Serotonin reduction in post-acute sequelae of viral infection.

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.

The enteric nervous system relays psychological stress to intestinal inflammation.

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-ß2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.

Normal Pressure Hydrocephalus.

Normal Pressure Hydrocephalus (NPH) occurs when there is an accumulation of cerebrospinal fluid due to impeded flow or excess production, resulting in gait and memory impairment and urinary incontinence. The authors present the case of a 67-year-old male, who had symptoms for a year prior to being diagnosed. His neurological exam was significant for a slow, and unsteady wide-based gait. No underlying cause for his NPH was found. He underwent a shunt procedure following which he made a complete recovery.

The Importance of Fracture Liaison Services to the Healthcare System: A Review.

Osteoporosis is an important public health concern, with secondary fragility fractures carrying a poor prognosis. The role of a Fracture Liaison Service (FLS) is to identify fragility fracture patients via investigation and risk assessment. This serves to address the osteoporosis treatment care gap that exists where the majority of patients with a new fragility fracture over 50-years-old fail to receive a bone mass density (BMD) scan and osteoporosis treatment, ultimately receiving inadequate care. Osteoporosis medication is effective in reducing secondary fragility fractures. However, treatment adherence poses a problem. The FLS serves to prevent more serious secondary fragility fractures such as hip fractures. This minimises operative costs and the cost of postoperative care and results in fewer secondary care and care home admissions, increasing healthcare savings. Implementation of the FLS is effective in increasing investigation, treatment initiation, and adherence, with a corresponding decrease in refracture rate and mortality. This paper aims to evaluate the previous osteoporosis treatment care gap, the effectiveness of osteoporosis medications currently available, and finally, the cost and clinical effectiveness of the FLS serving as a secondary prevention tool.

Ligament Reconstruction and Interposition Arthroplasty of the Acromioclavicular Joint.

Distal clavicle excision (DCE) for acromioclavicular (AC) joint primary osteoarthritis and post-traumatic arthritis has been shown to have good to excellent outcomes. However, there are studies that report significant rates of residual AC joint pain and distal clavicle instability after open and arthroscopic techniques. We describe a surgical technique for management of AC joint primary osteoarthritis, post-traumatic arthritis, and revision DCE that involves DCE with ligament reconstruction and tendon interposition arthroplasty. It provides distal clavicle stability and can theoretically reduce residual AC joint pain secondary to acromial abutment after DCE.

Mechanical circulatory device utilization in cardiac arrest: Racial and gender disparities and impact on mortality.

The objectives of this retrospective study include identifying the utilization trend of mechanical circulatory devices (MCD) such as Intra-Aortic Balloon Pump (IABP), Impella and Extracorporeal Membrane Oxygenation (ECMO) in admissions with cardiac arrest, determining whether racial or gender disparities exist in their usage, and discerning if their use is associated with a reduction in mortality. By leveraging the National Inpatient Sample, we identified 229,180 weighted adult cardiac arrest admissions between October 1, 2015 and December 31, 2018. MCD were used in 6005 admissions (2.6%). IABP had the highest utilization, representing 77.8% of all MCDs, followed by Impella at 24.8%. The utilization of IABP decreased from 90.6% to 71.6%, while the use of Impella increased from 13.5% to 29.8% in this study period; both trends were statistically significant. MCD use was found to be lower in women compared to men (1.4% vs 3.6, P < 0.001) and in the Black population compared to White (1.5% vs 2.8%, P < 0.001). There was no difference in MCD utilization between Hispanic and the White cohorts. In-hospital mortality was lower in admissions associated with MCD (31.4% vs 45.9%, P < 0.001). ECMO was associated with the lowest mortality rate at 14.3%, followed by IABP at 28.1%. The use of Impella and combination therapy were not associated with a significant decrease in mortality. In conclusion, MCD use may decrease mortality in cardiac arrest, however their utilization appears to be lower in African Americans and in women.

Linear Immunoglobulin A (IgA) Bullous Dermatosis Mimicking Stevens-Johnson Syndrome.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disease characterized by linear IgA deposition along the dermo-epidermal junction on direct immunofluorescence (DIF). LABD appears clinically as erythematous polycyclic lesions in younger patients but can show considerable phenotypic heterogeneity in older patients, often leading to misdiagnoses such as bullous pemphigoid, pemphigus vulgaris, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), or other bullous conditions. Cases of LABD mimicking SJS/TEN require prompt skin biopsies for histopathology and DIF for disease differentiation and medical decision-making. In cases of suspected drug-induced LABD or SJS/TEN, identification and removal of the offending agent are paramount. The preferred treatment for LABD is oral dapsone, while SJS/TEN may respond better to cyclosporine or a combination of intravenous immunoglobulin and systemic corticosteroids. This case highlights the rare occurrence of LABD mimicking SJS/TEN and emphasizes the details that clinicians must know to guide patient management.

