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Context: Chronic neuropathic pain is a common condition, and up to 11.9% of the population have been reported to suffer from uncontrolled neuropathic pain. Chronic pain leads to significant morbidity, lowered quality of life, and loss of workdays, and thus carries a significant price tag in healthcare costs and lost productivity. dorsal root ganglia (DRG) stimulation has been recently increasingly reported and shows promising results in the alleviation of chronic pain. This paper reviews the background of DRG stimulation, anatomical, and clinical consideration and reviews the clinical evidence to support its use., Evidence Acquisition: The DRG span the length of the spinal cord and house the neurons responsible for sensation from the periphery. They may become irritated by direct compression or local inflammation. Glial cells in the DRG respond to nerve injury, producing inflammatory markers and contribute to the development of chronic pain, even after the resolution of the original insult. While the underlying mechanism is still being explored, recent studies explored the efficacy of DRG stimulation and neuromodulation for chronic pain treatment., Results: Several reported cases and a small number of randomized trials were published in recent years, describing different methods of DRG stimulation and neuromodulation with promising results. Though evidence quality is mostly low, these results provide evidence to support the utilization of this technique., Conclusions: Chronic neuropathic pain is a common condition and carries significant morbidity and impact on the quality of life. Recent evidence supports the use of DRG neuromodulation as an effective technique to control chronic pain. Though studies are still emerging, the evidence appears to support this technique. Further studies, including large randomized trials evaluating DRG modulation versus other interventional and non-interventional techniques, are needed to further elucidate the efficacy of this method. These studies are also likely to inform the patient selection and the course of treatment., Competing Interests: Conflict of Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021, Author(s).)

Purpose The diagnosis of prostate transition zone cancer (PTZC) remains a clinical challenge due to their similarity to benign prostatic hyperplasia (BPH) on MRI. The Deep Convolutional Neural Networks (DCNNs) showed high efficacy in diagnosing PTZC on medical imaging but was limited by the small data size. A transfer learning (TL) method was combined with deep learning to overcome this challenge. Materials and methods A retrospective investigation was conducted on 217 patients enrolled from our hospital database (208 patients) and The Cancer Imaging Archive (nine patients). Using T2-weighted images (T2WIs) and apparent diffusion coefficient (ADC) maps, DCNN models were trained and compared between different TL databases (ImageNet vs. disease-related images) and protocols (from scratch, fine-tuning, or transductive transferring). Results PTZC and BPH can be classified through traditional DCNN. The efficacy of TL from natural images was limited but improved by transferring knowledge from the disease-related images. Furthermore, transductive TL from disease-related images had comparable efficacy to the fine-tuning method. Limitations include retrospective design and a relatively small sample size. Conclusion Deep TL from disease-related images is a powerful tool for an automated PTZC diagnostic system. In developing regions where only conventional MR scans are available, the accurate diagnosis of PTZC can be achieved via transductive deep TL from disease-related images., Competing Interests: This paper was sponsored by the National Key Research and Development Program of China (No. 2016YFC0107105 to Dr. Cui GB), the Innovation Foundation of Tangdu Hospital (No. 2016LCYJ001 to Dr. Cui GB) and Young Talent Grant of the University (to Dr. Wen Wang)., (Copyright © 2021, Hu et al.)

Context: Abdominal pain is a widespread complaint and is one of the common reasons leading patients to seek medical care, either in emergency situations or with their primary providers. While acute abdominal pain is a better defined, usually surgical condition, chronic abdominal pain requires longer, typically lifelong, therapy. Chronic abdominal pain may also present with acute flares and complications. Here we review seminal and novel evidence discussing the use of acupuncture in the treatment of abdominal pain, indications, and conditions that may benefit from this approach., Evidence Acquisition: Chronic abdominal pain is a common complaint causing significant morbidity and disability and has a hefty price tag attached. Recent studies show it may be prevalent in as much as 25% of the adult population. It is defined as three episodes of severe abdominal pain over the course of three months. Chronic abdominal pain could be the result of chronicity of acute pain or of chronic pain syndromes, most commonly IBD syndromes and IBS. While a plethora of treatments exists for both conditions, these treatments usually fall short of complete symptom control, and there is a need for complementary measures to curb disability and increase the quality of life in these patients. Acupuncture is a form of integrative medicine that has long been used in Chinese and traditional medicine, based on the rebalancing of the patient's Qi, or Ying/Yang balance. It has been shown to be effective in treating several other conditions, and novel evidence may expand its use into other fields as well. Clinical trials studying acupuncture in chronic pain conditions have been promising, and recent evidence supports the use of abdominal pain in chronic abdominal pain conditions as well. Though not curative, acupuncture is a complementary approach that helps reduce symptoms and improved quality of life., Conclusions: Chronic abdominal pain is a widespread condition, mostly affected by the IBS and IBD spectrum. Etiologies are still being studied for these conditions, and while novel treatment approaches are absolute game changers for these patients, many continue to experience some level of symptoms and disability. Acupuncture may provide further alleviation of these symptoms in select patients, thus improving quality of life, reducing disability, and saving healthcare dollars. It is a largely safe and inexpensive method that may significantly contribute to the quality of life of selected patients., Competing Interests: Conflict of Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021, Author(s).)

