Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.

Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. We found that two independent methods of slow delivery immunization of rhesus monkeys (RMs) resulted in more robust T follicular helper (TFH) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous nAbs. Using a new RM genomic immunoglobulin locus reference, we identified differential IgV gene use between immunization modalities. Ab mapping demonstrated targeting of immunodominant non-neutralizing epitopes by conventional bolus-immunized animals, whereas slow delivery-immunized animals targeted a more diverse set of epitopes. Thus, alternative immunization strategies can enhance nAb development by altering GCs and modulating the immunodominance of non-neutralizing epitopes.

Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion.

We examined the role of innate cells in acquired resistance to the natural murine parasitic nematode, Nippostrongylus brasiliensis. Macrophages obtained from lungs as late as 45 d after N. brasiliensis inoculation were able to transfer accelerated parasite clearance to naive recipients. Primed macrophages adhered to larvae in vitro and triggered increased mortality of parasites. Neutrophil depletion in primed mice abrogated the protective effects of transferred macrophages and inhibited their in vitro binding to larvae. Neutrophils in parasite-infected mice showed a distinct transcriptional profile and promoted alternatively activated M2 macrophage polarization through secretory factors including IL-13. Differentially activated neutrophils in the context of a type 2 immune response therefore prime a long-lived effector macrophage phenotype that directly mediates rapid nematode damage and clearance.

Incident Heart Failure Risk Reclassification With Race-Independent Estimated Glomerular Filtration Rate: A National Heart, Lung, and Blood Institute Pooled Cohorts Analysis.

BACKGROUND: This study compared the predictive value of the race-independent creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) and the race-dependent creatinine-based eGFR (eGFRcr) for incident heart failure (HF). METHODS: This study combined the participant-level data from ARIC (Atherosclerosis Risk in Communities) (visit 4) and MESA (Multi-Ethnic Study of Atherosclerosis) (visit 1) to calculate eGFRcr-cys and eGFRcr. The primary outcome of the study was adjudicated incident HF over a follow-up period of 10 years. Multivariable Cox models were used to assess the risk of incident HF with the quartiles of eGFRcr-cys and eGFRcr. RESULTS: Among 15,615 individuals (median age: 62 [57-68] years; 55.0% females; 23.9% Black), the median eGFRcr-cys and eGFRcr were 91.4 (79.4, 102.0) mL/min/1.73m2 and 84.7 (72.0, 94.7) mL/min/1.73m2, respectively. Compared with the fourth quartile of eGFRcr-cys, the hazard ratio for incident HF was 1.02 (95% CI:0.80-1.30) in the third quartile, 1.02 (95% CI:0.80-1.30) in the second quartile, and 1.47 (95% CI:1.16-1.86) in the first quartile. Compared with the 4th quartile of the eGFRcr, the risk of incident HF was similar in the 3rd (HRadj:0.90 [95% CI:0.73-1.12]), 2nd (HRadj: 0.96 [95% CI:0.77-1.20]), and 1st (HRadj:1.15 [95% CI:0.93-1.44]) quartiles. C-statistics were similar for the multivariable-adjusted Cox models for incident HF using eGFRcr (0.80 [0.79-0.81]) and eGFRcr-cys (0.80 [0.79-0.82]). CONCLUSION: The eGFRcr and eGFRcr-cys had comparable predictive values for incident HF.

Mother-daughter technique for kinked catheter retrieval from radial artery.

Catheter kinking is not an uncommon scenario during cardiac catheterization via transradial access in patients with tortuous vascular anatomy. Several noninvasive and invasive methods have been described to unkink and retrieve the kinked catheter out of the vessel. We present a novel mother-daughter technique to retrieve a kinked radial artery catheter.

Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS.

Telephonic follow-up after day case pediatric surgery in an upper middle income country: A pilot study.

