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Purpose of Review: This review aims to summarize current knowledge on the pathophysiology of pain and the role of neuro-immune crosstalk in the development of acute and chronic pain (CP). Specifically, the review focuses on the role of immune cells involved in the innate and acquired immune response, emphasizing their bidirectional interactions with the nervous systems and discussing the implications of this crosstalk on acute and CP management., Recent Findings: In the last two decades, multiple studies have uncovered the important role of the immune system in initiating, maintaining, and resolving pain stimuli. Furthermore, researchers discovered that the immune system interacts tightly with the nervous system, creating a bidirectional crosstalk in which immune cells influence the response of peripheral and central nerve fibers while neurotransmitters and neuropeptides released by nociceptors directly and indirectly modulate the immune response. The neuro-immune crosstalk in acute and CP is a complex and not fully understood process that comprise the interactions of multiple diverse molecules, bidirectional interferences, and numerous redundant processes. Despite the complexity, important steps have been taken in recent years toward explaining the specific roles of each immune cell type and molecule in the initiation, maintenance and resolution of pain. These findings may set the basis for innovative therapeutic options that target the immune system, overcoming the limitations of current treatments in providing pain relief and the disadvantages associated with opioid therapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Persistent spinal pain syndromes are pervasive and lead to functional impairment, increased healthcare utilization, potential disability, and high societal costs. Spinal (cervical, thoracic, lumbar, and sacroiliac joint) pain includes mechanical, degenerative, inflammatory, oncologic, and infectious etiologies. Regenerative medicine is a novel biotechnology targeting mechanical, degenerative, and inflammatory conditions believed to cause pain. Preparations including platelet-rich plasma, mesenchymal stem cells (adipose tissue and bone marrow aspirate concentrates), and growth factors are derived from an autologous donor. The goal of intervention through guided injection of the regenerative media is to reduce inflammation and reverse the degenerative cascade in hopes of restoring normal cellular composition (physiologic homeostasis) and anatomical function to improve pain and function. The authors review limited research supporting the use of platelet-rich plasma injections for facet joint arthropathy and sacroiliac joint pain compared to traditional steroid treatments, as well as the use of platelet rich plasma or mesenchymal stem cells for lumbar discogenic and radicular pain., Recent Findings: Current evidence to support regenerative medicine for spine-related pain is limited. Although several studies demonstrated a reduction in pain, many of these studies had a small number of participants and were case series or prospective trials. Regenerative medicine treatments lack evidence for the treatment of spine-related pain. Large randomized controlled trials are needed with consistent study protocols to make further recommendations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Spinal cord stimulation (SCS) is an increasingly utilized therapy for the treatment of neuropathic pain conditions. Though minimally invasive and reversable, there are several important device-related complications that physicians should be aware of before offering this therapy to patients. The aim of this review is to synthesize recent studies in device-related SCS complications pertaining to cylindrical lead implantation and to discuss etiologies, symptoms and presentations, diagnostic evaluation, clinical implications, and treatment options., Recent Findings: Device-related complications are more common than biologic complications. Device-related complications covered in this review include lead migration, lead fracture, lead disconnection, generator failure, loss of charge, generator flipping, hardware related pain, and paresthesia intolerance. The use of SCS continues to be an effective option for neuropathic pain conditions. Consideration of complications prior to moving forward with SCS trials and implantation is a vital part of patient management and device selection. Knowledge of these complications can provide physicians and other healthcare professionals the ability to maximize patient outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

Post-traumatic stress disorder (PTSD) stands as a pervasive psychiatric condition, exerting a profound impact on millions across the globe. Despite the availability of traditional therapeutic modalities, many individuals continue to grapple with suboptimal treatment outcomes, underscoring the urgent need for novel interventions. In recent years, stellate ganglion blocks (SGBs) have garnered attention as a promising avenue in the treatment landscape for PTSD, showcasing remarkable efficacy in ameliorating symptomatology and enhancing overall quality of life. This comprehensive review seeks to delve into the current landscape of research surrounding SGBs for PTSD, including proposed mechanisms of action, clinical efficacy across diverse patient populations, safety profile, and potential avenues for further exploration and refinement. By synthesizing the latest evidence and insights, this review aims to provide clinicians and researchers with a comprehensive understanding of the role of SGBs in PTSD management, ultimately informing clinical practice and guiding future research endeavors in this area of mental health intervention., (Copyright © 1964–2024 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Introduction: LX-9211 is a drug designed to treat neuropathic pain conditions. It functions by inhibiting the adaptor-associated kinase 1 (AAK1) enzyme which promotes clathrin-dependent endocytosis. Preclinical studies have shown that LX-9211 does produce a reduction in nociceptive related behaviors and produces no major adverse effects in rats. Thus, LX-9211 has advanced to clinical trials to assess its safety and efficacy in humans. So far, phase 1 and phase 2 clinical trials involving patients with postherpetic neuralgia and diabetic peripheral neuropathic pain have been conducted with phase 3 trials planned in the future., Areas Covered: This paper highlights preclinical studies involving LX-9211 in rodents. Additionally, phase 1 clinical trials examining the safety of LX-9211 in healthy subjects as well as phase 2 studies looking at the safety and efficacy of LX-9211 compared to placebo in patients with diabetic peripheral neuropathic pain and postherpetic neuralgia are also discussed., Expert Opinion: In phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety.

Purpose of Review: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent complication of cytotoxic chemotherapeutic agents; its incidence largely varies, depending on type, dose, agent and preexisting risk factors. Oral-and-perioral-CIPN (OCIPN) is underreported. Neurotoxic agents can cause jaw pain or numbness. This review aims to present available data on OCIPN RECENT FINDINGS: A narrative literature review, following SANRA guidelines was conducted. PubMed and Cochrane databases were searched until September 2023. Articles referring to neuropathy or neuropathic pain due to head and neck cancer, head and neck radiotherapy, oropharyngeal mucositis, infection or post-surgical pain were excluded. Platinum-based chemotherapeutics, taxanes, vinca alkaloids, immunomodulatory and alkylating agents can cause OCIPN. Platinum-based chemotherapeutics can cause orofacial cold sensitivity, orofacial and jaw pain, oral cavity tingling and teeth hypersensitivity. Taxanes may induce oral cavity and tongue numbness and tingling as well as hot hypersensitivity. Vinca alkaloids may cause jaw, teeth and lips pain and oral mucosa hyperalgesia. Immunomodulatory drugs can cause lips, tongue and perioral numbness, while alkylating agents induce tongue and lips tingling and teeth cold-hypersensitivity. Chemotherapy may cause OCIPN due to changes in cellular structure and function, like alterations in membrane receptors and neurotransmission. OCIPN should be documented and physicians, dentists and health care providers should be alerted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Neuropathic pain (NP) conditions involve lesions to the somatosensory nervous system leading to chronic and debilitating pain. Many patients suffering from NP utilize pharmacological treatments with various drugs that seek to reduce pathologic neuronal states. However, many of these drugs show poor efficacy as well as cause significant adverse effects. Because of this, there is a major need for the development of safer and more efficacious drugs to treat NP., Areas Covered: In this review, we analyzed current treatments being developed for a variety of NP conditions. Specifically, we sought drugs in phase II/III clinical trials with indications for NP conditions. Various databases were searched including Google Scholar, PubMed, and clinicaltrials.gov., Expert Opinion: All the mentioned targets for treatments of NP seem to be promising alternatives for existing treatments that often possess poor side effect profiles for patients. However, gene therapy potentially offers the unique ability to inject a plasmid containing growth factors leading to nerve growth and repair. Because of this, gene therapy appears to be the most intriguing new treatment for NP.

