most reported pathogen in hand infections at urban medical centers throughout the country. Antibiotic sensitivity trends are not well known. The purposes of this study were to examine and determine the drug resistance trends for MRSA infections of the hand and to provide recommendations for empiric antibiotic treatment based on sensitivity profiles. Methods: A 10-year longitudinal, retrospective chart review was performed on all culture-positive hand infections encountered at a single urban medical center from 2005 to 2014. The proportions of all organisms were calculated for each year and collectively. MRSA infections were additionally subanalyzed for antibiotic sensitivity. Results: A total of 815 culture-positive hand infections were identified. Overall, MRSA grew on culture in 46% of cases. A trend toward decreasing annual MRSA incidence was noted over the 10-year study period. There was a steady increase in polymicrobial infections during the same time. Resistance to clindamycin increased steadily during the 10-year study, starting at 4% in 2008 but growing to 31% by 2014. Similarly, levofloxacin resistance consistently increased throughout the study, reaching its peak at 56% in 2014. Conclusions: The annual incidence of MRSA in hand infections has declined overall but remains the most common pathogen. There has been an alternative increase in the number of polymicrobial infections. MRSA resistance to clindamycin and levofloxacin consistently increased during the study period. Empiric antibiotic therapy for hand infections should not only avoid penicillin and other beta-lactams but should also consider avoiding clindamycin and levofloxacin for empiric treatment.

Purpose To compare pain experience and opioid use after distal radius fracture repair surgery performed with perioperative infiltration of the local anesthesia bupivacaine hydrochloride (Marcaine; Pfizer, New York, NY) or bupivacaine liposome (Exparel; Pacira, Parsippany, NJ). Methods We conducted a prospective comparison of consecutive patients scheduled to undergo distal radius fracture repair surgery. Patients were randomized to either Marcaine or Exparel. Patients in the Marcaine group received 20 mL 0.5% bupivacaine without epinephrine into the incision and surgical site before incision. Patients in the Exparel group first received 10 mL 0.5% Marcaine with no epinephrine into the incision and surgical site before incision; then, upon completion of the surgery and wound closure, they also received 10 mL Exparel into the same site that had been preinjected with Marcaine. All operations were performed with the same surgical technique. Daily opioid pill consumption, pain levels, and any adverse reactions were recorded from postoperative days 0 to 5. Results On the day of surgery, patients in the Exparel group reported significantly lower pain levels (3.9 vs 5.8) and consumed significantly fewer prescribed opioid pills (1.2 vs 2.0) compared with patients in the Marcaine group. However, there were no other significant differences between the Exparel and Marcaine groups on any subsequent days or in the total number of pills consumed at the end of the study period (7.5 vs 8.9 pills, respectively). No major adverse reactions were noted in either group. Conclusions Exparel use was found to result in decreased pain and opioid consumption only on the day of surgery and not thereafter. Type of study/level of evidence Therapeutic II.

Purpose Prescription opioid misuse has become increasingly prevalent in the United States. Preoperative opioid counseling has been proposed to decrease opioid consumption after surgery. This study aimed to evaluate the effect of preoperative opioid counseling on patients' pain experience and opioid consumption after carpal tunnel release (CTR) surgery. Methods A prospective comparison of consecutive patients scheduled to undergo CTR surgery was conducted. Patients were randomized to receive either formal preoperative opioid counseling or no counseling. All operations were performed with the same mini-open CTR surgical technique, and the same number of opioids were prescribed after surgery. Daily opioid pill consumption, pain levels, and any adverse reactions were recorded. Results During the day of surgery and the first day following surgery, patients in the group with counseling reported significantly fewer prescribed opioid pills consumed compared with patients in the group without counseling, while experiencing no significant difference in pain level experience. In addition, patients in the group with counseling reported a significantly lower number of total pain pills consumed over the course of the study than the group without counseling. No major adverse reactions were noted in either group. Conclusions Preoperative opioid counseling was found to result in a significant decrease in overall opioid consumption after surgery. Type of study/level of evidence Therapeutic II.