BACKGROUND: One third of South African children live in households with no employed adult. Telemedicine may save patients and the strained public health sector significant resources. We aimed to determine the safety and benefits of telephonic post-operative follow-up of patients who presented for day case surgery at CHBAH from 1 January-31 March 2023. METHODS: A prospective descriptive study on patients undergoing day case surgery was performed. Healthy patients greater than 6 years old whose caregivers spoke English and had access to a smartphone were included. Data on the total number of telephonic follow-ups, operative complications, need for in person review, satisfaction with telephonic follow-up, and savings in transport costs and time by avoiding in person follow-up were collected. RESULTS: A total of 38 telephonic follow-ups were performed. Six (15.8%) patients presented for in person review due to the detection of major complications (2, 5.3%), minor complications (2, 5.3%), and parental concern (2, 5.3%) during telephonic follow-up. All caregivers reported being satisfied with telephonic follow-up. Total savings in transport costs were R4452 (US $ 248.45). The majority of patients (29, 76.3%) had at least one unemployed parent. Seven caregivers (18.4%) avoided taking paid leave and 2 (5.3%) unpaid leave from work due to follow-up being performed telephonically. CONCLUSIONS: Innovation is necessary in order to expand access to safe, affordable, and timely care. In this selected group, telephonic follow-up was a safe, acceptable, and cost-effective intervention. The expansion of such a program has the potential for significant savings for patients and the healthcare system.

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure. Methods: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to the standard of care. We hypothesized that cell therapy would be superior to sham control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis. Measurements and Main Results: At the third interim analysis, the data and safety monitoring board recommended that the trial halt enrollment as the prespecified mortality reduction from 40% to 23% was unlikely to be achieved (n = 222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (relative risk [RR], 0.88; 95% confidence interval, 0.64-1.21; P = 0.43). There were no significant differences in days alive off ventilation within 60 days (median rank, 117.3 [interquartile range, 60.0-169.5] in cell patients and 102.0 [interquartile range, 54.0-162.5] in control subjects; higher is better). Resolution or improvement of acute respiratory distress syndrome at 30 days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) control patients (odds ratio, 1.36; 95% confidence interval, 0.57-3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate and/or severe COVID-19-related acute respiratory distress syndrome.

Nonanemic Iron Deficiency in Cardiac Surgery: A Retrospective Observational Study.

OBJECTIVES: Anemia and iron deficiency in patients having cardiac surgery increases their perioperative risk. Nonanemic iron deficiency (NAID) in this group is less well-described. We aimed to investigate the incidence and outcomes of patients with NAID undergoing cardiac surgery. DESIGN: Retrospective observational study. SETTING: A single, tertiary referral center. PARTICIPANTS: Adult patients who were preassessed and underwent cardiac surgery during the study period had data collected. We enrolled 537 patients enrolled and divided them into 4 groups according to hemoglobin and ferritin: NAID, nonanemic iron replete, iron-deficiency anemia (IDA), and non-iron-deficiency anemia. INTERVENTIONS: This study was not interventional, but assessed the impact of anemia and iron deficiency on patient outcomes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of NAID. Secondary outcomes included the number of patients who became anemic awaiting surgery, allogeneic transfusion burden, length of stay, postoperative complications, and death. 179 of 537 patients (33.3%) had NAID. Seventeen patients (9.5%) became anemic in the NAID group compared with 7 (3.3%) in the nonanemic iron replete group while awaiting for surgery (p = 0.02). Patients with NAID were more likely to receive allogeneic transfusions (33% vs 23%; p = 0.04) and had poorer recovery of hemoglobin at follow-up (13.2 ± 1.46 g/dL vs 13.9 ± 1.46 g/dL; p < 0.001). CONCLUSIONS: NAID is common and can lead to progression to anemia and increased transfusion. Iron replacement should be considered in patients with NAID in the preoperative setting. A prospective interventional trial is required to demonstrate the benefit of being iron replete.

Which Interventions Are Effective in Treating Sleep Disturbances After THA or TKA? A Systematic Review.