Purpose of Review: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain., Recent Findings: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians., (© 2024. The Author(s).)

Purpose of Review: This is a comprehensive review of the literature regarding Lemborexant for the treatment of insomnia. It covers the background and management of insomnia and then reviews the body of existing evidence evaluating the use of Lemborexant for this purpose., Recent Findings: Insomnia leads to significant decreased in quality of life and economic burden due to decreased workplace performance and increased health care costs. Insomnia manifests as a single common pathway of hyperarousal due to a highly complex network of interactions between activation of the sympathetic system and the endocrine system. Lemborexant is a dual orexin 1/2 antagonist that blocks cortical arousal and promotes sleep state transition. Lemborexant was approved by the FDA in 2019 for use in insomnia. It belongs to a class of orexin neuropeptide inhibitors that is growing in popular clinical application., Summary: Insomnia is a crippling disorder of the sleep wake cycle that drives significant morbidity and mortality in the United States. It carries a high societal and economic toll due to direct and indirect effects to the healthcare system. Lemborexant is a new addition to the orexin antagonist class of drugs that already includes Almorexant and Suvorexant that has superior pharmacokinetic properties. While Lemborexant does have a mild side effect profile, its clinical safety and efficacy make it a promising insomnia drug of the future., (Copyright © 1964–2024 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Purpose of Review: This is a comprehensive review of the literature regarding the use of Solriamfetol for excessive daytime sleepiness. It covers the background and current therapeutic approaches to treating excessive daytime sleepiness, the management of common comorbidities, and the existing evidence investigating the use of Solriamfetol for this purpose., Recent Findings: Excessive daytime sleepiness leads to worse quality of life, a medical sequela and significant economic cost. There are multiple phenotypes of excessive daytime sleepiness depending on the comorbidity making treatment challenging. Due to the complexity of etiology there is not a cure for this ailment. Solriamfetol is a norepinephrine/dopamine dual reuptake antagonist that can be used to manage daytime sleepiness. Solriamfetol was first approved by the FDA in 2018 for use in excessive daytime sleepiness associated with obstructive sleep apnea and narcolepsy. Ongoing literature has proved this drug to be a safe and effective alternative pharmacotherapy., Summary: Recent epidemiological data estimate up to one-third of the general adult population suffers from excessive daytime sleepiness. There is no cure to daytime somnolence and current pharmacotherapeutic regimens have worrisome side effect profiles. Solriamfetol is a new class of drug that offers a safe and effective alternative option for clinical providers treating excessive daytime sleepiness., (Copyright © 1964–2024 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Bertolotti's syndrome, also known as lumbosacral transitional vertebrae, is a relatively rare spinal condition characterized by an anatomical variation in the lower spine. Conservative approaches such as physical therapy, anti-inflammatory medications and lifestyle modifications may be recommended for mild cases. In more severe cases or when conservative measures fail to provide relief, injections such as may be considered to alleviate pain. This case is unique in that we document a challenging technique of ipsilateral transforaminal epidural steroid injection in a patient with Bertolotti's syndrome.

Purpose of Review: It is essential to have validated and reliable pain measurement tools that cover a wide range of areas and are tailored to individual patients to ensure effective pain management. The main objective of this review is to provide comprehensive information on commonly used pain scales and questionnaires, including their usefulness, intended purpose, applicability to different patient populations, and associated advantages and disadvantages., Recent Findings: Acute pain questionnaires typically focus on measuring the severity of pain and the extent of relief achieved through interventions. Chronic pain questionnaires evaluate additional aspects such as pain-related functional limitations, psychological distress, and psychological well-being. The selection of an appropriate pain scale depends on the specific assessment objectives. Additionally, each pain scale has its strengths and limitations. Understanding the differences among these pain scales is essential for selecting the most appropriate tool tailored to individual patient needs in different settings., Conclusion: Medical professionals encounter challenges in accurately assessing pain. Physicians must be familiar with the different pain scales and their applicability to specific patient population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Spinal cord stimulation has been increasing in influence as an option to regulate pain, especially in the chronic pain patient population. However, even with the numerous changes made to this technology since its inception, it is still prone to various complications such as hardware issues, neurological injury/epidural hematoma, infections, and other biological concerns. The purpose of this article is to thoroughly review and evaluate literature pertaining to the complications associated with percutaneous spinal cord stimulation., Recent Findings: Lead migration is generally the most common complication of percutaneous spinal cord stimulation; however, recent utilization of various anchoring techniques has been discussed and experienced clinical success in decreasing the prevalence of lead migration and lead fractures. With newer high-frequency systems gaining traction to improve pain management and decrease complications as compared to traditional systems, rechargeable implantable pulse generators have been the preferred power source. However, recent findings may suggest that these rechargeable implantable pulse generators do not significantly increase battery life as much as was proposed. Intraoperative neuromonitoring has seen success in mitigating neurological injury postoperatively and may see more usage in the future through more testing. Though the occurrence of infection and biological complications, including dural puncture and skin erosion, has been less frequent over time, they should still be treated in accordance with established protocols. While many complications can arise following percutaneous spinal cord stimulator implantation, the procedure is less invasive than open implantation and has seen largely positive patient feedback. Hardware complications, the more common issues that can occur, rarely indicate a serious risk and can generally be remedied through reoperation. However, less common cases such as neurological injury, infections, and biological complications require prompt diagnosis to improve the condition of the patient and prevent significant damage., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction The Accreditation Council for Graduate Medical Education (ACGME) requires that residents in the Physical Medicine and Rehabilitation (PM&R) residency observe or perform certain interventional procedures, one of which is an interlaminar epidural steroid injection (ILESI). While the traditional learning model relying heavily on observation is commonplace, it leaves the practice phase of learning to happen on real patients. High-fidelity simulation may be a worthwhile alternative as a training approach to increase physician comfort with the procedure and improve patient safety. Methods Current PM&R residents from two programs between their second and fourth year, inclusively, who lacked prior training experience in ILESI attended one hour of either: (1) an experimental arm of supervised hands-on training on a simulation device or (2) a control arm observing the procedures performed by an attending on the same device. Assignments were made based on resident schedule availability. Pre-training knowledge, training, and post-training knowledge were assessed at the Multidisciplinary Pain Clinic at Montefiore Medical Center. Participants were assessed on their procedural competence using an adapted version of a previously published grading checklist before the session. Participants also evaluated their confidence in performing the procedure prior to and after training. Data was analyzed using the Wilcoxon signed-rank test and the Wilcoxon rank-sum test. SAS Version 9.4 was used for analysis. Results Fifteen residents initially participated, but three residents dropped out at the 15-week follow-up. There was a significant increase in test scores in both arms immediately after the intervention (p=0.008 in control, p=0.016 in the experiment), with greater improvement shown in the hands-on training group (p=0.063). At the 15-week follow-up, there was no significant change in test scores in the control arm (p=0.969) while there was a decrease in the experiment arm (p<0.001). Conclusion Hands-on learning with high-fidelity simulation demonstrated more improvement for short-term motor-skill acquisition, while observational learning with repetition showed more benefits for long-term retention. Optimal procedural training should employ both educational modalities for best short- and long-term results., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sim et al.)

