Major placenta previa among patients with and without previous cesarean section: Maternal characteristics, outcomes and risk factors.

OBJECTIVES: To compare maternal characteristics and outcomes among patients having major placenta previa (PP) with and without previous cesarean section (CS). And to determine if previous CS alone is a risk factor for associated adverse maternal outcomes in these patients. MATERIALS AND METHODS: This is a retrospective analysis including two groups of major PP patients, with previous CS (n = 184) and without CS (n = 115); who were admitted to Abha Maternity and Children's Hospital over the last ten-years (January 2012-December 2021), Aseer region, Saudi Arabia. RESULTS: Compared to those without previous CS, major PP patients with previous CS had significantly advanced ages with higher mean numbers of gravidity and parity, but significantly less rates of previous uterine surgery and IVF pregnancies. Moreover, they were more likely to acquire higher rates of adverse maternal outcomes. In the same way, these patients had an increased Odds Ratios of cesarean hysterectomy (OR of 20.462), urinary tract injuries (OR of 12.361), associated PAS (OR of 4.375), moderate/ heavy intra-operative bleeding (OR of 2.153) and the need for transfusion of 3+ units of packed RBCs (OR of 1.849). CONCLUSION: (1) Patients with combined existence of major PP and previous CS had significantly higher rates of adverse maternal outcomes (2) Alone, prior CS in major PP patients increased the Odds Ratios of cesarean hysterectomy, urinary tract injuries, diagnosis of PAS, excessive intra-operative bleeding and repeated packed RBCs transfusions. (3) Among our PP patients with previous CS, the increased rate and OR of PAS diagnosis could in-part explain the adverse maternal outcomes.

Benchmarking variational AutoEncoders on cancer transcriptomics data.

Deep generative models, such as variational autoencoders (VAE), have gained increasing attention in computational biology due to their ability to capture complex data manifolds which subsequently can be used to achieve better performance in downstream tasks, such as cancer type prediction or subtyping of cancer. However, these models are difficult to train due to the large number of hyperparameters that need to be tuned. To get a better understanding of the importance of the different hyperparameters, we examined six different VAE models when trained on TCGA transcriptomics data and evaluated on the downstream tasks of cluster agreement with cancer subtypes and survival analysis. We studied the effect of the latent space dimensionality, learning rate, optimizer, initialization and activation function on the quality of subsequent downstream tasks on the TCGA samples. We found ß-TCVAE and DIP-VAE to have a good performance, on average, despite being more sensitive to hyperparameters selection. Based on these experiments, we derived recommendations for selecting the different hyperparameters settings. To ensure generalization, we tested all hyperparameter configurations on the GTEx dataset. We found a significant correlation (ρ = 0.7) between the hyperparameter effects on clustering performance in the TCGA and GTEx datasets. This highlights the robustness and generalizability of our recommendations. In addition, we examined whether the learned latent spaces capture biologically relevant information. Hereto, we measured the correlation and mutual information of the different representations with various data characteristics such as gender, age, days to metastasis, immune infiltration, and mutation signatures. We found that for all models the latent factors, in general, do not uniquely correlate with one of the data characteristics nor capture separable information in the latent factors even for models specifically designed for disentanglement.

Adding colchicine to tocilizumab in hospitalized patients with severe COVID-19 pneumonia: An open-label randomized controlled trial.

INTRODUCTION: Colchicine acts upstream in the cytokines cascade by inhibiting the nod-like receptor protein 3 (NLRP3) inflammasome while interleukin 6 (IL-6) receptor antagonists, such as tocilizumab, block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm. METHODS AND ANALYSIS: We aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia who received tocilizumab according to our local guidelines. Enrolled patients will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up for 30 days. The primary outcome is the rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model. DISCUSSION: Given colchicine's ease of use, low cost, good safety profile, and having different anti-inflammatory mechanism of action than other IL-6 blockade, colchicine might serve as a potential anti-inflammatory agent among patients with severe COVID-19 pneumonia. This study will provide valuable insights on the use of colchicine in severe COVID-19 when added to IL-6 antagonists. ETHICS AND DISSEMINATION: The Medical Research Center and Institutional Review Board at Hamad Medical Corporation in Qatar approved the study protocol (MRC-01-21-299). Results of the analysis will be submitted for publication in a peer-reviewed journal.

