Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database.

BACKGROUND: Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo. OBJECTIVE: Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19. METHOD: We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded. RESULTS: A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively. CONCLUSIONS AND RELEVANCE: This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.

Anxiety and dysautonomia symptoms in patients with a NaV1.7 mutation and the potential benefits of low-dose short-acting guanfacine.

PURPOSE: Guanfacine is an α2A-adrenergic receptor agonist, FDA-approved to treat attention-deficit hyperactivity disorder and high blood pressure, typically as an extended-release formulation up to 7 mg/day. In our dysautonomia clinic, we observed that off-label use of short-acting guanfacine at 1 mg/day facilitated symptom relief in two families with multiple members presenting with severe generalized anxiety. We also noted anecdotal improvements in associated dysautonomia symptoms such as hyperhidrosis, cognitive impairment, and palpitations. We postulated that a genetic deficit existed in these patients that might augment guanfacine susceptibility. METHODS: We used whole-exome sequencing to identify mutations in patients with shared generalized anxiety and dysautonomia symptoms. Guanfacine-induced changes in the function of voltage-gated Na+ channels were investigated using voltage-clamp electrophysiology. RESULTS: Whole-exome sequencing uncovered the p.I739V mutation in SCN9A in the proband of two nonrelated families. Moreover, guanfacine inhibited ionic currents evoked by wild-type and mutant NaV1.7 encoded by SCN9A, as well as other NaV channel subtypes to a varying degree. CONCLUSION: Our study provides further evidence for a possible pathophysiological role of NaV1.7 in anxiety and dysautonomia. Combined with off-target effects on NaV channel function, daily administration of 1 mg short-acting guanfacine may be sufficient to normalize NaV channel mutation-induced changes in sympathetic activity, perhaps aided by partial inhibition of NaV1.7 or other channel subtypes. In a broader context, expanding genetic and functional data about ion channel aberrations may enable the prospect of stratifying patients in which mutation-induced increased sympathetic tone normalization by guanfacine can support treatment strategies for anxiety and dysautonomia symptoms.

SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome.

Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding protein family of transcription factors. ATF5 regulates stress responses and cell survival, proliferation, and differentiation and also plays a role in viral infections, cancer, diabetes, schizophrenia, and the olfactory system. Moreover, it was found to also have a critical cell cycle-dependent structural function at the centrosome. However, the mechanism that controls the localization of ATF5 at the centrosome is unclear. Here we report that ATF5 is small ubiquitin-like modifier (SUMO) 2/3-modified at a conserved SUMO-targeting consensus site in various types of mammalian cells. We found that SUMOylation of ATF5 is elevated in the G1 phase of the cell cycle and diminished in the G2/M phase. ATF5 SUMOylation disrupted the interaction of ATF5 with several centrosomal proteins and dislodged ATF5 from the centrosome at the end of the M phase. Of note, blockade of ATF5 SUMOylation deregulated the centrosome cycle, impeded ATF5 translocation from the centrosome, and caused genomic instability and G2/M arrest in HeLa cells. Our results indicate that ATF5 SUMOylation is an essential mechanism that regulates ATF5 localization and function at the centrosome.

Real-time single-molecule electronic DNA sequencing by synthesis using polymer-tagged nucleotides on a nanopore array.

DNA sequencing by synthesis (SBS) offers a robust platform to decipher nucleic acid sequences. Recently, we reported a single-molecule nanopore-based SBS strategy that accurately distinguishes four bases by electronically detecting and differentiating four different polymer tags attached to the 5'-phosphate of the nucleotides during their incorporation into a growing DNA strand catalyzed by DNA polymerase. Further developing this approach, we report here the use of nucleotides tagged at the terminal phosphate with oligonucleotide-based polymers to perform nanopore SBS on an α-hemolysin nanopore array platform. We designed and synthesized several polymer-tagged nucleotides using tags that produce different electrical current blockade levels and verified they are active substrates for DNA polymerase. A highly processive DNA polymerase was conjugated to the nanopore, and the conjugates were complexed with primer/template DNA and inserted into lipid bilayers over individually addressable electrodes of the nanopore chip. When an incoming complementary-tagged nucleotide forms a tight ternary complex with the primer/template and polymerase, the tag enters the pore, and the current blockade level is measured. The levels displayed by the four nucleotides tagged with four different polymers captured in the nanopore in such ternary complexes were clearly distinguishable and sequence-specific, enabling continuous sequence determination during the polymerase reaction. Thus, real-time single-molecule electronic DNA sequencing data with single-base resolution were obtained. The use of these polymer-tagged nucleotides, combined with polymerase tethering to nanopores and multiplexed nanopore sensors, should lead to new high-throughput sequencing methods.

