Maturation of germinal center B cells after influenza virus vaccination in humans.

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells.

Ultrasound of palpable lesions: a pictorial review.

Ultrasound (US) is the imaging modality of choice for evaluation of superficial palpable lesions. A large proportion of these lesions have characteristic sonographic appearance and can be confidently diagnosed with US without the need for biopsy or other intervention. The Society of Radiologists in Ultrasound (SRU) recently published a Consensus Conference Statement on superficial soft tissue masses. The goal of this manuscript is (a) to serve as a sonographic pictorial review for palpable lesions based on the SRU statement, (b) present the typical sonographic features of palpable lesions that can be confidently diagnosed with US, and (c) provide an overview of other palpable lesions with a framework to interpret the US studies and advise on appropriate further management.

Anxiety Predicts Worse Cardiorespiratory Fitness Outcomes in Cardiac Rehabilitation for Lower Socioeconomic Status Patients.

PURPOSE: The purpose of this study was to show that patients in cardiac rehabilitation (CR) with lower socioeconomic status (SES) have worse clinical profiles and higher rates of psychiatric difficulties and they have lower cardiorespiratory fitness (CRF) improvements from CR than their counterparts with higher SES. Improvement in CRF during CR predicts better long-term health outcomes. Research suggests that higher anxiety impairs CRF in structured exercise regimes and is overrepresented among patients with lower SES. However, no study has determined whether this relationship holds true in CR. METHODS: This study is a secondary analysis of a randomized controlled trial to improve CR attendance among patients with lower SES. Anxiety (ASEBA ASR; Achenbach System of Empirically Based Assessment, Adult Self Report) and CRF measures (metabolic equivalent tasks [METs peak ]) were collected prior to CR enrollment and 4 mo later. Regression was used to examine the association of anxiety with CRF at 4 mo while controlling for other demographic and clinical characteristics. RESULTS: Eight-eight participants were included in the analyses, 31% of whom had clinically significant levels of anxiety ( T ≥ 63). Higher anxiety significantly predicted lower exit CRF when controlling for baseline CRF, age, sex, qualifying diagnosis, and number of CR sessions attended ( ß =-.05, P = .04). Patients with clinically significant levels of anxiety could be expected to lose >0.65 METs peak in improvement. CONCLUSIONS: The results from this study suggest that anxiety, which is overrepresented in populations with lower SES, is associated with less CRF improvement across the duration of CR. The effect size was clinically meaningful and calls for future research on addressing psychological factor in CR.

Management of incidentally detected gallbladder polyps: a review of clinical scenarios using the 2022 SRU gallbladder polyp consensus guidelines.

Gallbladder (GB) polyps are a common incidental finding on sonography, but only a small fraction of polyps become GB cancer. The Society of Radiologists in Ultrasound (SRU) consensus committee recently performed an extensive literature review and published guidelines for GB polyp follow-up/management to provide clarity among the many heterogeneous recommendations that are available to clinicians. As these guidelines have become adopted into clinical practice, challenging clinical scenarios have arisen including GB polyps in primary sclerosing cholangitis (PSC), high risk geographic/genetic patient populations, shrinking polyps, pedunculated vs sessile polyps, thin vs thick stalked polyps, vascular polyps and multiple polyps. According to the SRU guidelines, clinicians should refer to gastroenterology guidelines when managing GB polyps in patients with known PSC. If patients at high geographic/genetic risk develop GB polyps, 'extremely low risk' polyps may be managed as 'low risk' and 10-14 mm 'extremely low risk' or '7-14 mm' low risk polyps that decrease in size by ≥ 4 mm require no follow-up. Thin-stalked or pedunculated polyps are 'extremely low risk' and thick-stalked pedunculated polyps are 'low risk'. Sessile polyps are 'low risk' but should receive immediate specialist referral if features suggestive of GB cancer are present. Neither polyp multiplicity nor vascularity impact risk of GB cancer and follow up should be based on morphology alone.

Percutaneous Core Biopsy Devices: A Detailed Review and Comparison of Different Needle Designs.

