Some Drugs Have Two Faces: Paradoxical Colitis in a Patient with Psoriatic Arthritis Previously Treated with Etanercept and IL-17 Inhibitors.

Tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) inhibitors are among the most potent treatments for inflammatory arthropathies including rheumatoid arthritis, psoriasis, and spondyloarthropathies. The availability of these biologic agents have revolutionized the management of these conditions and improved patient outcomes. Though generally safe, these biologics may contribute to the induction or exacerbation of colitis. This paradoxical colitis has been observed in patients on TNF-α inhibitor etanercept and IL-17 inhibitors (secukinumab and ixekizumab). We report a case of a 46-year-old female with psoriasis and psoriatic arthritis who presented with gastrointestinal symptoms after treatment with etanercept and IL-17 inhibitors. She was later diagnosed with paradoxical indeterminate colitis that was masked and treated by subsequent biologics given for her RA and psoriatic arthritis. In this report, we will discuss the importance of considering paradoxical colitis in the differential diagnosis for patients even several years after TNF-α/IL-17 inhibitor initiation and explain why careful consideration must be made when initiating these colitis-inducing agents to treat patients with inflammatory disorders.

Incidence and Trends of High Tibial Osteotomy and Unicompartmental Knee Arthroplasty Over the Past Decade: A Lost Art.

Background: After failed nonoperative treatment, unicompartmental osteoarthritis can be treated surgically by either unicompartmental knee arthroplasty (UKA) or high tibial osteotomy (HTO). The purpose of this retrospective study is to analyze utilization and demographic trends of UKA and HTO relative to total knee arthroplasty (TKA) over the past decade. Methods: A retrospective review was conducted using the PearlDiver database. Patients that received a UKA or HTO were identified. Trend analyses of surgical procedure utilization were performed with the Mann-Kendall trend test. Demographic data and the rates of various comorbidities were also queried. Results: A total of 103,465 UKAs, 2183 HTOs, and 1,413,425 TKAs, between 2010 and 2021 quarter 1, were analyzed. Trend analyses revealed that relative to TKA utilization, UKA utilization significantly increased (P < .001) while HTO utilization significantly decreased (P < .001). The compound annual growth rate of UKA utilization relative to TKA was +5.16% from 2010 to 2017 but was -10.61% from 2018 to 2021, while that of HTO relative to TKA was -9.69% from 2010 to 2021. Demographic analyses demonstrated the UKA cohort (63.1) was significantly older than the HTO cohort (46.5) (P < .001). Additionally, there were significantly more female patients who underwent UKA than HTO (P < .001). Conclusions: The present study demonstrated that relative to TKA, UKA utilization increased from 2010 to 2017, with a subsequent decrease afterward, whereas HTO utilization decreased since 2010. Demographic differences exist between the 2 operations, with HTOs more commonly performed in younger male patients, and UKAs in older female patients. Level of Evidence: Level III.

Age, female sex, and oral contraceptive use are risk factors for anterior cruciate ligament reconstruction: A nationwide database study.

BACKGROUND: The purpose of this study was to investigate risk factors affecting anterior cruciate ligament (ACL) tears and outcomes following ACL reconstruction in males versus females. This study also analyzed oral contraceptive pill (OCP) use, demographics (e.g., body mass index [BMI], age group), comorbidities (e.g., diabetes, hypertension), and post-operative systemic complications (e.g., anemia, malignant hyperthermia) in patients undergoing ACL reconstruction. METHODS: Medical records of patients undergoing ACL reconstruction from 2010-2018 were queried from the PearlDiver administrative claims database current procedural terminology (CPT) and international classification of disease (ICD) codes. The following information was collected using ICD-9/ICD-10 codes: concurrent use of OCPs, concomitant meniscus repair, demographics, age, comorbidities, and systemic complications. The number of ACL reconstructions in females and males were analyzed using multivariate regressions. RESULTS: Of 11,498 ACL reconstructions, 5,967 (51.9%) were in females and 5,531 (48.1%) were in males. The majority of patients were ages 15-19 (24.1%) and were not obese (BMI < 30 kg/m2) (35.9%). A greater proportion of female patients undergoing ACL reconstruction were between 15-19 years old (P < 0.001) and obese (BMI > 40 kg/m2) (P < 0.001). A larger proportion of females aged 15-39 taking OCPs underwent ACL reconstruction compared to those not taking OCPs within the same age group (P < 0.001). CONCLUSION: ACL tears are more common in female patients compared to males and are more commonly treated with ACL reconstruction. This study identified several factors that may be associated with the increased risk of ACL tears in females, including young age (age 15-39), obesity (BMI > 40 kg/m2), and the use of OCPs prior to ACL reconstruction, which warrant further investigation and attention from surgeons.