BACKGROUND: Poor sleep quality is a common complaint after total joint arthroplasty (TJA), and it is associated with reports of higher pain and worse functional outcomes. Several interventions have been investigated with the intent to reduce the incidence of postoperative sleep disturbance with varying effectiveness. An aggregate of the best available evidence, along with an evaluation of the quality of those studies, is needed to provide valuable perspective to physicians and to direct future research. QUESTIONS/PURPOSES: In this systematic review, we asked: (1) What is the reported efficacy of the most commonly studied medications and nonpharmacologic approaches, and (2) what are their side effects and reported complications? METHODS: This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search using a combination of controlled vocabulary and keywords was performed utilizing Medline (Ovid), Embase (Ovid), Cochrane Central, and Web of Science databases from database inception to 2023, with the last search occurring October 24, 2023, to identify studies that evaluated a sleep intervention on the effect of patient-reported sleep quality after THA or TKA. Inclusion criteria were clinical trials, comparative studies, and observational studies on adult patients who underwent primary TKA or THA for osteoarthritis and who completed validated sleep questionnaires to assess sleep quality postoperatively. We excluded studies on patients younger than 18 years, patients with sleep apnea, TKA or THA because of trauma or conditions other than osteoarthritis, revision TJA, studies in languages other than English, and studies from nonindexed journals or preprint servers. Two investigators independently screened 1535 studies for inclusion and exclusion criteria and extracted data from the included studies. Ultimately, 14 studies were included in this systematic review, including 12 randomized controlled trials and 2 prospective comparative studies. A total of 2469 participants were included, with a mean ± SD age of 65 ± 7 years and 38% men in control groups and 65 ± 7 years and 39% men in intervention groups. Sleep quality questionnaires utilized included the Pittsburgh Sleep Quality Index, Self-Rating Scale of Sleep, 100-mm VAS - Sleep, Sleep Disturbance Numeric Rating Scale, Likert scales, and one institutionally designed questionnaire. Quality analysis was performed utilizing the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Randomized Controlled Trials, where higher scores of 13 indicated a more reliable study, and the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies, where higher scores of 9 indicated a more reliable study and scores < 5 represented a high risk of bias. Two of the randomized controlled trials scored a 12 of 13, and the remaining 10 met every criteria of the JBI checklist. Both comparative studies scored 5 of 9 possible points of the Newcastle-Ottawa Scale. RESULTS: Melatonin and selective cyclooxygenase-2 inhibitor rofecoxib were found to provide a clinically important benefit to sleep quality within the first postoperative week after TJA. However, rofecoxib was withdrawn from the market globally in 2004 over concerns about increased risk of cardiovascular events. Another cyclooxygenase-2 inhibitor, celecoxib, remains available. No other intervention demonstrated a clinical benefit. Side effects of melatonin include dizziness, headache, paresthesia, and nausea, and it is contraindicated in patients with liver failure, autoimmune conditions, or who are receiving warfarin. Long-term adverse effects of rofecoxib include hypertension, edema, and congestive heart failure, and it is contraindicated in patients with renal insufficiency or who are receiving warfarin. Melatonin is considered safe in older patients, but more caution should be taken with rofecoxib. CONCLUSION: Owing to limited evidence in support of most of the interventions we studied, none of these interventions can be recommended for routine use after TJA. Melatonin and rofecoxib may provide a benefit to sleep quality in some patients, but physicians need to understand the adverse effects and contraindications before recommending these interventions. Additionally, rofecoxib is no longer commercially available. Future investigation is warranted to evaluate the effectiveness of interventions with minimal side effect profiles for providers to be able to make an informed decision about interventions for sleep improvement after TJA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Hydroxyapatite-Coated Femoral Stems in Primary Total Hip Arthroplasty: An Updated Meta-Analysis.

BACKGROUND: Most primary total hip arthroplasties (THAs) performed in the United States utilize cementless fixation with porous or hydroxyapatite (HA) coating. A previous meta-analysis comparing HA-coated versus non-HA-coated stems in primary THA published in 2013 found no significant difference between the 2. However, an updated analysis of the current literature is needed to assess the potential benefit of HA-coated stems in primary THA. METHODS: Various libraries were searched through May 2022 according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Studies included were randomized controlled trials comparing HA-coated femoral stems to non-HA-coated stems in primary THA. Outcomes included Harris Hip Score (HHS), endosteal bone formation, radiolucent lines, linear wear rate, revision for aseptic loosening, thigh pain, and heterotopic ossification. RESULTS: There were significantly fewer revisions for aseptic loosening (P = .004) and decreased postoperative thigh pain (P = .03) for patients who have with HA-coated stems. There was no significant difference in HHS (P = .20), endosteal bone formation (P = .96), radiolucent lines (P = .75), linear wear rate (P = .41), or heterotopic ossification (P = .71) between HA-coated and non-HA-coated stems. CONCLUSION: We found that HA-coated femoral stems in primary THA led to significantly fewer stem revisions for aseptic loosening and less postoperative thigh pain compared to non-HA-coated stems. These findings suggest HA-coated femoral stems should be preferred over non-HA-coated femoral stems in primary THA.

Stroke History and Time Elapsed are Predictors of Complications in Total Knee Arthroplasty.