Refractory Hyperammonemic encephalopathy in Fibrolamellar hepatocellular carcinoma, a case report and literature review.

Fibrolamellar hepatocellular carcinoma is a rare type of hepatocellular carcinoma with unclear etiology. Its prevalence ranges from 0.6%-5%. One of the rare manifestations of FHCC includes hyperammonemic hepatic encephalopathy (HAE). Data regarding HAE in FHCC is limited to case reports, and much is unknown, including its precipitating factors, clinical course, and management. We have reported one such case of FHCC associated HAE and presented an extensive literature review on the topic. We report the case of a 26-year-old Pakistani male who was diagnosed with fibrolamellar hepatocellular carcinoma. On day five after the first chemotherapy, he presented with nausea, vomiting, and confusion. His serum ammonia level was raised, and he was treated with lactulose and rifaximin. The patient continued chemotherapy and had recurrent admissions with HAE. A detailed workup revealed acquired ornithine transcarbamylase deficiency. Ammonia level peaked at 694 umol/L during the clinical course of his disease. He received treatment with multiple ammonia scavengers, including sodium benzoate + phenylacetate, with relief of symptoms and reduction in ammonia level. The patient was eventually lost to follow-up. HAE presents as a paraneoplastic manifestation of FHCC. Patients have laboratory features suggestive of acquired ornithine transcarbamylase deficiency. There is a variable frequency of episodes reported in the literature. Most patients respond well to ammonia scavenger therapies rather than conventional HE management with lactulose or rifaxmin.

Single-Cell Analysis of Refractory Celiac Disease Demonstrates Inter- and Intra-Patient Aberrant Cell Heterogeneity.

BACKGROUND & AIMS: Refractory celiac disease type II (RCDII) is a rare indolent lymphoma in the small intestine characterized by a clonally expanded intraepithelial intracellular CD3+surfaceCD3-CD7+CD56- aberrant cell population. However, RCDII pathogenesis is ill-defined. Here, we aimed at single-cell characterization of the innate and adaptive immune system in RCDII. METHODS: Paired small intestinal and blood samples from 12 RCDII patients and 6 healthy controls were assessed by single-cell mass cytometry with a 39-cell surface marker antibody panel, designed to capture heterogeneity of the innate and adaptive immune system. A second single-cell mass cytometry panel that included transcription factors and immune checkpoints was used for analysis of paired samples from 5 RCDII patients. Single-cell RNA sequencing analysis was performed on duodenal samples from 2 RCDII patients. Finally, we developed a 40-marker imaging mass cytometry antibody panel to evaluate cell-cell interactions in duodenal biopsy specimens of RCDII patients. RESULTS: We provide evidence for intertumoral and intratumoral cell heterogeneity within the duodenal and peripheral aberrant cell population present in RCDII. Phenotypic discrepancy was observed between peripheral and duodenal aberrant cells. In addition, we observed that part of the aberrant cell population proliferated and observed co-localization of aberrant cells with CD163+ antigen-presenting cells (APCs) in situ. In addition, we observed phenotypic discrepancy between peripheral and duodenal aberrant cells. CONCLUSIONS: Novel high-dimensional single-cell technologies show substantial intertumoral and intratumoral heterogeneity in the aberrant cell population in RCDII. This may underlie variability in refractory disease status between patients and responsiveness to therapy, pointing to the need for personalized therapy in RCDII based on patient-specific immune profiles.

Single-Cell Transcriptomics Reveals Discrete Steps in Regulatory T Cell Development in the Human Thymus.

