Decreased Positive Fecal Occult Blood Tests and Delayed Medical Presentation for Colorectal Cancer during the Initial COVID-19 Pandemic Period: A Single-center Experience.

Objectives: This study aimed to investigate the impact of the COVID-19 pandemic on the examination and treatment of colorectal cancer (CRC) and on the behaviors of patients and practitioners. Methods: This is a retrospective analysis of the CRC patients who presented to our department between April 2019 and March 2021 and underwent surgery. Clinical presentation of CRC and time from symptom onset to medical presentation were compared between the control (April 2019 to March 2020, n=124) and COVID-19 pandemic periods (April 2020 to March 2021, n=111). Results: Two hundred and thirty-five patients were reviewed. The rate of positive fecal occult blood tests was significantly lower during the COVID-19 pandemic period (13.5 vs. 25.0%, P = 0.027). Among the symptomatic patients who had melena and abdominal symptoms, the time from symptom onset to medical presentation was significantly longer during the COVID-19 period (115 vs. 31 days, P < 0.001). In addition, the interval between presenting to a practitioner and being referred to our department was similar between the two periods (19 vs. 13 days, P = 0.092). There were no significant differences in the stage of cancer between the two periods. The rate of preoperative sub-obstruction was significantly higher during the COVID-19 period (41.4 vs 23.4%, P = 0.003). There was no significant difference in overall survival and recurrence-free survival between two periods. Conclusions: Hesitation to seek examination and treatment for CRC was observed in patients but not in practitioners during the COVID-19 pandemic period. The prognosis did not change.

Synthetic hemozoin as a nanocarrier for cross-presentation.

It is known that conventional antigen presentation involves phagocytosis of antigens followed by its internalization in endocytic compartments and presentation of epitopes through MHC class II molecules for CD4 T cells. However, since 1976 a cross-presentation pathway has been studied, in which CD8 T cells are activated via MHC class I with antigens acquired through phagocytosis or endocytosis by dendritic cells (DCs). Among some important molecules involved in the cross-presentation, the C-type lectin receptor of the Dectin-1 cluster (CLECs), particularly the CLEC9A receptor, not only is expressed in dendritic cells but also presents a pivotal role in this context. In special, CLEC12A has been highlighted as a malaria pigment hemozoin (HZ) receptor. During Plasmodium infection, hemozoin crystals defend the parasite against heme toxicity within erythrocytes, as well as the released native HZ elicits pro-inflammatory responses and can induce cross-presentation. Particularly, this crystal can be synthesized from hematin anhydride and mimics the native form, and the gaps generated between the nanocrystal domains during its synthesis allow for substance coupling followed by its coating. Therefore, this study aimed to assess whether synthetic hemozoin (sHz) or hematin anhydride could be a nanocarrier and promote cross-presentation in dendritic cells. Firstly, it was verified that sHz can carry coated and coupled antigens, the compounds can associate to LAMP1-positive vesicles and decrease overall intracellular pH, which can potentially enhance the cross-presentation of ovalbumin and Leishmania infantum antigens. Thus, this study adds important data in the molecular intricacies of antigen presentation by showing not only the sHz immunomodulatory properties but also its potential applications as an antigen carrier.

Cavitary Consolidation in Pulmonary Infarct Secondary to Embolism: A Rare Presentation.

Obstruction of the pulmonary artery or one of its branches, often due to thrombi from the deep veins of the lower extremities can result in a life-threatening condition known as pulmonary embolism. Pulmonary infarction, an unusual complication of pulmonary embolism occurs when the blood supply to lung tissue is obstructed, leading to tissue necrosis. An 80-year-old man presented with a cough, breathlessness, and generalized weakness. He was vitally stable with no oxygen requirement, which could have suggested an infective etiology like pneumonia or tuberculosis. However, the presence of calf tenderness prompted us to perform a venous Doppler ultrasonography, which revealed deep venous thrombosis. This, combined with right atrial and ventricular dilation and moderate pulmonary artery hypertension observed on transthoracic echocardiography (2D ECHO), led us to recommend a CT pulmonary angiography. The angiography revealed an uncommon presentation of pulmonary embolism with multiple pulmonary infarcts. Here, we chronicle an unusual case of pulmonary infarction secondary to pulmonary embolism, which presented radiologically as consolidation with an aseptic cavity, a rare and atypical triple occurrence.