Novel multiple sclerosis agents-associated cardiotoxicity: A real-world pharmacovigilance study.

BACKGROUND: Emerging novel therapeutics have been developed to hamper the progression of multiple sclerosis (MS). However, the adverse events related to these new agents remain largely unknown. Therefore, we sought to investigate the cardiovascular complications of these drugs. METHODS: Utilizing data from the U.S. food and drug administration (FDA) adverse events reporting system (FAERS), we comprehensively evaluated the cardiovascular complications of the newly FDA-approved anti-MS modifying therapies approved since 2015. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with a 95% confidence interval of all cardiovascular adverse events since approval till 2021. RESULTS: After vetting the newly approved agents for MS, CD20 and CD25 inhibitors and sphingosine-1-phosphate receptors agonists were the latest approved medications for MS since 2015. Two CD20 (ocrelizumab, ofatumumab) and one CD25 inhibitors (daclizumab) were significantly associated with multiple cardiovascular adverse events. Among all the cardiotoxic events; coronary artery disease, cardiac failure and atrial fibrillation were the most predominant among CD20 or CD25 blockers. Interestingly, sphingosine-1-phosphate receptors (S1PR) agonists showed much fewer reported cardiac adverse events. However, fingolimod and siponimod were associated with significant AV block and bradycardia. CONCLUSIONS: Our data revealed the new MS agents are associated with various undefined cardiovascular complications. These findings potentially instigate further studies to personalize prescribing these agents for MS based on patient's cardiovascular profile.

Thumb Metacarpophalangeal Joint Ulnar Collateral Ligament: Early Outcomes of Suture Anchor Repair with Suture Tape Augmentation.

Introduction The purpose of this study was to evaluate the early outcomes of thumb metacarpophalangeal (MCP) joint ulnar collateral ligament (UCL) repair using suture anchors with suture tape augmentation. Materials and Methods Six patients underwent thumb UCL repair or reconstruction with suture tape augmentation and six patients underwent thumb UCL repair with intraosseous suture anchors between January 2013 and January 2018. The main outcome measures were range of motion, strength, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and complications. Results At final follow-up for patients who had suture tape augmentation, the average thumb MCP joint and interphalangeal (IP) joint flexion were 65 and 73 degrees, respectively. The average DASH score was 4.3. At final follow-up for patients who had intraosseous suture anchor repair, the average thumb MCP joint and IP joint flexion were 50 and 60 degrees, respectively. The average DASH score was 38. There were no complications or secondary procedures in either group. Conclusion The use of suture anchor repair with suture tape augmentation for thumb UCL injuries is a treatment option that allows for early range of motion with satisfactory early outcomes that are comparable to intraosseous suture anchor repair. Level of Evidence This is a level IV, case series article.

The effect of single-dose, preoperative intravenous tranexamic acid on early postoperative pain scores after rotator cuff repair: a double-blind, randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) is commonly used in upper and lower limb arthroplasty to limit blood loss and postoperative hematoma formation. The role of TXA in rotator cuff repair (RCR) surgery is less defined. This trial assessed the effect of preoperative TXA on early postoperative pain scores. METHODS: A randomized double-blind trail was conducted in 89 patients undergoing RCR. Patients were randomized to either 2 g of intravenous TXA or placebo at induction. The primary outcome was visual analog scale (VAS)-pain score at day 3 postoperation, with secondary outcomes including VAS-pain, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Constant scores at 2, 8, 24, and 52 weeks. RESULTS: There was no significant difference in VAS-pain scores between groups at day 3 postoperation. Pain scores were significantly better in the TXA group at 8 weeks. There was no difference between groups at any time point in the ASES or Constant score. The TXA group had improved motion at 6 months with a reduced rate of secondary adhesive capsulitis. CONCLUSION: TXA did not improve postoperative pain scores after RCR, however, patients who received the intervention demonstrated greater range of motion at 6 months with lower rates of secondary adhesive capsulitis.

The role of hydrogen peroxide in hip arthroplasty: A narrative review.

Hydrogen peroxide has become more commonly used in hip arthroplasties due to high risk of periprosthetic infections. Its purported roles include irrigation, haemostasis, reduction of aseptic loosening and attachment of antibiotics. However, current literature does not provide conclusive evidence on the efficacy of hydrogen peroxide in preventing aseptic loosening, with some controversy around whether it in fact contributes to aseptic loosening. The complications of hydrogen peroxide across medicine are well distinguished; however, the risks within orthopaedic surgery and hip arthroplasties are not well known. Beyond cytotoxicity, the most dangerous reported risk associated with hydrogen peroxide in hip arthroplasties was an oxygen embolism in an unvented femoral canal and acrylic bone cement, consequentially leading to cardiac arrest. However, it may be inappropriate to solely attribute the oxygen embolism to the use of hydrogen peroxide and thus if used appropriately, hydrogen peroxide may have a justifiable role in hip arthroplasty surgery. In this narrative review, we present the current uses of hydrogen peroxide while evaluating its associated risks. We have summarised the key indications and aggregated recommendations to provide guidelines for the use of hydrogen peroxide in hip arthroplasty.

