Neurological Complications of Elbow Arthroscopy

Elbow arthroscopy is an increasingly common procedure performed in orthopedic surgery. However, due to the presence of several major neurovascular structures in close proximity to the operative portals, it can have potentially devastating complications. The largest series of elbow arthroscopies to date described a 2.5% rate of post-operative neurological injury. All of these injuries were transient nerve injuries resolved without intervention. A recent report of major nerve injuries after elbow arthroscopy demonstrated that these injuries are likely under-reported in literature. A review of our records from 1998 to 2014 revealed six patients who had undergone elbow arthroscopy and developed neurological injury post-operatively. While complications after elbow arthroscopy are rare, the most common permanent nerve palsy post-operatively is the posterior interosseous nerve (PIN) followed by the ulnar nerve. Because of the surrounding neurovascular structures, familiarity with the normal elbow anatomy and portals will decrease the risk of damage to important structures. The purpose of this chapter is to review important steps in performing elbow arthroscopy with an emphasis on avoiding neurovascular injury. With a sound understanding of the important bony anatomic landmarks, sensory nerves, and neurovascular structures, elbow arthroscopy can provide both diagnostic and therapeutic intervention with little morbidity

Using Comparative Genomics for Inquiry-Based Learning to Dissect Virulence of Escherichia coli O157:H7 and Yersinia pestis

Genomics and bioinformatics are topics of increasing interest in undergraduate biological science curricula. Many existing exercises focus on gene annotation and analysis of a single genome. In this paper, we present two educational modules designed to enable students to learn and apply fundamental concepts in comparative genomics using examples related to bacterial pathogenesis. Students first examine alignments of genomes of Escherichia coli O157:H7 strains isolated from three food-poisoning outbreaks using the multiple-genome alignment tool Mauve. Students investigate conservation of virulence factors using the Mauve viewer and by browsing annotations available at the A Systematic Annotation Package for Community Analysis of Genomes database. In the second module, students use an alignment of five Yersinia pestis genomes to analyze single-nucleotide polymorphisms of three genes to classify strains into biovar groups. Students are then given sequences of bacterial DNA amplified from the teeth of corpses from the first and second pandemics of the bubonic plague and asked to classify these new samples. Learning-assessment results reveal student improvement in self-efficacy and content knowledge, as well as students’ ability to use BLAST to identify genomic islands and conduct analyses of virulence factors from E. coli O157:H7 or Y. pestis. Each of these educational modules offers educators new ready-to-implement resources for integrating comparative genomic topics into their curricula

Common neural basis of motor sequence learning and word recognition and its relation with individual differences in reading skill

To investigate the neural basis of a common statistical learning mechanism involved in motor sequence learning and decoding, we recorded brain activation from participants during a serial reaction time (SRT) task and a word reading task using functional magnetic resonance imaging. In the SRT task, a manual response was made depending on the location of a visual cue, and the order of the locations was either fixed or random. In the word reading task, visual words were passively presented. In the inferior frontal gyrus pars triangularis (IFGpTr) and the insula, differences in activation between the ordered and random condition in the SRT task and activation to printed words in the word reading task were correlated with the participants' decoding ability. We speculate that extraction of statistically predictable patterns in the IFGpTr and insula contributes to both motor sequence learning and orthographic learning, and therefore predicts individual differences in decoding skill

Quality of life for men with metastatic castrate-resistant prostate cancer participating in an aerobic and resistance exercise pilot intervention

Background: Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood. Methods: We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC. Here we report qualitative changes in QoL, consistent with the guidelines for pilot trials. Men were randomized to control, aerobic exercise, or resistance exercise. Exercise prescriptions were based on baseline cardiorespiratory and strength assessments. QoL outcomes were evaluated using self-reported questionnaires (e.g., QLQ-C30, PROMIS Fatigue, Pittsburgh Sleep Quality Index (PSQI), EPIC-26) collected at baseline and 12 weeks. Results: A total of 25 men were randomized (10 control, 8 aerobic, 7 resistance). Men were predominately white (76 %) with a median age of 71 years (range: 51 – 84) and 10.5 years (range: 0.9 – 26.3) post prostate cancer diagnosis. The men reported poor sleep quality and high levels of fatigue at enrollment. Other baseline QoL metrics were relatively high. Compared to the controls at 12 weeks, the resistance arm reported some improvements in social function and urinary irritative/obstruction symptoms while the aerobic arm reported some improvements in social function and urinary incontinence, yet worsening nausea/vomiting. Compared to the resistance arm, the aerobic arm reported worse urinary irritative/obstruction symptoms and self-rated QoL, yet some improvements in emotional function, insomnia, and diarrhea. Conclusions: The 3-month exercise intervention pilot appeared to have modest effects on QoL among mCRPC survivors on ADT. Given the feasibility, acceptability, and safety demonstrated in prior analyses, evaluation of the effect of the intervention on QoL in a larger sample and for extended duration may still be warranted

