mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron.

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.

SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters.

The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

Loss of Pfizer (BNT162b2) Vaccine-Induced Antibody Responses against the SARS-CoV-2 Omicron Variant in Adolescents and Adults.

Emerging variants, especially the recent Omicron variant, and gaps in vaccine coverage threaten mRNA vaccine mediated protection against SARS-CoV-2. While children have been relatively spared by the ongoing pandemic, increasing case numbers and hospitalizations are now evident among children. Thus, it is essential to better understand the magnitude and breadth of vaccine-induced immunity in children against circulating viral variant of concerns (VOCs). Here, we compared the magnitude and breadth of humoral immune responses in adolescents and adults 1 month after the two-dose Pfizer (BNT162b2) vaccination. We found that adolescents (aged 11 to 16) demonstrated more robust binding antibody and neutralization responses against the wild-type SARS-CoV-2 virus spike protein contained in the vaccine compared to adults (aged 27 to 55). The quality of the antibody responses against VOCs in adolescents were very similar to adults, with modest changes in binding and neutralization of Beta, Gamma, and Delta variants. In comparison, a significant reduction of binding titers and a striking lack of neutralization was observed against the newly emerging Omicron variant for both adolescents and adults. Overall, our data show that a two-dose BNT162b2 vaccine series may be insufficient to protect against the Omicron variant. IMPORTANCE While plasma binding and neutralizing antibody responses have been reported for cohorts of infected and vaccinated adults, much less is known about the vaccine-induced antibody responses to variants including Omicron in children. This illustrates the need to characterize vaccine efficacy in key vulnerable populations. A third (booster) dose of BNTb162b was approved for children 12 to 15 years of age by the Food and Drug Administration (FDA) on January 1, 2022, and pediatric clinical trials are under way to evaluate the safety, immunogenicity, and effectiveness of a third dose in younger children. Similarly, variant-specific booster doses and pan-coronavirus vaccines are areas of active research. Our data show adolescents mounted stronger humoral immune responses after vaccination than adults. It also highlights the need for future studies of antibody durability in adolescents and children as well as the need for future studies of booster vaccination and their efficacy against the Omicron variant.

Endosomal Wnt signaling proteins control microtubule nucleation in dendrites.

Dendrite microtubules are polarized with minus-end-out orientation in Drosophila neurons. Nucleation sites concentrate at dendrite branch points, but how they localize is not known. Using Drosophila, we found that canonical Wnt signaling proteins regulate localization of the core nucleation protein γTubulin (γTub). Reduction of frizzleds (fz), arrow (low-density lipoprotein receptor-related protein [LRP] 5/6), dishevelled (dsh), casein kinase Iγ, G proteins, and Axin reduced γTub-green fluorescent protein (GFP) at branch points, and two functional readouts of dendritic nucleation confirmed a role for Wnt signaling proteins. Both dsh and Axin localized to branch points, with dsh upstream of Axin. Moreover, tethering Axin to mitochondria was sufficient to recruit ectopic γTub-GFP and increase microtubule dynamics in dendrites. At dendrite branch points, Axin and dsh colocalized with early endosomal marker Rab5, and new microtubule growth initiated at puncta marked with fz, dsh, Axin, and Rab5. We propose that in dendrites, canonical Wnt signaling proteins are housed on early endosomes and recruit nucleation sites to branch points.

Rapid Detection and Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Variant in a Returning Traveler.

We describe rapid detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant using targeted spike single-nucleotide polymorphism polymerase chain reaction and viral genome sequencing. This case occurred in a fully vaccinated and boosted returning traveler with mild symptoms who was identified through community surveillance rather than clinical care.

VA-ECMO-assisted aspiration thrombectomy in a patient presenting with acute massive PE with absolute contraindications to thrombolytics.