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient's emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics., (Copyright © 1964–2021 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine., (Copyright © 1964–2021 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Infertility has many etiologies and can have devastating consequences for young couples attempting to bring children into the world. Uterine factor for infertility is related to either uterine agenesis (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome), unexpected hysterectomy, or presence of a nonfunctioning uterus. In this review, a patient with MRKH syndrome underwent donor uterus transplantation at the Cleveland Clinic, conceived, and delivered the first healthy baby in the United States and the second worldwide. Additionally, we review the pertinent literature on anesthesia problems. Donor-related uterine transplant is a recent medical innovation requiring multidisciplinary expertise. In patients who deliver successfully, according to the current literature, the transplanted uterus can be used for one more pregnancy only if the mother so desires, otherwise cesarean hysterectomy (C-Hyst) should be performed. In the observed case, C-Hyst was performed because the patient developed placenta accreta and the couple desired no further pregnancy. In summary, with our limited data, careful management of these patients is required to ensure the best outcome for the mother and the newborn fetus., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Shehata et al.)

ZULRESSO (Brexanolone) is a novel FDA-approved treatment for moderate-to-severe postpartum depression. Postpartum depression may be diagnosed in women experiencing depressive symptoms which can manifest as cognitive, behavioral, or emotional disturbances as early as the third trimester to 4 weeks following delivery. The efficacy of brexanolone suggests that neurosteroids such as allopregnanolone are important to treat PPD. However, it is currently unclear if brexanolone provides lasting relief of depressive symptoms at or beyond 30 days following administration. Further studies are necessary to make this determination., (Copyright © 1964–2019 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Infertility, the inability to establish a clinical pregnancy after 12 months of regular unprotected sexual intercourse, is caused by a wide variety of both male and female factors. Infertility is estimated to affect between 8-12% of couples trying to conceive globally. Female factor infertility can be subdivided into the following broad categories: ovulatory dysfunction, fallopian tubal disease, uterine causes, and oocyte quality. Hyperprolactinemia causes ovulary dysfunction along with other hormonal abnormalities, such as decreased estrogen, which can lead to infertility. In this regard, antipsychotics are commonly used for both schizophrenia and bipolar disorder. The use of these medications can be associated with hyperprolactinemia and hyperprolactinemia associated infertility. Antipsychotic-induced hyperprolactinemia occurs through blockade of D 2 receptors on lactotroph cells of the anterior pituitary gland. Discontinuation of the hyperprolactinemia-inducing antipsychotic is an option, but this may worsen the patient's psychosis or mood. If antipsychotics are determined to be the culprit of infertility, the degree of hyperprolactinemia symptoms, length of treatment with the antipsychotic, and risk of relapse should be assessed prior to discontinuation, reduction, or switching of antipsychotic medications. The treatment of a women's mental health and her desire to have children should always be considered as treatment may influence fertility while on the medication., (Copyright © 1964–2021 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Pain is highly prevalent and pharmacological therapy is not always efficacious. There are a few pathophysiological reasons to believe that neuromodulation would increase the rate of success of pain management. This review article is focused on that aspect, discussing non-invasive or minimally invasive neuromodulation techniques in both the inpatient and outpatient setting. This article provides an in-depth discussion of the multiple neuromodulation techniques available over time to be suitable and effective when used as analgesic therapies for chronic pain. We reviewed the literature and discussed all available neuromodulation options that were tested in the inpatient and outpatient setting. Neuromodulation plays a very important role in treating chronic pain in both inpatient and outpatient setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Abd-Elsayed et al.)

Purpose of Review: This review aims to provide relevant, aggregate information about a variety of disinfectants and antiseptics, along with potential utility and limitations. While not exhaustive, this review's goal is to add to the body of literature available on this topic and give interventional providers and practitioners an additional resource to consider when performing procedures., Recent Findings: In the current SARS-CoV2 epidemiological environment, infection control and costs associated with healthcare-associated infections (HAIs) are of paramount importance. Even before the onset of SARS-CoV2, HAIs affected nearly 2million patients a year in the USA and resulted in nearly 90,000 deaths, all of which resulted in a cost to hospitals ranging from US$28 billion to 45 billion. The onset SARS-CoV2, though not spread by an airborne route, has heightened infection control protocols in hospitals and, as such, cast a renewed focus on disinfectants and their utility across different settings and organisms. The aim of this review is to provide a comprehensive overview of disinfectants used in the inpatient setting.

Thoracic outlet syndrome comprises a group of disorders that result in compression of the brachial plexus and subclavian vessels exiting the thoracic outlet. Symptoms include pain, paresthesia, pallor, and weakness depending upon the compromised structures. While consensus in diagnostic criteria has not yet been established, a thorough patient history, physical exam, and appropriate imaging studies are helpful in diagnosis. General first-line therapy for thoracic outlet syndrome is a conservative treatment, and may include physical therapy, lifestyle modifications, NSAIDs, and injection therapy of botulinum toxin A or steroids. Patients who have failed conservative therapy are considered for surgical decompression. This article aims to review the epidemiology, etiology, relevant anatomy, clinical presentations, diagnosis, and management of thoracic outlet syndrome.

Musculoskeletal pain (excluding bone cancer pain) affects more than 30% of the global population and imposes an enormous burden on patients, families, and caregivers related to functional limitation, emotional distress, effects on mood, loss of independence, and reduced quality of life. The pathogenic mechanisms of musculoskeletal pain relate to the differential sensory innervation of bones, joints, and muscles as opposed to skin and involve a number of peripheral and central nervous system cells and mediators. The interplay of neurons and non-neural cells (e.g. glial, mesenchymal, and immune cells) amplifies and sensitizes pain signals in a manner that leads to cortical remodeling. Moreover, sex, age, mood, and social factors, together with beliefs, thoughts, and pain behaviors influence the way in which musculoskeletal pain manifests and is understood and assessed. The aim of this narrative review is to summarize the different pathogenic mechanisms underlying musculoskeletal pain and how these mechanisms interact to promote the transition from acute to chronic pain., Competing Interests: Conflict of interest statement: Giustino Varrassi is a member of the journal’s editorial board. The other authors do not have potential conflict of interest to declare., (© The Author(s), 2021.)