Impact of a simulator-based training program on the success rate of external cephalic version.

OBJECTIVE: To compare the success and complication rates of external cephalic version before and after the implementation of a simulator-based training program at a tertiary care university centre with a dedicated external cephalic version team. STUDY DESIGN: In this single-center intervention study, the success rate and the complication rates of external cephalic version in the two years before the implementation of a simulation-based training program for all specialists and residents, were compared with the two years following the event. T- student, Mann-Whitney, and Chi-square tests were used. All data were extracted from the hospital's electronic patient records. RESULTS: A total of 96 external cephalic versions were performed in the 2 years before the training program, and 74 after the training program. The overall success rates were similar between the two groups: 44.8 % before training and 43.2 % after training (p = 0.824). No major complications occurred, and no emergency cesarean deliveries were performed in either period. CONCLUSION: In a tertiary care university training center with a dedicated team in external cephalic version, a structured simulation-based training program did not impact the success rate or the complication rates of the procedure.

The impact of admission modes on the treatment outcome and in-hospital mortality rate of STEMI patients undergoing PPCI.

The current research on ST elevation myocardial infarction (STEMI) patients has been mostly limited to Door-to-Balloon (D-to-B) time. This study aimed to compare the effects of different hospital admission modes to on the time metrics of patients undergoing primary percutaneous coronary intervention (PPCI). It also examined the effects of these modes on in-hospital mortality and other influencing factors. The goal was to prompt healthcare facilities at all levels, including chest hospitals, the Centers for Disease Control and Prevention (CDC), and communities to take measures to enhance the treatment outcomes for patients with STEMI. A total of 1053 cases of STEMI patients admitted to Tianjin Chest Hospital from December 2016 to December 2023 and successfully underwent PPCI were selected for this study. They were divided into three groups based on the admission modes: the ambulances group (363 cases), the self-presentation group (305 cases), and the transferred group (385 cases). Multivariate logistic regression was used to explore the impact of different modes of hospital admission on the standard-reaching rate of key treatment time metrics. The results showed that the S-to-FMC time of transferred patients (OR = 0.434, 95% CI 0.316-0.596, P < 0.001) and self-presentation patients (OR = 0.489, 95% CI 0.363-0.659, P < 0.001) were more likely to exceed the standard than that of ambulance patients; The cath lab pre-activation time of self-presented patients was also less likely to meet the standard than that of ambulance patients (OR = 0.695, 95% CI 0.499-0.967, P = 0.031); D-to-W time of self-presentation patients was less likely to reach the standard than that of ambulance patients (OR = 0.323, 95% CI 0.234-0.446, P < 0.001);However, the FMC-to-ECG time of self-presentation patients was more likely to reach the standard than that of ambulance patients (OR = 2.601, 95% CI 1.326-5.100, P = 0.005). The Cox proportional hazards model analysis revealed that for ambulance patients, the time spent at each key treatment time point is shorter, leading to lower in-hospital mortality rate (HR0.512, 95% CI 0.302-0.868, P = 0.013) compared to patients admitted by other means. We found that direct arrival of STEMI patients to the PCI hospital via ambulance at the onset of the disease significantly reduces the S-to-FMC time, FMC-to-ECG time, D-to-W time, and catheterization room activation time compared to patients who self-present. This admission mode enhances the likelihood of meeting the benchmark standards for each time metric, consequently enhancing patient outcomes.

Rituximab therapy for adult refractory systemic lupus erythematosus with neurological and/or psychiatric presentations: a PRISMA-compliant meta-analysis.

