Current and emerging drugs for the treatment of pruritus: an update of the literature.

INTRODUCTION: Pruritus, particularly in its chronic form, often imposes significant suffering and reductions in patients' quality of life. The pathophysiology of itch is varied depending on disease context, creating opportunities for unique drug development and multimodal therapy. AREAS COVERED: The purpose of this article is to provide an update of the literature regarding current and emerging therapeutics in itch. We review the multitudes of drug targets available and corresponding drugs that have shown efficacy in clinical trials, with a particular emphasis on phase 2 and 3 trials and beyond. Broadly, these targets include therapies directed against type 2 inflammation (i.e. Th2 cytokines, JAK/STAT, lipid mediators, T-cell mediators, and other enzymes and receptors) and neural receptors and targets (i.e. PARs, TRP channels, opioid receptors, MRGPRs, GABA receptors, and cannabinoid receptors). EXPERT OPINION: Therapeutics for itch are emerging at a remarkable pace, and we are entering an era with more and more specialized therapies. Increasingly, these treatments are able to relieve itch beyond their effect on inflammation by directly targeting the neurosensory system.

Novel Topical Treatments for Itch.

The experience of itch often poses a burden on patient quality of life and has the capacity to inflict significant suffering. Topical therapies are a mainstay of treatment for many cutaneous and systemic diseases and afford patients the opportunity to manage their conditions without many of the systemic side effects of non-topical therapies. We review a multitude of new topical medications targeting the skin, immune system, and neural receptors. The list includes Janus kinase inhibitors, tyrosine kinase inhibitors, phosphodiesterase inhibitors, transient receptor vanilloid inhibitors, topical cannabinoids, and topical acetaminophen. Many of the topical therapies reviewed show promising data in phase 2-3 clinical trials, but further research is needed to compare therapies head-to-head and test their efficacy on a broader range of conditions.

Intravenous difelikefalin for the treatment of hemodialysis pruritus.

INTRODUCTION: Patients with chronic kidney disease (CKD) undergoing hemodialysis often experience significant itch secondary to their condition and a subsequent reduction in their overall quality of life. Current treatments are underwhelming, necessitating the search for new, effective therapeutic options to combat itch in this population. AREAS COVERED: The purpose of this review is to explore the available data for the use of intravenous difelikefalin in patients with CKD undergoing hemodialysis. The pathophysiology of CKD-associated itch is multifactorial, with one proposed mechanism involving an imbalance in the endogenous opioid system, favoring upregulation of itch-activating µ-opioid receptors (MORs) and downregulation of itch-inhibiting κ-opioid receptors (KORs). Dysregulation of the immune system is also involved. Difelikefalin is a recent FDA approved treatment that functions as peripherally acting KOR agonist, targeting this imbalance in the endogenous opioid system seen in CKD patients with itch and having an anti-inflammatory effect on immune cells. Clinical data on intravenous difelikefalin is promising regarding its ability to reduce itch in CKD patients on hemodialysis and improve patient quality of life, with few, mild adverse side effects. EXPERT OPINION: As intravenous difelikefalin becomes more widely used in the clinical setting, further studies assessing long-term efficacy and safety will be needed.

Research trends in testosterone deficiency and management: A bibliometric analysis approach to quality improvement in urology resident education.

INTRODUCTION: Previous work has demonstrated a deficiency in urology resident education when it comes to andrology and male infertility. We analyzed the top 100 most frequently cited and influential articles published on testosterone deficiency and its associated therapy, allowing trainees and clinicians to review and understand the characteristics of impactful literature for self-directed learning purposes. METHODS: The ISI Web of Knowledge database was used to find articles on testosterone deficiency, hypogonadism, and replacement therapies. Relevant, peer-reviewed, English articles were included. Article details, including title, citation count, publication year, and more, were gathered. Articles were classified based on content (e.g. clinical outcomes, anatomy, and trends) using defined criteria. RESULTS: The top 300 most cited were reviewed with 100 included. The most cited article had 774 citations, averaging 234 in the top 100. Publication years had peaks in 2003-2004 and 2006-2007. The US led in publications (56), followed by England (16), Germany (14), and Italy (13). Common affiliations included US Department of Veteran Affairs, Veterans Health Administration, RIC Research Education Clinical Center, and University of California System. Articles were categorized as LOE 2 (47), LOE 1 (22), and LOE 5 (21). Articles focused on clinical outcomes (71.7%), anatomy/biomechanics/physiology (14.1%), clinical guidelines (8.1%), and screening (4%). The "Journal of Clinical Endocrinology & Metabolism" published 26 of the top 100 cited articles. CONCLUSIONS: This analysis highlights influential articles regarding testosterone deficiency and management. The discussed articles have significant clinical and therapeutic implications for the practicing urologist which may bolster deficits in current resident education.

Itch: from the skin to the brain - peripheral and central neural sensitization in chronic itch.

Similar to chronic pain, chronic itch is frequently linked to neural sensitization, a phenomenon wherein the nervous system becomes hypersensitive to stimuli. This process of neural sensitization of chronic itch is orchestrated by various signaling pathways and mediators in both the peripheral and central nervous systems. At the level of the peripheral nervous system, inflammation and neuroimmune interactions induce plastic changes to peripheral nerve fibers, thereby amplifying the transmission of itch signaling. Neural sensitization in the central nervous system occurs at both the spinal cord and brain levels. At the level of the spinal cord, it involves hyperactivity of itch-activating spinal pathways, dysfunction of spinal inhibitory circuits, and attenuation of descending supraspinal inhibitory pathways. In the brain, neural sensitization manifests as structural and functional changes to itch-associated brain areas and networks. Currently, we have a diverse array of neuroimmune-modulating therapies targeting itch neural sensitization mechanisms to help with providing relief to patients with chronic itch. Itch research is a dynamic and continually evolving field, and as we grow in our understanding of chronic itch mechanisms, so will our therapeutic toolbox. Further studies exploring the peripheral and central neural sensitization mechanisms in the context of chronic itch are needed.