CD4+CD25+FOXP3+ regulatory T (Treg) cells control immunological tolerance. Treg cells are generated in the thymus (tTreg) or in the periphery. Their superior lineage fidelity makes tTregs the preferred cell type for adoptive cell therapy (ACT). How human tTreg cells develop is incompletely understood. By combining single-cell transcriptomics and flow cytometry, we in this study delineated three major Treg developmental stages in the human thymus. At the first stage, which we propose to name pre-Treg I, cells still express lineage-inappropriate genes and exhibit signs of TCR signaling, presumably reflecting recognition of self-antigen. The subsequent pre-Treg II stage is marked by the sharp appearance of transcription factor FOXO1 and features induction of KLF2 and CCR7, in apparent preparation for thymic exit. The pre-Treg II stage can further be refined based on the sequential acquisition of surface markers CD31 and GPA33. The expression of CD45RA, finally, completes the phenotype also found on mature recent thymic emigrant Treg cells. Remarkably, the thymus contains a substantial fraction of recirculating mature effector Treg cells, distinguishable by expression of inflammatory chemokine receptors and absence of CCR7. The developmental origin of these cells is unclear and warrants caution when using thymic tissue as a source of stable cells for ACT. We show that cells in the major developmental stages can be distinguished using the surface markers CD1a, CD27, CCR7, and CD39, allowing for their viable isolation. These insights help identify fully mature tTreg cells for ACT and can serve as a basis for further mechanistic studies into tTreg development.

Chronic myelogenous leukemia presenting with Morel Lavallée lesion: A case report of a rare presentation.

Chronic myelogenous leukemia is a myeloproliferative neoplasm characterized by the BCR-ABL1 fusion gene and the development of the Philadelphia chromosome, which leads to an increase in granulocytes and bone marrow myeloid precursors in the blood, it can lead to many possible complications depending on the disease stage at the time of diagnosis. The Morel-Lavallée lesion (MLL) is a closed traumatic soft-tissue degloving injury, that results from the separation of the hypodermis from the underlying fascia, with resultant hemo-lymphatic fluid collection between the tissue layers. We report a case of a 48-year-old male patient, with no chronic illnesses, who presented with 2 weeks history of posterior chest wall pain and swelling. Initial investigation showed a white blood cell count of 364.4 × 103/µl. Bone marrow pathology report findings were consistent with chronic myeloid leukemia (CML), and the BCR-ABL test came positive. CT chest with contrast showed a large chest wall lesion, suggestive of a Morel-Lavallee lesion. Ultrasound-guided aspiration of the lesion yielded 20 mm of fluid from the thick hematoma. Histopathology of the fluid showed Necrotic debris with mixed inflammation. Patient's condition improved, and he was discharged on Dasatinib with follow-up in hematology and surgery clinics.

Prevalence and correlates of university students' perceived stress in southwestern Saudi Arabia.

ABSTRACT: The university period can be stressful for most students. It may be due to exposure to various stressors. Objectives: To establish the prevalence and factors associated with high perceived stress among university undergraduates in south-western Saudi Arabia.A self-administered survey was conducted among a representative sample of King Khalid University students through a cross-sectional study. Data obtained included socio-economic, academic characteristics, and grade point average (GPA) scores. Stress was assessed using the Perceived Stress Scale.This study included 2467 students. The average Perceived Stress Scale score was 19.13 ±â€Š6.56, which was notably higher (P = .02) among health care undergraduates (19.45 ±â€Š6.49) compared to others (18.85 ±â€Š6.61). High perceived stress prevalence rate was 12.7% (13.6% in health care institutions and 12.0% in non-healthcare institutions). Multivariable analysis revealed that high perceived stress was considerably greater among females (adjusted odds ratio [aOR] = 2.35, 95% confidence interval:167-3.30), smokers (aOR = 1.65), those with an unsatisfactory income (aOR = 3.10), and healthcare students (aOR=1.33). In contrast, it was negatively associated with the GPA score (aOR= 0.77).High perceived stress is a substantial problem among university students. Female students and healthcare students are at a greater risk. High stress is correlated with smoking, lower GPA scores, and perceived insufficient family income.