BACKGROUND: A consensus has not been reached regarding the optimal timing of elective total knee arthroplasty (TKA) following a stroke. The purpose of this study was to examine the optimal period between stroke and TKA to minimize complications. Specifically, we assessed: (1) medical and surgical complications; (2) timing of stroke and TKA; (3) associated risk factors. METHODS: A national database identified 69,815 TKA patients that were separated into 6 exclusive cohorts using a stratum likelihood ratio: no stroke (n = 20,000), stroke within 6 (n = 17,764), 12 (n = 10,338), 18 (n = 8,370), 24 (n = 7,121), and 30 months (n = 6,222) prior to TKA. We analyzed 90-day, 1-year, and 2-year complications in each subgroup. Multivariate analyses were used to identify risk factors for periprosthetic joint infection (PJI). RESULTS: The multivariate regression model identified that patients with a stroke within 6 months of TKA had increased risk of PJI at all time points (P < .001). Also, stroke 12 to 18 months before TKA elevated PJI risk at 1 and 2 years (all P < .021), while those over 18 months did not show a significant risk compared to controls (P > .067). CONCLUSIONS: Stroke prior to TKA was associated with an increased risk of postoperative complications, specifically PJI. We recommend a minimum of 6 months between stroke and TKA, with 18 months offering the lowest risk.

Bilateral STA-MCA bypass for Moyamoya angiopathy associated with severe erythrodermic psoriasis.

OBJECTIVE: We report on the uncommon association between severe erythrodermic psoriasis and moyamoya angiopathy (MMA), a progressive cerebrovascular disorder characterized by steno-occlusive changes in the circle of Willis. Concomitant moyamoya and severe erythrodermic psoriasis is a rare pathology, with unknown pathogenesis. MMA with severe erythrodermic psoriasis, even in the setting of stroke, is often managed with non-curative medical intervention alone, due to concerns for surgical instability. Here we show with appropriate surgical consideration and medical management, patients can undergo curative surgical management, and remain stroke free during follow-up. CASE REPORT: The patient, a 52-year-old female, with refractory psoriasis, presented with neurological deficits, leading to the diagnosis of bilateral moyamoya arteriopathy. Patients with these co-existing conditions have historically only been medially managed, due to concerns for surgical instability and inadequate candidacy. A comprehensive stroke workup revealed severe stenosis in the internal carotid arteries. A two-stage surgical revascularization, including right superficial temporal artery-middle cerebral artery (STA-MCA) bypass and subsequent left STA-MCA bypass, was successfully performed. Postoperatively, the patient experienced a severe psoriasis flare, requiring meticulous management to ensure post-operative surgical stability. CONCLUSIONS: With appropriate medical and surgical management, the patient was amenable for curative surgical intervention. The successful surgical intervention, following medical optimization of psoriasis, demonstrated efficacy in preventing future cerebral ischemia events in this challenging patient.

Patient reported outcome measures (PROMs) as primary and secondary outcomes in total hip and knee arthroplasty randomized controlled trials: a systematic review.

BACKGROUND: Significant heterogeneity exists regarding patient reported outcome measures (PROMs) used in total hip (THA) and knee (TKA) arthroplasty randomized controlled trials (RCTs). This study investigates the PROMs used as primary and secondary outcomes in contemporary arthroplasty RCTs. METHODS: A literature search identified THA and TKA RCTs that were published in top ten impact factor orthopaedic journals from 2017 to 2021. Screening identified 241 trials: 76 THA, 157 TKA, and eight combined. Data were extracted to identify PROMs utilized as either primary or secondary outcomes and the time period of measurement. RESULTS: Visual Analog Scale (VAS) Pain was the most reported primary PROM in THA (9.2%) and TKA (22.9%) trials. This was followed by Numeric Rating Scale (NRS) Pain (7.9%) and the Harris Hip score (6.6%) in THA trials and NRS Pain (4.5%) and the Knee Society score (4.5%) in TKA trials. Many THA (37.0%) and TKA (52.1%) trials did not clearly specify primary outcome time points. Only pain scales were reported at time points less than one week, while various joint-specific functional outcomes were reported at later time points. As secondary outcomes, the Harris Hip score (28.9%) was most common in THA trials and the Knee Society score (26.1%) was most common in TKA trials. Indeterminate primary or secondary outcomes were reported in 18.2% of studies. CONCLUSIONS: Contemporary THA and TKA trials exhibit heterogeneity of PROMs as study outcomes after the first postoperative week. Our findings highlight the need for consensus in PROM reporting and better methodological reporting to improve the interpretability of RCT outcomes. PROSPERO REGISTRATION NUMBER: CRD42022337255.

