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.

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.

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.

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.

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.

Staphylococcus epidermidis activates keratinocyte cytokine expression and promotes skin inflammation through the production of phenol-soluble modulins.

Staphylococcus epidermidis is a common microbe on human skin and has beneficial functions in the skin microbiome. However, under conditions of allergic inflammation, the abundance of S. epidermidis increases, establishing potential danger to the epidermis. To understand how this commensal may injure the host, we investigate phenol-soluble modulin (PSM) peptides produced by S. epidermidis that are similar to peptides produced by Staphylococcus aureus. Synthetic S. epidermidis PSMs induce expression of host defense genes and are cytotoxic to human keratinocytes. Deletion mutants of S. epidermidis lacking these gene products support these observations and further show that PSMs require the action of the EcpA bacterial protease to induce inflammation when applied on mouse skin with an intact stratum corneum. The expression of PSMδ from S. epidermidis is also found to correlate with disease severity in patients with atopic dermatitis. These observations show how S. epidermidis PSMs can promote skin inflammation.

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.

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.

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.

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.

Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine.

Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an ex vivo tool for personalized medicine.

Antibiotic Prophylaxis in Alloplastic Breast Reconstruction: Regimens and Outcomes.

PURPOSE: Surgical site infections (SSI) in prosthesis-based breast reconstruction can have a significant impact on patient outcome. Despite current CDC (Centers for Disease Control and Prevention) guidelines recommending 24 hours of postoperative antibiotics, various perioperative antimicrobial regimens are reported in the literature. Consensus on the optimal duration of antibiotics remains unclear. In this study, the aim is to compare the incidence of surgical site infections following different antibiotic durations in alloplastic breast reconstruction. METHODS: In this retrospective cohort study, all consecutive patients who underwent expander/implant-based breast reconstruction between January 2009 and December 2014 at a tertiary centre were included. Data on patient demographics, risk factors, operative time, choice and timing of antibiotic used before surgery, and the duration of postoperative antibiotic use were collected. The primary outcome, SSI, is defined according to CDC criteria. RESULTS: A total of 507 consecutive expander/implant-based cases were included. Minimum follow-up time was 1 year. The overall infection incidence was 14% (95% CI: 11%-17%), and the rate of subsequent explantation was 8%. Of the infected cases, 80% (45/56) received 1 week of postoperative antibiotic, while 20% (11/56) had a prolonged course of antibiotics (2-3 weeks; P = .003, odds ratio [OR] = 2.9; 95% CI: 1.4-5.8). Most infections were superficial (65%). Prior history of radiation treatment was identified as a risk factor for developing surgical site infection (P = .02). CONCLUSION: Overall infection rate and risk factors for infections are in keeping with current literature. Prescribing one week of postoperative antibiotic was found to be associated with a higher incidence of SSI compared to a more prolonged antibiotic regimen.

OBJECTIF: Les infections au site opératoire (ISO) des reconstructions mammaires avec prothèse peuvent avoir des conséquences importantes sur le pronostic de la patiente. Malgré les directives à jour des Centers for Disease Control and Prevention (CDC) recommandant la prise d'antibiotiques pendant 24 heures après l'opération, les publications font état de diverses posologies antimicrobiennes périopératoires. La durée consensuelle optimale de la prise d'antibiotiques n'est pas bien établie. Dans la présente étude, les chercheurs comparent l'incidence d'ISO après une reconstruction mammaire alloplastique en fonction de diverses durées d'antibiothérapie. MÉTHODOLOGIE: Toutes les patientes consécutives qui ont subi une reconstruction mammaire par expanseurs ou par implants entre janvier 2009 et décembre 2014 dans un centre de soins tertiaires ont participé à la présente étude rétrospective de cohorte. Les chercheurs ont colligé les données sur la démographie, les facteurs de risque, la durée de l'opération, le choix et le moment de l'antibiothérapie préopératoire ainsi que la durée de l'antibiothérapie postopératoire. Le résultat clinique primaire, les ISO, est défini d'après les critères des CDC. RÉSULTATS: Au total, 507 cas consécutifs d'expanseurs ou d'implants ont été inclus dans l'étude. Le suivi était d'une durée minimale d'un an. L'incidence globale d'infection s'élevait à 14 % (IC à 95 %, 11 % à 17 %) et le taux d'explantations subséquent, à 8 %. De plus, 80 % des cas d'infection (45 sur 56) avaient reçu une antibiothérapie postopératoire d'une semaine, et 20 % (11 sur 56), une antibiothérapie prolongée (de 2 à 3 semaines; p=0,003, rapport de cote=2,9; IC à 95 %, 1,4 à 5,8). La plupart des infections étaient superficielles (65 %). Une radiothérapie antérieure était considérée comme un facteur de risque d'ISO (p=0,02). CONCLUSION: Le taux et les facteurs de risque globaux d'infection sont conformes aux publications à ce jour. La prescription d'antibiotiques pendant une semaine après l'opération était associée à une plus forte incidence d'ISO qu'une antibiothérapie plus longue.