Purpose of Review: The aim of this review is to educate healthcare professionals regarding buprenorphine for the use of opioid use disorder (OUD) as well as for chronic pain management. This review provides physicians and practitioners with updated information regarding the distinct characteristics and intricacies of prescribing buprenorphine., Recent Findings: Buprenorphine is approved by the US Food and Drug Administration (FDA) for acute pain, chronic pain, opioid use disorder (OUD), and opioid dependence. When compared to most other opioids, buprenorphine offers superior patient tolerability, an excellent half-life, and minimal respiratory depression. Buprenorphine does have notable side effects as well as pharmacokinetic properties that require special attention, especially if patients require future surgical interventions. Many physicians are not trained to initiate or manage patients on buprenorphine. However, buprenorphine offers a potentially safer alternative for medication management for patients who require chronic opioid therapy for pain or have OUD. This review provides updated information on buprenorphine for both chronic pain and OUD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic nonmalignant pain is recognized as a complex, dynamic, phenomenological interplay between biological, psychological, and social factors that are individual to the person suffering from it. Therefore, its management and treatment ought to entail the individual's biopsychosocial aspects that are often addressed by collaborative, inter/multidisciplinary multimodal care, as there is no biologic treatment. In an effort to enhance inter/multidisciplinary multimodal care, a narrative review of arts therapy as a mind-body intervention and its efficacy in chronic pain populations has been conducted. Changes in emotional and physical symptoms, especially pain intensity, during arts therapy sessions have also been discussed in in the context of attention distraction strategy. Arts therapy (visual art, music, dance/movement therapy, etc.) have been investigated to summarize relevant findings and to highlight further potential benefits, limitations, and future directions in this area. We reviewed 16 studies of different design, and the majority reported beneficial effects of art therapy in patients' management of chronic pain and improvement in pain, mood, stress, and quality of life. However, the results are inconsistent and unclear. It was discovered that there is a limited amount of high-quality research available on the implications of arts therapy in chronic nonmalignant pain management. Due to the reported limitations, low effectiveness, and inconclusive findings of arts therapy in the studies conducted so far, further research with improved methodological standards is required., (© 2023. The Author(s).)

Purpose of Review: Rib fractures are a common traumatic injury that has been traditionally treated with systemic opioids and non-opioid analgesics. Due to the adverse effects of opioid analgesics, regional anesthesia techniques have become an increasingly promising alternative. This review article aims to explore the efficacy, safety, and constraints of medical management and regional anesthesia techniques in alleviating pain related to rib fractures., Recent Findings: Recently, opioid analgesia, thoracic epidural analgesia (TEA), and paravertebral block (PVB) have been favored options in the pain management of rib fractures. TEA has positive analgesic effects, and many studies vouch for its efficacy; however, it is contraindicated for many patients. PVB is a viable alternative to those with contraindications to TEA and exhibits promising outcomes compared to other regional anesthesia techniques; however, a failure rate of up to 10% and adverse complications challenge its administration in trauma settings. Serratus anterior plane blocks (SAPB) and erector spinae blocks (ESPB) serve as practical alternatives to TEA or PVB with lower incidences of adverse effects while exhibiting similar levels of analgesia. ESPB can be performed by trained emergency physicians, making it a feasible procedure to perform that is low-risk and efficient in pain management. Compared to the other techniques, intercostal nerve block (ICNB) had less analgesic impact and required concurrent intravenous medication to achieve comparable outcomes to the other blocks. The regional anesthesia techniques showed great success in improving pain scores and expediting recovery in many patients. However, choosing the optimal technique may not be so clear and will depend on the patient's case and the team's preferences. The peripheral nerve blocks have impressive potential in the future and may very well surpass neuraxial techniques; however, further research is needed to prove their efficacy and weaknesses., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cholangiocarcinoma (CCA) is an aggressive and diverse malignancy with a poor prognosis. Related to a typical indolent course of progression, most cases of CCA are metastatic or locally advanced at the time of presentation. For patients with nonresectable tumors or metastatic disease, the mainstay of treatment is comprehensive with combination chemotherapy. The first-line chemotherapeutic combination for the treatment of CCA are cisplatin and gemcitabine-based chemotherapies. However, many locally advanced and progressive CCA cases are refractory to first-line management. Within the past few years, the increase in the incidence of metastatic CCA and its poor prognosis has brought to light the need for novel therapeutic approaches to treatment. With advancements in next-generation genome sequencing, multiple molecular pathways have been identified in the pathogenesis of CCA and have shown great potential as alternative treatments in cases of CCA refractory to surgical resection. FGFR2 fusions or rearrangements have been identified in 10-16% of all intrahepatic CCA and are thought to serve as a pathway of resistance for a number of nonresectable and refractory cases of cholangiocarcinoma. A novel therapeutic agent that has been discussed is infigratinib, a selective, ATP-competitive inhibitor of fibroblast growth factor receptor 2 (FGFR2). In a phase 1 trial, infigratinib showed a safe profile and showed remarkable clinical efficacy in advanced CCA with FGFR2 fusions or rearrangements in phase II trials. As of May 2021, the Food and Drug Administration (FDA) approved infigratinib for CCA largely based on tumor response and duration of response. As of 2021, infigratinib, futibatinib, and pemigatinib, similar novel selective FGFR inhibitors, have been approved by the FDA for the treatment of locally advanced or metastatic CCA harboring FGFR2 gene mutations. The present investigation reviews the development of infigratinib in particular and its clinical efficacy compared to other available treatment options for cholangiocarcinoma. While the side effect profile of infigratinib is minimal, particularly GI side effects, when compared with futibatinib and pemigatinib, the overall response rate (ORR) and median overall survival (mOS) for infigratinib (ORR=23.1%, mOS=3.8 months) was significantly lower than futibatinib (ORR=35.8%, mOS=21.1 months) and pemigatinib (ORR=35.5%, mOS=21.1 months). While there is ample promise for the use of infigratinib as molecular-directed therapy in the treatment of CCA harboring FGFR2 mutations, there is an appropriate concern for patient-acquired resistance. The heterogeneous nature of FGFR mutations and the emergence of different resistance mechanisms emphasize a need for more agents to inhibit FGFR rearrangements effectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, White et al.)