BackgroundA major systemic lupus erythematosus (SLE) susceptibility locus lies within a common inversion polymorphism region (encompassing 3.8 – 4.5 Mb) located at 8p23. Initially implicated genes includedFAM167A-BLKandXKR6, of whichBLKreceived major attention due to its known role in B-cell biology. Recently, additional SLE risk carried in non-inverted background was also reported.Objective and methodsIn this case –control study, we further investigated the ‘extended’ 8p23 locus (~ 4 Mb) where we observed multiple SLE signals and assessed these signals for their relation to the inversion affecting this region. The study involved a North American discovery data set (~1200 subjects) and a replication data set (> 10 000 subjects) comprising European-descent individuals.ResultsMeta-analysis of 8p23 SNPs, with p < 0.05 in both data sets, identified 51 genome-wide significant SNPs (p < 5.0 × 10−8). While most of these SNPs were related to previously implicated signals (XKR6-FAM167A-BLKsubregion), our results also revealed two ‘new’ SLE signals, includingSGK223-CLDN23-MFHAS1(6.06 × 10−9≤ meta p ≤ 4.88 × 10−8) andCTSB(meta p = 4.87 × 10−8) subregions that are located > 2 Mb upstream and ~ 0.3 Mb downstream from previously reported signals. Functional assessment of relevant SNPs indicated putativecis-effects on the expression of various genes at 8p23. Additional analyses in discovery sample, where the inversion genotypes were inferred, replicated the association of non-inverted status with SLE risk and suggested that a number of SLE risk alleles are predominantly carried in non-inverted background.ConclusionsOur results implicate multiple (known+novel) SLE signals/genes at the extended 8p23 locus, beyond previously reported signals/genes, and suggest that this broad locus contributes to SLE risk through the effects of multiple genes/pathways.

Purpose The interosseous ligament (IOL) is known to be an important longitudinal stabilizer of the forearm. We hypothesize that it may also contribute to transverse stability, with pronosupination tensioning of the radius relative to the ulna. Therefore, when injured, we predict the interosseous space should widen in the transverse plane, enough to be appreciable on plain radiographs. A measurable difference in interosseous space, comparing an injured with an uninjured forearm, can potentially be of diagnostic and clinical value. Methods Ten fresh-frozen cadaver arms (from 5 individuals) were radiographed in 6 different positions of forearm supination, first in an uninjured state and then with the IOL sectioned, both partially (central band only) and completely. The transverse interosseous distance was measured on radiographs using edge detection software and compared using analysis of variance and contrast analysis. The maximum range of pronosupination was also compared before and after injury, using a paired t test. Results Average maximum supination increased from 84° to 106°, and pronation from 69° to 84°, after the IOL was sectioned completely. Sectioning of the IOL led to a statistically significant increase in the interosseous distance, a minimum of 2 mm, in all but one forearm position. Conclusions The IOL of the forearm plays an important role in providing transverse stability to the radius and ulna. When the IOL is sectioned, the forearm exhibits increased pronosupination range of motion. Radiographs of bilateral forearms taken in identical rotational position can reliably differentiate between an intact and torn IOL in cadavers. Clinical relevance The IOL's stabilizing role during forearm rotation suggests a novel strategy for diagnosing forearm IOL injury using comparative radiographic measurements.

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, while the APOE2 allele is associated with a lower risk of Alzheimer’s dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer’s dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer’s dementia cases and controls. APOE2/2 was associated with a low Alzheimer’s dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer’s disease could have a major impact on the understanding, treatment and prevention of the disease., APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