Patient and oncologist perceptions regarding symptoms and impact on quality-of-life of oral mucositis in cancer treatment: results from the Awareness Drives Oral Mucositis PercepTion (ADOPT) study.

PURPOSE: This descriptive cross-sectional survey aims to assess the level of concordance between the perspectives of oncologists and those of patients regarding oral mucositis (OM) symptoms, and the impact of OM on various aspects of daily living and concurrent cancer management. METHODS: Oncologists involved in OM management (n = 105), and patients who developed OM during cancer treatment (n = 175), were recruited from seven Asian countries. Oncologists completed a face-to-face, quantitative interview; patients completed a face-to-face interview, and a self-reported questionnaire. RESULTS: Oncologists and patients ranked treatment-induced OM among the three most important toxicities of cancer therapy requiring intervention. The most frequent OM symptoms reported by patients were oral ulcers (74%), dry mouth (73%), and difficulty swallowing (62%). Oncologists expected mild OM symptoms to last slightly longer than 1 week, whereas patients reported mild symptoms for more than 2 weeks. In mild-to-moderate OM, oncologists underestimated patients' pain experience. Overall, only 45% of oncologists said they would initiate OM prophylaxis when cancer therapy started. Of the 87% of patients who said they used their prescribed medications, only 16% reported using prophylactically prescribed medication. While oncologists' concerns related to the delays and interruptions of cancer treatment, patients tended to focus on the effects of OM on eating, drinking, and talking. CONCLUSIONS: Oncologists' and patients' perceptions about treatment-induced OM differ. To overcome discordant perspectives, there is a need to raise general awareness and improve proactive management of OM. As noted in recent guidelines, supportive cancer care is critical for ensuring optimal therapy and for improving the patient's experience.

Resolution of Diplopia in Late Repair of Enophthalmos Following Facial Trauma.

Posttraumatic enophthalmos due to isolated or complex orbital fractures can contribute to diplopia. Current evidence recommends early repair. However, little is known about the outcome of enophthalmos correction when repair occurs beyond 30 days after trauma. In this systematic review, the authors aim to evaluate the current evidence on functional outcomes after delayed repair of posttraumatic enophthalmos.Two independent assessors undertook a systematic review of the literature using multiple databases. The authors' inclusion criteria identified studies involving patients at least 14 years of age who had surgical correction of persistent enophthalmos 30 days after initial trauma. Each eligible paper was included after critical appraisal using validated guidelines. Data on preoperative and postoperative enophthalmos and diplopia in each study was extracted. The pattern of fracture was also noted.The authors' search for the medical databases yielded 1053 articles, of which 6 eligible papers were included. Meta-analysis was performed. In patients with complex injuries involving orbital and mid-facial fractures, diplopia resolution was calculated to be 53%, and enophthalmos was corrected in 83% of the patients. In patients with isolated orbital fractures, 53% had resolution of their diplopia, and enophthalmos was corrected in 88% of the patients.Enophthalmos can be corrected to within 2 mm of the contralateral eye in both the isolated and complex orbital fractures in patients who present 30 days or greater after injury. Based on the studies reviewed, there is less predictability in diplopia resolution.

Characterization of neuronal death and functional deficits following nerve injury during the early postnatal developmental period in rats.

