Predictors of colorectal carcinoma and inflammatory bowel disease in patients with colonic wall thickening.

Background and Aim: Colonic wall thickening (CWT) is commonly associated with clinically significant pathologies, but predictive factors of such pathologies are not well known. This study aims to identify the predictors of clinically significant pathologies, such as colorectal carcinoma (CRC) and inflammatory bowel disease (IBD), in patients with CWT. Methods: Subjects with an abnormal abdominal computed tomography (CT) and a follow-up colonoscopy between 2010 and 2020 were retrospectively reviewed. Patients with CWT in the CT were included and examined in this study. A multivariable logistic regression analysis was performed to assess for factors independently associated with CRC or IBD in these subjects. Receiver operating characteristic (ROC) curve analysis was used to further examine significant parameters in multivariable logistic regression analysis. Results: Among 403 patients with CWT on CT scans who underwent a colonoscopy, 269 subjects who met the inclusion criteria were identified and studied. On multivariable logistic regression models, elevated platelet count, low hematocrit, and localized CWT were found to be independently associated with CRC, while elevated platelet count and younger age were independently associated with IBD. On ROC curve analysis for CRC, area under the curve (AUC) for hematocrit, platelets, and localized CWT was 0.76, 0.75, and 0.61, respectively. On ROC curve analysis for IBD, AUC for age and platelets was 0.90 and 0.69, respectively. Conclusion: Elevated platelet count, low hematocrit, and localized CWT can be potentially used as predictors of CRC in patients with CWT. Elevated platelet count and young age can be used to predict IBD in these patients.

Biology of COVID-19 and related viruses: Epidemiology, signs, symptoms, diagnosis, and treatment.

Coronaviruses belong to the family Coronaviridae order Nidovirales and are known causes of respiratory and intestinal disease in various mammalian and avian species. Species of coronaviruses known to infect humans are referred to as human coronaviruses (HCoVs). While traditionally, HCoVs have been a significant cause of the common cold, more recently, emergent viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a global pandemic. Here, we discuss coronavirus disease (COVID-19) biology, pathology, epidemiology, signs and symptoms, diagnosis, treatment, and recent clinical trials involving promising treatments.

Dorsal Root Ganglion (DRG) and Chronic Pain.

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.

Comprehensive Review and Update of Burning Eye Syndrome.

Keratoconjunctivitis sicca ("dry eye") is a common (14%-30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as "burning eye syndrome." This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome. Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment centers around symptomatic alleviation and reduction of inflammation. Conservative treatments focus on well-being and perception and include exercise, acupuncture, and cognitive behavioral therapy. Topical treatment consists of the anti-adhesion T-cell antagonist lifitegrast, corticosteroids, and cyclosporine; all have moderate efficacy and good safety. Autologous serum eye drops are a second-line topical that may promote corneal and neural healing on top of symptomatic relief. When these treatments fail, patients may trial neuromodulation with transcranial magnetic stimulation. Despite general treatment safety, more research is needed to develop novel approaches to this condition, possibly focusing more directly on the neurological component.

Factors associated with reduced infliximab exposure in the treatment of pediatric autoimmune disorders: a cross-sectional prospective convenience sampling study.