Age and Female Sex Are Important Risk Factors for Stress Fractures: A Nationwide Database Analysis.

BACKGROUND: Stress fractures are caused by micro-trauma due to repetitive stress on bone, common in active individuals and athletes. Previous studies demonstrate that the weightbearing bones of the lower extremities incur stress fractures most often, especially in women and older adults. HYPOTHESIS: Prior literature does not quantify the difference in frequency of stress fractures among different genders, age groups, or body mass indices (BMIs). We hypothesized that older female patients would have higher rates of lower extremity stress fractures than male patients. STUDY DESIGN: Epidemiological research. LEVEL OF EVIDENCE: Level 3. METHODS: Records of female and male patients with lower extremity stress fractures from 2010 to 2018 were identified from the PearlDiver administrative claims database using the International Classification of Diseases (ICD)-9/ICD-10 codes. Stress fractures were classified by ICD-10 diagnosis codes to the tibial bone, proximal femur, phalanges, and other foot bones. Comorbidities were incorporated into a regression analysis. RESULTS: Of 41,257 stress fractures identified, 30,555 (70.1%) were in women and 10,702 (25.9%) were in men. Our sample was older (>60 years old) (37.3%) and not obese (BMI <30 kg/m2, 37.1%). A greater proportion of female patients with stress fracture were older (P < 0.001) and had foot stress fractures (P < 0.001), while a greater proportion of male patients with stress fracture were younger than 19 years (P < 0.001) and had metatarsal (P < 0.001), hip (P = 0.002), and tibia stress fractures (P < 0.001). CONCLUSION: Stress fractures commonly occur in women and older adults with low BMIs. Metatarsal and tibia stress fractures were the most common, and a greater proportion of women had foot stress fractures. CLINICAL RELEVANCE: Our study examined the large-scale prevalence of different lower extremity stress fractures among a wide patient population sample of varying ages and BMIs. These findings can help clinicians identify active populations at greater risk for stress fracture injuries.

Similar Complication Rates for Humeral Shaft Fractures Treated With Humeral Nails Versus Open Reduction and Internal Fixation With Plating.

Humeral shaft fractures account for an estimated 3% of all adult fractures. When operative treatment is indicated, intramedullary (IM) nailing and open reduction and internal fixation with plating are the 2 most common techniques. Early IM nails were associated with poor outcomes, but with advancements in nail design, patient outcomes have been improving with this technique. This study used a nationwide database to quantify and compare the rates of postoperative complications between IM nails and plating for humeral shaft fractures in a national population. An administrative database was queried from the beginning of 2010 to the second quarter of 2017 for patients undergoing IM nailing vs open reduction and internal fixation with a plate for humeral shaft fractures. Systemic complications, fracture complications, and mean prescribed morphine milligram equivalents were collected and compared with statistical analysis. The overall rate of complications was high for both IM nailing (30.8%) and plating (34.2%). Patients were at greater risk for radial nerve palsy and infection at 90 days, 6 months, and 1 year if they received plate fixation (P<.05). The plate cohort had a lower risk of rotator cuff repair for all periods (P<.05). Patients in the IM nail cohort had higher rates of hardware removal for all periods (P<.05). Both IM nails and plates have overall similar rates of complications, and either can be used for humeral shaft fractures, based on surgeon preference, skill, and consideration of minor differences in complications between these 2 treatments. [Orthopedics. 2022;45(3):156-162.].

