Evolving Concepts of Pain Management in Elderly Patients.

PURPOSE OF REVIEW: The elderly population typically suffer from a variety of diseases that mostly reflect the degenerative changes linked with the aging process. These diseases may be exacerbated by acute pain or by an abrupt aggravation of previously stable chronic pain. RECENT FINDINGS: Physical and psychological changes associated with aging may influence one's experience of pain and, as a result, the severity of pain. Pain treatment in the elderly can be complex and is often a budgetary burden on the nation's health care system. These difficulties arise, in part, because of unanticipated pharmacodynamics, changed pharmacokinetics, and polypharmacy interactions. Therefore, it is critical to integrate a multidisciplinary team to develop a management strategy that incorporates medical, psychological, and surgical methods to control persistent pain conditions. It is in this critical process that pain prediction models can be of great use. The purpose of pain prediction models for the elderly is the use of mathematical models to predict the occurrence and intensity of pain and pain-related conditions. These mathematical models employ a vast quantity of data to ascertain the many risk factors for the development of pain problems in the elderly, whether said risks are adjustable or not. These models will pave the way for more informed medical decision making that are based on the findings of thousands of patients who have previously experienced the same illness and related pain conditions. However, future additional research needs to be undertaken to build prediction models that are not constrained by substantial legal or methodological limitations.

Tumor Necrosis Factor and Interleukin Modulators for Pathologic Pain States: A Narrative Review.

Chronic pain, a complex and debilitating condition, involves intricate interactions between central and peripheral inflammatory processes. Cytokines, specifically tumor necrosis factor (TNF) and interleukins (IL), are key mediators in the initiation and maintenance of chronic pain states. Sensory neurons expressing receptors for cytokines like TNF, IL-1, and IL-6 are implicated in peripheral sensitization, contributing to increased signaling of painful sensations. The potential of targeting TNF and IL for therapeutic intervention in chronic pain states is the focus of this review, with preclinical and clinical evidence supporting the use of TNF and IL modulators for pain management. The physiological and pathological roles of TNF in neuropathic pain is complex. Experimental evidence highlights the effectiveness of TNF modulation in mitigating pain symptoms in animal models and displays promising outcomes of clinical trials with TNF inhibitors, such as infliximab and etanercept. ILs, a diverse group of cytokines, including IL-1, IL-6, and IL-17, are discussed for their contributions to chronic pain through inflammation and peripheral sensitization. Specific IL modulators, such as secukinumab and tocilizumab, have shown potential in managing chronic neuropathic pain, as demonstrated in various studies and clinical trials. The pharmacokinetics, safety profiles, and challenges associated with TNF and IL modulators highlight the need for cautious medication monitoring in clinical practice. Comparative evaluations have revealed distinct efficacy and safety profiles among different cytokine modulators, emphasizing the need for personalized approaches based on the specific underlying causes of pain. Further research is necessary to elucidate the intricate mechanisms by which cytokines contribute to chronic pain, as well as to understand why they may affect pain differently in various contexts. Additionally, long-term safety profiles of cytokine modulators require more thorough investigation. This continued exploration holds the promise of enhancing our comprehension of cytokine modulation in chronic pain and shaping more potent therapeutic strategies for the future.

Neuropsychiatric Effects Associated with Opioid-Based Management for Palliative Care Patients.

