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Paper 32: Meniscus Repair Outcomes and Reoperation Rate in Patients Over the Age of 40
Duethman, Nicholas C., Odum, Susan M. , Piasecki, Dana P., Cregar, William M., Fleischli, James E., Saltzman, Brian, Meade, Joshua, Berk, Alexander N. , Trofa, David P , Saltzman, Brian

Orthopaedic Journal of Sports Medicine | July 31, 2023 | Volume: 11 | Issue: 7_suppl3 | Pages: No page available

10.1177/2325967123s00058 Get It

Objectives: Meniscus injuries remain a common source of morbidity in patients over the age of 40. Historically, meniscus injuries in this age group have been treated non-operatively or with surgical management limited to debridement procedures. There is strong evidence for repair over meniscectomy in younger patients, however literature remains sparce regarding repair outcomes and re-operation rates for patients over the age of 40. The objectives of this study were to document patient reported outcomes, complications, and re-operation rates for meniscus repairs in patients above the age of 40 and determine what patient demographics or injury characteristics correlated with reoperation. Methods: A retrospective chart review was conducted at a single academic institution after obtaining IRB approval. An initial query of patients over the age of 40, was performed via the CPT code 29882. Inclusion criteria consisted of patient age greater than 40 at time of initial meniscal repair. Exclusion criteria consisted of prior surgery in the ipsilateral knee, meniscal root repair, septic arthritis postoperatively, and any form of knee trauma postoperatively. Patients that met inclusion criteria were chart reviewed for relevant data including demographic information, comorbidities, surgical procedure information such as type of implant used, laterality of meniscus tear, type of tear and pattern, and revision/re-operation data. Patients were then contacted to answer full 100-point KOOS (Knee Injury and Osteoarthritis Outcome Score) questionnaires. Results: 413 total patients met inclusion criteria. The average age at time of surgery was 46 years (IQR, 43-51), and 214 patients were female (51.8%). KOOS scores were reported at a median follow-up of 24-months (IQR, 3-62). Median symptom, pain, activity of daily living (ADL), sport, and quality of life (QoL) subscales were reported as 78.6 (IQR, 60.7-92.9), 87.5 (IQR, 69.4-97.2), 94.1 (IQR, 82-100), 80.0 (IQR, 55-95), and 68.8 (IQR, 40.6-81.3), respectively. A total of 74 patients underwent reoperation (17.8%). There was no significant difference in reoperation rates when stratified by age group (40-49, 50-59, 60-69) (p=0.515). Reoperation rates were not affected by type of implant used for initial meniscus repair (Fast-fix anchor, Omnispan meniscal anchor, Meniscal cinch implant, Fiberwire, MaxBraid suture, Ethibond suture, PDS suture or Bionics meniscal arrow) (p>0.7). Average number of all-inside anchors used for repair was 2 (IQR, 2-3) and did not correlate with reoperation (p=0.49). Location of initial meniscus tear (body or posterior horn) and tear pattern did not correlate with reoperation rates (p>0.36, p>0.28 respectively). A total of 47 patients complained of postoperative stiffness, of which 28 (6.7%) underwent lysis of adhesions and/or arthroscopic debridement (p=.042). Twenty-five patients sustained a meniscal re-tear or injury, of which 17 underwent reoperation with partial or total meniscectomy. Of the total patient cohort, only seven patients ultimately went on to require ipsilateral total knee arthroplasty (1.6%). Conclusions: Patients over the age of 40 who underwent meniscus repair showed favorable reported outcomes at a mean 2-year follow-up. Reoperation rates were associated with postoperative stiffness and repeat injury. Re-operation rates in patients over 40 are comparable to reported rates of younger patients who undergo meniscus repair.
Identifying metabolic features of colorectal cancer liability using Mendelian randomization
Bull, Caroline J. , Hazelwood, Emma , Tan, Vanessa Y. , Constantinescu, Andrei‐Emil , Borges, Maria Carolina , Legge, Danny , Burrows, Kimberley , Huyghe, Jeroen R. , Brenner, Hermann , Castellvı́-Bel, Sergi , Li, Li , Pai, Rish K. , Figueiredo, Jane C. , Timpson, Nicholas J. , Vincent, Emma E. , Bull, Caroline J , Tan, Vanessa , Legge, Danny , Huyghe, Jeroen R , Vincent, Emma E , Borges, Maria C , Brenner, Hermann , Castellví-Bel, Sergi , Hazelwood, Emma , Bell, Joshua A. , Chan, Andrew T. , Kweon, Sun-Seog , Marchand, Loı̈c Le , Cheng, Iona C. , Murphy, Neil , Gunter, Marc J.

eLife | July 25, 2023 | Volume: 12 | Issue: No issue available | Pages: No page available