Efficacy and cost effectiveness of intravenous ferric carboxymaltose versus iron sucrose in adult patients with iron deficiency anaemia.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy. OBJECTIVE: To determine the efficacy and cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA. DATA SOURCES: Electronic medical record i.e. Cerner® system. TARGET POPULATION: Adults patients with iron deficiency anaemia. TIME HORIZON: A 12-month period (01/01/2018-31/12/2018). PERSPECTIVE: Hamad Medical Corporation (HMC, a public hospital). INTERVENTION: IV Ferric Carboxymaltose versus IV Iron Sucrose. OUTCOME MEASURES: With regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes. RESULTS OF BASE-CASE ANALYSIS: There was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes. RESULTS OF SENSITIVITY ANALYSIS: Not applicable. LIMITATIONS: The study did not consider the clinical or humanistic outcome. CONCLUSIONS: The higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.

Timing and localization of myasthenia gravis-related gene expression.

Myasthenia gravis (MG) is an acquired autoimmune disorder caused by autoantibodies binding acetylcholine receptors (AChR), muscle-specific kinase (MuSK), agrin or low-density lipoprotein receptor-related protein 4 (Lrp4). These autoantibodies inhibit neuromuscular transmission by blocking the function of these proteins and thereby cause fluctuating skeletal muscle weakness. Several reports suggest that these autoantibodies might also affect the central nervous system (CNS) in MG patients. A comprehensive overview of the timing and localization of the expression of MG-related antigens in other organs is currently lacking. To investigate the spatio-temporal expression of MG-related genes outside skeletal muscle, we used in silico tools to assess public expression databases. Acetylcholine esterase, nicotinic AChR α1 subunit, agrin, collagen Q, downstream of kinase-7, Lrp4, MuSK and rapsyn were included as MG-related genes because of their well-known involvement in either congenital or autoimmune MG. We investigated expression of MG-related genes in (1) all human tissues using GTEx data, (2) specific brain regions, (3) neurodevelopmental stages, and (4) cell types using datasets from the Allen Institute for Brain Sciences. MG-related genes show heterogenous spatio-temporal expression patterns in the human body as well as in the CNS. For each of these genes, several (new) tissues, brain areas and cortical cell types with (relatively) high expression were identified suggesting a potential role for these genes outside skeletal muscle. The possible presence of MG-related antigens outside skeletal muscle suggests that autoimmune MG, congenital MG or treatments targeting the same proteins may affect MG-related protein function in other organs.

Prevalence and factors associated with gastroesophageal reflux disease among primary health care attendants at Abha city, southwestern Saudi Arabia.

BACKGROUND: Gastroesophageal reflux disease (GERD) is an abnormal reflux of the gastric content into the esophagus. In Saudi Arabia the GERD prevalence is not recently well studied. OBJECTIVE: To investigate the prevalence of gastroesophageal reflux disease and associated factors among attendants of primary health care centers (PHCCs) at Abha city, Saudi Arabia. METHOD: A descriptive cross- sectional study was performed using GerdQ as diagnostic tool for the GERD. The GerdQ consisted of six questions. Four questions were about the positive GERD predictors. The other two questions were about the negative GERD predictors. The scoring of GerdQ relies on the frequency of GERD symptoms during the last seven days. Using stratified random sample technique a representative sample was slected from the study PHCCs taking into conmsideration the relative catchment population in each center among adult males and females attending the selected PHCCs for any reason. RESULTS: The present study included 320 persons. The study showed a prevalence of GERD of 67.8%. The prevalence of GERD with high impact on daily life (HIDL) was found to be 50%. By multiple logistic regression (enter method) only four significant independent factors associated with GERD were identified; being unmarried (aOR = 1.85, 95% CI:1.02-3.23); smoking (aOR = 2.11, 95% CI: 1.41-5.98), fast food intake (OR = 1.28, 95% CI:1.01-1.71), and subjective perception of stress (OR = 3.0, 95% CI:1.68-5.26). CONCLUSIONS: GERD is a public health problem among adults in the region. Community level awareness programs are recommended. Healthcare providers must be aware of community perceptions and practices.

Risk Factors of the First-Time Stroke in the Southwest of Saudi Arabia: A Case-Control Study.

