Intraoperative Fluoroscopy Versus Navigation to Determine Cup Anteversion in Direct Anterior Total Hip Replacement: A Technical Trick for Obtaining "True" Anteversion.

During acetabular cup positioning, intraoperative measurements of cup anteversion were taken using both fluoroscopy and navigation system. With the C-arm introduced at 40°, an anteroposterior view of the pelvis is taken. The C-arm is then centered over the hip, showing an anteverted cup with an approximate inclination of 40°. The axial C-arm is tilted away until the cup opening is visualized as a straight line, indicating that the beam of the fluoroscopy is aligned with the cup's anteversion. The tilt angle on the C-arm and anteversion reading on the navigation workstation were recorded. The high degree of agreement between fluoroscopic and navigation measurement of acetabular cup anteversion supports the use of fluoroscopy in settings with limited access to navigation systems in direct anterior total hip arthroplasty.

Bevacizumab-IRDye800CW for tumor detection in fluorescence-guided meningioma surgery (LUMINA trial): a single-center phase I study.

OBJECTIVE: Meningiomas are one of the most frequently occurring brain tumors and can be curatively treated with gross-total resection. A subtotal resection increases the chances of recurrence. The intraoperative identification of invisible tumor remnants by using a fluorescent tracer targeting an upregulated biomarker could help to optimize meningioma resection. This is called molecular fluorescence-guided surgery (MFGS). Vascular endothelial growth factor α (VEGFα) has been identified as a suitable meningioma biomarker and can be targeted with bevacizumab-IRDye800CW. METHODS: The aim of this prospective phase I trial was to determine the safety and feasibility of bevacizumab-IRDye800CW for MFGS for intracranial meningiomas by administering 4.5, 10, or 25 mg of the tracer 2-4 days prior to surgery. Fluorescence was verified during the operation with the standard neurosurgical microscope, and tissue specimens were postoperatively analyzed with fluorescence imaging systems (Pearl and Odyssey CLx) and spectroscopy to determine the optimal dose. Uptake was compared in several tissue types and correlated with VEGFα expression. RESULTS: No adverse events related to the use of bevacizumab-IRDye800CW occurred. After two interim analyses, 10 mg was the optimal dose based on ex vivo tumor-to-background ratio. Although the standard intraoperative imaging revealed no fluorescence, postoperative analyses with tailored imaging systems showed high fluorescence uptake in tumor compared with unaffected dura mater and brain. Additionally, tumor invasion of the dura mater (dural tail) and invasion of bone could be distinguished using fluorescence imaging. Fluorescence intensity showed a good correlation with VEGFα expression. CONCLUSIONS: Bevacizumab-IRDye800CW can be safely used in patients with meningioma; 10 mg bevacizumab-IRDye800CW provided an adequate tumor-to-background ratio. Adjustments of the currently available neurosurgical microscopes are needed to achieve visualization of targeted IRDye800CW intraoperatively. A phase II/III trial is needed to methodically investigate the benefit of MFGS with bevacizumab-IRDye800CW for meningioma surgery in a larger cohort of patients.

Different effects of bariatric surgery on epigenetic plasticity in skeletal muscle of individuals with and without type 2 diabetes.

AIM: Bariatric surgery is highly effective for the treatment of obesity in individuals without (OB1) and in those with type 2 diabetes (T2D2). However, whether bariatric surgery triggers similar or distinct molecular changes in OB and T2D remains unknown. Given that individuals with type 2 diabetes often exhibit more severe metabolic deterioration, we hypothesized that bariatric surgery induces distinct molecular adaptations in skeletal muscle, the major site of glucose uptake, of OB and T2D after surgery-induced weight loss. METHODS: All participants (OB, n = 13; T2D, n = 13) underwent detailed anthropometry before and one year after the surgery. Skeletal muscle biopsies were isolated at both time points and subjected to transcriptome and methylome analyses using a comprehensive bioinformatic pipeline. RESULTS: Before surgery, T2D had higher fasting glucose and insulin levels but lower whole-body insulin sensitivity, only glycemia remained higher in T2D than in OB after surgery. Surgery-mediated weight loss affected different subsets of genes with 2,013 differentially expressed in OB and 959 in T2D. In OB differentially expressed genes were involved in insulin, PPAR signaling and oxidative phosphorylation pathways, whereas ribosome and splicesome in T2D. LASSO regression analysis revealed distinct candidate genes correlated with improvement of phenotypic traits in OB and T2D. Compared to OB, DNA methylation was less affected in T2D in response to bariatric surgery. This may be due to increased global hydroxymethylation accompanied by decreased expression of one of the type 2 diabetes risk gene, TET2, encoding a demethylation enzyme in T2D. CONCLUSION: OB and T2D exhibit differential skeletal muscle transcriptome responses to bariatric surgery, presumably resulting from perturbed epigenetic flexibility.