Objective Type 1 diabetes (T1D) and rheumatoid arthritis (RA) are autoimmune diseases. It is known that certain genetic loci and factors that increase the overall autoimmunity risk can be shared among different autoimmune diseases. We sought to replicate seven T1D-related SNPs that have been previously reported to be associated with RA susceptibility in a small set of mixed family-based and case-control Pakistani sample in a relatively large and independent RA case-control sample from the same population. Seven T1D-associted SNPs (GLIS3/rs7020673, BACH2/rs11755527, SKAP2/rs7804356, GDSMB/rs2290400, C6orf173/rs9388489, LOC399716/rs947474 and DLK1-MEG2/rs941576) were genotyped in a large Pakistani RA case-control sample (n=1,959) using TaqMan® SNP genotyping assays. Results None of the tested SNPs showed statistically significant association with RA susceptibility; however, one SNP (GLIS3/rs7020673) showed a trend for association (OR= 0.88, p=7.99E-02). Our study has failed to replicate the previously reported association of seven T1D-associted SNPs with RA risk in a large sample from the same population. Thus, our results do not support a major role of these T1D SNPs in affecting RA susceptibility in the Pakistani population.

Hand and upper extremity surgery performed with the patient wide awake involves the use of a local anesthetic and epinephrine. Controversy persists as to whether epinephrine is safe for use in the hand. The goal of this study was to evaluate the safety of epinephrine in hand and upper extremity surgery. The hypothesis was that epinephrine is safe and can be used for a wide breadth of surgical procedures of the hand and upper extremity. A 4-year retrospective chart review was conducted of consecutive patients undergoing wide-awake surgery performed by 2 surgeons at a single institution. All procedures were performed with local anesthesia and epinephrine. Data collected included patient demographics, procedure volume, procedure type, surgical setting, and complications related to epinephrine use. During the study period, 4054 consecutive patients underwent 4287 wide-awake procedures with local anesthesia and epinephrine. Average patient age was 59 years, and 64% of patients were female. No complications occurred as a result of the use of epinephrine, and no tissue necrosis, phentolamine reversal, anaphylaxis, or readmissions occurred. No patients required conversion to general anesthesia or monitored anesthesia care. This analysis of more than 4000 consecutive patients undergoing wide-awake hand and upper extremity surgery with epinephrine confirmed that epinephrine use is safe, with no reported cases of tissue necrosis, reversal, readmission, anaphylaxis, or anesthetic conversion. Epinephrine is safe for use in the hand and upper extremity for patients undergoing wide-awake hand surgery with a local anesthetic. [ Orthopedics . 2020;43(6):e529–e532.]

ObjectiveTo explore long-term predictors of avoiding β-amyloid (Aβ) deposition and maintaining unimpaired cognition as outcomes in the oldest old.MethodsIn a longitudinal observational cohort study, 100 former participants of the Ginkgo Evaluation of Memory Study (GEMS; 2000–2008) completed biannual Pittsburgh compound B-PET imaging and annual clinical-cognitive evaluations beginning in 2010. Most recent Aβ status and cognitive status were selected for each participant. Longitudinal outcomes included change in serial Aβ and cognitive tests. Baseline predictors from GEMS included neuropsychological tests, daily functioning, APOE genotype, lifestyle variables, occupational measures, health history, sleep, subjective memory, physical and cognitive activities, depressive symptoms, and physical performance and health indices, among others.ResultsMean age at the last cognitive evaluation was 92.0 (range 86–100) years. Mean follow-up time from baseline to last measured Aβ status was 12.3 (SD 1.9) years and to last cognitive evaluation was 14.1 (SD 1.9) years. The APOE*2 allele predicted last Aβ status (n = 34 Aβ negative vs n = 66 Aβ positive). Baseline cognition predicted cognitive status (n = 30 unimpaired vs n = 70 impaired). Predictors of cognitive status among Aβ-positive participants only (n = 14 normal cognition vs n = 52 impaired) were baseline cognitive test scores and smoking history. Baseline pulse pressure predicted longitudinal Aβ increase; paid work engagement and life satisfaction predicted less cognitive decline.ConclusionsThe APOE*2 allele and lower pulse pressure predict resistance to Aβ deposition in advanced aging. Cognitive test scores 14 years prior, likely reflecting premorbid abilities, predict cognitive status and maintenance of unimpaired cognition in the presence of Aβ. Several lifestyle factors appear protective.