BACKGROUND: Inadequate systemic exposure to infliximab (IFX) is associated with treatment failure. This work evaluated factors associated with reduced IFX exposure in children with autoimmune disorders requiring IFX therapy. METHODS: In this single-center cross-sectional prospective study IFX trough concentrations and anti-drug antibodies (ADAs) were measured in serum from children diagnosed with inflammatory bowel disease (IBD) (n = 73), juvenile idiopathic arthritis (JIA) (n = 16), or uveitis (n = 8) receiving maintenance IFX infusions at an outpatient infusion clinic in a tertiary academic pediatric hospital. IFX concentrations in combination with population pharmacokinetic modeling were used to estimate IFX clearance. Patient demographic and clinical data were collected by chart review and evaluated for their relationship with IFX clearance. RESULTS: IFX trough concentrations ranged from 0 to > 40 µg/mL and were 3-fold lower in children with IBD compared to children with JIA (p = 0.0002) or uveitis (p = 0.001). Children with IBD were found to receive lower IFX doses with longer dosing intervals, resulting in dose intensities (mg/kg/day) that were 2-fold lower compared to children with JIA (p = 0.0002) or uveitis (p = 0.02). Use of population pharmacokinetic analysis to normalize for variation in dosing practices demonstrated that increased IFX clearance was associated with ADA positivity (p = 0.004), male gender (p = 0.02), elevated erythrocyte sedimentation rate (ESR) (p = 0.02), elevated c-reactive protein (CRP) (p = 0.001), reduced serum albumin concentrations (p = 0.0005), and increased disease activity in JIA (p = 0.009) and IBD (p ≤ 0.08). No significant relationship between diagnosis and underlying differences in IFX clearance was observed. Multivariable analysis by covariate population pharmacokinetic modeling confirmed increased IFX clearance to be associated with anti-IFX antibody positivity, increased ESR, and reduced serum albumin concentrations. CONCLUSIONS: Enhanced IFX clearance is associated with immunogenicity and inflammatory burden across autoimmune disorders. Higher systemic IFX exposures observed in children with rheumatologic disorders are driven primarily by provider drug dose and interval selection, rather than differences in IFX pharmacokinetics across diagnoses. Despite maintenance IFX dosing at or above the standard recommended range for IBD (i.e., 5 mg/kg every 8 weeks), the dosing intensity used in the treatment of IBD is notably lower than dosing intensities used to treat JIA and uveitis, and may place some children with IBD at risk for suboptimal maintenance IFX exposures necessary for treatment response.

Adverse Effects of Recreational and Medical Cannabis.

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.

Supply, Demand, and Quality: A Three-Pronged Approach to Blood Product Management in Developing Countries.

While transfusion of blood and blood products is instinctively linked to the provision of emergent care, blood and blood products are also routinely used for the treatment of subacute and chronic conditions. Despite the efforts of the World Health Organization and others, developing countries are faced with a three-part problem when it comes to access to and delivery of transfusions: insufficient supply, excessive demand, and inadequate quality of available supply. Developing countries rely heavily on replacement and remunerated donors rather than voluntary nonremunerated donors due to concerns regarding donation- and transfusion-transmitted infection as well as local and cultural beliefs. While increased awareness of HIV and improved testing techniques have jointly reduced infection-related apprehensions and improved the quality of available blood and blood products, continued efforts are warranted to bolster testing for other bloodborne pathogens. Similarly, although prevalence rates of anemia are high in some areas of the world, success in adequate widespread management of these conditions has been limited. One of the keys to expanding access to high-quality blood and blood products is thus to improve medical management of conditions that would otherwise require transfusion. Through a three-pronged approach to address quantity, quality, and demand, developing countries can enable themselves to build toward self-sufficient blood management services and increased independence from the support of international organizations.

A Comprehensive Review and Update of Post-surgical Cutaneous Nerve Entrapment.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding post-surgical cutaneous nerve entrapment, epidemiology, pathophysiology, and clinical presentation. It focuses mainly on nerve entrapment leading to chronic pain and the available therapies. RECENT FINDINGS: Cutaneous nerve entrapment is not an uncommon result (up to 30% of patients) of surgery and could lead to significant, difficult to treat chronic pain. Untreated, entrapment can lead to neuropathy and damage to enervated structures and musculature, and significant morbidity and financial loss. Nerve entrapment is defined as pressure neuropathy from chronic compression. It causes changes to all layers of the nerve tissue. It is most significantly associated with hernia repair and other procedures employing a Pfannenstiel incision. The initial insult is usually incising of the nerve, followed by formation of a neuroma, incorporation of the nerve during closing, or constriction from adhesions. The three most commonly involved nerves are the iliohypogastric, ilioinguinal, and genitofemoral nerves. Cutaneous abdominal nerve entrapment could occur during thoracoabdominal surgery. The presentation of nerve entrapment usually involved post-surgical pain in the territory innervated by the trapped nerve, possibly with radiation that tracks the nerve course. Once a suspected neuropathy is identified, it can be diagnosed with relief in pain after a nerve block has been instilled. Treatment is usually started with pharmaceutical solutions, topical first and oral if those fail. Most patients require escalation to a second line of treatment and see good result with injection therapy. Those that require further escalation can choose between ablation and surgical therapies. Post-surgical nerve entrapment is not uncommon and causes serious morbidity and financial loss. It is underdiagnosed and thus undertreated. Preventing nerve entrapment is the best treatment; when it does occur, options include topical and oral analgesics, nerve blocks, ablation therapy, and repeat surgery.