One-Week Kava Dietary Supplementation Increases Both Urinary N- and O-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified N-glucuronidated NNAL (NNAL-N-gluc), O-glucuronidated NNAL (NNAL-O-gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those UGT2B10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.

Otology: Vertigo.

Vertigo, an unexpected feeling of self-motion, is no longer characterized simply by symptom quality but by using triggers and timing. Evaluating vertigo by triggers and timing not only distinguishes serious central causes from benign peripheral causes, but also narrows the differential diagnosis by further classifying vertigo as spontaneous episodic vestibular syndrome, triggered episodic vestibular syndrome, or acute vestibular syndrome. A targeted physical examination can then be used to further delineate the cause within each of these three vestibular categories. Neuroimaging and vestibular testing are not routinely recommended. In the management of vertigo, vestibular hypofunction can be treated with vestibular rehabilitation, which can be self-administered or directed by a physical therapist. Pharmacotherapy sometimes is indicated for vertigo based on triggers, timing, and the specific condition, but it is not always beneficial and is used more often for symptom reduction than as a cure. Transtympanic corticosteroid or gentamicin injections are recommended for patients who do not benefit from nonablative therapy. Surgical ablative therapy is reserved for patients who have not benefited from less definitive therapy and have nonusable hearing.

Otology: Cerumen Impaction and Aural Foreign Bodies.

Cerumen lubricates and protects the external auditory canal, but excess accumulation can lead to ear fullness, itching, otalgia, discharge, hearing loss, and tinnitus. Cerumen should be treated whenever symptoms are present or if it limits diagnosis by preventing a needed otoscopic examination. Clinicians should evaluate for cerumen impaction in those using hearing aids and patients with intellectual disability. Cerumen impaction can be treated with cerumenolytics, ear irrigation, and manual removal with instrumentation. Aural foreign bodies can cause ear fullness, otalgia, discharge, and hearing loss. They are more common in children than adults. The most common type of aural foreign bodies in children is jewelry, followed by paper products, parts of pens or pencils, desk supplies (eg, erasers), BBs or pellets, and earplugs or earphones. In adults, the most common aural foreign bodies are cotton swabs or cotton, followed by hearing aid parts and jewelry or ear accessories. Patients should avoid using cotton tip applicators in the external auditory canal. Alligator forceps, small right angle hooks, and ear irrigation commonly are used to remove aural foreign bodies in an outpatient clinic setting, but the choice depends on the type of foreign body. Soft and irregularly shaped objects can be removed without referral to an otolaryngologist. Patients with hard, spherical, or cylindrical objects should be referred to an otolaryngologist if previous removal attempts have failed or if there is ear trauma to avoid worsening its position in the ear canal.

Otology: Hearing Loss.

Hearing loss is the cause of significant morbidity throughout the United States and the world. Because of numerous factors, such as ongoing noise exposure, poorly controlled chronic disease, and an aging population, the burden of hearing loss is expected to continue to increase. Hearing loss commonly is categorized as conductive, sensorineural, or mixed. The type of hearing loss can be determined through a combination of patient history and physical examination, and then confirmed with audiometry and tympanometry. Advanced imaging is not typically necessary, but it may be helpful in specific instances. The presentation of sudden sensorineural hearing loss should prompt urgent referral to an otolaryngologist and audiologist. Management of this condition is selective but may initially include oral corticosteroids. Management for chronic hearing loss involves the use of hearing aids, which can offer a large benefit to users but historically have been expensive and not covered by many insurance plans. Recent US legislation has made hearing aids more accessible and affordable by allowing direct-to-consumer marketing and offering over-the-counter hearing aids without a clinical evaluation.

Otology: Ear Infections.

Acute otitis media (AOM) is a common diagnosis in children who present with symptoms of otalgia, fever, or irritability and is confirmed by a bulging tympanic membrane or otorrhea on physical examination. It often is preceded by a viral infection, but the bacterial pathogens isolated most commonly are Streptococcus pneumonia, Haemophilus influenzae, and Moraxella catarrhalis. Watchful waiting may be appropriate in children 6 months or older with uncomplicated unilateral AOM. When antibiotics are indicated, amoxicillin is the first-line treatment in those without recent treatment with or allergy to this drug. Otitis media with effusion (OME) is fluid in the middle ear without symptoms of AOM and typically resolves within 3 months. Tympanostomy tube placement is the most common ambulatory surgery for children in the United States. It is used to ventilate the middle ear space and may be performed to treat recurrent AOM, persistent AOM, or chronic OME. Acute otitis externa is inflammation of the external ear canal, often due to infection. On examination, the ear canal is red and inflamed, with patients typically experiencing discomfort with manipulation of the affected ear. It is treated with a topical antibiotic with or without topical corticosteroid.