Artificial intelligence in dermatology for the clinician.

As medicine enters the era of artificial intelligence (AI)-augmented practice, dermatology is beginning to witness the integration of AI into the daily practice, particularly in the areas of diagnosis, prognosis, and treatment of skin diseases. Many of the current electronic medical records that dermatologists have incorporated provide guidance in billing, a form of AI at work. The recent advances in visual recognition AI make application and integration of the technology particularly suited for perceptual specialties such as radiology and dermatology. In dermatology, AI is poised to improve the efficiency and accuracy of traditional diagnostic approaches, including visual examination, skin biopsy, and histopathologic examination. This review highlights the current progress of AI in dermatology and provides a basic overview of the technology.

Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications.

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient's quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events.

Fibroblast growth factor 23 (FGF23) induces ventricular arrhythmias and prolongs QTc interval in mice in an FGF receptor 4-dependent manner.

Fibroblast growth factor 23 (FGF23) is a phosphate regulating protein hormone released by osteocytes. FGF23 becomes markedly elevated in chronic kidney disease (CKD), for which the leading cause of death is cardiovascular disease, particularly sudden cardiac death. Previously, we found that FGF23 increases intracellular Ca2+ in cardiomyocytes and alters contractility in mouse ventricles ex vivo via FGF receptor 4 (FGFR4). In the present study, we demonstrate that FGF23 induces cardiac arrhythmias and prolongs QTc interval in mice, and we tested whether these effects are mediated through FGFR4. In isolated Langendorff perfused hearts, FGF23 perfusion increased mechanical arrhythmias in the form of premature ventricular beats (PVBs), and induced runs of ventricular tachycardia in 6 of 11 animals, which were attenuated with pretreatment of an anti-FGFR4 blocking antibody. Ex vivo ECG analysis of isolated intact hearts showed increased ventricular arrhythmias and QTc prolongation after FGF23 infusion compared with vehicle. In vivo, injection of FGF23 into the jugular vein led to the emergence of premature ventricular contractions (PVCs) in 5 out of 11 experiments. FGF23 also produced a significant lengthening effect upon QTc interval in vivo. In vivo FGFR4 blockade ameliorated the arrhythmogenic and QTc prolonging effects of FGF23. Finally, FGF23 increased cardiomyocyte Ca2+ levels in intact left ventricular muscle which was inhibited by FGR4 blockade. We conclude that FGF23/FGFR4 signaling in the heart may contribute to ventricular arrhythmogenesis and repolarization disturbances commonly observed in patients with CKD via Ca2+ overload and may be an important therapeutic target to reduce cardiac mortality in CKD.NEW & NOTEWORTHY Here we provide direct evidence that fibroblast growth factor 23 (FGF23), a phosphaturic hormone elevated in chronic kidney disease, is proarrhythmic. FGF23 acutely triggered ventricular arrhythmias and prolonged corrected QT interval (QTc) in isolated mouse hearts and in vivo. FGF23 also increased Ca2+ levels in ventricular muscle tissue. Blockade of the FGF receptor 4 signaling pathway using a monoclonal antibody ameliorated ventricular arrhythmias, QTc prolongation, and elevated ventricular Ca2+ induced by FGF23, and may represent a potential therapeutic target in chronic kidney disease.

Artificial intelligence in dermatopathology: Diagnosis, education, and research.

Artificial intelligence (AI) utilizes computer algorithms to carry out tasks with human-like intelligence. Convolutional neural networks, a type of deep learning AI, can classify basal cell carcinoma, seborrheic keratosis, and conventional nevi, highlighting the potential for deep learning algorithms to improve diagnostic workflow in dermatopathology of highly routine diagnoses. Additionally, convolutional neural networks can support the diagnosis of melanoma and may help predict disease outcomes. Capabilities of machine learning in dermatopathology can extend beyond clinical diagnosis to education and research. Intelligent tutoring systems can teach visual diagnoses in inflammatory dermatoses, with measurable cognitive effects on learners. Natural language interfaces can instruct dermatopathology trainees to produce diagnostic reports that capture relevant detail for diagnosis in compliance with guidelines. Furthermore, deep learning can power computation- and population-based research. However, there are many limitations of deep learning that need to be addressed before broad incorporation into clinical practice. The current potential of AI in dermatopathology is to supplement diagnosis, and dermatopathologist guidance is essential for the development of useful deep learning algorithms. Herein, the recent progress of AI in dermatopathology is reviewed with emphasis on how deep learning can influence diagnosis, education, and research.