ABSTRACT: Percutaneous core-needle biopsy (PCNB) plays a growing and essential role in many medical specialties. Proper and effective use of various PCNB devices requires basic understanding of how they function. Current literature lacks a detailed overview and illustration of needle function and design differences, a potentially valuable reference for users ranging from early trainees to experts who are less familiar with certain devices. This pictorial aims to provide such an overview, using diagrams and magnified photographs to illustrate the intricate components of these devices. Following a brief historical review of biopsy needle technology for context, we emphasize distinctions in design between 2 major classes of PCNB devices (side- and end-cutting devices), focusing on practical implications for how each device is most effectively used. We believe a nuanced understanding of biopsy device function sheds light on certain lingering ambiguities in biopsy practice, such as the optimal needle gauge in organ biopsy, the benefits and risks associated with coaxial technique, the impact of needle selection and technique on bleeding, and the risk of unsuccessful sampling. In a subsequent pictorial, we will draw on the concepts presented here to illustrate examples of biopsy needle failure and how unrecognized needle failure can be an important and often preventable cause of increased biopsy risk and lower tissue yield.

Predictors of pain development for contralateral asymptomatic degenerative rotator cuff tears based on features of an ipsilateral painful cuff tear: a prospective longitudinal cohort study.

BACKGROUND: Prior rotator cuff disease natural history studies have focused on tear-related factors that predict disease progression within a given shoulder. The purpose of this study was to examine both patient- and tear-related characteristics of a painful rotator cuff tear that predict future pain development and functional impairment in a shoulder with a contralateral asymptomatic cuff tear. METHODS: This was a prospective longitudinal cohort study of patients aged ≤65 years who underwent surgery for a painful degenerative rotator cuff tear and possessed an asymptomatic contralateral tear. Patients were followed up prospectively by shoulder ultrasound, physical examination, and functional score assessment. The primary outcome was change in the American Shoulder and Elbow Surgeons (ASES) score at 2 years. Secondary outcomes included the Western Ontario Rotator Cuff Index (WORC) score, Patient-Reported Outcomes Measurement Information System (PROMIS) score, Hospital Anxiety Depression Scale (HADS) depression and anxiety scores, and Veterans RAND-12 (VR-12) mental component score (MCS). RESULTS: Sixty-five patients were included, with a mean follow-up period of 37 months (range, 24-42 months). In 17 patients (26%), contralateral shoulder pain developed at a median of 15.2 months (interquartile range [IQR], 10.5 months). No difference in age, sex, Charlson Comorbidity Index, or occupational demand was noted between patients in whom pain developed and those in whom pain did not develop. In the presenting painful shoulder, there was no difference in baseline tear size, muscle degeneration, or biceps pathology between groups. The mean baseline tear length (8.6 mm vs. 3.8 mm, P = .0008) and width (8.4 mm vs. 3.2 mm, P = .0004) were larger in asymptomatic shoulders in which pain subsequently developed compared with those in which pain did not develop. However, there was no difference in mean tear enlargement (P = .51 for length and P = .90 for width). There were no differences in baseline ASES, WORC, Patient-Reported Outcomes Measurement Information System (PROMIS), or HADS depression and anxiety scores between shoulders in which pain developed and those in which pain did not develop; however, patients in whom pain developed reported a lower baseline VR-12 MCS (53.3 vs. 57.6, P = .04). Shoulders in which pain developed had higher visual analog scale pain scores (2.9 [standard deviation (SD), 2.5] vs. 0.6 [SD, 1.0]; P = .016), lower ASES scores 75 [SD, 33] vs. 100 [SD, 11.6]; P = .001), and significant changes in all WORC scales with pain onset compared with those that remained asymptomatic. The study showed no significant difference in changes in the HADS anxiety and depression scores but found a significant increase in the VR-12 MCS in patients in whom pain developed (7.1 [interquartile range, 12.6] vs. -1.9 [interquartile range, 8.7]; P = .036). CONCLUSION: In one-quarter of patients with painful cuff tears, pain developed in a contralateral asymptomatic cuff tear that resulted in a measurable decline in function within 3 years. Our analysis showed that only the baseline tear size of the asymptomatic shoulder was predictive of pain development. There were no tear-related features of the presenting painful rotator cuff tear or indices of mental health and physical function or occupational demand that were predictive of future pain development at short-term follow-up.

Contrast-Enhanced Ultrasound for Image-Guided Procedures.