Worldwide, stroke is the second leading cause of death and a frequent cause of permanent disability. The objective was to identify the first-time stroke modifiable risk factors in the Aseer region, southwest Saudi Arabia. In a multicenter hospital-based case-control study design, all first stroke patients admitted to hospitals in the Aseer region were included consecutively over one year. Age, sex, and geographical residence-matched controls were selected and included in a ratio of 1:1. Data collected included altitude (low or high), nationality, marital status, educational level, family history of stroke, history of diabetes mellitus, history of systemic hypertension, high cholesterol level, current smoking, obesity, and regular exercise practice. The study included 1249 first-time stroke patients and 1249 age, sex, and residence-matched controls. Hypertension, diabetes mellitus, obesity, and high cholesterol were significantly highly prevalent among cases (57.7%, 49.4%, 42.0%, 29.4%, respectively) compared to controls (31.8%, 25.9%, 30.8%, 12.1%, respectively). Practicing regular exercise was significantly highly prevalent among controls (29.9%) compared to cases (13.1%). Multivariable logistic regression analysis revealed that systemic hypertension (adjusted odds ratio (aOR) = 2.12, 95%CI: 1.74-2.57), diabetes mellitus (aOR = 1.73, 95%CI: 1.41-2.21), obesity (aOR = 1.95, 95%CI: 1.61-2.28) and high cholesterol (aOR = 1.64, 95%CI: 1.28-2.10) were significant risk factors, while regular exercise practice was a significant protective factor (aOR = 0.12, 95%CI: 0.05-0.26) for stroke. Hypertension, diabetes mellitus, obesity, and high cholesterol are major risk factors for stroke in the Aseer region of southwest Saudi Arabia. The protective role of regular physical activity in reducing the risk of stroke is evident. The observed higher prevalence of potentially modifiable risk factors among stroke cases encourages an urgent need to develop and implement a national program to control these factors.

Identification and characterization of two consistent osteoarthritis subtypes by transcriptome and clinical data integration.

OBJECTIVE: To identify OA subtypes based on cartilage transcriptomic data in cartilage tissue and characterize their underlying pathophysiological processes and/or clinically relevant characteristics. METHODS: This study includes n = 66 primary OA patients (41 knees and 25 hips), who underwent a joint replacement surgery, from which macroscopically unaffected (preserved, n = 56) and lesioned (n = 45) OA articular cartilage were collected [Research Arthritis and Articular Cartilage (RAAK) study]. Unsupervised hierarchical clustering analysis on preserved cartilage transcriptome followed by clinical data integration was performed. Protein-protein interaction (PPI) followed by pathway enrichment analysis were done for genes significant differentially expressed between subgroups with interactions in the PPI network. RESULTS: Analysis of preserved samples (n = 56) resulted in two OA subtypes with n = 41 (cluster A) and n = 15 (cluster B) patients. The transcriptomic profile of cluster B cartilage, relative to cluster A (DE-AB genes) showed among others a pronounced upregulation of multiple genes involved in chemokine pathways. Nevertheless, upon investigating the OA pathophysiology in cluster B patients as reflected by differentially expressed genes between preserved and lesioned OA cartilage (DE-OA-B genes), the chemokine genes were significantly downregulated with OA pathophysiology. Upon integrating radiographic OA data, we showed that the OA phenotype among cluster B patients, relative to cluster A, may be characterized by higher joint space narrowing (JSN) scores and low osteophyte (OP) scores. CONCLUSION: Based on whole-transcriptome profiling, we identified two robust OA subtypes characterized by unique OA, pathophysiological processes in cartilage as well as a clinical phenotype. We advocate that further characterization, confirmation and clinical data integration is a prerequisite to allow for development of treatments towards personalized care with concurrently more effective treatment response.

The Role of Coronary Computed Tomography Angiography in Evaluation of High Troponin Patients with Narrow-Complex Supraventricular Tachycardia.