Purpose of Review: This is a comprehensive review of the superior hypogastric block for the management of chronic pelvic pain. It reviews the background, including etiology, epidemiology, and current treatment available for chronic pelvic pain. It then presents the superior hypogastric block and reviews the seminal and most recent evidence about its use in chronic pelvic pain., Recent Findings: Several definitions exist for chronic pelvic pain (CPP), making the diagnosis more challenging for the clinician; however, they commonly describe continuous pain lasting 6 months in the pelvis, with an overwhelming majority of patients being reproductive-aged women. This pain is often one of mechanical, inflammatory, or neuropathic. It is generally underdiagnosed and affects anywhere between 5 and 26% of women. The diagnosis of chronic pelvic pain is clinical, consisting of mainly of a thorough history and physical and ruling out other causes. The pathophysiology is often endometriosis (70%) and also includes PID, adhesions, adenomyosis, uterine fibroids, chronic processes of the GI and urinary tracts, as well as pelvic-intrinsic musculoskeletal causes. Treatment includes physical therapy, cognitive behavioral therapy, and oral and parenteral opioids. Interventional techniques provide an added tier of treatment and may help to reduce the requirement for chronic opioid use. Superior hypogastric plexus block is one of the available interventional techniques; first described in 1990, it has been shown to provide long-lasting relief in 50-70% of patients who underwent the procedure. Two approaches described so far, both under fluoroscopy, have seen similar results. More recently, ultrasound and CT-guided procedures have also been described with similar success. The injectate includes local anesthetic, steroids, and neurolytic agents such as phenol or ethanol. CPP is a common debilitating condition. It is diagnosed clinically and is underdiagnosed globally. Current treatments can be helpful at times but may fall short of satisfactory pain relief. Interventional techniques provide an added layer of treatment as well as reduce the requirement for opioids. Superior hypogastric plexus block provides long-lasting relief in many patients, regardless of approach. Evidence level is limited, and further RCTs could help provide better tools for evaluation and patient selection.

In the US, an estimated 1 - 2% of chronic venous insufficiency (CVI) patients (of 6 - 7 million nationwide) develop at least one venous stasis ulcer (VSU) during their illness. Of these, approximately 40% develop subsequent ulcers, making VSU prognostically poor. Current management of VSU is costly, with poor prognosis, high recurrence rate, inadequate pain management, and significantly reduced quality of life (QoL). Topical volatile anesthetic agents, such as sevoflurane, offer improved pain relief and symptom control in patients suffering from chronic VSU. The immediate impact of topical sevoflurane in reducing pain associated with ulcer bed debridement has several implications in improving the quality of life in patients with CVI induced ulcers and in the prognosis and healing of the ulcers. This review summarizes a topical formulation of a volatile anesthetic and its implications for the management of VSUs., Competing Interests: Conflict of Interests: The authors report no conflicts of interest., (Copyright © 2021, Author(s).)

Patient safety advocacy involves avoiding, preventing, and amelioration of adverse outcomes or injuries caused by the process of healthcare rather than a patient's underlying medical illness. Intraoperative hypotension (IOH), a common morbid event, reduces perfusion to critical organs and tissues and has a wide incidence, depending on how it is defined. IOH has adverse intraoperative and postoperative consequences, which make its prevention important to improve patient outcomes. Certain populations have even greater consequences related to IOH, and clinicians must understand these risks. In this narrative review, we examine the risk of intraoperative hypotension in the oncological patient population., Competing Interests: Conflict of Interests: The authors report no conflicts of interest., (Copyright © 2021, Author(s).)

Background: Chronic back and neck pain affects 20% of Americans. Spinal cord stimulation (SCS) is an effective therapy for otherwise refractory chronic pain. Traditional SCS relies on low-frequency stimulus in the 40 - 60 Hz range causing robust paresthesia in regions overlapping with painful dermatomes., Objectives: This study aims to determine the effect of superimposing sub-perception stimulation in patients who previously had good long-term relief with paresthesia., Methods: This is a prospective observational trial examining patients who had previously been implanted with paresthesia based SCS for failed back surgery syndrome (FBSS) or complex regional pain syndrome (CRPS). These patients presented for implantable pulse generator (IPG) replacement based on battery depletion with an IPG capable of combined sub-perception and paresthesia based SCS therapy. Patients were assessed immediately following the exchange and four weeks later using a telephone survey. Their pain was assessed on each follow up using a Numerical Rating scale (NRS); the primary outcome was the change in NRS after four weeks from the exchange day. Secondary outcomes included paresthesia changes, which included the subjective quality of sensation generated, the overall subjective coverage of the painful region, subjective variation of coverage with positional changes, and global perception of the percentage improvement in pain., Results: Based on our clinic registry, 30 patients were eligible for IPG exchange, 16 were consented for follow up and underwent an exchange, and 15 were available for follow up four weeks following. The average NRS decreased from 7.47 with traditional SCS to 4.5 with combination therapy. 80% of patients reported an improvement in the quality of paresthesia over traditional SCS therapy, and in most patients, this translated to significantly improved pain control., Conclusions: Our findings suggest improved pain relief in patients who had previously had good results with paresthesia based therapy and subsequently underwent IPG exchange to a device capable of delivering combined sub-perception stimulation. The mechanism of action is unclear though there may be an additive and/or synergistic effect of the two waveforms delivered. Larger studies with long-term follow-up are needed to elucidate the durability of pain relief and the precise mechanism by which combined subperception and paresthesia based SCS may improve overall patient outcomes., Competing Interests: Conflict of Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021, Author(s).)