Circadian Transcriptome Oscillations In Human Adipose Tissue Depend On Napping Status And Link To Metabolic And Inflammatory Pathways.

STUDY OBJECTIVES: Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity. METHODS: In this cross-sectional study, we extracted the RNA repeatedly across 24h from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using 6 consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers). RESULTS: With napping, there was a loss of rhythmicity in 88% of genes that showed circadian rhythmicity among non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes up-regulated in nappers. The top up-regulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation. CONCLUSION: These new findings may have implications for our understanding of napping's effects on obesity and metabolic disorders.

Intramedullary Fixation Versus Plate Fixation of Distal Fibular Fractures: A Systematic Review.

INTRODUCTION: The purpose of this systematic review and meta-analysis was to provide an update of the recent literature comparing clinical outcomes of surgically treated fibular fractures using intramedullary nailing (IMN) with open reduction and internal plate fixation (ORIF). METHODS: A literature search reporting clinical outcomes after IMN or ORIF of the distal fibula was conducted on PubMed. Inclusion criteria consisted of original studies; studies focusing on clinical outcomes after IMN or IMN and ORIF published before May 11, 2022; studies with at least 5 patients; and studies reporting union rates, complication rates, and patient-reported outcomes such as American Orthopaedic Foot and Ankle Society (AOFAS) and Olerud-Molander scores. RESULTS: Of 2,394 studies identified, a total of 29 studies (4 LOE-I, 2 LOE-II, 6 LOE-III, 17 LOE-IV) were included consisting of 1,850 IMN patients and 514 plate patients. The pooled mean age of IMN patients was 58 years (95% confidence interval [CI], 54 to 62, I2 = 42%) versus 57 years (95% CI, 53 to 62, I2 = 49%) in ORIF. Union rates for IMN patients revealed a 99% union rate (95% CI, 0.98 to 1.00, I2 = 20%) versus 97% union rate for ORIF patients (95% CI, 0.94 to 0.99, I2 = 0%). Studies that compared IMN with ORIF revealed no difference in union rates (risk ratio [RR] = 0.99, 95% CI, 0.96 to 1.02, I2 = 0%). IMN patients showed a 15% complication rate (95% CI, 0.09 to 0.23, I2 = 89%), whereas plate patients had a complication rate of 30% (95% CI, 0.18 to 0.46, I2 = 63%). When comparing studies with both treatments, IMN patients had a significantly lower risk of complications (RR = 0.49, 95% CI, 0.29 to 0.82, I2 = 50%). The IMN group trended toward a higher mean AOFAS and Olerud-Molander score than the plate group by 4.53 (95% CI, -14.58 to 23.65, I2 = 85%) and 3.54 (95% CI, -2.32 to 9.41, I2 = 76%) points, respectively. CONCLUSION: Current literature reveals near equivalence in union rates and a markedly lower risk of complications when comparing IMN with plate fixation. While IMN patients had higher AOFAS and Olerud-Molander scores, these differences were not statistically significant. Notably, subgroup analyses indicated that rates of symptomatic implant and removal of implant were comparable between IMN and ORIF, which may indicate that wound-related complications were reduced in the minimally invasive IMN technique. While the high cost of IMN implants remains a barrier to their widespread adoption, the long-term benefits of reducing complications, specifically associated with wound complications in high-risk populations, may greatly improve quality of care for patients with distal fibula fractures. Additional research and cost-effectiveness analyses are warranted to fully assess the long-term benefits and economic feasibility of using IMN fixation for distal fibula fractures. LEVEL OF EVIDENCE: Therapeutic Level IV.

Pyroelectricity in poled all-organic polar polynorbornene/polydimethylsiloxane-based stretchable electrets.

Pyroelectricity in a recently developed all-organic composite electret with a polar polynorbornene-based filler and polydimethylsiloxane (PDMS) matrix has been studied with the help of thermal and dielectric techniques. Measurement of the pyroelectric p coefficient using a quasi-static periodic temperature variation at RT shows a non-linear dependence with the applied poling field, which is uncharacteristic of amorphous materials. Dielectric relaxation spectroscopy (DRS) and the thermally stimulated depolarization current (TSDC) technique reveal that this behaviour can be attributed to Maxwell-Wagner interface (MWI) polarization that occurs at the filler-matrix interface. These charges released during the onset of dipolar α and ß relaxations of the filler particles contribute majorly to the observed pyroelectricity at RT. The saturation of both MWI TSDC shoulders and spontaneous polarization at higher electric fields correlates with the p coefficient value reaching a plateau at these applied fields. A maximum p coefficient of 0.54 µC m-2 K-1 is calculated for a poling field of 30 V µm-1.