Despite the ubiquity of normal age-related cognitive decline there is an absence of effective approaches for improving neurocognitive health. Fortunately, moderate intensity exercise is a promising method for improving brain and cognitive health in late life, but its effectiveness remains a matter of skepticism and debate because of the absence of large, comprehensive, Phase III clinical trials. Here we describe the protocol for such a randomized clinical trial called IGNITE (Investigating Gains in Neurocognition in an Intervention Trial of Exercise), a study capable of more definitively addressing whether exercise influences cognitive and brain health in cognitively normal older adults. We are conducting a 12-month, multi-site, randomized dose-response exercise trial in 639 cognitively normal adults between 65–80 years of age. Participants are randomized to (1) a moderate intensity aerobic exercise condition of 150 minutes/week (N=213), (2) a moderate intensity aerobic exercise condition at 225 minutes/week (N=213), or (3) a light intensity stretching-and-toning control condition for 150 minutes/week (N=213). Participants are engaging in 3 days/week of supervised exercise and two more days per week of unsupervised exercise for 12 months. A comprehensive cognitive battery, blood biomarkers and battery of psychosocial questionnaires is assessed at baseline, 6 and 12-months. In addition, brain magnetic resonance imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and positron emission tomography of amyloid deposition are assessed at baseline and at the 12-month follow-up. The results from this trial could transform scientific-based policy and health care recommendations for approaches to improve cognitive function in cognitively normal older adults.

Changes of cardiac-induced regional pulsatility can be associated with specific regions of brain volumetric changes, and these are related with cognitive alterations. Thus, mapping of cardiac pulsatility over the entire brain can be helpful to assess these relationships. A total of 108 subjects (age: 66.5 ± 8.4 years, 68 females, 52 healthy controls, 11 subjective cognitive decline, 17 impaired without complaints, 19 MCI and 9 AD) participated. The pulsatility map was obtained directly from resting-state functional MRI time-series data at 3T. Regional brain volumes were segmented from anatomical MRI. Multidomain neuropsychological battery was performed to test memory, language, attention and visuospatial construction. The Montreal Cognitive Assessment (MoCA) was also administered. The sparse partial least square (SPLS) method, which is desirable for better interpreting high-dimensional variables, was applied for the relationship between the entire brain voxels of pulsatility and 45 segmented brain volumes. A multiple holdout SPLS framework was used to optimize sparsity for assessing the pulsatility-volume relationship model and to test the reliability by fitting the models to 9 different splits of the data. We found statistically significant associations between subsets of pulsatility voxels and subsets of segmented brain volumes by rejecting the omnibus null hypothesis (any of 9 splits has p < 0.0056 (=0.05/9) with the Bonferroni correction). The pulsatility was positively associated with the lateral ventricle, choroid plexus, inferior lateral ventricle, and 3rd ventricle and negatively associated with hippocampus, ventral DC, and thalamus volumes for the first pulsatility-volume relationship. The pulsatility had an additional negative relationship with the amygdala and brain stem volumes for the second pulsatility-volume relationship. The spatial distribution of correlated pulsatility was observed in major feeding arteries to the brain regions, ventricles, and sagittal sinus. The indirect mediating pathways through the volumetric changes were statistically significant between the pulsatility and multiple cognitive measures (p < 0.01). Thus, the cerebral pulsatility, along with volumetric measurements, could be a potential marker for better understanding of pathophysiology and monitoring disease progression in age-related neurodegenerative disorders.