Dural arteriovenous fistula of the craniocervical junction.

Dural arteriovenous (AV) fistulas of the craniocervical junction can be challenging to diagnose. We describe a 70-year-old man with subacute progressive myelopathy whose MR scan of cervical spine showed serpiginous dorsal vessels, suggesting a dural AV fistula. However, a detailed diagnostic angiogram was normal, prompting additional work-up and a wider differential, which was non-revealing. His symptoms progressed over months, but the evolution of the lesion characteristics on repeat spinal imaging still suggested a dural AV fistula. Repeat angiogram identified an infratentorial dural AV fistula arising from the meningohypophyseal artery. He improved following retrosigmoid craniotomy and clipping. Initial angiography does not always demonstrate a dural AV fistula; if there is clinical and radiographic evolution, repeat angiography might identify a fistula with a rare arterial feeder.

Global, Regional, and National Economic Consequences of Stroke.

BACKGROUND: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries. METHODS: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP. RESULTS: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%). CONCLUSIONS: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.

Erroneous electrocardiographic interpretations and its clinical implications.

INTRODUCTION: The advancement of artificial intelligence (AI) has aided clinicians in the interpretation of electrocardiograms (ECGs) serving as an essential tool to provide rapid triage and care. However, in some cases, AI can misinterpret an ECG and may mislead the interpreting physician. Therefore, we aimed to describe the rate of ECG misinterpretation and its potential clinical impact in patient's management. METHODS: We performed a retrospective descriptive analysis of misinterpreted ECGs and its clinical impact from May 28, 2020 to May 9, 2021. An electrophysiologist screened ECGs with confirmed diagnosis of atrial fibrillation (AF), sinus tachycardia (ST), sinus bradycardia (SB), intraventricular conduction delay (IVCD), and premature atrial contraction (PAC) that were performed in the emergency department. We then classified the misinterpreted ECGs as wrongly diagnosed AF, ST, SB, IVCD, or PAC into the correct diagnosis and reviewed the misinterpreted ECGs and medical records to evaluate inappropriate use of antiarrhythmic drugs (AAD), beta-blockers (BB), calcium channel blockers (CCB), anticoagulation, or resource utilization of cardiology and/or electrophysiology (EP) consultation. RESULTS: A total of 4969 ECGs were screened with diagnoses of AF (2282), IVCD (296), PAC (972), SB (895), and ST (638). Among these, 101 ECGs (2.0%) were misinterpreted. Wrongly diagnosed AF (58.4%) was the most common followed by wrongly diagnosed PAC (14.9%), wrongly diagnosed ST (12.9%), wrongly diagnosed IVCD (7.9%), and wrongly diagnosed SB (6.0%). Patients with misinterpreted ECGs were aged 76.6 ± 11.6 years with male (52.5%) predominance and hypertension being the most prevalent (83.2%) comorbid condition. The misinterpretation of ECGs led to the inappropriate use of BB (19.8%), CCB (5.0%), AAD therapy (7.9%), anticoagulation (6.9%) in patients with wrongly diagnosed AF, as well as inappropriate resource utilization including cardiology (41.6%) and EP (8.9%) consultations. CONCLUSIONS: Misinterpretation of ECGs may lead to inappropriate medical therapies and increased resource utilization. Therefore, it is essential to encourage physicians to carefully examine AI interpreted ECG's, especially those interpreted as having AF.

Incidental coronary artery calcification on non-gated CT thorax correlates with risk of cardiovascular events and death.