To review the pharmacokinetics, efficacy, and adverse effects of vigabatrin (Sabril) and its role in managing refractory focal unaware seizures in adults. In the present investigation, a search of English-language literature from 1999 through 2023 was conducted using vigabatrin and Sabril as search terms to identify relevant studies and review articles. A 2000 double-blind, placebo-controlled multicenter study found that out of 90 adult patients, 48% of those treated with vigabatrin achieved a 50% or greater reduction in the frequency of complex partial seizures, compared to 26% of placebo-treated patients. This study also observed that vigabatrin was well tolerated by 72.4% of patients, with the most common side effects being drowsiness, dizziness, headache, and fatigue. Further studies with a significant risk of vigabatrin-associated visual field loss necessitate vigabatrin only being an option for refractory cases. Additional studies suggest that despite the potential risk of vision loss and adverse effects, adult patients continue to use vigabatrin long-term. Sabril is an antiepileptic medication prescribed as an additional treatment for refractory complex partial seizures in patients at least ten years old who have not responded well to other alternative therapies. Multiple clinical trials indicate that Sabril sufficiently reduces the frequency of seizures when used as an adjunct treatment of refractory complex focal seizures. However, it is important to carefully monitor patients for any adverse effects, particularly long-term use, and to discontinue the drug if serious side effects occur., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gatson et al.)

Heavy societal stigma of certain conditions has created an environment where individuals may be hesitant to seek professional care. Urology is a specialized field that focuses on many of these conditions that society has deemed taboo to discuss. In this review, we address barriers that have prevented patients from seeking urologic care in order to better understand and elucidate important concerns within development of the physician-patient relationship. Recognizing these concerns can also assist in public health outreach approaches to motivate patients for seeking urologic care. The scope of this review was limited to three highly prevalent conditions affecting both men and women, including urinary incontinence, erectile dysfunction, and genitourinary syndrome of menopause.

Thyroid eye disease (TED) can cause disfigurement and vision loss, most commonly in patients with Graves' disease. These symptoms are related to orbital inflammation subsequently cause proptosis and limited eye movement. Traditionally, TED is treated with corticosteroids to decrease inflammation and surgery once the disease stabilizes. However, multiple medications that play a role in immune modulation have been tested and found to be beneficial in treating TED, either as an adjuvant to steroids or in severe disease resistant to steroids. Teprotumumab-trbw, a novel monoclonal antibody sold under the trade name Tepezza ® , is the first immune modulator to be approved by the Unites States Food and Drug Administration (FDA) for TED. Teprotumumab-trbw targets the insulin-like growth factor-1 receptor, which is upregulated on orbital fibroblasts and decreases activation in patients with TED. The FDA approved this drug for patients with less than nine months of disease duration and high levels of disease activity. Multiple studies have shown significant positive results in disease modulation, as well as limited side effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bocklud et al.)

Lyme disease and its treatment implications have become an ever-increasing area of concern within the United States related to the markedly increased prevalence of infection within the last two decades. The presentation, pathophysiology, and epidemiology of Lyme disease have been well studied, and thus treatments for this disease are widely available. While the treatment of its early and late stages is relatively simple with 10-14 day and four-week courses of doxycycline, respectively, the main problem rests in the understanding of the etiology and pathology of post-treatment Lyme disease syndrome (PTLDS). With the time of symptoms onsetting approximately six months after treatment and potentially lasting indefinitely, this syndrome's effect on patients' quality of life could be devastating. Searching on PubMed, Google Scholar, MEDLINE, and ScienceDirect using keywords including Lyme disease, PTLDS, doxycycline, erythema migrans, azlocillin, and treatment, the authors have tried to make clear the different aspects. The authors have reviewed and discussed clinical studies of Lyme disease and its treatments/potential therapeutics as well as PTLDS and its sparse treatments/potential therapeutics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Talbot et al.)

Osteoporosis affects a significant number of postmenopausal women in the United States. Screening is performed using clinical assessments and bone mineral density scans via dual x-ray absorptiometry. Oral therapy is indicated to prevent pathologic fractures in those deemed at increased risk following screening. Bisphosphonates including alendronate, ibandronate, and risedronate are currently first-line oral therapeutics in fracture prevention following the diagnosis of osteoporosis. Hormonal therapies include estrogen-containing therapies, selective estrogen receptor modulators, and other compounds that mimic the effects of estrogen such as tibolone. Lifestyle modifications such as supplementation and physical activity may also contribute to the prevention of osteoporosis and are used as adjuncts to therapy following diagnosis. These therapeutics are limited primarily by their adverse effects. Treatment regimens should be tailored based on significant risk factors demonstrated by patients, adverse effects, and clinical response to treatment. The most severe risk factors relevant to pharmacological selection involve hormone replacement therapies, where concern for venous thrombosis, coronary artery disease, breast, and uterine cancer exist. Bisphosphonates are most commonly associated with gastrointestinal discomfort which may be mitigated with proper administration. Although adverse effects exist, these medications have proven to be efficacious in the prevention of vertebral and non-vertebral fractures in post-menopausal women. Fracture risk should be weighed against the risk of adverse events associated with each of the regimens, with clinical judgment dictating the treatment approach centered around patient goals and experiences., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Schroeder et al.)

Purpose of Review: The study sought to assess the prevalence of physician burnout among interventional pain physicians in 2022., Recent Findings: Physician burnout is major psychosocial and occupational health issue. Prior to the coronavirus disease of 2019 (COVID-19) pandemic, over 60% of physicians reported emotional exhaustion and burnout. Physician burnout was reported to become more prevalent in multiple medical specialties during the COVID-19 pandemic. An 18-question survey was distributed electronically to all ASPN members (n = 7809) in the summer of 2022 to assess demographics, burnout characteristics (e.g., Have you felt burned out due to COVID?), and strategies to cope with burnout and stress (e.g., reached out for mental health assistance). Members were able to complete the survey once and were unable to make changes to their responses once submitted. Descriptive statistics were used to assess the prevalence and severity of physician burnout within the ASPN community. Chi-square tests were used to examine differences in burnout by provider characteristics (age, gender, years practicing, and practice type) with p-values less than 0.05 indicating statistical significance. There were 7809 ASPN members that received the survey email, 164 of those members completed the survey, a response rate of 2.1%. The majority of respondents were male (74.1%, n = 120), 94% were attending physicians (n = 152), and 26% (n = 43) have been in practice for twenty years or longer. Most respondents expressed having experienced burnout during the COVID pandemic (73.5%, n = 119), 21.6% of the sample reported reduced hours and responsibilities during the pandemic, and 6.2% of surveyed physicians quit or retired due to burnout. Nearly half of responders reported negative impacts to their family and social lives as well as personal physical and mental health. A variety of negative (e.g., changes in diet, smoking/vaping) and positive coping strategies (e.g., exercise and training, spiritual enrichment) were employed in response to stress and burnout; 33.5% felt they should or had reached out for mental health assistance and suicidal ideations were expressed in 6.2% due to burnout. A high percentage of interventional pain physicians continue to experience mental symptoms that may lead to risk for significant issues going forward. Our findings should be interpreted with caution based on the low response rate. Evaluation of burnout should be incorporated into annual assessments given issues of survey fatigue and low survey response rates. Interventions and strategies to address burnout are warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adequate surgical view during various types of nasal procedures is essential for surgical operations to be performed in a safe, efficient, and successful manner. Minimizing bleeding during surgery is an important way of increasing visualization that is commonly achieved by using a vasoconstrictive agent to control intraoperative hemorrhage. Many otolaryngologists choose to employ topical cocaine to minimize bleeding during surgery owing to its vasoconstrictive properties, while simultaneously benefitting from its dual local anesthetic effects. The relative benefit of topical cocaine for otolaryngologic procedures when compared to other topical analgesics and vasoconstrictors remains a topic of discussion due to the multiple potential cardiac and central nervous system side effects associated with cocaine administration. Furthermore, there is not a scientifically backed maximal safe dose published; instead, most of the guidelines for intranasal cocaine use are based on untested clinical practice. Despite this, the short latency, adequate duration of action, and inherent vasoconstrictive and decongestive capabilities make cocaine a valuable anesthetic agent for use in clinical procedures. As the relative benefit of using topical cocaine compared to the use of other vasoconstrictors and analgesics for nasal procedures remains undetermined in the current literature, this leaves the need for a comprehensive review of research that explores the risks and benefits of using topical cocaine in nasal procedures based on clinical trials that compare intranasal cocaine with various other analgesics and vasoconstrictors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lutfallah et al.)