Importance Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals,ABCA7,TREM2, and an intergenic locus at 5q35 were previously implicated. Objective To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. Design, Setting, and Participants This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. Main Outcomes and Measures Diagnosis of Alzheimer disease. Results A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking geneEDEM1(3p26;P = 8.9 × 10−7), near the immune response geneALCAM(3q13;P = 9.3 × 10−7), withinGPC6(13q31;P = 4.1 × 10−7), a gene critical for recruitment of glutamatergic receptors to the neuronal membrane, and withinVRK3(19q13.33;P = 3.5 × 10−7), a gene involved in glutamate neurotoxicity, were identified. In addition, several loci associated with rare variants, including a genome-wide significant intergenic locus nearIGF1Rat 15q26 (P = 1.7 × 10−9) and 6 additional loci with suggestive significance (P ≤ 5 × 10−7) such asAPI5 at 11p12 (P = 8.8 × 10−8) andRBFOX1at 16p13 (P = 5.4 × 10−7) were identified. Gene expression data from brain tissue demonstrate association ofALCAM, ARAP1, GPC6, andRBFOX1with brain β-amyloid load. Of 25 known loci associated with Alzheimer disease in non-Hispanic White individuals, onlyAPOE,ABCA7,TREM2,BIN1,CD2AP,FERMT2, andWWOXwere implicated at a nominal significance level or stronger in African American individuals. Pathway analyses strongly support the notion that immunity, lipid processing, and intracellular trafficking pathways underlying Alzheimer disease in African American individuals overlap with those observed in non-Hispanic White individuals. A new pathway emerging from these analyses is the kidney system, suggesting a novel mechanism for Alzheimer disease that needs further exploration. Conclusions and Relevance While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non-Hispanic White individuals, the disease-associated loci within these pathways differ.

Background: There has been recent interest in wide awake hand surgery, also referred to as “wide awake local anesthesia with no tourniquet” (WALANT) surgery. Using a model of single trigger finger release (TFR) surgery, a hypothesis was made that WALANT would result in decreased hospital time and cost than patients receiving sedation with monitored anesthetic care (MAC). Methods: Consecutive cases of single TFR surgery with MAC were compared with WALANT. All surgeries were performed in the same manner, at the same facility, and by the same surgeon. Total operating room (OR) time, surgical time, recovery time, and anesthesia costs were analyzed. Results: There were 78 patients: 31 MAC and 47 WALANT. The MAC group averaged 27.2 minutes of OR time; the WALANT group averaged 25.2 minutes. The MAC group surgical time was 10.2 minutes versus WALANT of 10.4 minutes. Post-operatively, the MAC group averaged 72.3 minutes in the recovery room compared with WALANT group of 30.2 minutes. Each case performed under MAC had a minimum of excess charges from anesthesia of approximately $105. Conclusions: Patients undergoing single TFR surgery under WALANT trended toward less time in the OR, had similar surgical times, and spent significantly less time in the recovery room, compared with MAC, thereby resulting in less indirect costs. Each MAC case also had minimum direct excess anesthesia charges of $105, which knowingly underestimates overall charges as it excludes material and fixed costs associated with the delivery of anesthesia. Avoiding sedation for high-volume procedures such as TFR may result in significant systemic savings to payers, and in the future with bundling and episode-based payments can become increasingly important to patients, facilities, and surgeons.

Purpose To determine whether simplification of the Eaton-Glickel (E-G) classification of trapeziometacarpal (TMC) joint arthrosis (eliminating evaluation of the scaphotrapezial [ST] joint) and information about the patient's symptoms and examination influence interobserver reliability. We also tested the null hypotheses that no patient and/or surgeon factors affect radiographic rating of TMC joint arthrosis and that no surgeon factors affect the radiographic rating of ST joint arthrosis.Methods In an on-line survey, 92 hand surgeons rated TMC joint arthrosis and ST joint arthrosis separately on 30 radiographs (Robert, true lateral, and oblique views) according to the (modified) E-G classification. We randomly assigned 42 observers to review radiographs alone and also informed 50 of the patient's symptoms and examination. Information about symptoms and examination was randomized. Interobserver reliability was determined with the s* statistic. Because of the hierarchical data structure, cross-classified ordinal multilevel regression analyses were performed to identify factors associated with the severity of arthrosis.Results Shortening the E-G classification to the first 3 stages significantly improved the interobserver reliability, which approached substantial agreement. Providing clinical information to observers marginally improved interobserver reliability. Factors associated with a lower E-G stage for TMC joint arthrosis, among observers who rated the severity of TMC joint arthrosis based on radiographs and clinical information, included female surgeon, practice setting, supervising surgical trainees in the operating room, self-reported number of patients with TMC joint arthrosis typically treated annually, male patient, higher patient age, pain limiting daily activities, and shoulder sign. A self-reported larger number of patients with TMC joint arthrosis treated annually was the only variable associated with a higher modified E-G classification to rate ST joint arthrosis.Conclusions Our findings suggest that simpler classifications that focus on a single anatomical area are reliable and that surgeon and patient factors can bias interpretation of objective pathophysiology such as radiographic findings. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved.