PURPOSE OF REVIEW: The abundance of opioids administered in the palliative care setting that was once considered a standard of care is at present necessitating that providers evaluate patients for unintentional and deleterious symptomology related to aberrant opioid use and addiction. Polypharmacy with opioids is dynamic in affecting patients neurologically, and increased amounts of prescriptions have had inimical effects, not only for the individual, but also for their families and healthcare providers. The purpose of this review is to widen the perspective of opioid consequences and bring awareness to the numerous neuropsychiatric effects associated with the most commonly prescribed opioids for patients receiving palliative care. RECENT FINDINGS: Numerous clinical and research studies have found evidence in support for increased incidence of opioid usage and abuse as well as undesirable neurological outcomes. The most common and concerning effects of opioid usage in this setting are delirium and problematic drug-related behavioral changes such as deceitful behavior towards family and physicians, anger outbursts, overtaking of medications, and early prescription refill requests. Other neuropsychiatric effects detailed by recent studies include drug-seeking behavior, tolerance, dependence, addictive disorder, anxiety, substance use disorder, emotional distress, continuation of opioids to avoid opioid withdrawal syndrome, depression, and suicidal ideation. Opioid usage has detrimental and confounding effects that have been overlooked for many years by palliative care providers and patients receiving palliative care. It is necessary, even lifesaving, to be cognizant of potential neuropsychiatric effects that opioids can have on an individual, especially for those under palliative care. By having an increased understanding and awareness of potential opioid neuropsychiatric effects, patient quality of life can be improved, healthcare system costs can be decreased, and patient outcomes can be met and exceeded.

Advancing Treatment in Atopic Dermatitis: A Comprehensive Review of Clinical Efficacy, Safety, and Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, and Phosphodiesterase-4 Inhibitors as Topical Therapies.

Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. The present investigation features the emergence of crisaborole, a phosphodiesterase four inhibitor. Its innovative mode of action, benign safety profile, and applicability to mild and moderate AD are thoroughly evaluated. The review also includes challenges, particularly cost considerations, which constrain accessibility and necessitate nuanced implementation in therapeutic regimens. This study underscores the need for persistent investigation, teamwork, and innovations in managing AD. In this regard, AD requires a united approach between clinicians, researchers, affected individuals, and policymakers to refine patient-focused treatment and develop precise, economical strategies to address this chronic and frequently life-altering health condition.

The Significance of Equipment Availability and Anesthesia Educational Conferences to Decision-Making for EKG Lead V5 Abnormalities.

Introduction To predict postoperative myocardial infarction rates in patients who undergo noncardiac surgery, the Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management recommends assessment of brain natriuretic peptide (BNP) in certain patients. Serial troponins are measured if the BNP level is elevated. In certain cases, Revised Cardiac Risk Index (RCRI) alone does not perform well, for example, during vascular surgery. Cardiac events occur in 20% of all vascular surgery patients. The odds ratio for such events is 9.2 if ST segments were depressed by 1 mm intraoperatively (relative to the PR interval) within the first 48 hours postoperatively. Increasing the number of cables and pads from three to five for electrocardiogram (EKG) increases the sensitivity from around 30% to over 80% for ischemic events relative to a formal EKG stress test, and then the monitor continuously displays not only lead II but also lead V5. Methods Our hypothesis was that raising awareness about diagnostic and therapeutic options to reduce the risk of postoperative myocardial infarction would increase the use of five pads. We conducted open-ended surveys at six hospitals to assess the reasons for choosing three pads. In our university hospital practice, we measured a cross-sectional incidence of using three pads before and, once again, a month after an intervention during a single morning. Several resident conferences encouraged the use of five pads. Education included weekly lectures and informal discussions with other staff during surgery, demonstrating that using five pads allows interrogation of an entire 12-lead EKG. In comparison, three pads only allow viewing three leads. Results At baseline, only three pads were available in 96% of our 23 operating rooms. Five cables were available in eight of those surgeries, but two were taped off to the side. Surveys unveiled scarcity of equipment and, more importantly, disempowerment (i.e., knowing how to diagnose or when to treat ischemia). After several conferences, the prevalence of equipment availability of only three pads fell to 47%. Conclusions Education enumerated details of recognizing ischemic configurations of ST depression. Next, education revealed methods to interrupt the progression of ischemia to infarction such as elevated blood pressure and hematocrit, reducing heart rate, and calling a cardiology consultant if the anesthesiologist wishes to draw serial troponins. Barriers to implementing an enhanced recovery after surgery (ERAS) pathway began with a need for more access to manage stress tests or optimize blood pressure medications after a preoperative anesthesia evaluation. The intraoperative barrier was knowing what to do if ST depression occurs. Therefore, we began raising awareness by encouraging the addition of an element of a future ERAS pathway, adding a cost of only $1 to monitor lead V5. Future ERAS pathways can include preoperative stress tests and consults, as found in published guidelines.