Massive pulmonary embolism (PE) is a life-threatening complication of major surgery with a mortality rate up to 50%. First-line therapy for massive PE is systemic thrombolytics, but surgical patients are at high bleeding risk with absolute contraindications. As surgical thrombectomy carries a high burden of morbidity and mortality, endovascular interventions are becoming more common in these clinical scenarios. We report a case of a neurosurgical patient whose postoperative course was complicated by massive PE and subsequent cardiac arrest that required emergent venoarterial extracorporeal membrane oxygenation, followed by aspiration thrombectomy with the Inari FlowTriever Device (Inari Medical). The patient had immediate hemodynamic improvement with eventual recovery to baseline functional status.

Risk factors for failure to achieve minimal clinically important difference and significant clinical benefit in PROMIS computer adaptive test domains in patients undergoing rotator cuff repair.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) has emerged as a valid and efficient means of collecting outcomes in patients with rotator cuff tears. The purpose of this study was to establish threshold score changes to determine minimal clinically important difference (MCID) and substantial clinical benefit (SCB) in PROMIS computer adaptive test (CAT) scores following rotator cuff repair (RCR). Additionally, we sought to identify potential risk factors for failing to achieve MCID and SCB. METHODS: Patients undergoing arthroscopic RCR were identified over a 24-month period. Only patients who completed both preoperative and postoperative PROMIS CAT assessments were included in this cohort. PROMIS CAT forms for upper extremity physical function (PROMIS-UE), pain interference (PROMIS-PI), and depression (PROMIS-D) were used with a minimum of 1.5-year follow-up. Statistical analysis was performed to determine threshold score changes to determine anchor-based MCID and SCB, as well as risk factors for failure to achieve significant clinical improvement following surgery. RESULTS: Of 198 eligible patients, 168 (84.8%) were included in analysis. ΔPROMIS-UE values of 5.8 and 9.7 (area under the curve [AUC] = 0.906 and 0.949, respectively) and ΔPROMIS-PI values of -11.4 and -12.9 (AUC = 0.875 and 0.938, respectively) were identified as threshold predictors of MCID and SCB achievement. On average, 81%, 65%, and 55% of patients achieved MCID for PROMIS-UE, PROMIS-PI, and PROMIS-D whereas 71%, 61%, and 38% of patients in the cohort, respectively, achieved SCB. MCID achievement in PROMIS-UE significantly differed according to risk factors, including smoking status (likelihood ratio [LR]: 9.8, P = .037), tear size (LR: 10.4, P < .001), distal clavicle excision (LR: 6.1, P = .005), and prior shoulder surgery (LR: 19.2, P < .001). Factors influencing SCB achievement for PROMIS-UE were smoking status (LR: 9.3, P = .022), tear size (LR: 8.0, P = .039), and prior shoulder surgery (11.9, P < .001). Significantly different rates of MCID and SCB achievement in PROMIS-PI for smoking status (LR: 7.0, P = .030, and LR: 5.2, P = .045) and prior shoulder surgery (LR: 9.1, P = .002, and LR: 7.4, P = .006) were also identified. DISCUSSION AND CONCLUSION: The majority of patients showed clinically significant improvements that exceeded the established MCID for PROMIS-UE and PROMIS-PI following RCR. Patients with larger tear sizes, a history of prior shoulder surgery, tobacco users, and those who received concomitant distal clavicle excision were at risk for failing to achieve MCID in PROMIS-UE. Additionally, smokers and patients who underwent prior shoulder surgery demonstrated significantly lower improvements in pain scores following surgery.

Quality and Reliability of YouTube for Patient Information on Neurotoxins.