Aim: The aim of this study was to investigate the relation of high-sensitive cardiac troponin T (hs-cTnT) elevation with characteristics of supraventricular tachycardia (SVT) episode (duration and maximum heart rate) and coronary computed tomography angiography (CCTA) findings in patients with SVT who presented to the emergency room with palpitation. Methods: This retrospective, single-center, noninvasive study included all patients aged between 18 years and 65 years who presented to the emergency department due to narrow-complex SVT and underwent CCTA to rule out coronary artery disease (CAD) due to elevation of hs-cTnT and reverted back to sinus rhythm after intravenous adenosine. The first, second, and the maximum hs-cTnT levels were obtained from the database. The patients were classified into normal coronaries, nonobstructive CAD, and obstructive CAD according to findings of the CCTA. The findings of the groups were compared. Results: Eighty-five patients were enrolled in the study. Of them, 21 (26%) patients were female. Sixty-three patients (74%) had normal coronary arteries as per CCTA results, whereas 22 patients (22%) had nonobstructive CAD and two patients (2%) had obstructive CAD. The groups did not differ statistically in respect to hs-cTnT measurements, duration of the arrhythmia, and maximum heart rate at SVT episode. There was no significant statistical correlation between hs-cTnT and the study parameters except the maximum heart rate. Conclusion: Cardiac troponins may increase in patients with paroxysmal SVT irrespective of the presence of coronary lesions, and the CCTA may not be an appropriate investigation in the differential diagnosis of paroxysmal SVT with elevated hs-cTnT.

Unraveling the Complexity of the Cancer Microenvironment With Multidimensional Genomic and Cytometric Technologies.

Cancers are characterized by extensive heterogeneity that occurs intratumorally, between lesions, and across patients. To study cancer as a complex biological system, multidimensional analyses of the tumor microenvironment are paramount. Single-cell technologies such as flow cytometry, mass cytometry, or single-cell RNA-sequencing have revolutionized our ability to characterize individual cells in great detail and, with that, shed light on the complexity of cancer microenvironments. However, a key limitation of these single-cell technologies is the lack of information on spatial context and multicellular interactions. Investigating spatial contexts of cells requires the incorporation of tissue-based techniques such as multiparameter immunofluorescence, imaging mass cytometry, or in situ detection of transcripts. In this Review, we describe the rise of multidimensional single-cell technologies and provide an overview of their strengths and weaknesses. In addition, we discuss the integration of transcriptomic, genomic, epigenomic, proteomic, and spatially-resolved data in the context of human cancers. Lastly, we will deliberate on how the integration of multi-omics data will help to shed light on the complex role of cell types present within the human tumor microenvironment, and how such system-wide approaches may pave the way toward more effective therapies for the treatment of cancer.

Complete Superior and Inferior Vena Cava Obstruction Associated with Systemic-to-Pulmonary Venous Shunts in a Young Female with Heterozygous Prothrombin G20210A Gene Mutation.

Complete superior vena cava (SVC) and inferior vena cava (IVC) obstruction is not uncommon and most commonly associated with malignancy. The risk increases in patients with central lines and hypercoagulable states such as with malignancy, thrombophilia, or use of oral contraceptive pills. According to our knowledge, complete SVC and IVC obstruction associated with systemic-to-pulmonary venous shunts in patients with prothrombin G20210A gene mutation has not been reported in the literature. Here we report the case of a 34-year-old female with complete SVC and IVC obstruction presenting with oxygen desaturation and shortness of breath due to systemic-to-pulmonary venous shunts. The unusual collateral pathway was secondary to SVC obstruction. The patient was managed conservatively, and she remained stable.

Groove Pancreatitis Associated with Transient Liver Injury Mimicking Ampullary Neoplasm.

Groove pancreatitis is an unusual form of pancreatitis characterized by fibrous inflammation and pseudo-tumor in the area around the head of the pancreas. The underlying etiology is unknown but is strongly linked to alcohol abuse. We report a 52-year-old male smoker with hypertension, asthma, and alcohol abuse who was admitted with severe epigastric pain radiating to the back. He was found to have acute pancreatitis. A computed tomography scan of the abdomen showed a mass lesion in the peri-ampullary region. MRI of the abdomen revealed dilated common bile duct and duodenal mass and features suggestive of groove pancreatitis. During the hospital stay, bilirubin and liver enzymes started to rise and then decreased gradually to the previous normal range. The secondary workup for liver disease was unremarkable. The patient improved and was discharged. Six-month follow-up showed regression of the duodenal lesion and reduction in the common bile duct dilatation. Excluding malignancy remains the main challenge in managing groove pancreatitis, and a conservative approach is more reasonable in cases with a typical profile.