Social media as a tool for engaging medical students interested in orthopaedic surgery.

OBJECTIVE: Instagram and Twitter are two of the most popular social media platforms today. Beyond social communication, these platforms also have the potential to enhance medical education by providing early exposure and mentorship to students and residents in training. The purpose of this study was 1) to investigate orthopaedic surgery related content posted on Instagram and Twitter 2) to analyze who posts orthopaedic surgery related content and 3) to better understand how social media may be used to supplement medical education and exposure for students interested in orthopaedics. DESIGN: Three hashtags, #Orthopedics, #OrthopedicSurgery, and #OrthopedicSurgeon were searched on Instagram and Twitter from March 8 to March 18, 2020. Posts on both platforms were analyzed for the hashtag used, number of likes, source type (e.g. physician, company promoting a product), and type of post (e.g. advertisement, educational). Descriptive statistics were used to analyze the results. SETTING: This study was performed at the Tulane University School of Medicine, New Orleans, LA, by medical students, with guidance and supervision from faculty in the Tulane University Department of Orthopaedics. RESULTS: Data was collected from 212 (47.2%) Instagram and 237 (52.8%) Twitter posts over a 10-day period. Significantly more Instagram posts used the hashtags #Orthopedicsurgeon and #Orthopedicsurgery (P<.001), while more Twitter posts used the hashtag #Orthopedics (72.0% P<.001). Companies using these hashtags posted more frequently on Twitter than Instagram (P<.001), while a higher number of physicians, orthopaedic practices, and personal accounts utilized Instagram (P<.001). There was significantly more advertising content on Twitter (P<.001), while Instagram included more personal anecdotes, medical imaging and procedures (P<.001). CONCLUSION: This study demonstrated that content related to orthopaedic surgery is regularly posted on both Instagram and Twitter. Instagram is a visually driven platform that more frequently posted educational and personal content from medical professionals and individuals, while Twitter predominantly published advertisements from companies and orthopaedic practices. The current use of Instagram may make it better suited for providing information and early exposure to medical students interested in the field. LEVELS OF EVIDENCE: III.

Patients with Dupuytren's Contracture, Ledderhose Disease, and Peyronie's Disease are at higher risk of arthrofibrosis following total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a successful treatment for patients with late stage osteoarthritis, yet arthrofibrosis remains a consistent cause of TKA failure. Dupuytren's, Ledderhose and Peyronie's Diseases are related conditions of increased fibroblast proliferation. The aim of this study was to identify whether an association exists between these conditions and arthrofibrosis following TKA. METHODS: Patient records were queried from 2010 to 2016 using an administrative claims database to compare the rates of arthrofibrosis, manipulation under anesthesia (MUA), lysis of adhesions (LOA), and revision TKA in patients with independent chart diagnoses of Dupuytren's Contracture, Ledderhose, or Peyronie's Diseases versus those without. Complications were queried and compared using multivariate logistic regression. RESULTS: Patients with Dupuytren's (n = 5,232) and Ledderhose (n = 50,716) had a significantly higher rate of ankylosis following TKA: 30-days (OR, 1.54; OR, 1.23), 90-days (OR, 1.20; OR, 1.24), 6-months (OR, 1.23; OR, 1.23), and 1-year (OR, 1.28; OR, 1.23), while patients with Peyronie's (n = 1,186) had a higher rate of diagnosis at 6-months (OR, 1.37) and 1-year (OR, 1.35). Patients with diagnoses of any of the fibroproliferative diseases had a statistically higher risk of MUA at 90-days, 6-month, and 1-year following primary TKA. These cohorts did not have a significantly higher rate of revision TKA. CONCLUSION: There is an increased odds risk of arthrofibrosis and MUA in patients who have undergone TKA and have a diagnosis of Dupuytren's Contracture, Ledderhose, or Peyronie's Diseases. Improvements to frequency and application of post-operative treatment should be considered in these cohorts to improve outcomes.