Naltrexone is a mu-opioid receptor antagonist with a long half-life compared with naloxone. Both of these drugs, along with others, were developed with the intention of reversing the effects of opioid abuse or toxicity. Evidence has also shown that naltrexone has a benefit in preventing relapse by reducing opioid cravings and reducing symptoms of opioid withdrawal. The benefits of this drug were not only shown with opioid abuse. In 1984 this drug was also approved for alcohol abuse. Naltrexone has been proven to decrease alcohol relapse by decreasing the craving. Apart from these approved indications for the use of naltrexone, with time, it has been seen that this drug has a benefit in treating chronic pain. A number of studies have shown the benefits of this drug with inflammatory bowel disease, fibromyalgia, multiple sclerosis, diabetic neuropathy, and complex regional pain syndrome, among others. More studies are needed to approve this medication for specific chronic pain conditions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Lower Urinary Tract Symptoms (LUTS) are frequently present in the general population as patients age with approximately a third of individuals experiencing LUTS during their lifetime. LUTS can be further defined as having any of the following symptoms: urinary hesitancy, straining, nocturia, increased urination frequency, and dysuria. LUTS has the potential for patients to contribute their symptoms to what can normally occur as we age. This can lead to a decrease in patients seeking care and could negatively impact patients' health-related quality of life (HRQL). In conjunction with LUTS, we obtained from our analysis that LUTS and depression are closely related and worsening depressive symptoms may increase the severity of LUTS. We also discerned three categories of factors that can yield major depression namely adversity, internalizing, and externalizing factors. Within these categories, trauma, social support, genetic factors, and minimal education appeared to increase the risk of depression in patients. With the recent increase in mental health awareness and more access to mental health care amid the COVID-19 Pandemic, further screening, and collaboration between providers to treat both urological and psychiatric symptoms could improve patient outcomes. It is important for providers to have an increased understanding of the mental and physical impact both LUTS and depression can have on patients' wellbeing. This has the potential to help patients be more open about their symptoms with the aim of better addressing LUTS and depression to positively impact their HRQL.

There is a lack of evidence to support the effectiveness of long-term opioid therapy in patients with chronic, noncancer pain. Despite these findings, opioids continue to be the most commonly prescribed drug to treat chronic back pain and many patients undergoing spinal surgery have trialed opioids before surgery for conservative pain management. Unfortunately, preoperative opioid use has been shown repeatedly in the literature to negatively affect spinal surgery outcomes. In this review article, we identify and summarize the main postoperative associations with preoperative opioid use that have been found in previously published studies by searching on PubMed, Google Scholar, Medline, and ScienceDirect; using keywords: Opioid dependency, postoperative, spinal surgery, specifically (1) increased postoperative chronic opioid use (24 studies); (2) decreased return to work (RTW) rates (8 studies); (3) increased length of hospital stay (LOS) (9 studies); and (4) increased healthcare costs (8 studies). The conclusions from these studies highlight the importance of recognizing patients on opioids preoperatively to effectively risk stratify and identify those who will benefit most from multidisciplinary counseling and guidance., Competing Interests: The authors have no conflicts of interest to disclose, in terms of funding and research support, employment, personal financial interest, patents, and consultation fees within the last five years. One of the authors (FI) is on the editorial board of this journal. Based on journal policy this author was completely excluded from any review of this article., (Copyright © 2023, Fortier et al.)

Acetaminophen is an extremely common drug with many implications for its analgesic and antipyretic properties. It has a unique mechanism of action and downstream effects that separate it categorically from non-steroidal anti-inflammatory drugs. These differences come with potential adverse effects that range from mild drug reactions to severe life-threatening emergencies. While acetaminophen's toxic liver effects are well known, a lesser-known adverse effect of this drug is its association with the development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These dermatological emergencies involve similar pathological processes, including apoptosis of the epidermis and sloughing of the dermis and mucosa from the underlying layers with a positive Nikolsky sign. Currently, SJS and TEN are considered immune-mediated type IV hypersensitivity reactions predominantly involving CD8+ T lymphocytes. Other immune mediators, including regulatory T cells, natural killer cells, interleukins, and drug metabolites are speculated to be involved, but their mechanisms have not been entirely determined. These conditions are differentially diagnosed by the percentage of body area affected with SJS and TENS, involving <10% and >30%, respectively. Genomic variations in human leukocyte antigens (HLA) genes have been implicated in the susceptibility and severity of acetaminophen-induced SJS/TENS, however, details of these interactions remain unclear. Acetaminophen's widespread use and the morbidity of its associated skin pathologies SJS and TENS warrant an in-depth examination of the causative processes involved in their pathogenesis. It is critical that both physicians and patients be made aware that while acetaminophen is widely tolerated by most individuals, severe and potentially fatal interactions do occur, and further investigation is necessary to reduce these adverse effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Spillers et al.)

With the ongoing opioid epidemic in the United States there has been a strong transition towards utilizing multi-modal analgesia, interventional procedures, and non-opioid medications when managing acute and chronic pain. There has also been an increased interest in utilizing buprenorphine. Buprenorphine is a novel long-acting analgesic with partial mu-opioid agonist activity that can be utilized for analgesia as well as opioid use disorder. Buprenorphine also has a unique set of side effects as well pharmacodynamic and pharmacokinetic properties that require special attention, especially if these patients require future surgical interventions. Given the increased interest in this medication we believe that there needs to be increased education and awareness regarding this medication amongst physicians, specifically pain management physicians and trainees.