Tuberculoid Leprosy with External Jugular Vein Thrombosis: A Case Report and Literature Review.

Thrombotic disease represents a rare manifestation of leprosy. In this study, we report the case of an external jugular vein thrombosis associated with tuberculoid leprosy in a 23-year-old male patient. The patient presented with a 3-month history of painful cord-like swelling on the left side of the neck and a nearly 3-week history of skin lesions on the left cheek and right leg. Physical examination revealed cord-like, tender swelling on the left lateral aspect of the neck overlying the sternocleidomastoid muscle, and a hypopigmented, hypoaesthetic 6×7 cm lesion with an irregular margin on the left cheek. A Doppler ultrasound examination of the jugular vein showed thrombosis of the left external jugular vein. Three-dimensional reconstruction of the computed tomography scan showed the enlarged and enhanced left external jugular vein, as well as 1 of its tributaries, and the thickened skin patch. A skin punch biopsy from the left cheek lesion revealed granulomatous inflammation with occasional peri-adnexal granulomas, consistent with the clinical impression of tuberculoid leprosy. A diagnosis of leprosy with external jugular vein thrombosis was established. Anticoagulation therapy was initiated, and the patient was referred to an infectious disease clinic for treatment with anti-leprosy medications. LEARNING POINTS: Thickened cord-like neck swelling in leprosy can be vein thrombosis rather than a thickened nerve.Leprosy should be considered if a skin lesion is associated with thrombosis.The common causes of upper extremity DVT.

High-dimensional cytometric analysis of colorectal cancer reveals novel mediators of antitumour immunity.

OBJECTIVE: A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC. DESIGN: Thirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence. RESULTS: We discovered that a previously unappreciated innate lymphocyte population (Lin-CD7+CD127-CD56+CD45RO+) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103+CD69+) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and γδ T cells with highly similar activated (HLA-DR+CD38+PD-1+) phenotypes. Remarkably, activated γδ T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and γδ T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes. CONCLUSION: This work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting.

Awareness of stroke among patients attending primary healthcare services in Abha, Southwestern Saudi Arabia.

OBJECTIVE: To examine the awareness about major symptoms, risk factors, and response to stroke among the population in Abha, Southwestern Kingdom of Saudi Arabia. Improving stroke-related knowledge may advance stroke prevention and reduce pretreatment delay and disabilities. METHODS: We conducted a cross-sectional study among a representative sample of primary healthcare adult patients between January-May 2016 and used a validated Arabic questionnaire to evaluate the participants` awareness about stroke. RESULTS: The study involved 1472 adults. Only 63.6% and 43.7% of participants correctly recognized thrombosis and hemorrhage as types of stroke. Commonly identified risk factors were hypertension (55.8%), dyslipidemia (45.8%), and smoking (41.9%). Sudden severe headache (54.1%), dizziness (51.0%), and difficulty in speaking (44.3%) were the most frequently recognized symptoms. The most frequently reported correct responses to stroke were contacting a doctor (73.0%), going to the hospital (67.2%), and calling an ambulance (52.4%). Improper responses to stroke (ignoring the condition or self-prescription) were noted in 18.8% of participants. Logistic regression revealed that physicians, nurses, friends and relatives as a source of knowledge were significantly associated with a lower insufficient knowledge of stroke symptoms and risk factors. On the other hand, women, persons above 40 years old, and married persons were significantly more prone to have insufficient knowledge about a proper response to stroke. CONCLUSION: Our study revealed a notable deficit of knowledge about warning symptoms, risk factors, and proper response to stroke. Health education strategies to improve stroke awareness are required and could potentially prevent and improve the outcome of stroke.