Using the Equatorial Talar Line as a Radiographic Predictor of Sanders Type 3 and 4 Calcaneus Fractures and Lateral Wall Blowout.

OBJECTIVE: To assess the equatorial talar line (ETL) as a sensitive radiographic parameter to predict Sanders type III and IV fractures and the presence of lateral wall blowout. METHODS: Reliability of the ETL was assessed using the intraclass correlation coefficient (ICC) and receiver operating curve (ROC) to predict sensitivity. Using lateral ankle radiographs, raters determined whether the calcaneal tuberosity was "above" (predicting Sanders type I or II) or "below" (predicting Sanders type III or IV and lateral wall blowout). RESULTS: In determining the "above" or "below" location of the ETL, the calculated ICC was 1.0 for each session. As a predictor of Sanders fracture classification type, the calculated ICC was 0.93 for the first session and 0.89 for the second session for an overall ICC of 0.91. As a predictor of Sanders fracture type, ROC analysis yielded an overall sensitivity of 0.82. As a predictor of lateral wall blowout, ROC analysis yielded an overall sensitivity of 0.81. CONCLUSION: The ETL is a reproducible radiographic parameter that can be reliably used to crudely predict between Sanders type I or II (ETL is "above") and Sanders type III or IV (ETL is "below") calcaneus fractures as well as the presence of lateral wall blowout.

Melatonin decreases human adipose tissue insulin sensitivity.

Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase-shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). We used western blot analysis to determine insulin signaling (using the pAKT/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT/tAKT ratio compared with control (p < .0001). Furthermore, the addition of melatonin (I + M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1 h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.

Industry affiliation does not predict outcomes of randomized controlled trials for mesenchymal stem cells in knee osteoarthritis.

BACKGROUND: This research aims to determine the influence of industry on the outcomes of randomized controlled trials (RCTs) for Mesenchymal Stem Cell (MSC) treatments in knee osteoarthritis (OA). METHODS: PubMed, Scopus, and Web of Science were searched from 2010 onwards using the terms "knee osteoarthritis" and "mesenchymal stem cells". After identifying relevant RCTs, studies were categorized as industry-affiliated or non-industry-affiliated. They were also classified as favorable if they achieved statistically significant (p < 0.05) results with MSC injections compared to control. Chi-squared tests were employed to analyze the relationship between industry affiliation and study outcome. RESULTS: Post exclusion criteria, 38 studies were analyzed. Of these, there were 20 (52.6%) industry affiliated (IA) and 18 (47.4%) non-industry affiliated (NIA) studies. Among the 20 IA studies, 17 (85.0%) reported favorable outcomes for MSC treatment arm, with the remaining 3 (15.0%) showing analogous (no difference between treatment arms) results. For the 18 NIA studies, 15 (83.3%) were favorable, and 3 (16.6%) were analogous. No significant difference in outcomes was observed between IA and NIA studies (p = 0.888). Analysis of patient reported outcomes also revealed no significant difference. Of note, studies using allogeneic MSCs were more likely to be IA than studies using autologous MSCs (p = 0.005) CONCLUSION: This study demonstrated no strong association between industry affiliation and the outcomes of RCTs for MSC treatments in knee OA. Despite this, the potential influence of industry ties should always be considered when applying study findings to new treatment modalities for patient care.

Epidemiology, Etiology, and Pathophysiology of Pulmonary Embolism.

Over the last 20 years, there has been a progressive increase in the incidence of pulmonary embolism (PE) diagnosis in the United States, Europe, and Australia. Increased use of computed tomography pulmonary angiography has likely contributed in part to this rising incidence. However, it is pertinent to note that the burden of comorbidities associated with PE, such as malignancy, obesity, and advanced age, has also increased over the past 20 years. Time-trend analysis in North American, European, and Asian populations suggests that mortality rates associated with PE have been declining. The reported improved survival rates in PE over the past 20 years are likely, at least in part, to be the result of better adherence to guidelines, improved risk stratification, and enhanced treatment. Factors contributing to the development of venous thromboembolism (VTE) include stasis of blood, hypercoagulability, endothelial injury, and inflammation. In 70 to 80% of cases of PE, the thrombi embolizes from the proximal deep veins of the lower extremities and pelvis. Strong risk factors for VTE include lower extremity fractures and surgeries, major trauma, and hospitalization within the previous 3 months for acute myocardial infarction or heart failure with atrial fibrillation. Acute PE causes several pathophysiological responses including hypoxemia and right ventricle (RV) failure. The latter is a result of pulmonary artery occlusion and associated vasoconstriction. Hemodynamic compromise from RV failure is the principal cause of poor outcome in patients with acute PE.