Anatomical Study of the Posterior Spinal Artery Branches to the Medulla Oblongata.

BACKGROUND: The posterior spinal arteries (PSAs), branches of the intracranial segment of the vertebral artery or posterior inferior cerebellar artery, run bilaterally along the spinal cord and are integral to the blood supply primarily to the posterior one third of this structure. However, a less well-described distribution of the PSAs is their supply to the posterior medulla. The purpose of this study is to examine the medullary branches of the PSA anatomically. METHODS: We conducted a cadaveric study to evaluate for branches of the PSA supplying the medulla oblongata. RESULTS: All 14 sides had medullary branches arising from the PSAs. The average number of branches supplying the medulla oblongata on each side was 6. Most of these branches traveled laterally to anastomose with medullary branches arising from the anterior spinal artery. Additionally, lateral and ascending branches were noted. CONCLUSIONS: Physicians who interpret imaging of the craniocervical junction, in particular arteriograms, should be aware of ascending medullary branches arising from the anterior spinal artery. Additionally, neurosurgeons operating this region must be careful in dissecting over the posterior medulla and manipulating the cerebellar tonsils, as in telovelar approaches to the fourth ventricle, in order to avoid iatrogenic injury to these vessels. Additionally, variable stroke patterns involving the vertebral artery or posterior inferior cerebellar artery might include ischemia to the medulla oblongata via PSA branches, and this anatomy should be kept in mind by interventionalists, radiologists, and neurologists alike.

Arthrofibrosis after total knee arthroplasty: patients with keloids at risk.

BACKGROUND: Arthrofibrosis remains one of the leading causes for revision in primary total knee arthroplasty (TKA). Similar in nature to arthrofibrosis, hypertrophic scars and keloid formation are a result of excessive collagen formation. There is paucity in the literature on whether there is an association between keloid formation and the development of arthrofibrosis following TKA. Therefore, the purpose of this study was to utilize a large nationwide database to identify and compare the rates of postoperative complications related to arthrofibrosis after primary TKA in patients with history of hypertrophic scar and keloid disorders versus those without. METHODS: Patient records from 2010 to the second quarter of 2016 were queried from an administrative claims database, comparing rates of arthrofibrosis, manipulation under anesthesia (MUA), lysis of adhesions (LOA), and revision TKA in patients with chart diagnosis of keloids versus those without in patients who underwent primary TKA. Data analysis was performed using R statistical software (R Project for Statistical Computing, Vienna, Austria) utilizing multivariate logistic regression, chi square analysis, or Welch's t- test where appropriate with p values < 0.05 being considered statistically significant. RESULTS: Of 545,875 primary TKAs, 11,461 (2.1%) had a keloid diagnosis at any time point in their record, while 534,414 (97.9%) had not. Patients in the keloid cohort had a significantly higher association with ankylosis within 30 days (OR, 1.7), 90 days (OR, 1.2), 6 months (OR, 1.2), and 1 year (OR, 1.3) following primary TKA. The keloid cohort also had a significantly greater risk of MUA (90-day OR, 1.1; 6-month OR, 1.1; 1-year OR, 1.2) and LOA (90-day OR, 2.2; 6-month OR, 2.0; 1-year OR, 1.9). CONCLUSION: Patients with keloids have increased odds risk of arthrofibrosis following primary TKA. These patients are subsequently at a higher odds risk of undergoing the procedures necessary to treat arthrofibrosis, such as MUA and LOA. Future studies investigating confounding factors such as race, prior surgery, range of motion, and postoperative recovery are needed to confirm the association of keloid diagnosis and arthrofibrosis following primary TKA demonstrated in this study. LEVEL OF EVIDENCE: Level III retrospective comparative study.