BACKGROUND/OBJECTIVE: In population studies, most individuals with mild cognitive impairment (MCI) do not progress to dementia in the near term, but rather remain stable MCI or revert to normal cognition. Here, we characterized MCI subgroups with different outcomes over 5 years. SETTING/PARTICIPANTS: A population-based cohort (N=1603). MEASUREMENTS: Clinical Dementia Rating (CDR); self-reported medical conditions, subjective cognitive concerns, self-rated health, depressive symptoms, blood pressure, medications, blood pressure, APOE genotype, cognitive domain composite scores. DESIGN: We compared 3 MCI subgroups who progressed to dementia (n=86), stabilized at MCI (n=384), or reverted to normal (n=252), to those who remained consistently normal (n=881), defining MCI as CDR = 0.5 and dementia as CDR≥1. Using multinomial logistic regression models adjusted for demographics, we examined the associations of each group with selected baseline characteristics. RESULTS. With the normal group for reference, worse subjective cognitive concerns, functional impairments, self-rated health, and depressive symptoms were associated with being in any MCI group. Taking more prescription medications was associated with being in the stable MCI and reverter groups; diabetes and low diastolic blood pressure were associated with stable MCI. The APOE4 genotype was associated with stable and progressive MCI; stroke was associated with progressive MCI. All MCI subgroups had lower mean composite scores in all cognitive domains and more operationally defined impairments in attention, language, and executive function; reverters lacked memory and visuospatial impairments. CONCLUSIONS: MCI subgroups with different 5-year outcomes had some distinct characteristics suggesting different underlying causes. The progressors, unlike the reverters, had a profile broadly typical of Alzheimer’s disease; the stable MCIs had other, including vascular, morbidity. These data shed light on the heterogeneity of MCI in the population.

ObjectivesTo test the hypothesis that brain structural integrity (i.e., hippocampal [HIP] volume), white matter lesions (WMLs), and β-amyloid deposition are associated with long-term increased risk of incident dementia and mortality in 183 cognitively normal individuals and patients with mild cognitive impairment (MCI) aged 80 years and older.MethodsAll participants had a brain structural MRI scan and PET scan with 11C-labeled Pittsburgh compound B in 2009 and were reexamined yearly through 2015 (mean follow-up time 5.2 ± 1.3 years).ResultsIn the last evaluation through 2010–2015, 56 (31%) participants were cognitively normal, 67 (37%) had MCI, and 60 (33%) had dementia. Fifty-seven (31%) died during follow-up, and 20 (35%) developed dementia before their death. All 3 biomarkers were independent predictors of incident dementia in all participants. After adjusting for the risk of dying, amyloid deposition and WMLs remained strong predictors. Of the 60 participants with incident dementia, 54 (90%) had at least one imaging abnormality. Participants with no biomarker positivity had a very low risk of dementia (16%), while 75% of the participants with the 3 biomarkers progressed to dementia. HIP volume and β-amyloid deposition were associated with death only in participants with MCI.ConclusionsThis study showed the presence of more than one biomarker was a stronger long-term predictor of incident dementia than any biomarker alone. After adjusting for the risk of dying, amyloid deposition and WMLs were stronger predictors of dementia than HIP volume. The risk of dying during follow-up was associated with both neurodegeneration and amyloid deposition, especially in individuals with MCI.