10.7554/elife.87894 | PMID 38127078 Get It

Background: Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. Methods: To investigate whether changes in circulating metabolites characterize the early stages of colorectal cancer (CRC) development, we examined the associations between a genetic risk score (GRS) associated with CRC liability (72 single-nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N = 6221). Linear regression models were applied to examine the associations between genetic liability to CRC and circulating metabolites measured in the same individuals at age 8 y, 16 y, 18 y, and 25 y. Results: The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P < 0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N = 118,466, median age 58 y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. Conclusions: These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism and suggest that fatty acids may play an important role in CRC development. Funding: This work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used the computational facilities of the Advanced Computing Research Centre, University of Bristol - http://www.bristol.ac.uk/acrc/ .
Identifying metabolic features of colorectal cancer liability using Mendelian randomization
Bull, Caroline J. , Hazelwood, Emma , Tan, Vanessa Y. , Constantinescu, Andrei‐Emil , Borges, Maria Carolina , Legge, Danny , Burrows, Kimberley , Huyghe, Jeroen R. , Li, Li , Pai, Rish K. , Figueiredo, Jane C. , Borges, Maria C , Bull, Caroline J , Legge, Danny , Hazelwood, Emma , Bell, Joshua A. , Brenner, Hermann , Castellvı́-Bel, Sergi , Chan, Andrew T. , Kweon, Sun-Seog , Marchand, Loı̈c Le , Cheng, Iona C. , Murphy, Neil , Gunter, Marc J. , Timpson, Nicholas J. , Vincent, Emma E.

No container title available | July 25, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.7554/elife.87894.1 Get It

Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years. The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development.
Inspiratory Muscle Strength is Related to Exertional Dyspnoea in Heart Failure with Preserved Ejection Fraction
Warner, Brit, Bruhn, Eric J., Olson, Thomas P. , Bissen, Thomas G. , Smith, Joshua R. , Smith, Joshua R. , Smith, Joshua R , Borlaug, Barry A.

European Journal of Heart Failure | July 21, 2023 | Volume: 25 | Issue: 9 | Pages: 1716-1717

10.1002/ejhf.2980 | PMID 37476916 Get It

Modest Effects of Osteoclast‐Specific ERα Deletion after Skeletal Maturity
Doolittle, Madison L. , Eckhardt, Brittany, Vos, Stephanie J. B. , Grain, Sarah, Rowsey, Jennifer L. , Ruan, Ming, Saul, Dominik , Farr, Joshua N. , Weivoda, Megan , Khosla, Sundeep , Eckhardt, Brittany A, Vos, Stephanie J, Weivoda, Megan M, Monroe, David G , Khosla, Sundeep , Farr, Joshua N , Saul, Dominik , Vos, Stephanie J., Monroe, David G.

JBMR Plus | July 13, 2023 | Volume: 7 | Issue: 10 | Pages: No page available

10.1002/jbm4.10797 | PMID 37808391 Get It

ABSTRACT Estrogen regulates bone mass in women and men, but the underlying cellular mechanisms of estrogen action on bone remain unclear. Although both estrogen receptor (ER)α and ERβ are expressed in bone cells, ERα is the dominant receptor for skeletal estrogen action. Previous studies using either global or cell‐specific ERα deletion provided important insights, but each of these approaches had limitations. Specifically, either high circulating sex steroid levels in global ERα knockout mice or the effects of deletion of ERα during growth and development in constitutive cell‐specific knockout mice have made it difficult to clearly define the role of ERα in specific cell types in the adult skeleton. We recently generated and characterized mice with tamoxifen‐inducible ERα deletion in osteocytes driven by the 8‐kb Dmp1 promoter (ERαΔOcy mice), revealing detrimental effects of osteocyte‐specific ERα deletion on trabecular bone volume (−20.1%) and bone formation rate (−18.9%) in female, but not male, mice. Here, we developed and characterized analogous mice with inducible ERα deletion in osteoclasts using the Cathepsin K promoter (ERαΔOcl mice). In a study design identical to that with the previously described ERαΔOcy mice, adult female, but not male, ERαΔOcl mice showed a borderline (−10.2%, p = 0.084) reduction in trabecular bone volume, no change in osteoclast numbers, but a significant increase in serum CTx levels, consistent with increased osteoclast activity. These findings in ERαΔOcl mice differ from previous studies of constitutive osteoclast‐specific ERα deletion, which led to clear deficits in trabecular bone and increased osteoclast numbers. Collectively, these data indicate that in adult mice, estrogen action in the osteocyte is likely more important than via the osteoclast and that ERα deletion in osteoclasts from conception onward has more dramatic skeletal effects than inducible osteoclastic ERα deletion in adult mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Esophageal Lichen Planus
Aby, Elizabeth S. , Eckmann, Jason D. , Katzka, David A. , Beveridge, Claire , Triggs, Joseph , Abdi, Tsion, Turner, Kevin , Antunes, Catiele , Zhuo, Justin , Kamal, A. N. , Gyawali, C. Prakash , Sloan, Joshua A. , Abimansour, Jad, Sloan, Joshua A , Gyawali, C P , AbiMansour, Jad P. , Dbouk, Mohamad H. , Kamal, Afrin N., Patel, Parth