A Rare Occurrence of Tularemia in New Jersey.

Tularemia has been well described clinically in the United States since the early 1900s. Worldwide, the infection has manifested in a variety of forms through various vectors with geography and local prevalence often considered in the diagnostic work-up. We present a case of a 57-year-old patient who lived in an area with low tularemia infection rates and presented with fever and a tender, swollen elbow. Though initially diagnosed with cellulitis, she was eventually found to have tularemia after further interviewing and questioning, followed by successful treatment with doxycycline. A thorough history including exposures and daily activities should always be considered in an effort to rule out rare infections, even in areas of low disease prevalence.

Surgical Repair of Triangular Fibrocartilage Complex Tears: A Systematic Review.

Objective This study systematically reviews the outcomes of surgical repair of triangular fibrocartilage complex (TFCC) tears. Existing surgical techniques include capsular sutures, suture anchors, and transosseous sutures. However, there is still no consensus as to which is the most reliable method for ulnar-sided peripheral and foveal TFCC tears. Methods A systematic review of MEDLINE and EMBASE was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The focus was on traumatic Palmer 1B ulna-sided tears. Twenty-seven studies were included, including three comparative cohort studies. Results There was improvement in all functional outcome measures after repair of TFCC tears. The outcomes following peripheral and foveal repairs were good overall: Mayo Modified Wrist Evaluation (MMWE) score of 80.1 and 85.1, Disabilities of the Arm, Shoulder and Hand (DASH) score of 15.7 and 15.8, grip strength of 80.3 and 92.7% (of the nonoperated hand), and pain intensity score of 2.1 and 1.7, respectively. For peripheral tears, transosseous suture technique achieved better outcomes compared with capsular sutures in terms of grip strength, pain, Patient-Rated Wrist Evaluation (PRWE), and DASH scores (grip 85.8 vs. 77.7%; pain 1.5 vs. 2.2; PRWE 11.6 vs. 15.8; DASH 14.4 vs. 16.1). For foveal tears, transosseous sutures achieved overall better functional outcomes compared with suture anchors (MMWE 85.4 vs. 84.9, DASH 10.9 vs. 20.6, pain score 1.3 vs. 2.1), but did report slightly lower grip strength than the group with suture anchors (90.2 vs. 96.2%). Arthroscopic techniques achieved overall better outcomes compared with open repair technique. Conclusion Current evidence demonstrates that TFCC repair achieves good clinical outcomes, with low complication rates. Level of Evidence This is a Level IV, therapeutic study.

Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism.

BACKGROUND: The human orbitofrontal cortex (OFC) is involved in assessing the emotional significance of events and stimuli, emotion-based learning, allocation of attentional resources, and social cognition. Little is known about the structure, connectivity and excitatory/inhibitory circuit interactions underlying these diverse functions in human OFC, as well as how the circuit is disrupted in individuals with autism spectrum disorder (ASD). METHODS: We used post-mortem brain tissue from neurotypical adults and individuals with ASD. We examined the morphology and distribution of myelinated axons across cortical layers in OFC, at the single axon level, as a proxy of excitatory pathways. In the same regions, we also examined the laminar distribution of all neurons and neurochemically- and functionally-distinct inhibitory neurons that express the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR). RESULTS: We found that the density of myelinated axons increased consistently towards layer 6, while the average axon diameter did not change significantly across layers in both groups. However, both the density and diameter of myelinated axons were significantly lower in the ASD group compared with the Control group. The distribution pattern and density of the three major types of inhibitory neurons was comparable between groups, but there was a significant reduction in the density of excitatory neurons across OFC layers in ASD. LIMITATIONS: This study is limited by the availability of human post-mortem tissue optimally processed for high-resolution microscopy and immunolabeling, especially from individuals with ASD. CONCLUSIONS: The balance between excitation and inhibition in OFC is at the core of its function, assessing and integrating emotional and social cues with internal states and external inputs. Our preliminary results provide evidence for laminar-specific changes in the ratio of excitation/inhibition in OFC of adults with ASD, with an overall weakening and likely disorganization of excitatory signals and a relative strengthening of local inhibition. These changes likely underlie pathology of major OFC communications with limbic or other cortices and the amygdala in individuals with ASD, and may provide the anatomic basis for disrupted transmission of signals for social interactions and emotions in autism.

Disseminated Neisseria gonorrhea of the wrist.

Disseminated gonococcal infection (DGI) is seen in about 0.5-3% of patients with Neisseria gonorrhoeae. Patients with DGI present with mucosal involvement, septic arthritis and sometimes bacteremia. We present a case of a 62-year-old female with a history of HIV and rheumatoid arthritis admitted with DGI and septic arthritis of the wrist without mucosal involvement or systemic symptoms. The patient underwent incision and drainage with arthrotomy of the right wrist by hand surgery and received a 2-week course of intravenous ceftriaxone. After surgery and initiation of antibiotic treatment, there was marked improvement of her symptoms and she remains asymptomatic at follow-up.