Valtoco ® is a new FDA-approved nasal spray version of diazepam indicated for the treatment of acute, intermittent, and stereotypic episodes of frequent seizure activity in epilepsy patients six years of age and older. Although IV and rectal diazepam are already used to treat seizure clusters, Valtoco ® has less variability in plasma concentration compared to rectal diazepam. Furthermore, the intranasal administration of Valtoco ® is more convenient and less invasive than rectal or IV diazepam, making it ideal for self-administration outside of a hospital setting. Multiple clinical trials have taken place comparing Valtoco ® to the oral, rectal, and IV forms of diazepam. Aside from mild nasal irritation and lacrimation, Valtoco ® was found to have no increased safety risk in comparison to traditional forms of diazepam. This review of Valtoco ® will include a history of diazepam prescribing and withdrawal treatment, Valtoco ® drug information, its mechanism of action, pharmacokinetics and pharmacodynamics, and a comprehensive review of clinical studies.

Context: Pelvic pain is described as pain originating from the visceral or somatic system localizing to the pelvis, the anterior abdominal wall at the level of or below the umbilicus, lumbosacral back in either men or women., Evidence Acquisition: Narrative review., Results: Chronic pelvic pain can be a complex disorder that may involve multiple systems such as urogynecological, gastrointestinal, neuromusculoskeletal, and psychosocial systems. The etiopathogenesis for chronic pain remains unknown for many patients. For achieving optimal patient management, a multimodal and individualized assessment of each patient is the best strategy., Conclusions: There are non-pharmacologic treatments as well as pharmacologic treatments. In addition to these treatment options, inferior hypogastric plexus block is a promising treatment modality., Competing Interests: Conflict of Interests: None., (Copyright © 2021, Author(s).)

Context: The anatomy of the radial nerve is prone to entrapment, each with different symptomology. Compression of entrapment of the radial nerve can occur near the radiocapitellar joint, the spiral groove, the arcade of Frohse, the tendon of the extensor carpi radialis brevis (ECRB), and at the radial tunnel. Those who require repetitive motions are at increased risk of peripheral neuropathy syndromes, including repetitive pronation and supination, trauma, or systemic disease; however, t the influence of all risk factors is not well understood. Depending on the location of entrapment, radial nerve entrapment syndrome presents different symptoms. It may include both a motor component and a sensory component. The motor component includes a dropped arm, and the sensory component can include pain and paresthesia in the distribution of the radial nerve that resolves with rest and exacerbates by repetitive pronation and supination., Evidence Acquisition: Diagnostic evaluation for radial nerve entrapment, apart from clinical symptoms and physical exam, includes electromyography, nerve conduction studies, ultrasonography, and magnetic resonance imaging. Conservative management for radial nerve entrapment includes oral anti-inflammatory medications, activity modification, and splinting. Some recently performed studies mentioned promising minimally invasive techniques, including corticosteroid injections, peripheral nerve stimulation, and pulsed radiofrequency., Results: When minimally invasive techniques fail, open or endoscopic surgery can be performed to release the nerve., Conclusions: Endoscopic surgery has the benefit of decreasing incision size and reducing time to functional recovery., Competing Interests: Conflict of Interests: The authors declare no conflict of interest., (Copyright © 2021, Author(s).)

Context: The International Association for the Study of Pain (IASP) defines chronic pain as pain that persists or recurs for longer than 3 months. Chronic pain has a significant global disease burden with profound effects on health, quality of life, and socioeconomic costs., Evidence Acquisition: Narrative review., Results: There are several treatment options, including pharmacological therapy, physical rehabilitation, psychological therapies, and surgical interventions, for chronic pain management. Magnesium has been FDA-approved for several indications including hypomagnesemia, arrhythmia, prevention of seizures in eclampsia/preeclampsia, and constipation. Magnesium has been used for numerous off-label uses, notably for acute and chronic pain management. The mechanism of magnesium in pain management is primarily through its action as a voltage-gated antagonist of NMDA receptors, which are involved in pain transduction., Conclusions: This narrative review will focus on the current evidence and data surrounding the utilization of magnesium as a treatment option for chronic pain., Competing Interests: Conflict of Interests: None., (Copyright © 2021, Author(s).)

Background Midazolam is commonly used preoperatively for anxiety. Adverse effects data in pediatric patients with obstructive sleep apnea (OSA) undergoing tonsillectomy and adenoidectomy (T&A) is limited. Aims We hypothesized that preoperative midazolam increases the time to emergence from anesthesia and postoperative discharge. Secondary objectives assessed if patients receiving midazolam experienced increased side effects or complications from treatment. Methods This study was a retrospective chart review of patients undergoing T&A from July 2014 to December 2015. Midazolam receiving patients (midazolam group: MG) were compared to patients who did not (non-midazolam group: NMG). Multivariable analyses were performed and adjusted for predefined potential cofounder variables. Results Emergence and discharge times were 5.2 minutes (95% CI [-7.1, 17.4]; p=0.41) and 10.1 minutes (95% CI [-6.7, 26.8]; p=0.24) longer in MG. These results were not statistically significant. Comparing by OSA status, there was no statistical difference in emergence and discharge times between mild, moderate and severe OSA groups or between MG and NMG within each OSA group. Emergence and discharge times in moderate OSA was 6.1 minutes (95% CI [-17.6, 29.8]; p=0.61) and 18.8 minutes (95% CI [-16.4, 53.9]; p=0.29) longer than mild OSA, and in the severe OSA group, 2.6 minutes (95% CI [-19.9, 25.1]; p=0.82) shorter and 2.8 minutes (95% CI [-30.3, 35.9]; p=0.87) longer. The incidence of postoperative complications was comparable between MG and NMG groups. Conclusions Premedication with midazolam was not associated with prolonged emergence or discharge time or higher incidence of complications after anesthesia for T&A in patients with OSA., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Garcia et al.)