In contrast to adult rat nerve injury models, neonatal sciatic nerve crush leads to massive motor and sensory neuron death. Death of these neurons results from both the loss of functional contact between the nerve terminals and their targets, and the inability of immature Schwann cells in the distal stump of the injured nerve to sustain regeneration. However, current dogma holds that little to no motoneuron death occurs in response to nerve crush at postnatal day 5 (P5). The purpose of the current study was to fully characterize the extent of motor and sensory neuronal death and functional recovery following sciatic nerve crush at mid-thigh level in rats at postnatal days 3-30 (P3-P30), and then compare this to adult injured animals. Following nerve crush at P3, motoneuron numbers were reduced to 35% of that of naïve uninjured animals. Animals in the P5 and P7 group also displayed statistically fewer motoneurons than naïve animals. Animals that were injured at P30 or earlier displayed statistically lower sensory neuron counts in the dorsal root ganglion than naïve controls. Surprisingly, complete behavioral recovery was observed exclusively in the P30 and adult injured groups. Similar results were observed in muscle twitch/tetanic force analysis, motor unit number estimation and wet muscle weights. Rats in both the P5 and P7 injury groups displayed significant neuronal death and impaired functional recovery following injury, challenging current dogma and suggesting that severe deficits persist following nerve injury during this early postnatal developmental period. These findings have important implications concerning the timing of neonatal nerve injury in rats.

A prospective study of pediatric hand fractures and review of the literature.

OBJECTIVE: Hand fractures represent a leading cause of morbidity in children. However, little information exists correlating the mechanisms and environment of injury with outcomes and treatments. We examine the demographics, etiology, anatomic location, mechanism, and management of pediatric hand fractures in our center's hand unit. METHODS: We conducted a prospective observational study on all children with acute hand fractures evaluated in the Plastic Surgery Emergency Clinic during a 3-month period in 2010. Data pertaining to demographics, referral patterns, injury pattern, clinical outcomes, and other factors related to hand fractures were then analyzed and interpreted. RESULTS: Most children were referred by our institution's emergency department. More than 60% were boys, and nearly half were between 10 and 15 years old. The right and left hands were injured at equal rates. Most of the injuries (90%) occurred in the afternoon or evening. More than 85% occurred in urban, rather than rural, environments. Crush injuries were the leading cause in toddlers, whereas sports-related injuries became the major cause of injury in older groups. Proximal phalanges were the most common bone injured, and the fifth digit was the most commonly injured digit. More than 80% of the fractures were managed nonsurgically. CONCLUSIONS: The pattern of pediatric hand fracture in different age groups is highlighted in this article. The observations from this study will hopefully encourage further review with a larger cohort and a focus on preventative measures for pediatric hand fractures.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

CXCL12+ dermal fibroblasts promote neutrophil recruitment and host defense by recognition of IL-17.

The skin provides an essential barrier for host defense through rapid action of multiple resident and recruited cell types, but the complex communication network governing these processes is incompletely understood. To define these cell-cell interactions more clearly, we performed an unbiased network analysis of mouse skin during invasive S. aureus infection and revealed a dominant role for CXCL12+ fibroblast subsets in neutrophil communication. These subsets predominantly reside in the reticular dermis, express adipocyte lineage markers, detect IL-17 and TNFα, and promote robust neutrophil recruitment through NFKBIZ-dependent release of CXCR2 ligands and CXCL12. Targeted deletion of Il17ra in mouse fibroblasts resulted in greatly reduced neutrophil recruitment and increased infection by S. aureus. Analogous human CXCL12+ fibroblast subsets abundantly express neutrophil chemotactic factors in psoriatic skin that are subsequently decreased upon therapeutic targeting of IL-17. These findings show that CXCL12+ dermal immune acting fibroblast subsets play a critical role in cutaneous neutrophil recruitment and host defense.

Increased LL37 in psoriasis and other inflammatory disorders promotes LDL uptake and atherosclerosis.