Purpose Adequate postoperative pain control in hand surgery is a multifactorial issue affecting patient satisfaction, outcomes, and safety. However, prescription opioid abuse is becoming an increasingly prevalent problem in the Unites States. The purpose of this study was to determine if there was a difference in pain levels or pill consumption when using nonopioids, ibuprofen (IBU) and acetaminophen (ACE), versus an opioid, oxycodone (OXY), after carpal tunnel release (CTR) performed exclusively under local anesthesia without sedation. Methods Patients scheduled for primary unilateral CTR under local anesthesia alone were randomized to receive 10 deidentified opaque capsules of either OXY 5 mg, IBU 600 mg, or ACE 500 mg after surgery. Both the patient and the surgeon were blinded to the distributed medication. Patients reported the worst pain experienced daily (0–10 scale), the number of pills consumed daily, and any adverse effects from postoperative days 0–5. Results Analgesic pill-type distribution between the 105 patients who completed the study was 37 OXY, 34 IBU, and 34 ACE. For the endoscopic CTR group, mean total pills consumed from the day of surgery through postoperative day 5 for OXY, IBU, and ACE were 2.9, 4.2, and 2.7, respectively. The average worst daily pain scores for all days for the OXY, IBU, and ACE groups were 2.8, 2.5, and 2.8, respectively. For the open CTR group, mean total pills consumed from the day of surgery through postoperative day 5 for OXY, IBU, and ACE were 3.7, 5.1, and 4.2, respectively. The average worst daily pain scores for all days for the OXY, IBU, and ACE groups were 3.4, 2.5, and 2.3, respectively. Four of 5 adverse events were reported by OXY group patients, but all were minor with no reoperations or readmissions. Conclusions We recommend using nonopioids such as ACE and IBU in the postoperative management after CTR surgery, and regardless of the medication prescribed, we advise prescribing no more than 5–10 pills after surgery. Type of study/level of evidence Therapeutic II.

Categorizing people with late-onset Alzheimer's disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer's disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p 10

We compared risk of progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) in an academic memory clinic versus a population-based study.Older adults presenting at a memory clinic were classified as SCD (n = 113) or as noncomplainers (n = 82). Participants from a population study were classified as SCD (n = 592) and noncomplainers (n = 589) based on a memory complaint score. Annual follow-up performed for a mean of 3 years.The adjusted hazard ratio for SCD was 15.97 (95% confidence interval: 6.08-42.02, P .001) in the memory clinic versus 1.18 (95% confidence interval: 1.00-1.40, P = .047) in the population study, where reported "worry" about memory further increased SCD-associated risk for MCI.SCD is more likely to progress to MCI in a memory clinic than the general population; participants' characteristics vary across settings. Study setting should be considered when evaluating SCD as a risk state for MCI and dementia.

Aim To identify risk alleles contributing towards type 1 diabetes in Pakistani patients. Introduction Type 1 diabetes (T1D) is an autoimmune disease which is caused by destruction of insulin producing β cells by immune system. Genetic predisposition as well as environmental factors contribute to its etiology. To date more than 40 risk loci have been identified for T1D. Methodology A total of 191 family-based and unrelated T1D cases and controls were recruited. DNA was extracted and 32 genome-wide significant single nucleotide polymorphisms (SNPs) previously reported in Europeans were genotyped. Genotyping was performed using TaqMan SNP genotyping assays and the data was analyzed using FamCC software. Results Our results showed significant association of 10 single nucleotide polymorphisms (SNPs) with T1D at p HLA -DQA 1 /rs9272346, ERBB3 /rs2292239, SIRPG /rs2281808, IL2-KIAA1109 /rs4505848, GLIS3 /rs7020673, CD226 /rs763361, PTPN2 /rs478582, IKZF1 /rs10272724, BACH2 /rs11755527, C6orf173 /rs9388489, whereas 5 more SNPs showed their association at 0.01 p Conclusion We have replicated many of the T1D loci established among Europeans in a Pakistani population.