Contrast-enhanced ultrasound (CEUS) uses intravenously injected gas microbubbles as a pure blood pool contrast agent to demonstrate blood flow and tissue perfusion at a much higher sensitivity than color Doppler and power Doppler ultrasound. CEUS has gained traction in abdominal diagnostic imaging for improved lesion detection and characterization and a complementary problem-solving tool to CT and MRI. In addition to its diagnostic applications, CEUS has also proven useful for pre-procedure planning, procedure guidance, and post-procedure evaluation. This review provides a practical overview and guides to the application of CEUS in percutaneous, ultrasound-guided, needle-driven procedures, focusing on 2 common procedures, which illustrate the many benefits of CEUS- core needle biopsy (CNB) and percutaneous hepatic lesion ablation.

Antigen-specific CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans.

SARS-CoV-2 infection and mRNA vaccination induce robust CD4+ T cell responses that are critical for the development of protective immunity. Here, we evaluated spike-specific CD4+ T cells in the blood and draining lymph node (dLN) of human subjects following BNT162b2 mRNA vaccination using single-cell transcriptomics. We analyze multiple spike-specific CD4+ T cell clonotypes, including novel clonotypes we define here using Trex, a new deep learning-based reverse epitope mapping method integrating single-cell T cell receptor (TCR) sequencing and transcriptomics to predict antigen-specificity. Human dLN spike-specific T follicular helper cells (TFH) exhibited distinct phenotypes, including germinal center (GC)-TFH and IL-10+ TFH, that varied over time during the GC response. Paired TCR clonotype analysis revealed tissue-specific segregation of circulating and dLN clonotypes, despite numerous spike-specific clonotypes in each compartment. Analysis of a separate SARS-CoV-2 infection cohort revealed circulating spike-specific CD4+ T cell profiles distinct from those found following BNT162b2 vaccination. Our findings provide an atlas of human antigen-specific CD4+ T cell transcriptional phenotypes in the dLN and blood following vaccination or infection.

International Expert Consensus on US Lexicon for Thyroid Nodules.

Multiple US-based systems for risk stratification of thyroid nodules are in use worldwide. Unfortunately, the malignancy probability assigned to a nodule varies, and terms and definitions are not consistent, leading to confusion and making it challenging to compare study results and craft revisions. Consistent application of these systems is further hampered by interobserver variability in identifying the sonographic features on which they are founded. In 2018, an international multidisciplinary group of 19 physicians with expertise in thyroid sonography (termed the International Thyroid Nodule Ultrasound Working Group) was convened with the goal of developing an international system, tentatively called the International Thyroid Imaging Reporting and Data System, or I-TIRADS, in two phases: (phase I) creation of a lexicon and atlas of US descriptors of thyroid nodules and (phase II) development of a system that estimates the malignancy risk of a thyroid nodule. This article presents the methods and results of phase I. The purpose herein is to show what has been accomplished thus far, as well as generate interest in and support for this effort in the global thyroid community.

Spatiotemporal development of the human T follicular helper cell response to Influenza vaccination.

We profiled blood and draining lymph node (LN) samples from human volunteers after influenza vaccination over two years to define evolution in the T follicular helper cell (TFH) response. We show LN TFH cells expanded in a clonal-manner during the first two weeks after vaccination and persisted within the LN for up to six months. LN and circulating TFH (cTFH) clonotypes overlapped but had distinct kinetics. LN TFH cell phenotypes were heterogeneous and mutable, first differentiating into pre-TFH during the month after vaccination before maturing into GC and IL-10+ TFH cells. TFH expansion, upregulation of glucose metabolism, and redifferentiation into GC TFH cells occurred with faster kinetics after re-vaccination in the second year. We identified several influenza-specific TFH clonal lineages, including multiple responses targeting internal influenza proteins, and show each TFH state is attainable within a lineage. This study demonstrates that human TFH cells form a durable and dynamic multi-tissue network.

Improving the Efficacy of ACR TI-RADS Through Deep Learning-Based Descriptor Augmentation.