Journal of Clinical Gastroenterology | July 12, 2023 | Volume: 58 | Issue: 5 | Pages: 427-431

10.1097/mcg.0000000000001885 | PMID 37436831 Get It

Goals: To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP). Background: ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series. Study: A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States. Results: Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers. Conclusions: Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.
Late recurrence in surgically managed pediatric atypical mycobacterial lymphadenitis: A case report and review of the literature
Green, Katerina J. , Denton, Alexa, Graves, Jeffrey , Wiedermann, Joshua P. , Green, Katerina , Wiedermann, Joshua

World Journal of Otorhinolaryngology - Head and Neck Surgery | July 8, 2023 | Volume: 9 | Issue: 4 | Pages: 357-364

10.1002/wjo2.118 | PMID 38059148 Get It

AbstractObjectiveThe purpose of this study is to identify existing literature on recurrent atypical mycobacterial cervicofacial lymphadenitis to augment our understanding of a unique patient who presented to our tertiary‐care center 5‐years posttreatment with recurrence following curettage.Data SourcesOVID Medline, Scopus, and Web of Science.MethodsA literature search was conducted yielding 49 original articles which were screened twice by two independent reviewers resulting in 14 studies meeting inclusion criteria for data extraction using Covidence software. Two independent reviewers extracted data on recurrence of atypical mycobacterial cervicofacial lymphadenitis and consensus was reached on data points from all included studies.ResultsThis study illuminated the paucity of recurrence reporting in the literature regarding atypical mycobacterial lymphadenitis. Sixteen studies identified in our review included discussions on recurrence with few elaborating beyond the rate of recurrence to describe their management. Fourteen out of sixteen studies provided recurrence rates for their cohort, 11 out of 14 specified the initial treatment modality, and only five out of eight studies that described initial treatment with surgery differentiated recurrence rates between complete and incomplete excision. The mean length of follow‐up in the included studies was 20 months. There was one previously reported case of late recurrence at 5‐years.ConclusionsWe identified few reports that discussed the management of recurrence of atypical mycobacterial cervicofacial lymphadenitis. There was minimal data on recurrence rates between surgical treatment modalities. The case discussed in our study showcases that treatment with curettage has the potential to present with late recurrence.
Radiosynthesis and Preliminary Evaluation of [11C]SSI-4 for the Positron Emission Tomography Imaging of Stearoyl CoA Desaturase 1
Li, Kang‐Po , Gleba, Justyna J., Copland, John A. , Cai, Hancheng , Trynda, Justyna , Cai, Hancheng , Gleba, Justyna , Parent, Ephraim E. , Knight, Joshua A.

Molecular Pharmaceutics | July 6, 2023 | Volume: 20 | Issue: 8 | Pages: 4129-4137

10.1021/acs.molpharmaceut.3c00273 | PMID 37409698 Get It

Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review
Adeleye, Olufunmilola , Winkler, Ethan A. , Hartke, Joelle N., Karahalios, Katherine , Mihaljević, Sandra, Rani, Anupama , Raikwar, Sudhanshu P. , Rulney, Jarrod, Scherschinski, Lea , Ducruet, Andrew F. , Albuquerque, Felipe C. , Lawton, Michael T. , Raikwar, Sudhanshu , Scherschinski, Lea , Adeleye, Olufunmilola , Naik, Anant , Koester, Stefan Wolfgang , Desai, Shashvat M. , Catapano, Joshua S , Jadhav, Ashutosh P. , Jha, Ruchira Menka

International Journal of Molecular Sciences | June 30, 2023 | Volume: 24 | Issue: 13 | Pages: 10902

10.3390/ijms241310902 | PMID 37446092 Get It

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.
Anaplasma phagocytophilum Encephalitis: A Case Report and Literature Review of Neurologic Manifestations of Anaplasmosis
Cosiquien, Ronin Joshua S. , Stojiljkovic, Nenad , Nordstrom, Charles W. , Amadi, Emeka, Lutwick, Larry I., Dumic, Igor , Dumic, Igor

Infectious Disease Reports | June 30, 2023 | Volume: 15 | Issue: 4 | Pages: 354-359

10.3390/idr15040035 | PMID 37489389 Get It

Anaplasma phagocytophilum is an obligate intracellular, Gram-negative pathogen, causative agent of Human Granulocytic Anaplasmosis (HGA). HGA usually manifests as a non-specific febrile illness, accompanied by evidence of leucopenia, thrombocytopenia, and an alteration in liver enzymes. Neurologic manifestations of anaplasmosis are rare and rarely reported. We describe a 62-year-old man who developed encephalitis due to an Anaplasma phagocytophilum infection. The patient favorably responded to intravenous doxycycline and recovered without neurological sequela. In the tick endemic area, clinicians should have a high index of suspicion for tick-borne diseases in patients presenting with neurological deficits. A prompt diagnosis and treatment lead to improvements in morbidity and mortality.