Is Morgellons an organic disease? structural and functional abnormalities implicated in the pathophysiology of delusional infestation.

Little is known about the pathophysiology of delusional infestation (DI), a psychodermatologic condition in which patients have a fixed, false belief of being infested with parasites or inanimate material in their skin, despite lack of objective evidence. Because some delusional states, such as schizophrenia and psychotic state in bipolar disorder have been found to be associated with brain structural and functional abnormalities, a literature review was conducted to summarize available data on structural and functional abnormalities that are found to be associated with DI. A review of the literature found cases of brain imaging studies in patients with primary DI, as well as patients with secondary DI. Accumulating evidence from the studies reviewed suggests that dysfunction of the fronto-striato-thalamo-parietal network may explain how delusions manifest in DI and suggest that DI has an organic etiology. Abnormalities in the striato-thalamo-parietal network may cause false sensations of infestation through dysfunction in visuo-tactile regulation, whereas abnormalities in the frontal region may impair judgement. Delusional infestation patients also exhibit increased activation of brain structures implicated in itch processing. Furthermore, patients at high risk for cerebrovascular disease who present with secondary DI may benefit from brain imaging studies to rule out brain ischemic insult.

ORIF of Distal Humerus Fractures with Modern Pre-contoured Implants is Still Associated with a High Rate of Complications.

BACKGROUND: The purpose of this study was to identify complications after operative treatment of distal humerus fractures with anatomic, pre-contoured, locking distal humeral plates. We hypothesized that these fractures have high complication rates despite the use of these modern implants. MATERIALS AND METHODS: Between 2010 and 2018, 43 adult patients with a distal humerus fracture underwent open reduction and internal fixation (ORIF) at a Level I trauma center. Pre-operative variables, including medical comorbidities, mechanism of injury, open or closed fracture, AO/OTA fracture classification (Type A, B, or C), and nerve palsy, were recorded. Intra-operative variables including surgical approach, ulnar nerve transposition, and plate configuration were recorded. Anatomic, pre-contoured, locking distal humeral plates were used in all patients. Various plating systems were used based on surgeon preference and fracture pattern. Post-operative complications including infection, nonunion, malunion, painful implants, nerve palsy, heterotopic ossification, stiffness, and post-traumatic arthritis were recorded. RESULTS: Most fractures were Type C (53%). The posterior olecranon osteotomy approach (51%) and parallel plate configuration (42%) were used in most cases. At a mean follow-up of 15 months, the complication rate was 61% (26/43 patients). Among all patients, 49% (21/43 patients) required a reoperation. Elbow stiffness (19%) was the most common complication followed by nerve palsy (16%). There were four fracture nonunions (9%), deep infections (9%), painful implants (9%), post-traumatic arthritis (9%), and heterotopic ossification (9%). CONCLUSIONS: Distal humerus fractures treated with ORIF utilizing anatomic, pre-contoured, locking distal humeral plates have a high complication rate, with many requiring reoperation. LEVEL OF EVIDENCE: Therapeutic Level IV.

What is the Real Rate of Radial Nerve Injury After Humeral Nonunion Surgery?

OBJECTIVES: To determine the radial nerve palsy (RNP) rate and predictors of injury after humeral nonunion repair in a large multicenter sample. DESIGN: Consecutive retrospective cohort review. SETTING: Eighteen academic orthopedic trauma centers. PATIENTS/PARTICIPANTS: Three hundred seventy-nine adult patients who underwent humeral shaft nonunion repair. Exclusion criteria were pathologic fracture and complete motor RNP before nonunion surgery. INTERVENTION: Humeral shaft nonunion repair and assessment of postoperative radial nerve function. MAIN OUTCOME: Measurements: Demographics, nonunion characteristics, preoperative and postoperative radial nerve function and recovery. RESULTS: Twenty-six (6.9%) of 379 patients (151 M, 228 F, ages 18-93 years) had worse radial nerve function after nonunion repair. This did not differ by surgical approach. Only location in the middle third of the humerus correlated with RNP (P = 0.02). A total of 15.8% of patients with iatrogenic nerve injury followed for a minimum of 12 months did not resolve. For those who recovered, resolution averaged 5.4 months. On average, partial/complete palsies resolved at 2.6 and 6.5 months, respectively. Sixty-one percent (20/33) of patients who presented with nerve injury before their nonunion surgery resolved. CONCLUSION: In a large series of patients treated operatively for humeral shaft nonunion, the RNP rate was 6.9%. Among patients with postoperative iatrogenic RNP, the rate of persistent RNP was 15.8%. This finding is more generalizable than previous reports. Midshaft fractures were associated with palsy, while surgical approach was not. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.