Patients with chronic inflammatory disorders such as psoriasis have an increased risk of cardiovascular disease and elevated levels of LL37, a cathelicidin host defense peptide that has both antimicrobial and proinflammatory properties. To explore whether LL37 could contribute to the risk of heart disease, we examined its effects on lipoprotein metabolism and show that LL37 enhanced LDL uptake in macrophages through the LDL receptor (LDLR), scavenger receptor class B member 1 (SR-B1), and CD36. This interaction led to increased cytosolic cholesterol in macrophages and changes in expression of lipid metabolism genes consistent with increased cholesterol uptake. Structure-function analysis and synchrotron small-angle x-ray scattering showed structural determinants of the LL37-LDL complex that underlie its ability to bind its receptors and promote uptake. This function of LDL uptake is unique to cathelicidins from humans and some primates and was not observed with cathelicidins from mice or rabbits. Notably, Apoe-/- mice expressing LL37 developed larger atheroma plaques than did control mice, and a positive correlation between plasma LL37 and oxidized phospholipid on apolipoprotein B (OxPL-apoB) levels was observed in individuals with cardiovascular disease. These findings provide evidence that LDL uptake can be increased via interaction with LL37 and may explain the increased risk of cardiovascular disease associated with chronic inflammatory disorders.

Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair.

The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide-glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation.

Functional recovery following peripheral nerve injury in the transgenic Thy1-GFP rat.

Transgenic mice have been previously used to assess nerve regeneration following peripheral nerve injury. However, mouse models are limited by their small caliber nerves, short nerve lengths, and their inability to fully participate during behavioral assessments. The transgenic Thy1 GFP rat is a novel transgenic rat model designed to assess regeneration following peripheral nerve injury. However, return of functional and behavioral recovery following nerve injury has not yet been evaluated in these rats. In this study, we ask whether differences in anatomy, recovery of locomotion, myological, and histomorphological measures exist between transgenic Thy1 GFP rats when compared to wild type (WT) Sprague Dawley rats following unilateral sciatic nerve injury. We found that both motor and sensory neuronal architecture, overground and skilled locomotion, muscle force, motor unit number estimation (MUNE) and wet muscle weights, and histomorphometric assessments are similar between both genetic phenotypes. Overall, these data support the use of the transgenic Thy1-GFP rat in experiments assessing functional and behavioral recovery following nerve injury and repair.

Pronounced State-Level Disparities in Prescription of Cannabinoids to Medicaid Patients.

Introduction: Dronabinol is approved in the USA for chemotherapy-induced nausea as well as vomiting and HIV-induced anorexia, while cannabidiol is primarily approved for childhood epileptic disorders Lennox-Gastaut and Dravet syndrome. The use pattern for these prescription cannabinoids in the USA is unknown. This study examined Medicaid claims for two FDA-approved prescription cannabinoids, dronabinol and cannabidiol, approved in 1985 and 2018, respectively, from 2016-2020 to better understand the pharmacoepidemiologic trends and distribution of these drugs in US Medicaid amidst the increasing use of non-pharmaceutical formulations of cannabis. Methods: The longitudinal study analyzed Medicaid prescription claims that were calculated by extracting the prescriptions on a state level from 2016 to 2020 for two cannabinoids, dronabinol and cannabidiol, where outcomes over each year were calculated. Outcomes were (1) the number of prescriptions for each state corrected for the number of Medicaid enrollees and (2) dronabinol and cannabidiol spending. Spending refers to the amount reimbursed by the state Medicaid program. Results: Dronabinol prescriptions per state decreased by 25.3% from 2016 to 2020, while cannabidiol prescriptions increased by 16,272.99% from 2018 to 2020. The spending on these drugs parallels that of their prescription trend with a 66.3% decrease in reimbursement for dronabinol ($5.7 million in 2020), whereas cannabidiol increased by +26,582.0% ($233.3 million in 2020). Dronabinol prescriptions, when corrected for the number of enrollees, in Connecticut were 136.4 times larger than in New Mexico, and seventeen states had zero prescriptions. Idaho's prescriptions of cannabidiol (27.8/10,000 enrollees) were significantly elevated relative to the national average and were 15.4-fold higher than Washington, DC (1.8/10K enrollees). Conclusions: The prescriptions of pharmaceutical-grade tetrahydrocannabinol decreased while those of cannabidiol increased. This study also identified pronounced state-level variation in cannabinoid prescribing to Medicaid patients. State formularies and prescription drug list variation may contribute to the drug reimbursements in Medicaid, though further research is needed to identify the health policy or pharmacoeconomic origins of these disparities.

Variation in adverse drug events of opioids in the United States.