Immune modulation by group B Streptococcus influences host susceptibility to urinary tract infection by uropathogenic Escherichia coli

Urinary tract infection (UTI) is most often caused by uropathogenic Escherichia coli (UPEC). UPEC inoculation into the female urinary tract (UT) can occur through physical activities that expose the UT to an inherently polymicrobial periurethral, vaginal, or gastrointestinal flora. We report that a common urogenital inhabitant and opportunistic pathogen, group B Streptococcus (GBS), when present at the time of UPEC exposure, undergoes rapid UPEC-dependent exclusion from the murine urinary tract, yet it influences acute UPEC-host interactions and alters host susceptibility to persistent outcomes of bladder and kidney infection. GBS presence results in increased UPEC titers in the bladder lumen during acute infection and reduced inflammatory responses of murine macrophages to live UPEC or purified lipopolysaccharide (LPS), phenotypes that require GBS mimicry of host sialic acid residues. Taken together, these studies suggest that despite low titers, the presence of GBS at the time of polymicrobial UT exposure may be an overlooked risk factor for chronic pyelonephritis and recurrent UTI in susceptible groups, even if it is outcompeted and thus absent by the time of diagnosis

Investigating the effect of sexual behaviour on oropharyngeal cancer risk:a methodological assessment of Mendelian randomization

BACKGROUND: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02233-3

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Lower pretreatment HBV DNA levels are associated with better off-treatment outcomes after nucleo(s)tide analogue withdrawal in patients with HBeAg-neegative chronic hepatitis B:A multicentre cohort study

Background &amp; Aims: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. Methods: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA &gt;2,000 IU/ml + alanine aminotransferase &gt;2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. Results: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (&lt;20,000 IU/ml) in 150 (20%) and high (&gt;20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels &lt;20,000 IU/ml vs. 60% among patients with pretreatment HBV DNA levels &gt;20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p &lt;0.001). In multivariable analysis, pretreatment HBV DNA levels &lt;20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p &lt;0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p &lt;0.001). Conclusions: Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations. Impact and Implications: A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal and guide intensity of off-treatment monitoring.</p

HBV DNA and HBsAg Levels at 24 Weeks Off-Treatment Predict Clinical Relapse and HBsAg Loss in HBeAg-Negative Patients Who Discontinued Antiviral Therapy

Background &amp; Aims: Patients who discontinue nucleo(s)tide analogue therapy are at risk of viral rebound and severe hepatitis flares, necessitating intensive off-treatment follow-up. Methods: We studied the association between hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels at off-treatment follow-up week 24 (FU W24), with subsequent clinical relapse, and HBsAg loss in a multicenter cohort of hepatitis B e antigen (HBeAg)–negative patients with chronic hepatitis B who discontinued nucleo(s)tide analogue therapy. Results: We studied 475 patients, 82% Asian, and 55% treated with entecavir. Patients with higher HBV DNA levels at FU W24 had a higher risk of clinical relapse (hazard ratio [HR], 1.576; P &lt;.001) and a lower chance of HBsAg loss (HR, 0.454; P &lt;.001). Similarly, patients with higher HBsAg levels at FU W24 had a higher risk of clinical relapse (HR, 1.579; P &lt;.001) and a lower chance of HBsAg loss (HR, 0.263; P &lt;.001). A combination of both HBsAg &lt;100 IU/mL and HBV DNA &lt;100 IU/mL at FU W24 identified patients with excellent outcomes (9.9% clinical relapse and 58% HBsAg loss at 216 weeks of follow-up). Conversely, relapse rates were high and HBsAg loss rates negligible among patients with both HBsAg &gt;100 IU/mL and HBV DNA &gt;100 IU/mL (P &lt;.001). Conclusions: Among HBeAg-negative patients with chronic hepatitis B who discontinued antiviral therapy and who did not experience clinical relapse before FU W24, serum levels of HBV DNA and HBsAg at FU W24 can be used to predict subsequent clinical relapse and HBsAg clearance. A combination of HBsAg &lt;100 IU/mL with HBV DNA &lt;100 IU/mL identifies patients with a low risk of relapse and excellent chances of HBsAg loss and could potentially be used as an early surrogate end point for studies aiming at finite therapy in HBV.</p