First report of the clinical characteristics and outcomes of cardiac amyloidosis in Saudi Arabia.

AIMS: Cardiac amyloidosis (CA) is a potentially fatal multisystemic disease that remains significantly underdiagnosed, particularly in the Middle East. This study aims to evaluate the prevalence and clinical characteristics of CA in a high-risk population at a tertiary centre in Saudi Arabia. METHODS: This cross-sectional, retrospective, single-centre study was conducted at a tertiary hospital in Riyadh, Saudi Arabia. We reviewed the medical records of heart failure patients seen between August 2018 and July 2022 who exhibited red flags for CA and subsequently underwent CA screening. Red flags that prompted the workup included at least two of the following factors: the presence of unilateral or bilateral carpal tunnel syndrome, a family history of transthyretin amyloid (ATTR) amyloidosis and specific electrocardiographic features (relative/absolute low QRS voltage, pseudoinfarct pattern and atrioventricular/interventricular conduction abnormalities). Echocardiographic red flags included mainly increased wall thickness (≥12 mm), significant diastolic dysfunction, reduced left ventricular (LV) longitudinal function, right ventricular (RV) dysfunction and elevated right atrial (RA)/pulmonary artery (PA) pressure. Cardiac magnetic resonance (CMR) red flags included aspects similar to those in an echocardiogram as well as a subendocardial or transmural late gadolinium enhancement (LGE) pattern. These patients were assessed for CA through technetium-99m pyrophosphate ([99mTc]Tc-PYP) bone scintigraphy, serum and urine protein electrophoresis with immunofixation and a serum-free light chain assay. RESULTS: A total of 177 patients were screened, of which 21.0 (11.9%) patients were diagnosed with transthyretin amyloid CA (ATTR-CA) and 13 (7.3%) patients were diagnosed with light chain CA (AL-CA). Compared with patients with negative/equivocal [99mTc]Tc-PYP scans (grades 0-1), patients with positive [99mTc]Tc-PYP scans (grades 2-3) were older (78.0 vs. 68.0 years, P < 0.001), had higher levels of troponin (P = 0.003) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P < 0.001), had a higher LV mass index (P < 0.001), displayed a more depressed global longitudinal strain (GLS) (P < 0.001) with a greater prevalence of a relative apical sparing pattern (P < 0.001) and demonstrated a higher incidence of first-degree atrioventricular block (P = 0.008) and low voltage patterns on electrocardiography (P < 0.001). Patients with ATTR-CA and AL-CA were more likely to have a subendocardial or transmural LGE pattern on CMR (P < 0.001) and had a significantly lower overall survival (P < 0.001) when compared with other heart failure aetiologies. CONCLUSIONS: This is the first study to describe the clinical characteristics and outcomes of CA in the Middle East and Saudi Arabia. The prevalence of CA among screened heart failure patients here aligns with major international studies, suggesting significant underdiagnosis in the region. Therefore, larger multicentric studies and regional screening programmes are urgently needed to accurately characterize the epidemiology and outcomes of CA in the Middle East.

Intradermal Syringocystadenoma Papilliferum on the Popliteal Fossa: A Rare Dermal Variant in an Atypical Location.

Syringocystadenoma papilliferum (SCAP) is a benign adnexal tumor commonly found on the scalp and face, and often associated with nevus sebaceous, with about half of cases appearing in early childhood. SCAP exhibits cystic invaginations with papillary structures and a double-layered glandular epithelium linked to the epidermal surface and stromal plasma cells. We are reporting a rare instance of intradermal SCAP in a 55-year-old male. He sought evaluation for a long-standing asymptomatic dark-pink papule in his left popliteal fossa, measuring 0.7 x 0.5 x 0.4 cm. A shave biopsy revealed papillary dermal fibrosis, glandular epithelium with apocrine secretion, and papillary projections without an epidermal connection. Infundibulofollicular keratinization was observed, along with stromal plasma cells. The patient chose local excision as the treatment option. This case highlights the rarity of intradermal SCAP, especially in the left popliteal fossa, with only one other reported case in the literature.