YouTube is a common source of medical information for patients. This is the first study to assess the reliability and educational value of YouTube videos on neurotoxin procedures. YouTube.com was searched on June 15, 2020 using the keyword "Botox" or "neurotoxin." A total of 100 videos were reviewed. Sixty-one videos met the inclusion criteria and were included in the final analysis. Video characteristics were noted, and a score was assigned to each video using the Journal of the American Medical Association (JAMA) benchmark criteria and the Global Quality Score (GQS) to measure source reliability and educational value, respectively. A total of 61 videos that met the inclusion criteria had an average length of 589 seconds (9 minutes and 49 seconds), 210,673 views, 5,295 likes, 318 dislikes, and 478 comments. A total of 30 videos (49%) were posted with an intention to educate patients while 31 videos (51%) were posted with the intention to detail a personal experience with neurotoxin. Patient education videos were significantly more reliable (P JAMA< 0.001) and had more educational value (P GQS < 0.001) but were less popular than "personal experience videos." Personal-experience videos posted by patients had higher popularity, more likes and comments, yet lower scores on reliability and education. Patients will continue to seek educational material online, and clinicians should utilize this information to help primarily educate patients with standardized and accurate information about their treatment. KEY POINTS: · Question: Are YouTube videos pertaining to neurotoxin reliable and contain useful information to educate patients to make informed decisions about their neurotoxin treatment?. · Findings: Roughly half of videos reviewed were vlogs (video logs), which were of low quality and educational value, but were more popular compared with videos that were intended to educate patients on neurotoxin treatment.. · Meaning: Patients who use YouTube as a source of information about neurotoxin treatment may be misled with inaccurate and unreliable information. Physicians must be aware of these findings to properly educate patients with standardized and accurate information about their treatment..

Raw regulates glial population of the eye imaginal disc.

Glia are critical for proper development, support, and function of the nervous system. The Drosophila eye has proven an excellent model for gaining significant insight into the molecular mechanisms regulating glial development and function. Recent studies have demonstrated that Raw is required in glia of the central and peripheral nervous systems; however, the function of Raw in glia of the developing eye has not been explored. These studies demonstrate that raw knockdown results in a reduction in the number of glia in the third instar eye imaginal disc and reduced glial spreading across the field of differentiating photoreceptor neurons. Expression of a raw enhancer trap reveals that raw is expressed in eye disc glia. Exploration of the mechanism by which raw knockdown results in glial reduction reveals that Raw is required for glial proliferation and migration into the eye disc. In addition, Raw negatively regulates Jun N-terminal kinase (JNK) signaling in glia of the developing eye and increased JNK signaling results in a reduction in the number of glia populating the eye disc, similar to that observed upon raw knockdown. Thus, Raw functions as a critical regulator of glial population of the eye imaginal disc by regulating glial proliferation and migration and inhibiting JNK signaling.

Cost-Effectiveness Analysis of Nefecon versus Best Supportive Care for People with Immunoglobulin A Nephropathy (IgAN) in the United States.

Purpose: To estimate the cost-effectiveness of Nefecon in addition to the best supportive care (BSC) vs BSC in a hypothetical cohort of commercially insured adult patients with primary immunoglobulin A nephropathy (IgAN) from a United States (US) societal perspective. Methods: A lifetime horizon, semi-Markov model was developed that consisted of nine health states: chronic kidney disease (CKD) stage 1, 2, 3a, 3b, 4, end-stage renal disease (ESRD) with dialysis, ESRD without dialysis, post-kidney transplant, and death. Health state occupancy was estimated from individual patient-level data from the Phase 3 randomized controlled trial NefIgArd Part A (NCT03643965). Additional scenarios evaluated the impact of varying the time horizon, discounting, costs included, rounds of treatment, and the method used to calculate transition probabilities. Results: In the deterministic base case analysis over a lifetime horizon, Nefecon plus BSC (hereafter Nefecon) had an incremental cost of $3,810 vs BSC. Nefecon resulted in a mean survival gain of 0.247 quality-adjusted life years (QALYs), 0.195 life years (LYs), and 0.244 equal value life years (evLYs) vs BSC alone - this resulted in incremental cost-effectiveness ratios (ICERs) of $15,428 per QALY, $19,502 per LY, and $15,611 per evLY gained. Probabilistic sensitivity analyses estimated that with willingness to pay thresholds of $100,000, $150,000, and $250,000 per QALY gained, Nefecon would be cost-effective over BSC in 66.70%, 75.02%, and 86.82% of cases, respectively. In the scenario analysis, Nefecon remained cost-effective with 4 rounds of treatment. Conclusion: Nefecon was associated with LY and QALY gains vs BSC, with an incremental cost of $3,810. Based on these values, with a willingness to pay threshold of $100,000 per QALY gained, Nefecon was found to be a cost-effective treatment for US adults with primary IgAN.