Clinical and economic burden of postoperative nausea and vomiting: Analysis of existing cost data.

Postoperative nausea and vomiting (PONV) is an undesirable outcome that occurs in up to 30% of patients. Over the years, the cost of treating PONV has decreased due to the availability of cheaper yet effective antiemetics. Limiting PONV development benefits the hospital system as studies have shown that prevention is associated with shorter post-anesthesia care unit (PACU) stays as well as decreased supply costs and staffing burden. The financial burden for prophylaxis against PONV has been shown to be less than what patients are willing to pay to prevent the development of PONV. Studies have also shown that prevention of initial development of PONV limits readmission rates, which is beneficial to both the patient and the hospital. Owing to recent economic analysis and reductions in antiemetic prices, the patient's preference for comfort, the hospital's commitment to providing the best care, and the system's desire for fiscal prudence are aligned. This culminates in recommending PONV prophylaxis for all patients undergoing anesthesia.

Treatment recommendations for chronic knee osteoarthritis.

Primary osteoarthritis (OA) hinders an aging global population as one of the leading causes of years-lost-to-disability (YLD). OA in most patients is considered to be an overuse injury that results in degenerative inflammation of the joints with the associated formation of bony outgrowths. Due to the escalating nature of this chronic pain disease, treatment management for OA can initially begin with a more conservative approach. It can eventually lead to more invasive surgical procedures. At present, the standard of care remains initial conservative management with lifestyle changes, including weight loss with concurrent anti-inflammatory regimens. Injections are frequently used for the escalation of care, but a significant number of patients ultimately resort to total knee arthroplasty. This review will focus specifically on knee OA, providing a brief overview of risk factors and early management and in-depth exploration of the invasive interventions that can offer symptomatic relief and return of function.

Pharmacological options for the treatment of chronic migraine pain.

Migraine is a debilitating neurological condition with symptoms typically consisting of unilateral and pulsating headache, sensitivity to sensory stimuli, nausea, and vomiting. The World Health Organization (WHO) reports that migraine is the third most prevalent medical disorder and second most disabling neurological condition in the world. There are several options for preventive migraine treatments that include, but are not limited to, anticonvulsants, antidepressants, beta blockers, calcium channel blockers, botulinum toxins, NSAIDs, riboflavin, and magnesium. Patients may also benefit from adjunct nonpharmacological options in the comprehensive prevention of migraines, such as cognitive behavior therapy, relaxation therapies, biofeedback, lifestyle guidance, and education. Preventative therapies are an essential component of the overall approach to the pharmacological treatment of migraine. Comparative studies of newer therapies are needed to help patients receive the best treatment option for chronic migraine pain.

Treatment and management of myofascial pain syndrome.

Myofascial Pain Syndrome (MPS) is a regional pain disorder that affects every age-group and is characterized by the presence of trigger points (TrPs) within muscles or fascia. MPS is typically diagnosed via physical exam, and the general agreement for diagnostic criteria includes the presence of TrPs, pain upon palpation, a referred pain pattern, and a local twitch response. The prevalence of MPS among patients presenting to medical clinics due to pain ranges anywhere from 30 to 93%. This may be due to the lack of clear criteria and guidelines in diagnosing MPS. Despite the prevalence of MPS, its pathophysiology remains incompletely understood. There are many different ways to manage and treat MPS. Some include exercise, TrP injections, medications, and other alternative therapies. More research is needed to form uniformly-accepted diagnostic criteria and treatments.

A comprehensive review of partial opioid agonists for the treatment of chronic pain.