Avoidable emergency department visits among palliative care cancer patients: novel insights from Saudi Arabia and the Middle East.

BACKGROUND: Several studies emerging from developed countries have highlighted a significant number of potentially avoidable emergency department (ED) visits by cancer patients during the end-of-life period. However, there is a paucity of information from developing nations regarding palliative care practices and the utilization of the ED by palliative care patients. Herein, we aim to characterize ED admissions among patients receiving palliative care at our tertiary center in Saudi Arabia. METHODS: This is a retrospective, cross-sectional study evaluating ED visits amongst adult patients with advanced cancer who were receiving treatment under the palliative care department. This study took place over a period of 12 months from July 2021 through to July 2022. Three palliative care specialist physicians independently and blindly reviewed each patient's ED visits and determined whether the visit was avoidable or unavoidable. RESULTS: A total of 243 patients were included in the final analysis, of which 189 (78.1%) patients had unavoidable visits and 53 (21.9%) patient visits were classified as avoidable. A significantly higher proportion of breast cancer patients presented with unavoidable admissions (14.3% vs. 3.8%, P = 0.037) compared to other cancer types. The incidence of dyspnea (23.8% vs. 5.7%, P < 0.001) and fevers/chills (23.3% vs. 5.7%, P = 0.005) was significantly higher in patients with unavoidable visits. Patients with avoidable visits had a significantly greater proportion of visits for dehydration (13.2% vs. 2.1%, P = 0.002). Notably, although hospital stay was significantly longer in the unavoidable group (P = 0.045), mortality for palliative care patients-regardless of whether their ED visit was avoidable or unavoidable-was not statistically different (P=-0.069). CONCLUSION: To our knowledge, this is the largest and most comprehensive study from Saudi Arabia and the Middle East providing insights into the utilization of palliative care services in the region and the propensity of advanced cancer patients towards visiting the ED. Future studies ought to explore interventions to reduce the frequency of avoidable ED visits.

Cellular senescence in brain aging and cognitive decline.

Cellular senescence is a biological aging hallmark that plays a key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate the effectiveness of senotherapies for these diseases. However, the impact of senescence on brain aging and cognitive decline in the absence of neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic brain injury survivors, obese individuals, obstructive sleep apnea patients, and chronic kidney disease patients can suffer age-related brain changes like cognitive decline prematurely, suggesting that they may suffer accelerated senescence in the brain. Understanding the role of senescence in neurocognitive deficits linked to these conditions is crucial, especially considering the rapidly evolving field of senotherapeutics. Such treatments could help alleviate early brain aging in these patients, significantly reducing patient morbidity and healthcare costs. This review provides a translational perspective on how cellular senescence plays a role in brain aging and age-related cognitive decline. We also discuss important caveats surrounding mainstream senotherapies like senolytics and senomorphics, and present emerging evidence of hyperbaric oxygen therapy and immune-directed therapies as viable modalities for reducing senescent cell burden.

Non-Mixture Cure Model Estimation in Bladder Cancer Patients: A Novel Approach with Exponentiated Weibull Exponential Distribution.

OBJECTIVE: Cure models are frequently used in survival analysis to account for a cured fraction in the data. When there is a cure rate present, researchers often prefer cure models over parametric models to analyse the survival data. These models enable the ability to define the probability distribution of survival durations for patients who are at risk. Various distributions can be considered for the survival times, such as Exponentiated Weibull Exponential (EWE), Exponential Exponential (EE), Weibull and lognormal distribution. The objective of this research is to choose the most appropriate distribution that accurately represents the survival times of patients who have not been cured. This will be accomplished by comparing various non-mixture cure models that are based on the EWE distribution with its sub-distributions, and distributions distinct from those belonging to the EWE distribution family. MATERIAL AND METHODS: A sample of 85 patients diagnosed with superficial bladder tumours was selected to be used in fitting the non-mixture cure model. In order to estimate the parameters of the suggested model, which takes into account the presence of a cure rate, censored data, and covariates, we utilized the maximum likelihood estimation technique using R software version 3.5.7. RESULT: Upon conducting a comparison of various parametric models fitted to the data, both with and without considering the cure fraction and without incorporating any predictors, the EE distribution yields the lowest AIC, BIC, and HQIC values among all the distributions considered in this study, (1191.921/1198.502, 1201.692/1203.387, 1195.851/1200.467). Furthermore, when considering a non-mixture cure model utilizing the EE distribution along with covariates, an estimated ratio was obtained between the probabilities of being cured for placebo and thiotepa groups (and its 95% confidence intervals) were 0.76130 (0.13914, 6.81863). CONCLUSION: The findings of this study indicate that EE distribution is the optimal selection for determining the duration of survival in individuals diagnosed with bladder cancer.