Thyroid nodules occur in up to 68% of people, 95% of which are benign. Of the 5% of malignant nodules, many would not result in symptoms or death, yet 600,000 FNAs are still performed annually, with a PPV of 5-7% (up to 30%). Artificial intelligence (AI) systems have the capacity to improve diagnostic accuracy and workflow efficiency when integrated into clinical decision pathways. Previous studies have evaluated AI systems against physicians, whereas we aim to compare the benefits of incorporating AI into their final diagnostic decision. This work analyzed the potential for artificial intelligence (AI)-based decision support systems to improve physician accuracy, variability, and efficiency. The decision support system (DSS) assessed was Koios DS, which provides automated sonographic nodule descriptor predictions and a direct cancer risk assessment aligned to ACR TI-RADS. The study was conducted retrospectively between (08/2020) and (10/2020). The set of cases used included 650 patients (21% male, 79% female) of age 53 ± 15. Fifteen physicians assessed each of the cases in the set, both unassisted and aided by the DSS. The order of the reading condition was randomized, and reading blocks were separated by a period of 4 weeks. The system's impact on reader accuracy was measured by comparing the area under the ROC curve (AUC), sensitivity, and specificity of readers with and without the DSS with FNA as ground truth. The impact on reader variability was evaluated using Pearson's correlation coefficient. The impact on efficiency was determined by comparing the average time per read. There was a statistically significant increase in average AUC of 0.083 [0.066, 0.099] and an increase in sensitivity and specificity of 8.4% [5.4%, 11.3%] and 14% [12.5%, 15.5%], respectively, when aided by Koios DS. The average time per case decreased by 23.6% (p = 0.00017), and the observed Pearson's correlation coefficient increased from r = 0.622 to r = 0.876 when aided by Koios DS. These results indicate that providing physicians with automated clinical decision support significantly improved diagnostic accuracy, as measured by AUC, sensitivity, and specificity, and reduced inter-reader variability and interpretation times.

Clinical Considerations for Implanted Neurological Devices in Patients Undergoing Hyperbaric Oxygen Therapy: A Case Report and Review of Manufacturer Guidelines.

Patients with implanted medical devices are increasingly referred for hyperbaric oxygen therapy (HBOT), and the safety of exposing some of these devices to hyperbaric environments has not previously been explored. There is a paucity of evidence surrounding the management of implanted neurological devices such as neurostimulators and intrathecal drug delivery (IDD) pumps in the context of HBOT. However, these devices can be expected to harbor unique risks; for example, vacant space in the reservoir of an implanted IDD pump may change in pressure and volume during the compression and decompression phases of HBOT, resulting in a damaged or dysfunctional device. We present the case of a 27-year-old woman with cerebral palsy referred for HBOT to manage a necrotizing soft tissue infection cultured from a dehiscent abdominal wound at the previous implantation site of an intrathecal baclofen pump. An HBOT protocol was ultimately chosen in partnership with the patient and her family, but treatment was not performed due to a paucity of evidence that the implanted IDD pump could safely withstand hyperbaric exposure. In this review, we have synthesized manufacturer recommendations regarding the management of implanted neurological devices before, during, and after HBOT to inform future decision-making in this setting. Among these recommendations, we highlight that neurostimulators should be switched off for the duration of HBOT and implanted pumps should be refilled prior to each treatment session to minimize empty reservoir space.

Evaluation of survivorship of asymptomatic degenerative rotator cuff tears in patients 65 years and younger: a prospective analysis with long-term follow-up.