Nonhormonal Pharmacotherapies for the Treatment of Postmenopausal Vasomotor Symptoms.

An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset. However, despite increasing prevalence, these hot flashes remain hard to treat and have a negative effect on the quality of life. Though hormone replacement therapy is commonly utilized as a standard treatment for VMSs, this therapy is not recommended for all women. Specifically, the oral form of hormone replacement therapy is associated with several contraindications, including a history of thromboembolic disease, migraine headache with aura, liver failure, heart disease, and hormone-dependent cancers. For women with these medical conditions, current literature indicates that nonhormonal therapies such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are suitable alternatives to reduce the frequency and intensity of VMSs. Currently, the only SSRI that is FDA-approved for the treatment of VMSs is paroxetine, but studies show that fluoxetine, citalopram, escitalopram, and sertraline are also proven to provide similar benefits. Similarly, the SNRI venlafaxine has also been well tolerated and has been shown to reduce the frequency and severity of hot flashes. The present investigation reviews the physiology of VMSs and examines the evidence for the use of nonhormonal pharmacologic therapies as treatment for women experiencing hot flashes. These interventions should be considered whenever hormone replacement therapy is contraindicated, with therapy individualized based on the severity of symptoms.

Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.

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.

Anesthesia Liability Related to Pre-existing Conditions.

In 1985, the American Society of Anesthesiologists initiated a quality improvement closed claims analysis project for anesthetic injury to elevate patient safety. To date, there have been a total of 8954 documented claims, describing injuries contracted under sedation, regional anesthesia, or failure to attend to a patient's post-operative needs. The Closed Claims database reveals that the most highly documented health care complications were a loss of life at 2%, nerve injuries at 2%, and damage to the brain at 9%. The highest documented cases of damage from anesthesia involved regional-block-related events at 20%, followed by respiratory-related adverse effects at 17%, cardiovascular-related events at 13%, together with apparatus-linked events at 10%. Injury may result from several causes. First, multiple techniques and interventions are used during surgery, and all have potential adverse effects. Additionally, many patients scheduled for surgery have extensive past medical histories and medical comorbidities, thereby increasing their baseline risk for injury. From the Closed Claims database, improved evaluation of clinical-related implications linked to injuries within the handling of airway, sedation, non-operational room locales, obstetric anesthesia, along with chronic pain management. In summary, anesthesia departments should review outcomes of their patients on a routine basis. Assessing factors when an adverse outcome occurs may allow for changes in techniques or other anesthesia considerations to help lessen or prevent future complications.

Marijuana Use, Vaping, and Preoperative Anesthetic and Surgical Considerations in Clinical Practice.

In recent years, marijuana and vaping have acquired widespread popularity, with millions of people using them for a variety of reasons, including recreational purposes. However, these practices have often overlooked the implications on surgery and the preoperative anesthesia considerations. Marijuana can influence a patient's response to anesthesia, alter postoperative pain management, and increase the risk of complications, whereas vaping can have negative effects on the respiratory system and hinder the body's ability to recover after surgery.

Testosterone replacement therapy: clinical considerations.