BACKGROUND: Rituximab (RTX) is used off-label for refractory cases of Systemic lupus erythematosus (SLE) with extrarenal activity, including neurological and/or psychiatric (N/P) presentations. However, evidence from randomized controlled trials is limited. OBJECTIVE: This study aimed to conduct a pooled analysis of the effectiveness and safety of RTX therapy for adult refractory SLE with N/P manifestations. METHODS: Electronic searches in databases and statistical analysis were conducted in this study. RESULTS: Electronic searches in PubMed, Epistemonikos, and ICTRP in May 2023 identified 20 studies (25 reports). A total of 59 patients (53 females; 90%) were included, with a mean age of 33.5±10.6 years and a median disease duration of 3.5 years (range, 0.08 to 25.0) who were followed up post-RTX therapy for a median time of 12 months (range, 3.0 to 46.2). The rate of clinical response (partial or major) was 90% (95% CI, 83 to 96) (n = 57 patients). A third of responders relapsed after a median time of 9.5 months (range, 3.0 to 33.0). Pooled pre-RTX/post-RTX scores for Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (n = 13) were 19±15/7±5 and for neurological British Isles Lupus Assessment Group (BILAG) (n = 29) were A/D (13), A/C (5), B/D (7), B/C (2), and A/A (2). Patients without mood disorder had a higher chance of clinical response {relative risk (RR) 1.4 (1.03 to 1.48)}. Patients who benefited the most from RTX therapy were those with psychosis (a higher chance of major clinical response; RR 1.9 (1.02 to 2.34)), without acute confusional state (a lower chance of relapse; RR 0.08 (0.006 to 0.791)), and with disease duration <3 years (a lower chance of relapse; RR 0.18 (0.014 to 0.992)). Infection rate during treatment was 33% (7/21). CONCLUSIONS: RTX therapy had good effectiveness. The pooled evidence for safety outcomes was limited and of low certainty.

Unusual Presentation of Cerebral Fat Embolism Syndrome Post-femur Fracture: A Case Study and Diagnostic Insights.

Cerebral fat embolism syndrome (CFES) is a rare but certainly devastating impediment following long bone fractures. The diagnosis of CFES primarily depends on identifying clinical manifestations like respiratory distress, petechial rash, and neurological symptoms. However, in rare instances, CFES can manifest with atypical or absent clinical features, posing diagnostic challenges. Here, we present a rare case report of a woman in her 20s who developed CFES after suffering a femur shaft fracture devoid of conventional clinical features. The diagnosis of CFES was built upon clinical suspicion and a typical MRI brain finding of a starfield pattern. Our case highlights the importance of including CFES in the differential diagnosis of neurological deterioration, especially after long bone fractures. We suggest early plate osteosynthesis to stop more emboli from forming in people with FES, as well as continuous neuromonitoring and a reminder that CFES can show up without any other signs or symptoms in the body.

Atypical Presentation of Probable Sporadic Creutzfeldt-Jakob Disease: A Patient Without Mental Deterioration.

Creutzfeldt-Jakob Disease (CJD) is a prion disease that leads to rapid mental deterioration and is always fatal. Prions are glycoproteins found in the brain. While their function is not completely understood, irregular folding of these proteins leads to prion disorders and neurodegenerative disease. CJD is extremely rare (1-2 cases per million people). A 68-year-old woman presented to the family medicine clinic with symptoms of weakness, paresthesia, and foot drop. Some weeks later she presented at the emergency department with left ankle and foot pain. All symptoms were on the left side of the body. An initial workup with labs was performed which all returned normal. Subsequently, a cerebrospinal fluid (CSF) panel was run and findings included elevated neuron-specific enolase and 14-3-3 gamma indicating a neurodegenerative disease. Further, an indeterminate real-time quaking-induced conversion (RT-QuIC) led to our diagnosis of a probable sporadic CJD. The patient was treated for symptoms and died four months following the initial presentation. Typically CJD presents with similar physical symptoms such as myoclonus. CJD is typically accompanied by severe mental deterioration including depression, memory loss, and dementia. CJD presentation without mental deterioration has only been reported in two other cases. Presenting here is a unique presentation of probable CJD that involved all the physical symptoms, including death, but the mental deterioration was absent. Clinicians should be aware of CJD and that presentation is not always standard.