Context: Piriformis syndrome is a solely clinical diagnosis that often eludes the practitioner and goes underdiagnosed. PS is a pain syndrome and for those it affects, causes persistent pain and limits daily activity and work capacity. It is a form of deep gluteal syndrome that needs to be considered on the differential of low back pain as it comprises between 0.3% - 6% of all low back pain cases and is frequently underdiagnosed. Piriformis syndrome may be primary due anatomic anomalies or secondary, though the majority of cases are secondary to some insult. The objective of this manuscript is to provide a description of the epidemiology and presentation of piriformis as well as both non-operative and operative treatment options. We review all of the recent clinical evidence regarding the aforementioned therapies., Evidence Acquisition: Literature searches were performed using the below MeSH Terms using Mendeley version 1.19.4. Search fields were varied until further searches revealed no new articles. All articles were screened by title and abstract. Decision was made to include an article based on its relevance and the list of final articles was approved three of the authors. This included reading the entirety of the article. Any question regarding the inclusion of an article was discussed by all authors until an agreement was reached., Results: Medical management and physical therapy show some promise; however, when conservative treatment fails minimally invasive methods such as steroid injections, botulinum toxin injections, dry needling are all efficacious and there is substantial clinical evidence regarding these therapies. In those patients in which minimally invasive techniques do not result in an adequate relief of pain and return of function, endoscopic release can be considered. Endoscopic release is far superior to open release of the piriformis syndrome given the higher success and lower rate of complications., Conclusions: Piriformis syndrome is an important differential diagnosis in the work up of lower back pain and should not be ruled out with proper examination and testing. Clinicians should consider medical management and conservative management in the initial treatment plan for piriformis syndrome. There are many options within the conservative management and the literature shows much promise regarding these. Physical therapy, steroid injections, botulinum toxin injections, and dry needling are all potentially effective therapies with few adverse effects. Surgical options remain as gold standard, but only when conservative management has failed and the symptoms are significant to affect daily living activities. Endoscopic decompression of the sciatic nerve with or without release of the piriformis muscle has a reported high likelihood of success and a low complication rate. Current literature supports the preference of the endoscopic approach over the open approach due to improved outcomes and decreased complications. Further research is to well define the metrics for the diagnosis of piriformis syndrome and may include a need to develop diagnostic criteria., Competing Interests: Conflict of Interests: The authors report no conflicts of interest., (Copyright © 2021, Author(s).)

Migraine is a neurobiological headache disorder that affects around 16% of adults in the United States. Medical treatment of mild to moderate migraines include non-prescription non-steroidal anti-inflammatory drugs, acetaminophen, or aspirin and caffeine-containing combination analgesics. Additionally, moderate to severe migraines and those that are mild to moderate that have not responded to analgesics can be treated with triptans, which are drugs specific for migraine treatment. Non-pharmacological treatments include cognitive behavioral therapy and relaxation training. Medications for the prevention of migraines have also been developed since they are more affective in offsetting the symptoms. Ubrogepant's high specificity and selectivity for calcitonin gene-related peptide (CGRP) sets it apart from certain other drugs, which previously limited the treatment of migraines with or without aura due to their decreased selectivity. The most frequently reported side effects are oropharyngeal pain, nasopharyngitis, and headache. Most studies found that participants receiving Ubrogepant were free from pain within 2 h when compared to placebo. Patients taking Ubrogepant should avoid taking it when pregnant or with end stage renal disease. In summary, Ubrogepant has good tolerability and an overall favorable safety profile. It appears to hold promise for the acute treatment of migraines with or without aura in adults.

Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.

Purpose of Review: This evidence-based systematic review will focus on the use of acupuncture and its role in the treatment of low back pain to help better guide physicians in their practice. It will cover the background and the burden of low back pain and present the current options for treatment and weigh the evidence that is available to support acupuncture as a treatment modality for low back pain., Recent Findings: Low back pain (LBP), defined as a disorder of the lumbosacral spine and categorized as acute, subacute, or chronic, can be a debilitating condition for many patients. Chronic LBP is more typically defined by its chronicity with pain persisting > 12 weeks in duration. Conventional treatment for chronic LBP includes both pharmacologic and non-pharmacologic options. First-line pharmacologic therapy involves the use of NSAIDs, then SNRI/TCA/skeletal muscle relaxants, and antiepileptics. Surgery is usually not recommended for chronic non-specific LBP patients. According to the 2016 CDC Guidelines for Prescribing Opioids for Chronic Pain and the 2017 American College of Physicians (ACP) clinical practice guidelines for chronic pain, non-pharmacologic interventions, acupuncture can be a first-line treatment for patients suffering from chronic low back pain. Many studies have been done, and most show promising results for acupuncture as an alternative treatment for low back pain. Due to non-standardized methods for acupuncture with many variations, standardization remains a challenge.