Morphologic and molecular analysis of early-onset gastric cancer.

BACKGROUND: Evidence suggests that early-onset gastric cancers are distinct from traditional gastric cancers; however, detailed genomic and morphologic characterization of these cancers has not been performed. METHODS: Genomic analysis was performed for 81 patients with gastric cancer who were 50 years old or younger; pathology slides were available for 53 of these patients, and they were re-reviewed to perform a morphologic-molecular correlation analysis. The results were compared with corresponding cBioPortal data and The Cancer Genome Atlas (TCGA) analysis, which represent traditional gastric cancers. The TP53 molecular signature was established to determine the pattern of somatic mutational damage. Variants of potential germline origin were also identified from next-generation sequencing data. RESULTS: A higher rate of CDH1 mutations (22.2% of early-onset gastric cancers vs 11.4% of traditional gastric cancers; P = .0042) but a similar rate of TP53 mutations (63% of early-onset gastric cancers vs 56.6% of traditional gastric cancers; P = .2674) were seen in early-onset cancers in comparison with traditional gastric cancers. The diffuse/mixed types correlated with the TCGA genomically stable type, and the remaining Lauren types correlated with the TCGA chromosomal instability type. Diffuse and indeterminate histologic types (overall survival, 26.25 months for the intestinal type, 20.5 months for the mixed type, 12.62 months for the diffuse type, and 9 months for the indeterminate type; P = .027) and the presence of a CDH1 gene mutation (overall survival, 9 months for mutant CDH1 and 22 months for wild-type CDH1; P = .013) significantly correlated with worse survival. The TP53 gene frequently showed transition mutations (65.5%) involving the CpG sites (49%). Variants of potential germline origin were seen in high-penetrance genes (CDH1 and APC) and moderate-penetrance genes (ATM, NBN, and MUTYH) in 9.9% of cancers. CONCLUSIONS: Early-onset gastric cancer has distinct genomic alterations, such as CDH1 mutations, but shares with traditional gastric cancers a high frequency of TP53 mutations and the TP53 mutagenic signature. Diffuse and indeterminate histologic types and the presence of a CDH1 mutation are associated with worse overall survival. Endogenous factors leading to cytosine deamination and potential germline alterations in moderate-penetrance cancer susceptibility genes may be implicated in the pathogenesis of these cancers.

Deep sequencing analysis of HCV NS3 resistance-associated variants and mutation linkage in liver transplant recipients.

Viral variants with decreased susceptibility to HCV protease inhibitors (PIs) occur naturally and preexist at low levels within HCV populations. In patients failing PI monotherapy, single and double mutants conferring intermediate to high-level resistance to PIs have been selected in vivo. The abundance, temporal dynamics and linkage of naturally occurring resistance-associated variants (RAVs), however, have not been characterized in detail. Here, using high-density pyrosequencing, we analyzed HCV NS3 gene segments from 20 subjects with chronic HCV infection, including 12 subjects before and after liver transplantation. Bioinformatics analysis revealed that Q80 substitution was a dominant variant in 40% of the subjects, whereas other RAVs circulate at low levels within quasispecies populations. Low frequency mutation linkage was detectable by Illumina paired-end sequencing in as low as 0.5% of the mock populations constructed from in vitro RNA transcripts but were uncommon in vivo. We show that naturally occurring RAVs are common and can persist long term following liver transplant at low levels not readily detectable by conventional sequencing. Our results indicate that mutation linkage at low levels could be identified using the Illumina paired-end approach. The methods described here should facilitate the analysis of low frequency HCV drug resistance, mutation linkage and evolution, which may inform future therapeutic strategies in patients undergoing direct acting antiviral therapies.

In vivo validation of custom-designed silicon-based microelectrode arrays for long-term neural recording and stimulation.

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays' insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays' recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation.