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IntroductionSolid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear.MethodsWe investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination.ResultsWe corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion.DiscussionOur study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.

Introductionour objective was to analyze the trends in the leading causes of death among the pediatric population aged 1–19 years in Mexico and the United States (US) from 2000 to 2022. Methods. Data for Mexico were sourced from the National Institute of Statistics and Geography (INEGI), while the US data were extracted from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) databases.ResultsHomicide has been the leading cause of death since 2017 in Mexico and since 2019 in US youths aged 1–19. In Mexico, it reached 6.5 deaths per 100,000 people in 2022. Despite the overall pediatric mortality decline from 2000 to 2022 in both countries, the pediatric homicide rate has increased by 93.3 and 35.8% In Mexico and the US, respectively, and suicide by 86.6 and 36.9%. In both countries, death by firearm-related injuries had risen in a parallel sense. In the US, deaths by drug overdose and poisoning have increased by 314.8%.ConclusionDespite advancements in infant healthcare over the past two decades in Mexico, there remains a significant gap in the provision of healthcare services to the adolescent population. Addressing issues related to violence, mental health, and substance abuse through targeted public policies is imperative for both Mexico and the US, especially given their shared border region.

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression. Monocytes, which are key players in MF inflammation, were identified as a source of S100A8/A9 but not HMGB1 release, while both DAMPs correlated with cell death parameters, such as serum LDH and cell-free DNA, indicating that passive release is an additional mechanism leading to increased DAMPs. HMGB1 and S100A8/A9 promote inflammation through binding to Toll-like receptor (TLR) 4, whereas the former also binds TLR2. Monocytes from MF patients were shown to be hyperactivated at baseline, as reflected by higher CD11b and tissue factor exposure and increased expression levels of proinflammatory cytokines IL-1β and IL-6. Patient monocytes showed preserved TLR4 and TLR2 expression and were able to mount normal or even exacerbated functional responses and cytokine upregulation following stimulation of TLR4 and TLR2. Elevated levels of endogenous TLR ligands HMGB1 and S100A8/A9 coupled to the finding of preserved or hyperreactive TLR-triggered responses indicate that DAMPs may promote monocyte activation and cytokine production in MF, fueling inflammation. Plasma IL-1β and IL-6 were elevated in MF and correlated with DAMPs levels, raising the possibility that DAMPs could contribute to cytokine generation in vivo. In conclusion, this study highlights that, in cooperation with classic proinflammatory cytokines, DAMPs represent additional inflammatory mediators that may participate in the generation of MF inflammatory state, potentially providing novel biomarkers of disease progression and new therapeutic targets.

To systematically review the effect of different types of water sources on dental unit waterline (DUWL) contamination. 5 databases were searched from their inception to December 23, 2023. Two reviewers independently extracted the data and assessed the quality of the literature. The risk ratio (RR) was used as measure of effect size in meta-analysis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for evaluating quality of the evidence. Meta-analysis was completed by RevMan 5.4.5 studies involving 561 water samples were quantified for meta-analysis. The results indicated that no significant differences were found in view of contamination rate (RR = 1.01; 95 % CI, 0.72–1.41; P = 0.96, I2 = 62 %; GRADE low)and detection rate of Pseudomonas aeruginosa (RR = 0.78; 95 % CI, 0.15–4.13; P = 0.77; I2 = 83 %; GRADE very low) between using purified water and tap water as water sources of DUWL. The available evidence suggests that there is no significant difference between purified water and tap water in controlling DUWL contamination. However, the conclusions need to be further validated through more randomized controlled trials with robust design and a large sample size.

Background: Sleeve gastrectomy has gained prominence in obesity treatment, yet it is not without complications, such as the development of anemia in the medium term. Given the high prevalence of Helicobacter pylori infection in Peru, it is imperative to explore its potential association with this postoperative complication. Objective: To evaluate the association between the presence of Helicobacter pylori and the development of anemia 12 months after sleeve gastrectomy. Methods: A retrospective cohort study was carried out based on an analysis of secondary data from a private clinic in Lima, Peru, which included two groups of people over 18 years of age who had undergone sleeve gastrectomy between 2010 and 2020. We considered the subjects who had the previous diagnosis of Helicobacter pylori as well as those who did not have the infection, according to the detection of the bacteria by endoscopy before surgery. Results: A total 313 individuals were analyzed, and it was found that the prevalence of Helicobacter pylori was 46.0% and the incidence of anemia 12 months after sleeve gastrectomy was 18.2%. The presence of Helicobacter pylori increased the risk of de novo anemia (Relative Risk = 1.56; 95% confidence intervals: 1.02–2.41; p = 0.043). When stratifying by sex, the association was maintained only for the male group (Relative Risk = 2.84; 95% confidence intervals: 1.02–7.02; p = 0.047). Conclusions: It was identified that the presence of Helicobacter pylori had a significant association with the development of de novo anemia, mainly in male subjects, 1 year after undergoing sleeve gastrectomy.

Academic global surgery is a rapidly growing field that aims to improve access to safe surgical care worldwide. However, no universally accepted competencies exist to inform this developing field. A consensus-based approach, with input from a diverse group of experts, is needed to identify essential competencies that will lead to standardization in this field. A task force was set up using snowball sampling to recruit a broad group of content and context experts in global surgical and perioperative care. A draft set of competencies was revised through the modified Delphi process with two rounds of anonymous input. A threshold of 80% consensus was used to determine whether a competency or sub-competency learning objective was relevant to the skillset needed within academic global surgery and perioperative care. A diverse task force recruited experts from 22 countries to participate in both rounds of the Delphi process. Of the n = 59 respondents completing both rounds of iterative polling, 63% were from low- or middle-income countries. After two rounds of anonymous feedback, participants reached consensus on nine core competencies and 31 sub-competency objectives. The greatest consensus pertained to competency in ethics and professionalism in global surgery (100%) with emphasis on justice, equity, and decolonization across multiple competencies. This Delphi process, with input from experts worldwide, identified nine competencies which can be used to develop standardized academic global surgery and perioperative care curricula worldwide. Further work needs to be done to validate these competencies and establish assessments to ensure that they are taught effectively.

Abstract We report a case of cutaneous lymphangitic carcinomatosis arising from cervical cancer in a 66‐year‐old woman. No standardized treatment protocol currently exists for cutaneous lymphangitic carcinomatosis; in our case, treatment with carboplatin and paclitaxel induced a positive clinical skin response, but the patient passed away from metastatic disease.

Background Incidental findings are commonly noted in advanced imaging studies. Few data exist regarding the rate of incidental findings on computed tomography (CT) for preoperative shoulder arthroplasty planning. This study aims to identify the incidence of these findings and the rate at which they warrant further work-up to help guide orthopedic surgeons in counseling patients. Methods A retrospective review was performed to identify patients with available preoperative shoulder CT who subsequently underwent shoulder arthroplasty procedures at a single institution between 2015 and 2021. Data including age, sex, and smoking status were obtained. Radiology reports for CTs were reviewed for incidental findings and categorized based on location, tissue type, and/or body system. The rate of incidental findings and the rate at which further follow-up was recommended by the radiologist were determined. Results A total of 617 patients was identified. There were 173 incidental findings noted in 146 of these patients (23.7%). Findings ranged from pulmonary (59%), skin/soft tissue (16%), thyroid (13%), vascular (9%), spinal (2%), and abdominal (1%) areas. Of the pulmonary findings, 50% were pulmonary nodules and 47% were granulomatous disease. Overall, the final radiology report recommended further follow-up for 50% of the patients with incidental findings. Conclusions Incidental findings are relatively common in preoperative CTs obtained for shoulder arthroplasty, occurring in nearly one-quarter of patients. Most of these findings are pulmonary in nature. Overall, half of the patients with incidental findings were recommended for further follow-up. These results establish population data to guide orthopedic surgeons in patient counseling. Level of evidence III.