Purpose of Review: This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It reviews the role of cannabis in the treatment of chronic pain, cognitive and neurological adverse effects, special cases and addiction., Recent Findings: Cannabinoids work through the endocannabinoids system and inhibit the release of GABA and glutamate in the brain, impact neuromodulation, as well as dopamine, acetylcholine and norepinephrine release. They affect reward, learning and pain. The use of cannabis is increasing nationally and world-wide for both recreational and medicinal purposes, however, there is relatively only low quality evidence to the efficacy and adverse effects of this. Cannabis and its derivatives may be used for treatment of chronic pain. They are via CB1 receptors that are thought to modulate nociceptive signals in the brain. CB2 receptors in the DRG likely affect pain integration in the afferent pathways, and peripherally CB2 also affects noradrenergic pathways influencing pain. A large proportion of users may see more than 50% of chronic pain alleviation compared with placebo. Cannabis affects cognition, most notably executive function, memory and attention, and may deteriorate the boundary between emotional and executive processing. Cannabis impairs memory in the short run, which become more significant with chronic use, and may also be accompanied by poorer effort, slower processing and impacted attention. It is generally believed that long-term use and earlier age are risk factor for neurocognitive deficits; neuroimaging studies have shown reduced hippocampal volume and density. Executive functions and memory are worse in adolescent users versus adults. Cannabis addiction is different and likely less common than other addictive substances, but up to 10% of users meet criteria for lifetime cannabis dependence. Addiction patterns may be linked to genetic and epigenetic differences. It is still unclear whether abstinence reverses patterns of addiction, and more research is required into this topic., Summary: Cannabis use has become more abundant for both medical and recreational use. It carries likely benefits in the form of analgesia, anti-emesis and improved appetite in chronic patients. The evidence reviewing adverse effects of this use are still limited, however, exiting data points to a clear link with neurocognitive deterioration, backed by loss of brain volume and density. Addiction is likely complex and variable, and no good data exists to support treatment at this point. It is becoming clear that use in earlier ages carries a higher risk for long-term deficits. As with any other drug, these risks should be considered alongside benefits prior to a decision on cannabis use., (Copyright © 1964–2019 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Context: Chronic pain accounts for one of the most common reasons patients seek medical care. The financial burden of chronic pain on health care is seen by direct financial cost and resource utilization. Many risk factors may contribute to chronic pain, but there is no definite risk. Managing chronic pain is a balance between maximally alleviating symptoms by utilizing a therapeutic regimen that is safe for long-term use. Currently, non-opioid analgesics, NSAIDs, and opioids are some of the medical treatment options, but these have numerous adverse effects and may not be the best option for long-term use. However, Lidocaine can achieve both central and peripheral analgesic effects with relatively few side effects, which may be an ideal compound for managing chronic pain., Evidence Acquisition: This is a Narrative Review., Results: Infusion of lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide), an amino-amide compound, is emerging as a promising option to fill the therapeutic void for treatment of chronic pain. Numerous studies have outlined dosing protocols for lidocaine infusion for the management of perioperative pain, outlined below. While there are slight variations in these different protocols, they all center around a similar dosing regimen to administer a bolus to reach a rapid steady state, followed by infusion for up to 72 hours to maintain the therapeutic analgesic effects., Conclusions: Lidocaine may be a promising pharmacologic solution with a low side effect profile that provides central and peripheral analgesia. Even though the multifaceted mechanism is not entirely understood yet, lidocaine may be a promising novel remedy in treating chronic pain in various conditions., Competing Interests: Conflict of Interests: None declared., (Copyright © 2020, Author(s).)

Background: Twelfth rib syndrome, or slipping of the 12th rib, is an often overlooked cause for chronic chest, back, flank, and abdominal pain from irritation of the 12th intercostal nerve. Diagnosis is clinical and follows the exclusion of other causes of pain. This syndrome is usually accompanied by long-suffering, consequent psychiatric comorbidities, and increased health care costs, which are secondary to the delayed diagnosis., Objectives: This manuscript is a review of twelfth rib syndrome and its management options. The review provides etiology, pathophysiology, and epidemiology of twelfth rib syndrome. Additionally, diagnosis and current options for treatment and management are presented., Study Design: This is a narrative review of twelfth rib syndrome., Setting: A database review., Methods: A PubMed search was conducted to ascertain seminal literature regarding twelfth rib syndrome., Results: Conservative treatment is usually the first line, including local heat or ice packs, rest, and oral over-the-counter analgesics. Transcutaneous stimulation and 12th intercostal nerve cryotherapy have also been described with some success. Nerve blocks can additionally be tried and are usually effective in the immediate term; there is a paucity of evidence to suggest long-term efficacy. Surgical removal of all or part of the 12th rib and possibly the 11th rib, as well as the next line of therapy, may provide long-lasting relief of pain., Limitations: Further large scale clinical studies are needed to assess the most effective management of twelfth rib syndrome., Conclusions: Twelfth rib syndrome is usually diagnosed late and causes significant morbidity and suffering. The actual epidemiology is unclear given the difficulty of diagnosis. Nerve blocks and surgical rib resection appear to be effective in treating this syndrome, however, further evidence is required to properly evaluate them. Familiarity with this syndrome is crucial in reaching a prompter diagnosis.

Introduction: Non-pharmacologic alternative therapies for pain have been around for a long time, some for hundreds of years. They have been used throughout history to treat many issues., Recent Findings: Currently, alternative medicine is most frequently used to treat musculoskeletal pain, and between 59 and 90% of patients utilizing alternative therapies for chronic pain claimed they were helpful and can serve as an effective adjunctive for the treatment of chronic pain. Some examples of alternative therapies that will be discussed in this review include acupuncture, tai chi, osteopathic manipulation, and chiropractic care. Acupuncture, traditionally a Chinese practice, is becoming more popular across the world to attempt to relieve pain. It involves the placement of thin needles at various points in the body. The efficacy of acupuncture for pain is heavily debated. More research and discussion are necessary to determine the exact role it plays in the treatment of chronic pain. Tai chi is also a traditional Chinese practice that is often used as a form of meditation and for potential health benefits. Tai chi involves a series of complex movements such as squatting combined with deep breathing to achieve relaxation and pain reduction. Osteopathic manipulative treatment (OMT) is a technique used by both osteopathic physicians (DO) as well as other health professionals to manage a wide range of conditions in any given patient. The technique involves utilization and manipulation of the musculoskeletal system to achieve potential health benefits. OMT has been used as therapy for many issues but is commonly used for pain conditions. Alternative therapies may serve as an effective adjunctive treatment modality for the management of chronic pain conditions. There has been a tremendous amount of research dictating the effectiveness of alternative therapies for chronic pain management. The purpose of this review is to provide a comprehensive evidence-based update of alternative therapy used for the management of chronic pain conditions.