Pre-Visit Digital Messaging Improves Patient-Reported Outcome Measure Participation Prior to the Orthopaedic Ambulatory Visit: Results from a Double-Blinded, Prospective, Randomized Controlled Trial.

BACKGROUND: Patient-reported outcome measures (PROMs) are metrics that assess physical health, mental health, pain, and satisfaction. However, PROM collection in orthopaedic clinics presents numerous logistical and financial challenges. These challenges are reduced when PROMs are completed before clinic encounters, relieving the workflow constraints of in-office PROM collection. The purpose of this study was to determine the efficacy of 3 different methods with respect to pre-visit electronic PROM completion. METHODS: Consecutive adult orthopaedic patients with no previous PROM participation were enrolled. Patients who registered with the electronic medical record (EMR) patient portal (MyChart) and with active e-mail addresses were randomly assigned to 1 of 3 arms: control (no pre-visit messages), MyChart (EMR patient portal pre-visit messages), and e-mail (e-mail pre-visit messages). The primary outcome measure was pre-visit PROM completion rates in orthopaedic patients, and the secondary outcome measures were time to pre-visit PROM form completion and PROM form completion rates according to patient demographic characteristics. By default, the Patient-Reported Outcomes Measurement Information System (PROMIS) forms were available for completion through the portal by 7 days before scheduled visits. Pre-visit messages were sent 7 days prior to the scheduled visit except in the control group, with reminders sent 3 days prior if still not completed. The patients in each arm who completed all assigned forms were labeled as having total PROM completion, and those who completed at least 1 completed form were considered as having partial PROM completion. Multivariable logistic regression models were used to assess differences in PROM completion rates between study arms. Kruskal-Wallis tests were performed to compare the date of the form completion. RESULTS: A total of 291 patients were included. The pre-visit total completion rates for assigned PROMs were higher in the MyChart arm (49% of 97 patients; p = 0.005) and the e-mail arm (52% of 100 patients; p = 0.002) in comparison with the control arm (30% of 94 patients). Male patients were more likely than female patients to have partial pre-visit PROM completion (odds ratio [OR], 1.74; p = 0.03), and Caucasian patients were more likely to have partial pre-visit PROM completion than African American patients (OR, 2.28; p = 0.01). CONCLUSIONS: Orthopaedic patients receiving either e-mail or patient portal messages demonstrated higher pre-visit PROM completion rates. Pre-visit messaging appears to be a useful strategy for increasing PROM completion rates and limiting the clinical workflow strain imposed by in-clinic PROM administration. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Morphologic Severity of Atypia Is Predictive of Lung Cancer Diagnosis.

In cytologic analysis of lung nodules, specimens classified as atypia cannot be definitively diagnosed as benign or malignant. Atypia patients are typically subject to additional procedures to obtain repeat samples, thus delaying diagnosis. We evaluate morphologic categories predictive of lung cancer in atypia patients. This retrospective study stratified patients evaluated for primary lung nodules based on cytologic diagnoses. Atypia patients were further stratified based on the most severe verbiage used to describe the atypical cytology. Logistic regressions and receiver operator characteristic curves were performed. Of 129 patients with cytologic atypia, 62.8% later had cytologically or histologically confirmed lung cancer and 37.2% had benign respiratory processes. Atypia severity significantly predicted final diagnosis even while controlling for pack years and modified Herder score (p = 0.012). Pack years, atypia severity, and modified Herder score predicted final diagnosis independently and while adjusting for covariates (all p < 0.001). This model generated a significantly improved area under the curve compared to pack years, atypia severity, and modified Herder score (all p < 0.001) alone. Patients with severe atypia may benefit from repeat sampling for cytologic confirmation within one month due to high likelihood of malignancy, while those with milder atypia may be followed clinically.