Background: The American Board of Medical Specialties definition of medical professionalism cites the need to acquire, maintain, and advance a value system serving the patients' and public's interests above self-interests. 4 Medical professionalism is a one of the core physician competencies assessed by both the ACGME training program evaluation and the ABA certification process. However, a growing concern for the decline of professionalism and altruism in medicine resulted in increased publications on the matter, citing various potential sources for the issue., Methods: All residents and fellows (Focus Group 1) of the Anesthesiology Department of Montefiore Medical Center in Bronx, NY were invited to participate in a semi-structured interview via Zoom, held on two separate dates. A separate invitation was sent to the faculty of the department (Focus Group 2), held on one date. During the interview, guiding questions were provided by the 4 interviews to facilitate discussion. The interviewers, all members of the anesthesia faculty, took notes as the interviews progressed. The notes were reviewed for common themes as well as supporting and contradicting quotations., Results: A total of 23 residents and fellows and a total of 25 faculty members within the Anesthesiology department at Montefiore Medical Center were interviewed. Amongst the findings, common discussions concerned motivating and demotivating factors contributing to the professionalism and altruism exhibited by the residents and fellows when caring for critical COVID-19 patients during the height of the pandemic. It was widely regarded that patient improvement, community and team support, as well as intrinsic desire to help greatly motivated the team while continuous patient deterioration, uncertainty in staffing and treatment, and concerns for personal and family safety were sources of discouragement. Overall, faculty perceived an increased demonstration of altruism amongst residents and fellows. The statements made by the residents and fellows during their interviews supported this observation., Conclusions: The actions of the Montefiore Anesthesiology residents and fellows demonstrated that altruism and professionalism were readily available amongst physicians. Increased levels of empathy and responsibility contributed to a demonstration of professionalism that challenges previous views of a perceived decline of these attributes in the medical field. The findings of this study stress the importance of creating a curriculum and exercise that stress empathy-based care and altruism in order to improve resident satisfaction and decrease feelings of burnout. Additionally, curriculum additions to facilitate professionalism are proposed.

Burning mouth syndrome is a condition characterized by a painful burning sensation in the oral mucosa lasting at least 3-6 months with no definitive etiology. The pathophysiology is not well understood, though there appears to be a connection with other neuropsychiatric conditions such as depression, anxiety, and mood disorders. We briefly discuss our experience with a patient who suffered from this conidtion and how it was treated with mandibular and maxillary nerve blocks after failing more conservative pharmacological options.

Purpose of Review: Notalgia paresthetica (NP) is a chronic cutaneous neuropathy primarily characterized by localized pruritus and associated dysesthesias, including sensations of pain, numbness, and tingling. The sensory neuropathy characteristic of NP is thought to result from spinal nerve entrapment caused by degenerative changes in the spine or musculoskeletal compression. This review summarizes the current medical literature with a focus on the past five years regarding NP, its pathophysiology, presentation, and current treatment options., Recent Findings: Though treatments exist with varying efficacy, to date, there exists no definitive treatment for NP. Treatment options for NP are varied and range from topical and oral agents to interventional procedures and physical therapy. Of the treatments evaluated, topical capsaicin remains the most efficacious treatment for NP., Conclusions: The lack of established treatment guidelines makes treating NP complicated as it dramatically affects patients' quality of life. Further research with larger sample sizes is needed to evaluate better the most effective treatment and dosing regimen for patients afflicted with NP.

Introduction: In recent years, the erector spinae plane block (ESPB) has seen widespread use to treat acute and chronic pain in the regions of the thoracic spine. While limited data suggest its increasing utilization for pain management distal to the thoracic, abdomen and trunk, the anesthetic spread and analgesic mechanism of ESPB at the level of the lumbar spine has not been fully described or understood., Methods: This is an observational anatomic cadaveric study to assess the distribution of solution following an ESPB block performed at the fourth lumbar vertebrae (L4) using ultrasound guidance to evaluate the spread of a 20 ml solution consisting of local anesthetic and methylene blue. The study was performed in an anatomy lab in a large academic medical center. Following injection of local anesthetic with contrast dye, cadaveric dissection was performed to better understand the extent of contrast dye and to determine the degree of staining to further predict analgesic potential. We reviewed the findings of other ESPB cadaveric studies currently available for comparison., Results: Following cadaveric dissection in an anatomy lab, the contrast dye was observed in the ESP space, and staining was found most cranially at L2 and extending caudally underneath the sacrum. Evaluating the depth of its spread, we found it to be confined to the posterior compartment of the spine sparing the nerve roots bilaterally, which is consistent with the only other cadaveric study of ESPB performed at L4., Conclusion: Our results demonstrate the clinical utility of lumbar ESPB where posterior confinement of local anesthesia is preferred. However, further investigation is needed to determine the efficacy of ESPB in lower extremity analgesia which is predicated on ventral nerve root involvement., (© 2022. The Author(s).)

Background: Amyloidosis is a group of diseases with the common pathophysiology of protein misfolding and aberrant deposition in tissue. There are both acquired and hereditary forms of this disease, and this review focuses on the latter hereditary transthyretin-mediated (hATTR). hATTR affects about 50,000 individuals globally and mostly appears as one of three syndromes - cardiac, polyneuropathy, and oculoleptomeningeal. Polyneuropathy is the most common form, and there is usually some overlap in individual patients., Results: Recently, novel therapeutic options emerged in the form of groundbreaking drugs, Patisiran and Inotersen, small interfering RNA molecules that target TTR and reduce the production of this protein. By targeting TTR mRNA transcripts, Inotersen decreases protein translation and production, reducing the deposition of misfolded proteins. It was shown to be both effective and safe for use and specifically formulated to concentrate in the liver - where protein production takes place., Conclusion: hATTR is a rare, progressive, and debilitating disease. Its most common presentation is that of polyneuropathy, and it carries a very poor prognosis and a natural history conveying a median survival of < 12 years. Novel therapeutic options are groundbreaking by providing disease-modifying specific, targeted therapies against TTR production and deposition. The use of RNA interference (RNAi) opens the door to the treatment of hereditary diseases by targeting them at the genetic level., Competing Interests: There are no conflict of interests with the authors.

Spinal cord stimulation (SCS) is a viable treatment option for chronic pain. One of the primary indications for SCS implantation is persistent pain after spinal surgery. Studies have demonstrated that these patients have a better response to SCS over conservative management or repeat surgery. Traditional SCS therapy uses parasthesias to overlap a patient's pain pattern and provide relief, though some patients find this uncomfortable. To avoid the use of paresthesias, a 10kHz waveform can be utilized to provide a subthreshold level of high frequency stimulation to provide superior pain relief without paresthesias. Additionally, 10kHz stimulation may be used to salvage therapy when other forms of SCS have failed. Here, we present a case in which a patient was switched from traditional SCS to 10kHz in the middle of a SCS trial with lead placement revision to salvage SCS therapy.