Objectives: Spinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS., Methods: Patients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy., Results: Between 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.12 to 1.77; P = 0.003; Hispanic patients: OR = 1.41; 95% CI, 1.10 to 1.81; P = 0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR = 1.24; 95% CI, 1.08 to 1.43; P = 0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR = 0.50; 95% CI, 0.36 to 0.70; P < 0.001)., Conclusions: Our study suggests that socioeconomic disparities may exist in the utilization of SCS among hospitalized patients with CRPS I and FBSS the United States. However, confirming these data from other administrative databases, in the outpatient setting, may shed more insight., (© 2020 World Institute of Pain.)

Context: Carpal tunnel syndrome (CTS) is the most frequent peripheral compression-induced neuropathy observed in patients worldwide. Surgery is necessary when conservative treatments fail and severe symptoms persist. Traditional Open carpal tunnel release (OCTR) with visualization of carpal tunnel is considered the gold standard for decompression. However, Endoscopic carpal tunnel release (ECTR), a less invasive technique than OCTR is emerging as a standard of care in recent years., Evidence Acquisition: Criteria for this systematic review were derived from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two review authors searched PubMed, MEDLINE, and the Cochrane Database in May 2018 using the following MeSH terms from 1993-2016: 'carpal tunnel syndrome,' 'median nerve neuropathy,' 'endoscopic carpal tunnel release,' 'endoscopic surgery,' 'open carpal tunnel release,' 'open surgery,' and 'carpal tunnel surgery.' Additional sources, including Google Scholar, were added. Also, based on bibliographies and consultation with experts, appropriate publications were identified. The primary outcome measure was pain relief., Results: For this analysis, 27 studies met inclusion criteria. Results indicate that ECTR produced superior post-operative pain outcomes during short-term follow-up. Of the studies meeting inclusion criteria for this analysis, 17 studies evaluated pain as a primary or secondary outcome, and 15 studies evaluated pain, pillar tenderness, or incision tenderness at short-term follow-up. Most studies employed a VAS for assessment, and the majority reported superior short-term pain outcomes following ECTR at intervals ranging from one hour up to 12 weeks. Several additional studies reported equivalent pain outcomes at short-term follow-up as early as one week. No study reported inferior short-term pain outcomes following ECTR., Conclusions: ECTR and OCTR produce satisfactory results in pain relief, symptom resolution, patient satisfaction, time to return to work, and adverse events. There is a growing body of evidence favoring the endoscopic technique for pain relief, functional outcomes, and satisfaction, at least in the early post-operative period, even if this difference disappears over time. Several studies have demonstrated a quicker return to work and activities of daily living with the endoscopic technique., Competing Interests: Conflict of Interests: Alan Kaye is on the Speakers Bureau for Merck Pharmaceuticals., (Copyright © 2020, Author(s).)

Context: Ulnar nerve entrapment is a relatively common entrapment syndrome second only in prevalence to carpal tunnel syndrome. The potential anatomic locations for entrapment include the brachial plexus, cubital tunnel, and Guyon's canal. Ulnar nerve entrapment is more so prevalent in pregnancy, diabetes, rheumatoid arthritis, and patients with occupations involving periods of prolonged elbow flexion and/or wrist dorsiflexion. Cyclists are particularly at risk of Guyon's canal neuropathy. Patients typically present with sensory deficits of the palmar aspect of the fourth and fifth digits, followed by motor symptoms, including decreased pinch strength and difficulty fastening shirt buttons or opening bottles., Evidence Acquisition: Literature searches were performed using the below MeSH Terms using Mendeley version 1.19.4. Search fields were varied until further searches revealed no new articles. All articles were screened by title and abstract. Decision was made to include an article based on its relevance and the list of final articles was approved three of the authors. This included reading the entirety of the artice. Any question regarding the inclusion of an article was discussed by all authors until an agreement was reached., Results: X-ray and CT play a role in diagnosis when a bony injury is thought to be related to the pathogenesis (i.e., fracture of the hook of the hamate.) MRI plays a role where soft tissue is thought to be related to the pathogenesis (i.e., tumor or swelling.) Electromyography and nerve conduction also play a role in diagnosis. Medical management, in conjunction with physical therapy, shows limited promise. However, minimally invasive techniques, including peripheral percutaneous electrode placement and ultrasound-guided electrode placement, have all been recently studied and show great promise. When these techniques fail, clinicians should resort to decompression, which can be done endoscopically or through an open incision. Endoscopic ulnar decompression shows great promise as a surgical option with minimal incisions., Conclusions: Clinical diagnosis of ulnar nerve entrapment can often be delayed and requires the suspicion as well as a thorough neurological exam. Early recognition and diagnois are important for early institution of treatment. A wide array of diagnostic imaging can be useful in ruling out bony, soft tissue, or vascular etiologies, respectively. However, clinicians should resort to electrodiagnostic testing when a definitive diagnois is needed. Many new minimally invasive techniques are in the literature and show great promise; however, further large scale trials are needed to validate these techniques. Surgical options remains as a gold standard when adequate symptom relief is not achieved through minimally invasive means., Competing Interests: Conflict of Interests: We have no conflicts of interest., (Copyright © 2020, Author(s).)