Combining single-cell spatial transcriptomics and molecular simulation to develop in vivo probes targeting the perineural invasion region of adenoid cystic carcinoma.

Background and objectives: Perineural invasion (PNI) refers to the invasion, encasement, or penetration of tumor cells around or through nerves. Various malignant tumors, including pancreatic cancer, head and neck tumors, and bile duct cancer, exhibit the characteristic of PNI. Particularly, in head and neck-skull base tumors such as adenoid cystic carcinoma (ACC), PNI is a significant factor leading to incomplete surgical resection and postoperative recurrence. Methods: Spatial transcriptomic and single-cell transcriptomic sequencing were conducted on a case of ACC tissue with PNI to identify potential probes targeting PNI. The efficacy of the probes was validated through in vivo and in vitro experiments. Results: Spatial transcriptomic and single-cell RNA sequencing revealed phenotypic changes in Schwann cells within the PNI region of ACC. Peptide probes were designed based on the antigen-presenting characteristics of Schwann cells in the PNI region, which are dependent on Major Histocompatibility Complex II (MHC-II) molecules. Successful validation in vitro and in vivo experiments confirmed that these probes can label viable Schwann cells in the PNI region, serving as a tool for dynamic in vivo marking of tumor invasion into nerves. Conclusions: Peptide probes targeting Schwann cells' MHC-II molecules have the potential to demonstrate the occurrence of PNI in patients with ACC.

A critical review of mpox outbreaks, risk factors, and prevention efforts in Africa: lessons learned and evolving practices.

Objectives: In recent years, mpox, a zoonotic disease caused by the mpox virus, has transcended its primary association with Central and West Africa, emerging as a global public health concern. The virus poses a substantial threat, particularly, to vulnerable demographics such as young children and individuals with compromised immune systems. This critical literature review aimed to comprehensively evaluate the burden, risk factors, and current management strategies associated with mpox in Africa. Methods: This critical literature review was guided by Jesson & Laccy's guidelines on conducting critical literature reviews. We searched PubMed and Google Scholar databases and websites of the World Health Organization and health ministries in different African countries. We included articles written in English and published between 2010 and 2023. The synthesis of findings involved several steps, including summarizing themes, integrating themes, and linking themes to research questions. Results: A total of 25 articles were included in this review. The review revealed that mpox cases are concentrated in Central African countries. The risk factors for mpox identified include being in contact with bushmeat or rodents, not having been vaccinated against smallpox, being HIV-positive, and having close physical contact with someone with the disease. The clinical presentation of mpox revealed in this review includes a skin rash, fever, lymphadenopathy, headache, pruritus, sore throat, and body aches. Four themes arose on strategies to prevent and control mpox in Africa. Conclusions: The prevention and control of mpox in Africa require an improvement in community education, vaccination, disease surveillance, and infection control measures.

Assessing and Evaluating the Perfectionism Social Disconnection Model: Social Support, Loneliness, and Distress Among Undergraduate, Law, and Medical Students.

The current research evaluates the Perfectionism Social Disconnection Model (PSDM) by considering the links between measures of trait perfectionism and perfectionistic self-presentation and measures of social support, loneliness, and distress in cross-sectional research. A particular focus is on perfectionism and levels of social support as assessed by the Social Provisions Scale. The current study also uniquely evaluates levels of perfectionism and perfectionistic self-presentation in undergraduate students, medical students, and law students. The results across samples provided evidence that loneliness mediates the link between interpersonal perfectionism and distress in keeping with the predictions of the PSDM. Correlational results found robust links between loneliness and low levels of social support. Moreover, socially prescribed perfectionism and perfectionistic self-presentation were associated negatively with social support, and this was especially evident in terms of the facet tapping the nondisclosure of imperfections. Group comparisons of perfectionism yielded few significant differences in accordance with expectations. Levels of perfectionism tended to be lower among medical students. However, the links between perfectionism and distress were clearly evident among undergraduates, medical students, and law students, thus attesting to the vulnerability of perfectionistic students in general. Overall, the results further confirm the relevance of perfectionism in distress among students and applicability of the PSDM in various types of students.

Perfectionism, Self-Image Goals and Compassionate Goals in Health and Mental Health: A Longitudinal Analysis.

This research focuses on ego-focused self-image goals as central to understanding the vulnerability inherent in perfectionism and the link that perfectionism has with poorer health and emotional well-being. The present study expands theory and research on perfectionism from a unique motivational perspective through a longitudinal investigation of perfectionism, the pursuit of self-image goals related to self-improvement, and mental and physical health among 187 university students. Our central finding was that trait and self-presentational perfectionism were associated longitudinally with self-image goals and poorer mental and physical health. Longitudinal analyses showed that perfectionistic self-presentation predicted subsequent self-image goals, controlling for initial self-image goals. Additionally, self-image goals were associated with worse mental and physical health and greater loneliness and social anxiety. Collectively, our results illustrate the benefits of assessing problematic personal goals in perfectionism and the need to revise existing motivational accounts by recognizing the important role ego-involved goals play in guiding much of what perfectionists do and how they act in their daily lives.

Transcriptomic observations of intra and extracellular immunotherapy targets for pediatric brain tumors.

OBJECTIVES: Despite surgical resection, chemoradiation, and targeted therapy, brain tumors remain a leading cause of cancer-related death in children. Immunotherapy has shown some promise and is actively being investigated for treating childhood brain tumors. However, a critical step in advancing immunotherapy for these patients is to uncover targets that can be effectively translated into therapeutic interventions. METHODS: In this study, our team performed a transcriptomic analysis across pediatric brain tumor types to identify potential targets for immunotherapy. Additionally, we assessed components that may impact patient response to immunotherapy, including the expression of genes essential for antigen processing and presentation, inhibitory ligands and receptors, interferon signature, and overall predicted T cell infiltration. RESULTS: We observed distinct expression patterns across tumor types. These included elevated expression of antigen genes and antigen processing machinery in some tumor types while other tumors had elevated inhibitory checkpoint receptors, known to be associated with response to checkpoint inhibitor immunotherapy. CONCLUSION: These findings suggest that pediatric brain tumors exhibit distinct potential for specific immunotherapies. We believe our findings can guide investigators in their assessment of appropriate immunotherapy classes and targets in pediatric brain tumors.

Delayed presentation of traumatic cervical epidural hematoma: a case report and review of the pertinent literature.

A delayed presentation of traumatic spinal epidural hematoma (SEH) is a rare disease in which most patients are asymptomatic for days to weeks after the injury, followed by pain and then a neurological deficit. A 66-year-old woman who suffered a fractured right clavicle due to a bicycle accident 42 days previously, presented with left shoulder pain and left hemiplegia. The manual muscle test (MMT) scores of the left upper and lower limbs were all 1. Computed tomography and magnetic resonance imaging showed no cervical fracture but showed cervical epidural hematoma. She underwent surgery for the removal of the SEH. Her MMT score improved to 4 at 10 days after surgery. Even in cases with a delayed presentation, suspecting SEH can help clinicians make an early diagnosis. Additionally, the prompt surgical evacuation of the SEH can lead to favorable neurological outcomes in symptomatic cases.

Trends in invasive Haemophilus influenzae serotype b (Hib) disease in England; 2012/13 to 2022/23.