Chronic pain is a common condition that is being increasingly recognized, diagnosed, and treated in a variety of settings. Opioids can be used to treat chronic pain but at the cost of adverse effects and risk of dependence. Recently, there has been a movement to improve analgesic care in the setting of the opioid epidemic and the overprescribing of opioids, causing over-accessibility, dependence, and large numbers of overdose deaths. Opioid-specific receptors, including the µ, δ, κ, and opioid receptor like-1 (ORL-1) receptors, are each 7-transmembrane spanning proteins, which affect the G-protein and ß-arrestin cascades. Each opioid class can act differently on the receptors, resulting in full, partial, or antagonizing effects. This comprehensive review looks at different agents in major classes, nonselective and mixed/partial agonists/antagonists, including the nonselective partial agonists, levorphanol and tramadol. Mixed partial agonists/antagonists include buprenorphine, pentazocine, nalbuphine, and butorphanol. Oliceridine is the only current selective partial agonist that agonizes specific pathways to promote analgesic effects and discourage adverse effects.

Use of cannabidiol (CBD) for the treatment of chronic pain.

Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach. Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment. The exact mechanism for CBD is currently unknown, but unlike the CBD's psychoactive counterpart, THC, the side effects of CBD itself have been shown to be overall much more benign. The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising. This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.

Use of spinal cord stimulation for the treatment of post total knee arthroplasty pain.

Total knee arthroplasty (TKA), a common elective surgical procedure, is indicated in patients with knee pain that becomes refractory to nonsurgical interventions, such as weight loss, physical activity, physical therapy, and pharmacologic treatment. However, postoperative chronic pain is frequently reported and may lead to opioid use and dependence. Due to the increasing concern of the overuse of opioids in medical treatments, a search for other viable options is recognized. As a consequence, alternative therapies, such as transcutaneous electrical nerve stimulation (TENS), pulsed radiofrequency (PRF), and spinal cord stimulation (SCS) are being tried to potentially replace traditional opioid use in treating persistent postsurgical pain (PPSP), thus reducing opioid dependence across the nation. Here, we provide a brief overview of persistent pain following TKA procedures, with a particular emphasis on the role of promising therapies, such as TENS, PRF, and SCS for the treatment of post-TKA pain.

An Evidence-Based Review of Galcanezumab for the Treatment of Migraine.

PURPOSE OF REVIEW: This is a comprehensive review of the current literature on the usage of galcanezumab for migraine treatment. It reviews the biology, pathophysiology, epidemiology, diagnosis, and conventional treatment of migraines, then compares the literature available for galcanezumab with historical treatment options. RECENT FINDINGS: Migraine is a common headache disorder and constitutes a significant source of distress from both a personal and societal perspective. Conventional treatment includes abortive and preventive treatment. Treatment options are limited and may be only partially or minimally effective in some of the population. Recent evidence points to metabolic changes in the brain as possible causes of migraine, via reduced available energy or a spiking need for it, resulting in a relative insufficiency. This leads to trigeminocervical complex (TCC) activation and a headache episode, modulated by calcitonin gene-related peptide (CGRP). Galcanezumab (Emgality) is a monoclonal antibody targeting CGRP that is given in a monthly injection for the prevention of migraines. Its safety was previously shown in phase 1 and 2 trials, and recent phase 3 trials showed efficacy, with up to 50% reduction in monthly migraine days and improved functional capacity in migraineurs. Studies show that the drug is well tolerated and safe. Migraine headache is a common neurological syndrome that causes great pain and suffering. Treatment options today are limited. Galcanezumab does not prevent migraines, but it is effective in decreasing their frequency and length. It is also much better tolerated than the currently existing therapies. While it is unlikely to provide monotherapy for migraines, it is a novel therapy that may be added for cases of severe or frequent migraines.

Management of Patients With Chronic Pain in Ambulatory Surgery Centers.