OBJECTIVES: To assess coronary artery calcification (CAC) on non-contrast non-ECG-gated CT thorax (NC-NECG-CTT) and to evaluate its correlation with short-term risk of cardiovascular disease (CVD) events and death. METHODS: Single-institution retrospective study including all patients 40-70 years old who underwent NC-NECG-CTT over a period of 6 months. Individuals with known CVD were excluded. The presence of CAC was assessed and quantified by the Agatston score (CACS). CAC severity was defined as mild (< 100), moderate (100-400), or severe (> 400). CVD events (including CVD death, myocardial infarction, revascularisation procedures, ischaemic stroke, acute peripheral atherosclerotic ischaemia), and all-cause mortality over a median of 3.5 years were recorded. Cox proportional-hazards regression modelling was performed including CACS, age, gender and CVD risk factors (smoking, hypertension, diabetes mellitus, dyslipidaemia, and family history of CVD). RESULTS: Of the total 717 eligible cases, 325 (45%) had CAC. In patients without CAC, there was only one CVD event, compared to 26 CVD events including 5 deaths in patients with CAC. The presence and severity of CAC correlated with CVD events (p < 0.001). A CACS > 100 was significantly associated with both CVD events, hazard ratio (HR) 5.74, 95% confidence interval: 2.19-15.02; p < 0.001, and all-cause mortality, HR 1.7, 95% CI: 1.08-2.66; p = 0.02. Ever-smokers with CAC had a significantly higher risk for all-cause mortality compared to never-smokers (p = 0.03), but smoking status was not an independent predictor for CVD events in any subgroup category of CAC severity. CONCLUSIONS: The presence and severity of CAC assessed on NC-NECG-CTT correlates with short-term cardiovascular events and death. KEY POINTS: • Patients aged 40-70 years old without known CVD but with CAC on NC-NECG-CTT have a higher risk of CVD events compared to those without CAC. • CAC (Agatston) score above 100 confers a 5.7-fold increase in the risk of short-term CVD events in these patients. • The presence and severity of CAC on NC-NECG-CTT may have prognostic and therapeutic implications.

Sympathetic Blocks as a Predictor for Response to Ketamine Infusion in Patients with Complex Regional Pain Syndrome: A Multicenter Study.

BACKGROUND: Ketamine infusions are frequently employed for refractory complex regional pain syndrome (CRPS), but there are limited data on factors associated with treatment response. Sympathetic blocks are also commonly employed in CRPS for diagnostic and therapeutic purposes and generally precede ketamine infusions. OBJECTIVES: We sought to determine whether demographic and clinical factors, and technical and psychophysical characteristics of sympathetic blocks are associated with response to ketamine infusion. METHODS: In this multi-center retrospective study, 71 patients who underwent sympathetic blocks followed by ketamine infusions at 4 hospitals were evaluated. Sympathetically maintained pain (SMP) was defined as ≥ 50% immediate pain relief after sympathetic block and a positive response to ketamine was defined as ≥ 30% pain relief lasting over 3 weeks. RESULTS: Factors associated with a positive response to ketamine in univariable analysis were the presence of SMP (61.0% success rate vs 26.7% in those with sympathetically independent pain; P = .009) and post-block temperature increase (5.66 ± 4.20 in ketamine responders vs 3.68 ± 3.85 in non-responders; P = .043). No psychiatric factor was associated with ketamine response. In multivariable analysis, SMP (OR 6.54 [95% CI 1.83, 23.44]) and obesity (OR 8.75 [95% 1.45, 52.73]) were associated with a positive ketamine infusion outcome. CONCLUSIONS: The response to sympathetic blocks may predict response to ketamine infusion in CRPS patients, with alleviation of the affective component of pain and predilection to a positive placebo effect being possible explanations.

The Role of Cryotherapy After Total Knee Arthroplasty: A Systematic Review.

BACKGROUND: Previous research shows conflicting evidence regarding the postoperative role of cryotherapy after total knee arthroplasty (TKA). This systematic review aims to further investigate the effect of various methods of cryotherapy on the following: (1) pain; (2) swelling; (3) postoperative opioid use; and (4) range of motion (ROM). METHODS: A strategic keyword search of Medline, Cochrane, Embase, and CINAHL retrieved randomized controlled trials examining cryotherapy following TKA published between February 1, 2017, and February 24, 2022. The studied outcomes included pain ratings, knee/limb swelling, opioid use, and ROM. Six studies were selected for inclusion in this review. RESULTS: Opioid use was significantly decreased in cryotherapy groups compared to noncryotherapy groups within the first postoperative week only (P < .05). This effect may be augmented by the use of computer-assisted (temperature regulated) cryotherapy devices, compared to other modalities including ice packs. Pain ratings also decrease, but this decrease may not be clinically relevant. Cryotherapy appears to confer no consistent benefit to ROM and swelling at any time point. Computer-assisted cryotherapy may be associated with decreased opioid consumption after TKA compared to traditional ice packs. CONCLUSION: Cryotherapy's role after TKA appears to be in decreasing opioid consumption primarily in the first postoperative week. Pain ratings also decrease consistently with cryotherapy use, but this decrease may not be clinically relevant. Study heterogeneity requires further research focusing on optimizing cryotherapy modalities within the first postoperative week, and analyzing cost associated with modern outpatient postoperative TKA protocols.