Objectives: The potentially different effects of commonly used anaesthetic agents propofol and sevoflurane on T-cell immune function and Th cell differentiation were investigated in patients with severe mycoplasmal pneumonia (SMPP) undergoing fibreoptic bronchoscopy., Methods: Sixty children (2-12 years of age) with SMPP were randomized into the sevoflurane group and the propofol group. Patients in the sevoflurane group were anaesthetised with inhalational sevoflurane and intravenous remifentanil. Patients in the propofol group were anaesthetised with intravenous propofol and remifentanil. Patients in both groups underwent fibreoptic bronchoscopy and lavage therapy. We compared the clinical outcomes, cellular immunity function, and Th cell differentiation into Th1 and Th2 levels in both groups., Results: There was no significant difference in clinical outcomes and hospital stay between the two groups (7.94 vs 7.36, p  > .05). However, the CD3 + T cells, CD4 + T cells, and CD4 + /CD8 + in the propofol group were significantly higher than those in the sevoflurane group (T1 51.96 vs 48.33, T2 58.08 vs 55.31, p  < .05). The ratio of Th 1 /Th 2 in the two groups was significantly increased postoperatively in both groups (Sevoflurane 8.53 vs 7.23, Propofol 9.35 vs 7.18), and the propofol group was significantly higher than the sevoflurane group (9.35 vs 8.53, p  < .05)., Conclusions: Propofol might have a less inhibitory effect on T lymphocytes in children with SMPP than sevoflurane. And propofol may have less impact on the differentiation of Th cells into Th 1 cells and better preserving the Th 1 /Th 2 ratio than sevoflurane. KEY MESSAGESThe pathogenesis of SMPP is still unclear, likely through alveolar infiltration with neutrophils and lymphocytes, lymphocyte/plasma cell infiltrates in the peri-bronchovascular area, and immune dysfunction.Recent experimental and clinical studies showed that sevoflurane might have immunosuppressive effects, and multiple studies confirmed that the immune function of children with SMPP had been reduced.This study found that propofol administered in children with SMPP had a less inhibitory effect on T lymphocytes than inhalational sevoflurane, had little inhibitory effect on the differentiation of Th cells into Th1 cells, and better preserve Th1/Th2 ratio and maintain the balanced immune function.

Background: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine., Objectives/study Design: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists., Methods: In this study, all 114 pain program directors listed on the Accreditation Council for Graduate Medical Education (ACGME) website, or their administrative assistants were directly contacted via email. All email addresses were obtained from the ACGME website. The survey opened in September 2021, with reminder emails sent before the closing of the survey in December 2021. A final reminder email was sent 4 weeks prior to the closing of the survey., Results: Of all the respondents, 79 (89.77%) were currently practicing pain medicine, and 9 (10.23%) were no longer practicing pain medicine., Limitations: Our study has a major limitation as we are unable to determine the response rate and are limited in the data points gathered., Conclusion: We hope this study will allow for pain medicine fellowship program directors to improve recruitment and retention of pain fellows in the field while addressing the pros and cons of future career aspirations with anesthesiology residents prior to fellowship selection. A larger, more thorough study with an exact response rate can compare the various outcomes based upon different types of settings, such as private practice, partnership, and academia, as well as geographical locations.

Introduction: Despite the growing evidence for the anticancer effect of metformin or its combination with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), the efficacies and side effects of such strategies in non-small cell lung cancer (NSCLC) patients with or without type 2 diabetes mellitus (T2DM) are not well understood. This meta-analysis was performed to determine the efficacy and side effects of metformin combined with EGFR-TKIs (MET-EGFR-TKIs) for the treatment of NSCLC with or without T2DM., Methods: PubMed and Cochrane Library databases were used to retrieve relevant studies through August 2020 using the keywords "metformin", "EGFR-TKIs" ("gefitinib" or "erlotinib" or "afatinib" or "icotinib" or "dacomitinib") and "lung cancer". The patients in the experimental group received MET-EGFR-TKIs, while those in the control group received only EGFR-TKIs. The outcome analysis reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Random-effect models and fixed-effect models were used to estimate the combined hazard ratio (HR) and odds ratio (OR) depending on the data heterogeneity. Three studies (including 1996 patients) were included in the current meta-analysis., Results: There were significant differences in PFS (HR 0.84; 95% confidence interval (CI) 0.75-0.95; P = 0.004) and OS (HR 0.77; 95% CI, 0.50-1.04; P < 0.001) between the MET-EGFR-TKI and EGFR-TKI groups. Although the ORR (OR 1.38; 95% CI 0.66-2.88; P = 0.105) and DCR (OR 2.61, 95% CI 0.68-9.95, P = 0.160) were improved, there was no statistical significance. OS subgroup analysis showed that the combination was more effective in NSCLC with T2DM than in NSCLC without T2DM (HR 0.84; 95% CI 0.74-0.95; P < 0.005)., Conclusions: MET-EGFR-TKIs provided benefits for PFS and OS, and OS subgroup analysis showed that patients with NSCLC with T2DM received greater benefit than NSCLC patients without T2DM. However, further large-scale, well-designed randomized controlled trials (RCTs) are warranted to confirm the findings in the present investigation., (© 2022. The Author(s).)

Patients diagnosed with cancer often experience pain during their treatment course, making it difficult to care for themselves and continue with their activities of daily living. When cancer is found at later stages, the pain can become severe and constant; reducing their quality of life and significantly affecting mental and physical well-being. Despite opioids being known to provide adequate analgesia for higher pain levels, they are often the reason for under-dosing because of their adverse effects and concern for addiction. There are also patients who do not respond well to opioids because of genetic anomalies or personal preference. Therefore, there is a need for novel non-opioid cancer pain treatments. There are many new cancer pain treatments that are emerging. This manuscript discusses cancer pain, risk factors, epidemiology, guidelines for the treatment of cancer pain, personalization of cancer pain therapy, breakthrough pain, cancer-induced peripheral neuropathy, established cancer pain treatment options, and novel emerging cancer pain treatment options., (Published by Elsevier Masson SAS.)

Background: Depression is a common disorder that affects millions globally and is linked to reduced quality of life and mortality. Its pathophysiology is complex and there are several forms of treatment proposed in the literature with differing side effect profiles. Many patients do not respond to treatment which warrants augmentation with other treatments and the investigation of novel treatments. One of these treatments includes testosterone therapy which evidence suggests might improve depressed mood in older patients with low levels of testosterone and helps restore physical impairments caused by age-related hormonal changes., Objective: The objective of this review is to synthesize information regarding clinical depression, its treatment options, and the efficacy and safety of testosterone treatment for the treatment of depression., Methods: This review utilized comprehensive secondary and tertiary data analysis across many academic databases and published work pertaining to the topic of interest., Results: Within some subpopulations such as men with dysthymic disorder, treatment resistant depression, or low testosterone levels, testosterone administration yielded positive results in the treatment of depression. Additionally, rodent models have shown that administering testosterone to gonadectomized male animals reduces symptoms of depression. Conversely, some studies have found no difference in depressive symptoms after treatment with testosterone when compared with placebo. It was also noted that over administration of testosterone is associated with multiple adverse effects and complications., Conclusion: The current evidence provides mixed conclusions on the effectiveness of testosterone therapy for treating depression. More research is needed in adult men to see if declining testosterone levels directly influence the development of depression.