Epigenetic changes including genomic imprinting may affect risk of late-onset Alzheimer's disease (LOAD). There are >100 known imprinted genes and most of them are expressed in human brain. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in 93 imprinted genes with LOAD risk in 1291 LOAD cases and 958 cognitively normal controls. We performed single-site, gene-based, and haplotype analyses. Single-site analysis showed 14 significant associations at p < 0.01. The most significant SNP (rs11770199; p = 0.0003) in single-site analysis was located on chromosome 7 in the GRB10 gene. Gene-based analyses revealed four significant associations in the WT1, ZC3H12C, DLGAP2, and GPR1 genes at p < 0.05. The haplotype analysis also revealed significant associations with three genes (ZC3H12C, DLGAP2, and GPR1). These findings suggest a possible role of imprinted genes in AD pathogenesis that show specific expression in the brain.

Genome-wide association studies have identified several loci associated with plasma lipid levels but those common variants together account only for a small proportion of the genetic variance of lipid traits. It has been hypothesized that the remaining heritability may partly be explained by rare variants with strong effect sizes. Here, we have comprehensively investigated the associations of both common and uncommon/rare variants in the lipoprotein lipase (LPL) gene in relation to plasma lipoprotein–lipid levels in African Blacks (ABs). For variant discovery purposes, the entire LPL gene and flanking regions were resequenced in 95 ABs with extreme high-density lipoprotein cholesterol (HDL-C) levels. A total of 308 variants were identified, of which 64 were novel. Selected common tagSNPs and uncommon/rare variants were genotyped in the entire sample (n=788), and 126 QC-passed variants were evaluated for their associations with lipoprotein–lipid levels by using single-site, haplotype and rare variant (SKAT-O) association analyses. We found eight not highly correlated (r2A, rs8176337:G>C, rs74304285:G>A, rs252:delA, rs316:C>A, rs329:A>G, rs12679834:T>C, and rs4921684:C>T) nominally (P

Background: This study aims to test the hypothesis that: (1) radiation exposure is increased with the intended use of Flat Surface Image Intensifier (FSII) units above the operative surface compared with the traditional below-table configuration; (2) this differential increases in a dose-dependent manner; and (3) radiation exposure varies with body part and proximity to the radiation source. Methods: A surgeon mannequin was seated at a radiolucent hand table, positioned for volar distal radius plating. Thermoluminescent dosimeters measured exposure to the eyes, thyroid, chest, hand, and groin, for 1- and 15-minute trials from a mini C-arm FSII unit positioned above and below the operating surface. Background radiation was measured by control dosimeters placed within the operating theater. Results: At 1-minute of exposure, hand and eye dosages were significantly greater with the flat detector positioned above the table. At 15-minutes of exposure, hand radiation dosage exceeded that of all other anatomic sites with the FSII in both positions. Hand exposure was increased in a dose-dependent manner with the flat detector in either position, whereas groin exposure saw a dose-dependent only with the flat detector beneath the operating table. Conclusions: These findings suggest that the surgeon’s hands and eyes may incur greater radiation exposure compared with other body parts, during routine mini C-arm FSII utilization in its intended position above the operating table. The clinical impact of these findings remains unclear, and future long-term radiation safety investigation is warranted. Surgeons should take precautions to protect critical body parts, particularly when using FSII technology above the operating with prolonged exposure time.

Distal radius fractures are among the most common injuries in the upper extremity. While many studies have looked at the maintenance of reduction with volar locking plates, there is a paucity of literature comparing the ability of different plates to maintain reduction over time. This study reviews the ability of various plates to maintain radiographic reduction at union after distal radius fracture treatment. Loss of some aspect of fracture reduction was routinely observed following locked volar plating regardless of implant. However, choice of implant did have a significant impact on final radiographic alignment, particularly with respect to volar tilt and ulnar variance. Yet, selecting between a fixed angle versus a variable angle was not found to make a difference in maintaining reduction. The authors recommend that surgeons take these findings into consideration when selecting a volar locking plate. (Journal of Surgical Orthopaedic Advances.