Charcot spine arthropathy (CSA), a result of reduced afferent innervation, is an occurrence of Charcot joint, a progressive, degenerative disorder in vertebral joints, related mostly to spinal cord injury. The repeated microtrauma is a result of a lack of muscle protection and destroys cartilage, ligaments, and disc spaces, leading to vertebrae destruction, joint instability, subluxation, and dislocation. Joint destruction compresses nerve roots, resulting in pain, paresthesia, sensory loss, dysautonomia, and spasticity. CSA presents with back pain, spinal deformity and instability, and audible spine noises during movement. Autonomic dysfunction includes bowel and bladder dysfunction. It is slowly progressive and usually diagnosed at a late stage, usually, on average, 20 years after the first initial insult. Diagnosis is rarely clinical related to the nature of nonspecific symptoms and requires imaging with computed tomography (CT) and magnetic resonance imaging (MRI). Conservative management focuses on the prevention of fractures and the progression of deformities. This includes bed rest, orthoses, and braces. These could be useful in elderly or frail patients who are not candidates for surgical treatment, or in minimally symptomatic patients, such as patients with spontaneous fusion leading to a stable spine. Symptomatic treatment is offered for autonomic dysfunction, such as anticholinergics for bladder control. Most patients require surgical treatment. Spinal fusion is achieved with open, minimally-open (MOA) or minimally-invasive (MIS) approaches. The gold standard is open circumferential fusion; data is lacking to determine the superiority of open or MIS approaches. Patients usually improve after surgery; however, the rarity of the condition makes it difficult to estimate outcomes. This is a review of the latest and seminal literature about the treatment and chronic management of Charcot spine. The review includes the background of the syndrome, clinical presentation, and diagnosis, and compares the different treatment options that are currently available., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

BACKGROUND Icosapent ethyl, a form of eicosapentaenoic acid with anti-inflammatory activity, has been approved as an adjunctive treatment with statins in patients with hypertriglyceridemia. Icosapent ethyl is currently undergoing clinical trials to determine its anti-inflammatory effects in patients with coronavirus disease 2019 (COVID-19). This report describes 3 intensive care unit (ICU) patients with moderate to severe COVID-19 pneumonia treated with icosapent ethyl as part of their supportive care who had favorable outcomes. CASE REPORT Case 1 was a 75-year-old man with a past medical history of hyperlipidemia, hypertension, type 2 diabetes mellitus, obesity, and benign prostatic hyperplasia. Case 2 was a 23-year old man with a past medical history of type 2 diabetes mellitus and obesity. Case 3 was a 24-year old man with a history of autism. All cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were confirmed from a nasopharyngeal swab using the Becton Dickinson nasopharyngeal reverse-transcription polymerase chain reaction. All patients in these cases were treated with a course of 2 g of icosapent ethyl twice a day by nasogastric tube. CONCLUSIONS This report of 3 cases describes the use of icosapent ethyl as a component of supportive treatments in ICU patients with moderate to severe COVID-19 pneumonia. However, as of yet there are no evidence-based treatments for SARS-CoV-2 infection from controlled clinical trials. The outcomes of ongoing clinical trials are awaited to determine whether icosapent ethyl has anti-inflammatory effects in patients with SARS-CoV-2 infection and which patients might benefit from the use of this adjunctive treatment.

Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and disability. PD is caused by a loss of dopaminergic, cholinergic, serotonergic, and noradrenergic neurons in the central nervous system (CNS), and peripherally; the syndromic parkinsonism symptoms of movement disorder, gait disorder, rigidity and tremor are mostly driven by the loss of these neurons in the basal ganglia. Unfortunately, a significant proportion of patients taking levodopa, the standard of care treatment for PD, will begin to experience a decrease in effectiveness at varying times. These periods, referred to as "off episodes", are characterized by increased symptoms and have a detrimental effect on quality of life and disability. Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa/carbidopa in patients experiencing "off episodes". It promotes dopaminergic activity by antagonizing adenosine in the basal ganglia. This review will discuss istradefylline as a treatment for PD patients with off episodes.

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing-remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

Hereditary variant transthyretin amyloidosis (ATTRv) is a rare genetic defect that affects about 5000-10,000 people worldwide, causing amyloidosis secondary to misfolding of mutant transthyretin (TTR) protein fibrils. TTR mutations can cause protein deposits in many extracellular regions of organs, but those deposits in cardiac and axonal cells are the primary cause of this clinical syndrome. Treatment options are limited, but new drugs are being developed. Patisiran, a novel drug, is a liposomal siRNA against TTR that specifically targets this protein, reducing the accumulation of TTR in tissues, with subsequent improvement in both neuropathy and cardiac function. Patisiran is likely to serve as a prototype for the development of further intelligent drug solutions for use in targeted therapy. In this review we summarize the evidence currently available on the treatment of polyneuropathy in people with ATTRv with patisiran. We review the evidence on its efficacy, safety, and indications of use, citing novel and seminal papers on these subjects.

Acupuncture is a form of traditional Chinese medicine that is performed by placing needles or pressure in specific locations on a patient's skin to achieve a therapeutic effect. Although used to treat a variety of disorders, one of the most common applications of acupuncture is to treat chronic pain, especially headache and migraine pain. Migraines are difficult to treat, and pharmacotherapies are often the first line of treatment, although these options have many unwanted side effects, such as exacerbation of headache pain in those with chronic migraine. Many complimentary and integrative therapies are available to treat migraine (including nutraceuticals, yoga, tai chi, and biofeedback), among which acupuncture as a treatment is gaining increasing attention. In this review, we provide an overview of the current understanding of both acupuncture and migraine and of current research investigating the effectiveness of acupuncture in treating migraine and chronic migraine.