Objective: Spinal Cord Stimulation (SCS) is a vital treatment for chronic intractable pain. In the last few years, the field has undergone dramatic changes in new waveform and frequency introduction as well as device miniaturization. It is important to understand contemporary practice patterns regarding these parameters., Methods: We surveyed the active membership of Spine Intervention Society (SIS), and American Society of Regional Anesthesia (ASRA) on their practices regarding various aspects of Spinal Cord Stimulation therapy. Here we report on SCS waveform usage, battery types, and causes of explant in this cohort of providers., Results: There was similar degree of usage of tonic, burst, and 10 kHz usage at 71.5%, 74.1% and 61.7% respectively. Dorsal root ganglion stimulation was used by 32.6% and other modes of stimulation by 13.5%. Rechargeable systems were often or always used by 67.2% whereas 10% never used a rechargeable system. Most common cause of explant was loss of effectiveness, reported by 53.7%., Conclusion: There has been significant adoption of new waveforms in daily practice of spinal cord stimulation therapy and there is robust mixed usage of new waveforms and frequencies. Rechargeable systems are the most commonly used but primary cell is also used in significant numbers. Loss of efficacy remains the most common cause of explant for the majority of practitioners. This survey establishes practice patterns of SCS usage regarding these important variables against which future changes can be gauged.

The knee is the most common joint in adults associated with morbidity. Many pathologies are associated with knee damage, such as gout or rheumathoid arthritis, but the primary condition is osteoarthritis (OA). Not only can osteoarthritis cause significant pain, but it also can result in signficant disability as well. Treatment for this condition varies, starting off with oral analgesics and physical therapy to surgical total knee replacmenet. In the gamut of this various treatments, a conservative approach has included intra articular steroid injections. With time, researchers and clinicians determined that other components injected to the knee may additionally provide relief of this condition. In this investigation, we describe different types of knee injections such as platelet-rich plasma (PRP), hyaluronic acid, stem cells, and prolotherapy. Additionally, we describe the role of geniculate knee injections, radiofrequency, and periopheral nerve stimulation. These treatments should be considered for patients with knee pain refractory to conservative therapies., Competing Interests: None

Management of mental health illnesses and needs are important in fostering psychosocial support, interprofessional coordination, and greater adherence to treatment protocols in the field of urology. This can be especially true for mental health conditions that may greatly impact the presentation of a patient in the healthcare setting with urologic symptoms. This review describes the history, epidemiology, pathophysiology, clinical presentation, and treatment of somatic symptom disorder, illness anxiety disorder, compulsive sexual behavior/hypersexuality, factitious disorder, malingering symptoms, and conversion disorder in the realm of urology. Given the newly updated psychiatric diagnoses in the Diagnostic and Statistical Manual of Mental Disorders , fifth edition, there has been a lack of studies reviewing how these illnesses may present in a urology patient encounter. Additionally, as these mental health illnesses may carry a rare incidence compared to other well-known mental health illness such as generalized depression or generalized anxiety disorder, we have found that the lack of provisions and recognition of the diseases can prolong the timeline for diagnosis and lead to an increased cost in both healthcare and quality of life of patients with these mental health illnesses. This review provides awareness on these mental health conditions which may greatly impact patient history and presentation within the field of urology. Additionally, urologic care providers may have an improved understanding of interdisciplinary management of such illnesses and the common symptoms patients may present with such diseases.

For decades, chronic pain was managed with an almost conventional approach of using a wide range of analgesic spectrum, surgical approaches and complex interventional pain techniques to modulate or even interrupt pain pathways. These different approaches carry many pharmacological hazards together with the lack of efficacy and safety of many interventional and surgical management techniques for chronic pain have mandated searching for other effective therapies including alternative treatments. Cannabinoids are naturally occurring substances that are derived from Cannabis sativa L. The usage of cannabinoids and their related synthetic chemical compounds has emerged as a choice in the management of different chronic pain conditions is being evaluated, however, the efficacy is still not consistently established. In the present investigation, therefore, we discuss the different aspects related to cannabinoids and their implications in the management of chronic pain conditions. This review will also discuss the safety profile of the cannabinoids together with the legal considerations that hinder their use in different countries.

Purpose of Review: Attention deficit hyperactivity disorder (ADHD) is a widely diagnosed neurodevelopmental disorder giving rise to symptoms of hyperactivity, impulsivity, and inattentiveness that can impair daily functioning. Stimulants, such as methylphenidate and amphetamines, are the mainstay of treatment for ADHD. However, nonstimulant drugs such as viloxazine, atomoxetine, guanfacine, and clonidine are becoming more popular due to minimal adverse effects when compared to stimulants., Recent Findings: Viloxazine is a selective norepinephrine reuptake inhibitor (NRI) originally used to treat depression in adults with activity in both the noradrenergic as well as serotonergic pathways. Studies have demonstrated its efficacy for its use in the treatment of ADHD. Unlike stimulants, viloxazine has a decreased chance of substance abuse, drug dependance, and withdrawal symptoms upon the cessation of therapy. Additionally, dopamine levels in the nucleus accumbens after treatment with viloxazine are elevated considerably less in comparison with traditional stimulant ADHD treatments. Viloxazine provides an alternative, nonstimulant approach to treating ADHD., Summary: Viloxazine is a recently approved, non-stimulant medication functions by inhibiting the uptake of norepinephrine which has been seen to be decreased in patients with ADHD. When patients do not respond to first-line stimulants, cannot tolerate the side effects, or have contraindications to stimulants, viloxazine may be a nonstimulant option offering patients an increasing arsenal of medications to treat ADHD., Competing Interests: There are no conflict of interests with the authors.

Background: Chronic pain is a multifactorial condition that is afflicting populations worldwide causing an increasing economic, physical, mental, and emotional burden. Treatments range from medications to interventional procedures to complementary and alternative medicine (CAM), such as acupuncture. This review aims to discuss the use of acupuncture in the treatment of chronic pain, proposed mechanisms, indications, and efficacy for various chronic pain conditions., Results: Evidence is varied on the efficacy and quality of data on the use of acupuncture in the treatment of chronic pain. Recent studies have demonstrated promising results in the support of acupuncture for the use in the treatment of cancer, neck, and back pain, functional dyspepsia, and various chronic abdominal pain syndromes., Conclusion: Acupuncture, deemed well-tolerated and safe to use, has been increasingly studied and is regarded as effective in clinical practice, but its efficacy is limited by the lack of well-conducted, high-quality clinical trials, lower quality evidence, and conflicting study results. Additionally, the exact analgesic mechanism of acupuncture remains to be fully elucidated. Increasing evidence supports the role of acupuncture as therapy in the treatment of cancer, neck, and back pain and functional dyspepsia. Further rigorous studies are needed to fully assess the use of acupuncture in various chronic pain conditions, determine its indications, and optimal treatment schedule. Overall, future studies could benefit from better designed experimental studies, larger groups, and more objectives ways to measure pain reduction and symptom improvement., Competing Interests: There are no conflict of interests with the authors.