Many patients fail to achieve MCID for PROMIS upper extremity and pain interference following nonoperative management of rotator cuff tears.

Background: Efficacy of nonoperative treatment for rotator cuff tears has been debated, especially for full-thickness tears. The purpose of this study was to a) define the minimal clinically important difference (MCID) of nonoperative treatment with regard to Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference (PI) and upper extremity (UE), and b) determine the proportion of patients with both partial and full-thickness tears (PTRCT, FTRCT) who achieve this improvement following initial nonoperative treatment. We hypothesized that >75% of PTRCT and FTRTC patients would achieve MCID for PROMIS PI and UE. Methods: We performed a retrospective cohort study evaluating nonoperatively managed patients with image-confirmed PTRCT and FTRCT. Treatment modalities and follow-up PROMIS scores at least 6 months after their initial visit were recorded. Using a distribution technique, MCID was calculated. Results: A total of 111 FTRCT and 68 PTRCT patients were included with at least 6 months of follow-up. At 6 months from initial presentation, the MCID for PROMIS UE was 3.75 and 3.95 for FTRCT and PTRCT patients, respectively. For PROMIS PI, the MCID was 3.35 and 3.90 for FTRCT and PTRCT, respectively. In total, 41% of FTRCT and 41% of PTRCT achieved MCID for PROMIS UE. Thirty-four percent of FTRCT and 35% of PTRCT achieved MCID for PROMIS PI. Conclusion: The majority of patients undergoing nonoperative treatment for supraspinatus/infraspinatus rotator cuff tears did not achieve MCID at 6 months for PROMIS PI (34% for FTRCT and 35% for PTRCT) or UE (41% for FTRCT and 41% for PTRCT).

Perception of Medical Undergraduate Students about an Electronic Practical Examination In Orthopaedics During the COVID-19 Pandemic.

Background/purpose of study: No study has evaluated the perception of medical undergraduate students to the electronic objective structured practical examination (e-OSPE) in orthopaedics. The aim of the present study is to evaluate the feasibility and perception of the medical undergraduate students to e-OSPE conducted by the department of Orthopaedics to assess problem-solving and clinical decision-making skills of medical undergraduate students. Methods: Medical undergraduate students of second and third year at our medical college who completed the orthopaedic clinical posting and appeared for the orthopaedic practical examination during the second wave of the COVID-19 pandemic were included in this prospective observational study. Students appearing for the exams from 20th March 2021 to 26th June 2021 were invited to complete the questionnaire immediately after the e-OSPE. Internal consistency of the survey questions was assessed using Cronbach's alpha. Results: 272 out of 312 eligible students completed the survey and the survey response rate was 87.2%. Nine groups of medical undergraduate students gave the orthopaedic practical exams from 20th March 2021 to 26th June 2021. 91.2% students felt that the e-OSPE represented a valid modality of evaluation of essential orthopaedic practical knowledge during the COVID-19 pandemic. The overall reliability of the 19 questions included in our survey was very high (Internal consistency: Cronbach's alpha = 0.88). Conclusion: The e-OSPE was well received by the medical undergraduate students at our institute and the students had a positive perception about the new examination technique used in orthopaedics during the COVID-19 pandemic.

Clostridioides difficile Pyogenic Liver Abscess With an Empyema.

INTRODUCTION: Reports of extraintestinal manifestations of Clostridioides difficile (C difficile) infections are rare. The frequency of these infections comprises approximately 0.17% to 0.6% of all C difficile infections. While they are becoming more frequent worldwide, the precise trend is unclear. CASE PRESENTATION: An 83-year-old female patient presented with pleuritic chest pain 2 to 3 months after a needle biopsy of her liver abscess confirmed C difficile. She was found to have extension of the liver abscess into the chest cavity, leading to empyema, and was treated with intravenous antimicrobials. DISCUSSION: This is the fifth known reported case of C difficile leading to a pyogenic liver abscess and the first case where the C difficile liver abscess was associated with an empyema. While long-term metronidazole is considered effective for managing extra intestinal C difficile infection, our patient was treated with vancomycin and meropenem. CONCLUSION: To determine epidemiology and a proper treatment regimen for extraintestinal C difficile infection, a greater accumulation of cases is necessary.