INTRODUCTION: As an increasingly popular therapeutic option, testosterone replacement therapy (TRT) has gained significant notoriety for its health benefits in indicated populations, such as those suffering from hypogonadism. AREAS COVERED: Benefits such as improved libido, muscle mass, cognition, and quality of life have led to widened public interest in testosterone as a health supplement. No therapy exists without side effects; testosterone replacement therapy has been associated with side effects such as an increased risk of polycythemia, benign prostate hypertrophy (BPH), prostate cancer, gynecomastia, testicular atrophy, and infertility. Testosterone replacement therapy is often accompanied by several prophylactic co-therapies aimed at reducing the prevalence of these side effects. Literature searches for sections on the clinical benefits and risks associated with TRT were performed to include clinical trials, meta-analyses, and systematic reviews from the last 10 years. EXPERT OPINION: Data from clinical studies over the last decade suggest that the benefits of this therapy outweigh the risks and result in overall increased quality of life and remission of symptoms related to hypogonadism. With this in mind, the authors of this review suggest that carefully designed clinical trials are warranted for the investigation of TRT in symptomatic age-related hypogonadism.

Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

Exploring Orthopedic Stem-Cell Approaches for Osteoarthritis Management: Current Trends and Future Horizons.

PURPOSE OF REVIEW: Osteoarthritis (OA) is a prevalent and debilitating condition characterized by joint degeneration and pain. Current treatment options aim to alleviate symptoms and slow disease progression but lack curative potential. Stem cell therapies have emerged as a promising alternative. This article explores the epidemiology, pathophysiology, clinical manifestations of hip and knee OA, and the evolving role of stem cell therapies in their treatment. RECENT FINDINGS: The global prevalence of OA, with knee OA being the most common form, has fueled the demand for stem cell therapies. Despite limited robust evidence supporting their efficacy, clinical trials investigating stem-cell treatments for OA have reported encouraging radiological and clinical improvements. Stem cell therapies offer potential disease-modifying benefits through immunomodulatory actions, growth factor secretion, and chondrogenic capabilities. Adipose-derived mesenchymal stem cells (ADMSCs) have shown promise in clinical trials for OA treatment, offering potential pain relief and functional improvement. ADMSCs possess advantages such as accessibility and a favorable safety profile, making them a viable option for OA management. Although other stem-cell types, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have been used in OA treatment, ADMSCs have demonstrated superior outcomes. By providing a comprehensive overview of the evolving landscape of stem cell therapies for hip and knee OA, this article highlights the potential of stem-cell treatments to address the limitations of current therapies. However, further research is required to establish their long-term efficacy, identify optimal stem-cell types, and develop standardized protocols.

Effectiveness of Virtual Reality-Based Rehabilitation Interventions in Improving Postoperative Outcomes for Orthopedic Surgery Patients.

PURPOSE OF REVIEW: The surge in orthopedic surgeries strains the US healthcare system, necessitating innovative rehabilitation solutions. This review examines the potential of virtual reality (VR)-based interventions for orthopedic rehabilitation. RECENT FINDINGS: The effectiveness of VR-based interventions in orthopedic surgery patients is scrutinized. While some studies suggest better patient-reported outcomes and satisfaction, mixed results emerge from others, demonstrating comparable or varied results compared to traditional rehabilitation. The underlying mechanisms of VR-based rehabilitation are elucidated, showing its positive impact on proprioception, pain management, agency, and balance. Challenges of unfamiliarity, patient engagement, and drop-out rates are identified, emphasizing the need for tailored approaches. VR technology's immersive environments and multisensory experiences offer a novel approach to addressing functional deficits and pain post-surgery. The conclusion drawn is that VR-based rehabilitation complements rather than replaces conventional methods, potentially aiding in pain reduction and functional improvement. VR-based rehabilitation holds promise for enhancing orthopedic surgery outcomes, presenting a dynamic approach to recovery. Its potential to reshape healthcare delivery and reimbursement structures underscores its significance in modern healthcare. Overall, VR-based rehabilitation offers a promising avenue for optimizing postoperative recovery in orthopedic surgery patients.

Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

Topical Medications for Atopic Dermatitis and Effects on Increasing Lymphoma Risks.