BACKGROUND: The purpose of this prospective study is to describe the mid- to long-term natural history of untreated asymptomatic degenerative rotator cuff tears in patients 65 years and younger. METHODS: Subjects with an asymptomatic rotator cuff tear in one shoulder and a contralateral painful cuff tear aged 65 years or younger were enrolled in a previously described prospective longitudinal study. Annual physical and ultrasonographic evaluations and surveillance for pain development were performed using independent examiners for the asymptomatic shoulder. RESULTS: Two hundred twenty-nine participants (mean age 57.1 years) were followed for a median of 7.1 (range 0.3-13.1) years. Tear enlargement occurred in 138 (60%) shoulders. Full-thickness tears were at greater risk for enlargement compared with partial-thickness (hazard ratio [HR] 2.93, 95% confidence interval [CI] 1.71-5.03, P < .0001) and control shoulders (HR 18.8, 95% CI 4.63-76.1, P < .0001). Mean survival rates from Kaplan-Meier analyses indicate that full-thickness tears enlarged earlier (mean 4.7, 95% CI 4.1-5.2 years) than partial-thickness (mean 7.4, 95% CI 6.2-8.5 years) and control shoulders (mean 9.7, 95% CI 9.0-10.4 years). Tear presence in the dominant shoulder was associated with a greater enlargement risk (HR 1.70, 95% CI 1.21-1.39, P = .002). Patient age (P = .37) and gender (P = .74) were not associated with tear enlargement. The 2-, 5-, and 8-year survivorship free of tear enlargement for full-thickness tears was 74%, 42%, and 20%, respectively. Shoulder pain developed in 131 (57%) shoulders. Pain development was associated with tear enlargement (HR 1.79, 95% CI 1.24-2.58, P = .002) and was more common in full-thickness tears compared with controls (P = .0003) and partial tears (P = .01). An analysis of progression of muscle degeneration was performed in 138 shoulders with full-thickness tears. Tear enlargement was seen in 104 of 138 (75%) of these shoulders during follow-up (median 7.7 [interquartile range 6.0] years). Progression of muscle fatty degeneration was seen in the supraspinatus in 46 (33%) and the infraspinatus in 40 (29%) shoulders. Adjusting for age, both the presence of fatty muscle degeneration and the progression of muscle changes for both the supraspinatus (P < .0001) and infraspinatus (P < .0001) muscles were associated with tear size. For both the supraspinatus (P = .03) and infraspinatus (P = .03) muscles, tear enlargement was significantly associated with progression of muscle fatty degeneration. Anterior cable integrity was significantly associated with the risk of muscle degeneration progression for both the supraspinatus (P < .0001) and the infraspinatus (P = .005) muscles. CONCLUSIONS: Asymptomatic degenerative rotator cuff tears progress in patient 65 years and younger. Full-thickness rotator cuff tears have a higher risk of continued tear enlargement, progression of fatty muscle degeneration, and pain development than partial-thickness tears.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants1-4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5-9. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes.

Self-Reported Executive Function in Hospitalized Cardiac Patients and Associations With Patient Characteristics and Cardiac Rehabilitation Attendance.

PURPOSE: Executive function (ExF), the ability to do complex cognitive tasks like planning and refraining from impulsive behavior, is associated with compliance with medical recommendations. The present study identified associations between self-reported ExF and demographics of patients with cardiac disease as well as with cardiac rehabilitation (CR) attendance. METHODS: Self-reported ExF impairment was measured using the Behavior Rating Inventory of Executive Function (BRIEF) on 316 individuals hospitalized for CR-qualifying cardiac events. Scores were calculated for a global measure (Global Executive Composite [GEC]) and the two BRIEF indices: Behavioral Regulation Index and Metacognition Index (MCI). Participants were followed up post-discharge to determine CR attendance. Univariate logistic regressions between ExF measures and demographic variables were conducted, as were multiple logistic regressions to identify significant, independent predictors. Analyses were conducted using clinical (T scores ≥ 65) and subclinical (T scores ≥ 60) criteria for significant ExF impairment as outcomes. One-way analyses of variance were performed between ExF impairment and CR attendance. RESULTS: Self-reported ExF deficits were relatively rare; 8.9% had at least subclinical scores on the GEC. Using the subclinical criterion for the MCI, having diabetes mellitus (DM) and being male were significant, independent predictors of MCI impairment. No significant relationship was found between ExF and CR attendance. CONCLUSION: Using the subclinical criterion only, individuals with DM and males were significantly more likely to have MCI impairment. No significant effect of ExF impairment on CR attendance was found, suggesting that self-reported ExF measured in the hospital may not be an appropriate measure for predicting behavioral outcomes.

Persons with HIV Develop Spike-Specific Lymph Node Germinal Center Responses following SARS-CoV-2 Vaccination.

COVID-19 disproportionately affects persons with HIV (PWH) in worldwide locations with limited access to SARS-CoV-2 vaccines. PWH exhibit impaired immune responses to some, but not all, vaccines. Lymph node (LN) biopsies from PWH demonstrate abnormal LN structure, including dysregulated germinal center (GC) architecture. It is not clear whether LN dysregulation prevents PWH from mounting Ag-specific GC responses in the draining LN following vaccination. To address this issue, we longitudinally collected blood and draining LN fine needle aspiration samples before and after SARS-CoV-2 vaccination from a prospective, observational cohort of 11 PWH on antiretroviral therapy: 2 who received a two-dose mRNA vaccine series and 9 who received a single dose of the Ad26.COV2.S vaccine. Following vaccination, we observed spike-specific Abs, spike-specific B and T cells in the blood, and spike-specific GC B cell and T follicular helper cell responses in the LN of both mRNA vaccine recipients. We detected spike-specific Abs in the blood of all Ad26.COV2.S recipients, and one of six sampled Ad26.COV2.S recipients developed a detectable spike-specific GC B and T follicular helper cell response in the draining LN. Our data show that PWH can mount Ag-specific GC immune responses in the draining LN following SARS-CoV-2 vaccination. Due to the small and diverse nature of this cohort and the limited number of available controls, we are unable to elucidate all potential factors contributing to the infrequent vaccine-induced GC response observed in the Ad26.COV2.S recipients. Our preliminary findings suggest this is a necessary area of future research.