More Than Skin Deep: An Unusual Case of a Migrating Pacemaker Lead.

Pacemakers are commonly utilized in clinical practice and are generally well tolerated; therefore, clinicians may not be exposed to potential complications associated with pacemakers. This case report aims to illustrate the clinical presentation of a pacemaker lead migration, an uncommon potential complication. We present an 83-year-old male with a past medical history of complete atrioventricular block managed with a permanent pacemaker who presented with an open wound on his right chest. He had capped, abandoned right-sided leads from a previous pacemaker. At presentation, there was blood-tinged, yellow drainage and visible erosion of his electrodes. Computed tomography showed the right ventricular pacing lead perforating the right ventricle. Pacemaker lead migration outside of the chest wall is rare. Perforations may present asymptomatically or strikingly with effusions, pneumothoraces, hemothoraces, or cardiac tamponade. Management options include lead repositioning or extraction.

Effects of immunocompromised status on diagnostic criteria in septic arthritis.

Introduction: Septic arthritis is an orthopaedic emergency, with permanent cartilage damage possible within hours of the onset of symptoms. Diagnostic criteria for septic arthritis in immunocompetent patients are well established, however, there is a paucity of literature evaluating diagnostic criteria in immunocompromised patients. The purpose of this retrospective case-control study was to evaluate the laboratory and clinical information of immunocompromised patients with septic arthritis and compare them to immunocompetent patients with septic arthritis to enable physicians to diagnose septic arthritis more accurately in this population. Methods: All patients at our institution, a level I trauma center, with a clinical diagnosis of septic arthritis between January 1, 2006 and November 1, 2021 were identified and reviewed retrospectively. Patients 18 years old or older were screened for immunocompromised status and those meeting criteria were included for review. The control cohort was matched by the joint affected and age. Data were analyzed using the Shapiro-Wilk test, Turkey's test, Mann-Whitney U test, independent sample t-test, and chi-square analysis. A p-value of <0.05 was considered significant. Results: A total of 36 patients with positive joint aspirate cultures were compared (18 immunocompetent and 18 immunocompromised). The immunocompromised group had a significantly longer length of hospital stay than the immunocompetent group (p = 0.044). There was no significant difference in erythrocyte sedimentation rate (ESR) (p = 0.852), peripheral white blood cell count (pWBC) (p = 0.696), joint aspirate white blood cell count (aWBC) (p = 0.901), polymorphonuclear cell percentage (PMN%) (p = 0.325), or total operations performed per patient (p = 0.365). Conclusion: At our institution, immunocompromised patients with septic arthritis did not have significantly different diagnostic laboratory values when compared to immunocompetent patients. This suggests that immunocompromised patients with suspicion of septic arthritis can be assessed with similar diagnostic criteria as immunocompetent individuals; however, a larger cohort study is needed to assess the difference more precisely in laboratory values.

Characteristics and trends of the most cited papers in robotic assisted arthroplasty.

Purpose: To compile and analyze the top 50 most frequently cited articles published on robotic-assisted arthroplasty, allowing clinicians to effectively identify the most influential literature pertaining to this topic. Methods: Guidelines set by the Preferred Reporting Items for Systematic Reviews were used as the foundation for data collection and analysis. All papers pertaining to robotic-assisted arthroplasty were retrieved using the Scopus database. Data including: manuscript title, authors, total citation count, level of evidence, journal, publication year, and country of publication was extracted from a final list of articles. Results: The top 50 publications regarding robotic assisted arthroplasty were cited a total of 4530 times (including self-citations), with an average total of 91. The years with the most publications in the top 50 were: 2017, 2018, and 2019, producing 7, 6, and 5 papers, respectively. Only 4 papers in the top 50 were published prior to the year 2003. The most common level of evidence was level V, and the most common category was Clinical Outcomes (74%). The United States contributed half of the 50 articles, and Princess Grace Hospital and University of London were the most contributory institutions, each with 6 of the top 50 articles. Conclusion: This analysis provides a comprehensive review of the most cited and influential papers in robotic-assisted arthroplasty. Understanding these trends in the literature will ultimately pave the way for physicians and researchers to continue to innovate and research in a targeted manner as they gain an understanding of what has been studied and what remains inadequately explored. Level of evidence: 3.

A Case of a Carotid Cavernous Fistula.

CASE PRESENTATION: A 73-year-old male presented to the emergency department complaining of pain in his right eye for four weeks. He denied any trauma, and the pain was accompanied by ptosis, proptosis, swelling, redness, blurred vision, and a frontal headache. On examination, conjunctival arterialization was also appreciated. Magnetic resonance imaging and angiography showed evidence of a carotid cavernous fistula for which the patient underwent successful transvenous coiling and embolization. DISCUSSION: Carotid cavernous fistulas are classified as higher flow, direct fistulas or lower flow, indirect fistulas; the latter is more insidious in onset. Classic symptoms include conjunctival arterialization, proptosis, ptosis, palpebral edema, ocular palsy, vibratory sensation, elevated intraocular pressure without pupillary or visual acuity deficits, and headache. The treatment of choice is transvenous embolization.