Atopic dermatitis is an immune-mediated skin condition that causes relapsing, pruritic skin lesions. Flares of this disease are often treated with topical corticosteroids; however, the use of these drugs can cause unwanted side effects, such as cutaneous atrophy and impaired wound healing. To minimize these common side effects, severe forms of this disease have been treated with topical calcineurin inhibitors, which previously had no known long-term side effects. Recently, there has been debate on the immunosuppressive effects of these drugs and whether chronic use could result in non-melanoma skin cancer. Systemic absorption of topical calcineurin inhibitors is extremely limited compared to oral formulation, although it is directly proportional to the total body surface area applied with medication. Patients with atopic dermatitis can have an increased risk of lymphoma, so it is hard to distinguish the causative factor, e.g., severe atopic dermatitis or being treated with calcineurin inhibitors. While inconclusive, the Food and Drug Administration recently issued a black box warning, and currently, topical calcineurin inhibitors are considered a second-line treatment. The present investigation reviews the findings of multiple studies conducted to determine if there is a link between the usage of topical calcineurin inhibitors and lymphoma.

Mechanisms and Treatment Options for Hyperthyroid-Induced Osteoporosis: A Narrative Review.

Normal thyroid hormone levels are crucial for the homeostasis of many metabolic cycles and processes throughout the human body. Thyroid dysfunction, such as thyrotoxicosis, can result from many different etiologies, including Graves' disease (GD), toxic multinodular goiter (MNG), and toxic adenoma. These hyperthyroid disease states can cause devastating complications and disease, including the disruption of the bone remodeling cycle and skeletal development, which can result in osteoporosis. Osteoporosis is characterized by a decrease in bone mineral density and a propensity for fragility fractures. In addition to patients with overt hyperthyroidism, studies have provided evidence of other high-risk patient demographics, such as individuals with subclinical hyperthyroidism and postmenopausal women, who may be at an increased risk for the development of secondary osteoporosis. The treatment of patients with hyperthyroid-induced osteoporosis often requires a multifaceted management plan that may be unique to each patient's situation. Antithyroid therapy is often the first step in treating this disease and may include thioamide medications. Radioactive iodine-131 therapy (RAI) and the surgical removal of the thyroid gland may also be reasonable approaches for restoring normal thyroid function. Following thyrotoxicosis mitigation, antiresorptive drugs such as bisphosphonates, calcitonin, and selective estrogen receptor modulators (SERMs) may be used to counteract decreased bone mineral density (BMD). Additionally, the implementation of vitamin D, calcium supplements, and weight-bearing exercise may also reduce bone loss. While the effects of thyroid stimulating hormone (TSH) and triiodothyronine (T3) on bone remodeling have been studied in the past, more research is needed to identify unknown mechanisms and develop future improved treatments for this condition.

Infigratinib for the Treatment of Metastatic or Locally Advanced Cholangiocarcinoma With Known FGFR2 Gene Fusions or Rearrangements.

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.

Overview of Median Arcuate Ligament Syndrome: A Narrative Review.

Median arcuate ligament syndrome (MALS) is a rare disorder caused primarily by compression of the celiac trunk by the median arcuate ligament (MAL). This disorder typically results in patients presenting with bloating, weight loss, nausea, vomiting, and abdominal pain. The MALS diagnosis is one of exclusion, as the disorder has no specific diagnostic criteria. Imaging modalities are often utilized to assist in making the diagnosis, such as ultrasound, computed tomography angiography (CTA), and magnetic resonance angiography (MRA). These imaging modalities typically reveal a stenosed celiac artery with post-stenotic dilation in patients. This disorder is usually treated by dividing the MAL, thus relieving the compression of the celiac artery. The surgery may be done through either an open approach or a minimally invasive approach, which can be either laparoscopic or robot-assisted. Most patients respond well to this treatment, though certain factors that predict a poorer response to treatment include elderly age, a history of alcohol abuse, and psychiatric illness.

The Effects of Opioid Dependency Use on Postoperative Spinal Surgery Outcomes: A Review of the Available Literature.

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.

Teprotumumab-trbw as a Novel Monoclonal Antibody for Thyroid Eye Disease: A Literature Review.

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.