Background: The United States (US) ranks high, nationally, in opioid consumption. The ongoing increase in the misuse and mortality amid the opioid epidemic has been contributing to its rising cost. The worsening health and economic impact of opioid use disorder in the US warrants further attention. We, therefore, assessed commonly prescribed opioids to determine the opioids that were over-represented versus under-represented for adverse drug events (ADEs) to better understand their distribution patterns using the Food and Drug Administration's Adverse Event Reporting System (FAERS) while correcting for distribution using the Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS). Comparing the ratio of the percentage of adverse drug events as reported by the FAERS relative to the percentage of distribution as reported by the ARCOS database is a novel approach to evaluate post-marketing safety surveillance and may inform healthcare policies and providers to better regulate the use of these opioids. Methods: We analyzed the adverse events for 11 prescription opioids, when correcting for distribution, and their ratios for three periods, 2006-2010, 2011-2016, and 2017-2021, in the US. The opioids include buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Oral morphine milligram equivalents (MMEs) were calculated by conversions relative to morphine. The relative ADEs of the selected opioids, opioid distributions, and ADEs relative to distribution ratios were analyzed for the 11 opioids. Results: Oxycodone, fentanyl, and morphine accounted for over half of the total number of ADEs (n = 667,969), while meperidine accounted for less than 1%. Opioid distributions were relatively constant over time, with methadone repeatedly accounting for the largest proportions. Many ADE-to-opioid distribution ratios increased over time, with meperidine (60.6), oxymorphone (11.1), tapentadol (10.3), and hydromorphone (7.9) being the most over-represented for ADEs in the most recent period. Methadone was under-represented (<0.20) in all the three periods. Conclusion: The use of the FAERS with the ARCOS provides insights into dynamic changes in ADEs of the selected opioids in the US. There is further need to monitor and address the ADEs of these drugs.

Determining the optimal radiologic wrist and forearm position to visualize screw protrusion in scaphoid fixation.

BACKGROUND: Surgical fixation of scaphoid fractures may result in unrecognized screw protrusion and subsequent cartilage damage to the adjacent joints. The purpose of this study was to use a three-dimensional (3D) scaphoid model to determine the wrist and forearm positioning that will allow intra-operative fluoroscopic visualization of screw protrusions. METHODS: Two 3D scaphoid models, with the wrist in neutral and 20° ulnar deviated, were reconstructed from a cadaveric wrist using the Mimics software. The scaphoid models were divided into three segments and further divided into four quadrants in each of the three segments along the scaphoid axes. Two virtual screws, with a 2 and 1 mm groove from the distal border, were placed so that the screws protrude from each quadrant. The wrist models were rotated along the long axis of the forearm and the angles at which the screw protrusions were visualized were recorded. RESULTS: One-millimetre screw protrusions were visualized at a narrower range of forearm rotation angles compared to 2 mm screw protrusions. One-millimetre screw protrusions in the middle dorsal ulnar quadrant could not be detected. Visualization of the screw protrusion in each quadrant varied with forearm and wrist positioning. CONCLUSION: In this model, all screw protrusions, except 1 mm protrusions in the middle dorsal ulnar quadrant, were visualized with the forearm in pronation, supination or in the mid-pronation position and with the wrist in neutral or 20° ulnar deviated.

A 40-Year-Old Man with Anemia, Proctitis, Rectal Bleeding, and a Perianal Rash Due to Mpox (Monkeypox) Infection.

BACKGROUND A recently described zoonotic viral infection, mpox (monkeypox), is an Orthopoxvirus transmitted by close contact, which causes symptoms similar to smallpox, although less severe. This report presents the case of a 40-year-old man with anemia, proctitis, rectal bleeding, and a perianal rash due to mpox infection. CASE REPORT A 40-year-old man with a medical history of human immunodeficiency virus (HIV) and syphilis presented multiple times with progressive and painful perianal lesions. On initial presentation, swabbing of the lesions and polymerase chain reaction (PCR) testing confirmed a diagnosis of mpox infection, and treatment with a 14-day course of Tecovirimat was started. Nine days after initiating Tecovirimat, the patient presented again with worsening perianal pain and associated hematochezia resulting in acute symptomatic anemia. Despite a blood transfusion to treat his anemia, the patient's status declined as his viral symptoms progressed. Computed tomography (CT) investigation demonstrated significant proctitis with interval development of small perianal abscesses. A multidisciplinary approach for medical management and treatment was instituted. The resolution of the patient's anemia and mpox proctitis was confirmed on follow-up. CONCLUSIONS Despite treatment with antiviral agents, mpox infection can progress quickly; thus, swift management with a multidisciplinary approach and close follow-up is needed to treat and prevent secondary complications such as anemia and proctitis. Further data collection regarding the sexual practices of those with diagnoses of mpox as well as seminal, anorectal, and genital swabbing would be valuable to confirm the mode of transmission and cause of mpox proctitis.