INTRODUCTION: Haemophilus influenzae serotype b (Hib) conjugate vaccines have been highly successful in reducing the Hib disease worldwide. Recently, several European countries have reported an increase in invasive Hib disease. We aimed to describe the epidemiology, clinical characteristics, genomic trends, and outcomes of invasive Hib disease over the past 11 years in England. METHODS: The UK Health Security Agency (UKHSA) conducts national surveillance of invasive H influenzae disease and hosts a national reference laboratory for confirmation and serotyping. General practitioners are contacted to complete a surveillance questionnaire for confirmed Hib cases. Invasive Hib isolates routinely undergo whole genome sequencing. RESULTS: During 2012/13-2022/23, there were 6,881 invasive H. influenzae infections, of which 5,852 (85%) were serotyped; most isolates (4,881, 83%) were non-typeable H. influenzae, followed by Hif (591, 10%), Hie (189, 3%), Hib (118, 2%) and Hia (54, 1.0%). The median age for invasive Hib disease was 51 years and most cases (84%, 99/118) were in adults. Children accounted for 19 cases (16%), including 13 (11%) in <1 year-olds and 6 (5%) in 1-5-year-olds. Bacteraemic pneumonia was the most common diagnosis (66/118, 56%). Hib case-fatality rate was 5.9% (7/118), with the last fatality reported in 2016. Among 64 sequenced strains during 2016/17-2022/2023, most (56/64, 88%) belonged to the CC6 lineage (representing ST6 and single locus variants of ST6). CONCLUSIONS: In England, invasive Hib disease remains rare with no evidence of any increase in incidence and is rarely fatal, affecting mainly adults with underlying conditions, who typically develop pneumonia.

Individual differences in the impostor phenomenon and its relevance in higher education in terms of burnout, generalized anxiety, and fear of failure.

Few theoretical and empirical works have described impostor phenomenon (IP) and no study explored impostorism from a dark perspective. We adopted a person-centered approach to identify clusters of impostors based on scores on the IP, perfectionistic self-presentation and the Dark Triad using a sample of 306 university students (Mage = 22.82). The latent profile analysis suggested a 6-cluster solution, which was further compared in terms of psychopathology symptoms (i.e., burnout, generalized anxiety, and fear of failure) by means of (M)ANOVAs. Our results indicated that impostorism relies on a self-presentation strategy. Moreover, individuals scoring high on IP experienced enhanced levels of psychopathology symptoms. Looking at IP from a continuum perspective might improve our understanding about what makes someone suffer from impostorism.

Monocytic Phagocytes in the Immunopathogenesis of Cytokine Storm Syndromes.

Cytokine storm syndromes (CSSs) are caused by a dysregulated host immune response to an inciting systemic inflammatory trigger. This maladaptive and harmful immune response culminates in collateral damage to host tissues resulting in life-threatening multisystem organ failure. Knowledge of the various immune cells that contribute to CSS pathogenesis has improved dramatically in the past decade. Monocytes, dendritic cells, and macrophages, collective known as monocytic phagocytes, are well-positioned within the immune system hierarchy to make key contributions to the initiation, propagation, and amplification of the hyperinflammatory response in CSS. The plasticity of monocytic phagocytes also makes them prime candidates for mediating immunoregulatory and tissue-healing functions in patients who recover from cytokine storm-mediated immunopathology. Therefore, approaches to manipulate the myriad functions of monocytic phagocytes may improve the clinical outcome of CSS.

The dual nature of TDC - bridging dendritic and T cells in immunity.

TDC are hematopoietic cells with unique features that provide intriguing insights into the interplay between innate and adaptive immunity. They express a combination of conventional dendritic cell (DC) and T-cell markers and are found in secondary lymphoid organs (SLOs), lungs and liver of naïve mice, as well as in human blood. When analyzed ex vivo, TDC can behave either as DCs or as T cells, depending on the provided stimuli. Notably, TDC numbers and activation significantly increase in SLOs following viral infection, suggesting a potential role for TDC in antiviral immune responses. In this review, we discuss the properties of these fascinating cells, which call for more investigation on their physiological role during immune responses to both pathogens and tumors.