In the setting of increasingly streamlined surgical techniques and perioperative care, the United States healthcare system is seeing a steady rise in the number of procedures being carried out at ambulatory surgery centers. Concurrently, awareness and diagnosis of both chronic pain conditions and substance use disorders have also improved in recent years. As a result of these two shifts, the demographic characteristics of patients undergoing procedures at ambulatory surgery centers are actively evolving. Chronic pain and substance use disorders are difficult to manage in both the outpatient and inpatient settings and present unique challenges in the context of perioperative planning. Both conditions are associated with worsened postoperative outcomes, including refractory pain, decreased functional status, increased length of stay, increased readmission rates, and increased economic costs. There has been a recent movement to include a preoperative risk stratification calculation for these patients, followed by the implementation of enhanced recovery after surgery (ERAS) protocols in these patient cohorts. Taking a step further, patients benefit when standard ERAS protocols are augmented by integrating designated pain specialists into the ambulatory surgery team. This multimodal and multidisciplinary approach must be assessed in the context of the human and financial resources of a given institution and surgery center, but has been shown to improve the quality and safety of perioperative care effectively.

Maximization of Non-Opioid Multimodal Analgesia in Ambulatory Surgery Centers.

Ambulatory surgery centers aid the healthcare system by not only providing a cost-effective option for delivery of care but also by helping to reduce overwhelming case volumes at inpatient facilities. While outpatient protocols have been designed for an increasing number of surgical procedures, the inpatient to outpatient transition of surgery remains limited by both procedure type and patient comorbidities. This limitation stems in part from the heavy emphasis on accelerated discharge following outpatient procedures, given that prolonged recovery time is associated with delayed turnover and increased nursing care demands. Since its inception, enhanced recovery after surgery (ERAS) has aimed to primarily reduce the disruption of physiologic homeostasis that occurs secondary to surgery. More recently, the aim of ERAS has evolved to help transition inpatient procedures to outpatient settings and may even be useful in more emergent cases. It should be noted, however, that outpatient surgery even in combination with ERAS is not the best option for all patients, and the use of ERAS protocols should be complemented with predictive assessments of patient risk. Beyond augmenting the efficiency of outpatient surgery, ERAS protocols, when used in eligible patients and especially when combined with regional anesthetic techniques, are effective in delivering opioid-sparing pain management while increasing overall outcomes and patient satisfaction rates.

Investigating the Impact of Gadolinium-Based Contrast Agents on the Corrected QT Interval.

Introduction The manufacturing labels for all currently marketed gadolinium-based MRI contrast agents describe adverse cardiac events reported during post-market use. The goal of this study was to determine prolongation of the rate-corrected QT interval occurs in the immediate setting after gadolinium-based MRI contrast agent injection. Methods This study enrolled adults scheduled to have a gadolinium-based MRI contrast agent injection as part of a diagnostic MRI. A single-lead electrocardiogram was recorded using the AliveCor Kardia® ECG (Mountain View, CA) device before and after injection. The rate-corrected QT interval was subsequently measured by two independent investigators. The QT interval was corrected for rate using the two most common formulas, originally cited by Bazett and Fridericia. These rate-corrected QT intervals from before and after gadolinium-based MRI contrast agent injection were compared using the Wilcoxon signed-rank test paired analysis. Results A total of 24 consenting adults had electrocardiogram that were free of motion artifact. The mean age of the final patient cohort was 59.4 years. There was an equal split of 12 men and 12 women. The mean pre-injection, rate-corrected QT interval, corrected using Bazett's formula, was 395 msec. The mean post-injection, rate-corrected QT interval, corrected using Bazett's formula, was 396 msec. The corrections using Fridericia's formula were 384 and 381 msec, respectively. There was no statistically significant change in Bazett-corrected QT interval (QTc-B) when pre-injection and post-injection values were directly compared. Discussion The results of the present investigation support the conclusion that gadolinium-based MRI contrast agents do not commonly affect rate-corrected QT interval in routine clinical use. While the frequency of rate-corrected QT interval prolongation might be overstated, the severity of adverse events is definitively not. A role for concomitant rate-corrected QT interval-prolonging drugs or unidentified rare factors such as genetic predisposition cannot be ruled out. The limitations of this study include its relatively small size and the implementation of a single-lead electrocardiogram to measure rate-corrected QT interval. Conclusion The present investigation revealed that significant rate-corrected QT interval prolongation, while previously reported in as many as 55% of patients after gadolinium-based MRI contrast agent injection, is not a common occurrence in the routine clinical setting.