Clinical Practice Guidelines for the Detection and Treatment of Depression in Multiple Sclerosis: A Systematic Review.

Purpose of Review: The association of multiple sclerosis (MS) with depression has been well documented; however, it frequently remains undiagnosed, untreated, or undertreated, with consequences to the person, family, and economy. The aim of this study was to determine the quality, scope, and consistency of available guidelines and consensus statements to guide clinicians managing people with comorbid MS and depression. Recent Findings: Based on our systematic search of the literature, 6 guidelines and consensus statements met the inclusion criteria. Of these, 4 presented recommendations on depression screening in MS and 5 offered recommendations for treatment. Despite most guidelines presenting evidence-based recommendations, they were generally of low-quality evidence overall. Inconsistencies identified across guidelines and consensus statements included variations in recommendation for routine screening and which screening tool to use. Most guidelines lacked detail, often referring to general population guidelines without describing to what extent they can be applied to people with MS. Summary: The findings of this review highlight the need to develop high-quality, comprehensive clinical practice guidelines with clear recommendations that can be globally implemented by healthcare clinicians working with people with MS.

Radiation Therapy in the Last Month of Life: Association With Aggressive Care at the End of Life.

CONTEXT: Half of the patients with cancer who undergo radiation therapy do so with palliative intent. OBJECTIVES: To determine the proportion of undergoing radiation in the last month of life, patient characteristics, cancer course, the type and duration of radiation, whether palliative care was involved, and the of radiation with aggressive cancer care metrics. METHODS: One thousand seven hundred twenty-seven patients who died of cancer between January 1, 2018, and December 31, 2019, were included. Demographics, cancer stage, palliative care referral, advance directives, use of home health care, radiation timing, and survival were collected. Type of radiation, course, and intent were reviewed. Chi-square analysis was utilized for categorical variables, and Kruskal-Wallis tests for continuous variables. A stepwise selection was used to build a Cox proportional hazard model. RESULTS: Two hundred thirty-three patients underwent radiation in the last month of life. Younger patients underwent radiation 67.3 years (SD 11.52) versus 69.2 years (SD 11.96). 42.6% had radiation within two weeks of death. The average fraction number was 5.5. Individuals undergoing radiation were more likely to start chemotherapy within the last 30 days of life, continue chemotherapy within two weeks of death, be admitted to the ICU, and have two or more hospitalizations or emergency room visits. Survival measured from the date of diagnosis was shorter for those undergoing radiation, 122 days (IQR 58-462) versus 474 days (IQR 225-1150). Palliative care consultations occurred later in those undergoing radiation therapy. CONCLUSION: Radiation therapy in the last month of life occurs in younger patients with rapidly progressive cancer, who are subject to more aggressive cancer care, and have late palliative care consults.

Severe Gastrointestinal Hemorrhage due to Monkeypox Virus-Associated Proctocolitis.

Monkeypox is primarily a painful cutaneous disease with occasional systemic manifestations. Monkeypox is transmitted predominantly through close physical contact and occasionally sexual contact. The first case was reported in the United States on May 17, 2022, in a recent monkeypox worldwide outbreak. We present a case of severe gastrointestinal bleeding as an atypical manifestation of monkeypox infection in a 40-year-old male with HIV. In our case, monkeypox-induced proctocolitis progressed to severe rectal bleeding requiring one unit of packed red blood cells transfusion despite one week of tecovirimat (TPOXX) therapy. So, patients should be educated about the possibility of unusual complications of monkeypox infection, i.e., bleeding in immunocompromised hosts.