Optimization of Patient Positioning for the Sonographic Evaluation of Gallstone Impaction: Analysis of Gallbladder Orientation Based on Computed Tomography.

ABSTRACT: An important sonographic sign of cholecystitis is stone impaction in the gallbladder neck. Demonstration of stone mobility excludes impaction. The purpose of this study is to analyze the orientation of the gallbladder on computed tomography and determine the patient position most likely to facilitate stone mobility. ImageJ processing software was used to determine the x (transverse), y (anterior-posterior), and z (craniocaudal) coordinates for the gallbladder neck and fundus in 544 consecutive computed tomography examinations. The differences in the fundal and neck coordinates were used to determine the likelihood of moving a stone from the neck to the fundus for the left and right lateral decubitus positions ( x coordinates), the prone position ( y coordinates), and the upright position ( z coordinates). The coordinate with the largest difference was considered to predict the position most likely to facilitate stone motion. The difference in position of the fundus and neck was greatest in the y -, z -, and x -axis in 232 (42.6%), 194 (35.7%), and 118 (21.7%) of patients, respectively. For body mass index (BMI) less than 25 kg/m 2 , the difference was greatest in the z -axis (59.8%). For BMI greater than 25 kg/m 2 , the difference was greatest in the y -axis (47.1%). Based on their relative location, the optimal position to facilitate gallstone mobility from the gallbladder neck to fundus was most often prone (especially in high BMI patients), followed by upright (especially in low BMI patients), followed by right lateral decubitus. The left lateral decubitus position was never optimal.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones 1-4 . SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs) 5-9 . It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants. Here, we show that boosting with the original SARS- CoV-2 spike vaccine (mRNA-1273) or a B.1.351/B.1.617.2 (Beta/Delta) bivalent vaccine (mRNA-1273.213) induces robust spike-specific GC B cell responses in humans. The GC response persisted for at least eight weeks, leading to significantly more mutated antigen-specific MBC and bone marrow plasma cell compartments. Interrogation of MBC-derived spike-binding monoclonal antibodies (mAbs) isolated from individuals boosted with either mRNA-1273, mRNA-1273.213, or a monovalent Omicron BA.1-based vaccine (mRNA-1273.529) revealed a striking imprinting effect by the primary vaccination series, with all mAbs (n=769) recognizing the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted approach, we isolated mAbs that recognized the spike protein of the SARS-CoV-2 Omicron (BA.1) but not the original SARS-CoV-2 spike from the mRNA-1273.529 boosted individuals. The latter mAbs were less mutated and recognized novel epitopes within the spike protein, suggesting a naïve B cell origin. Thus, SARS-CoV-2 boosting in humans induce robust GC B cell responses, and immunization with an antigenically distant spike can overcome the antigenic imprinting by the primary vaccination series.

Management of Incidentally Detected Gallbladder Polyps: Society of Radiologists in Ultrasound Consensus Conference Recommendations.

Gallbladder polyps (also known as polypoid lesions of the gallbladder) are a common incidental finding. The vast majority of gallbladder polyps smaller than 10 mm are not true neoplastic polyps but are benign cholesterol polyps with no inherent risk of malignancy. In addition, recent studies have shown that the overall risk of gallbladder cancer is not increased in patients with small gallbladder polyps, calling into question the rationale for frequent and prolonged follow-up of these common lesions. In 2021, a Society of Radiologists in Ultrasound, or SRU, consensus conference was convened to provide recommendations for the management of incidentally detected gallbladder polyps at US. See also the editorial by Sidhu and Rafailidis in this issue.