Demographic differences in the treatment of unilateral vocal fold paralysis.

Objective: To determine the impact of patient demographics and social determinants of health on treatment pathways for unilateral vocal fold paralysis (UVFP) at a tertiary laryngology clinic. Study design: Retrospective medical record review. Methods: Patient demographics (age, gender, race, ethnicity, and insurance status) were extracted for adults diagnosed with UVFP between 2009 and 2019. Odds ratios for the associations between sociodemographic factors and UVFP treatment pathways were determined by chi-square analyses. Results: A total of 1490 UVFP diagnoses were identified during the study period with the majority being female (58%), White (85%), non-Hispanic (97%), and publicly insured (54%). Five treatment pathways were identified: observation, injection laryngoplasty, voice therapy, laryngeal framework surgery/thyroplasty, and reinnervation surgery. There were 538 patients who underwent observation, 512 injection laryngoplasty, 366 voice therapy, 136 thyroplasty, and 26 laryngeal reinnervation surgery. Males were more likely to undergo injection laryngoplasty than females (OR 1.32; CI 1.08-1.61), whereas females were more likely to undergo voice therapy (OR 1.39; CI 1.09-1.76). Patients with public insurance (OR 1.48; CI 1.03-2.14) and Hispanics (OR 2.60; CI 1.18-5.72) were more likely to undergo thyroplasty. Patients who underwent reinnervation surgery were younger than those in other treatment pathways (median: 39.1 years vs. 50.7-56.1 years). Conclusions: Gender, ethnicity, and insurance status were significantly associated with specific UVFP treatment pathways. Patients with public insurance were more likely to undergo surgical intervention than voice therapy. This data overall supports differences in care pathway utilization for UVFP based on social determinants of health. Level of evidence: Level IV.

Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern.

PURPOSE: We investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants. METHODS: 82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated. RESULTS: Binding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients. CONCLUSIONS: Binding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.

Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant.

PURPOSE: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort (P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers (P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower (P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase (P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

Staple Line Erosion in a Neobladder Causing Postoperative Hematuria.

Erosion of metal surgical staples is a rare but described surgical complication. Staple erosion in a bladder may present with hematuria, urinary tract infection (UTI), bladder pain, or fistula. We present a 64-year-old male with a history of urothelial carcinoma treated by cystoprostatectomy with neobladder reconstruction. Over the next two to three years, he developed hematuria and had multiple urine cytologies suspicious for cancer. The cystoscopic evaluation revealed staple line erosion but no cancer. We believe this to be the first published case of symptomatic staple erosion in a neobladder. Clinicians should be aware that staple line erosion in a neobladder can occur and mimic malignancy recurrence.

A Case of Diffuse Brucellar Spondylodiscitis.

Diffuse brucellar spondylodiscitis is the most severe subtype of osteoarticular brucellosis and is defined as a brucellar infection involving an entire vertebral body, typically a lumbar vertebra, with spread to the adjacent disc space, vertebra, and even extravertebral spaces, including epidural, paraspinal, or intramuscular locations. Although it is a relatively rare diagnosis in the US healthcare system, it should be considered in all patients with severe back pain, radicular symptoms, and a history of extensive exposure to an endemic area. Any delays in treatment can be associated with an increased risk of permanent neurological deficits or death. Here, we present a case of diffuse brucellar spondylodiscitis in a patient who presented to our facility with a history of extensive exposure to an endemic area. While an MRI can reveal pathognomonic findings in brucellar spondylodiscitis, for our case, it was nonspecific. The MRI provided early evidence of an infectious etiology which prompted immediate broad-spectrum antimicrobial coverage until causal organisms were identified and culture sensitivities directed targeted antibiotic therapy. The patient was able to recover over the course of four months without surgical intervention. At her final clinical follow-up, she had no neurological deficits and had complete resolution of her radicular symptoms.