Bispecific Antibodies in Hematological Malignancies: A Scoping Review.

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgkin's lymphoma, acute myelogenous leukemia, and acute lymphoblastic leukemia. However, despite their generally favorable safety profiles, particular toxicities such as infections, cytokine release syndrome, myelosuppression, and neurotoxicity after BiAb/BiTE therapy raise valid concerns. Moreover, target antigen loss and the immunosuppressive microenvironment of hematological neoplasms facilitate resistance towards BiTEs/BiAbs. This review aims to highlight the most recent evidence from clinical trials evaluating the safety and efficacy of BiAbs/BiTEs. Additionally, the review will provide mechanistic insights into the limitations of BiAbs whilst outlining practical applications and strategies to overcome these limitations.

Corrigendum: Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy.

[This corrects the article DOI: 10.3389/fimmu.2023.1200941.].

Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy.

This review focuses on the immunosuppressive effects of tumor angiogenesis and coagulation on the tumor microenvironment (TME). We summarize previous research efforts leveraging these observations and targeting these processes to enhance immunotherapy outcomes. Clinical trials have documented improved outcomes when combining anti-angiogenic agents and immunotherapy. However, their overall survival benefit over conventional therapy remains limited and certain tumors exhibit poor response to anti-angiogenic therapy. Additionally, whilst preclinical studies have shown several components of the tumor coagulome to curb effective anti-tumor immune responses, the clinical studies reporting combinations of anticoagulants with immunotherapies have demonstrated variable treatment outcomes. By reviewing the current state of the literature on this topic, we address the key questions and future directions in the field, the answers of which are crucial for developing effective strategies to reprogram the TME in order to further the field of cancer immunotherapy.

Comparison of a modified pediatric protocol versus a hyper-CVAD protocol in adolescents and young adults with Philadelphia-negative acute lymphoblastic leukemia: A multicenter retrospective analysis.

BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.

Comparison of Migraine Characteristics in Patients With and Without Inflammatory Bowel Disease: A Retrospective Cohort Study.

BACKGROUND: Survey studies have found an increased prevalence of migraine in patients with inflammatory bowel disease (IBD). However, the clinical characteristics of migraines in this population are unknown. We conducted a retrospective medical record review study to characterize migraines in the IBD population. METHODS: Six hundred seventy-five migraine patients (280 with IBD, 395 without IBD) who were evaluated at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida between July 2009 and March 2021 were included. Patients with ICD codes for migraine and either Crohn's disease (CD) or ulcerative colitis (UC) were selected. Electronic health care records were reviewed. Patients confirmed to have IBD and migraine were included. Demographic, IBD, and migraine characteristics were collected. Statistical analysis was completed using SAS. RESULTS: Patients with IBD were less often male (8.6% vs 21.3%, P < .001) and had a higher Charlson Comorbidity Index (>2: 24.6% vs 15.7%, P = .003); 54.6% had CD and 39.3% had UC. Patients with IBD had migraine with aura and without aura more frequently ( OR 2.20, P < .001 and OR 2.79, P < .001, respectively) than non-IBD patients. Additionally, those with IBD less commonly had chronic migraine (OR 0.23, P < .001) and less commonly had chronic migraine or treatment for migraine (ORs 0.23-0.55, P ≤ .002). CONCLUSIONS: Migraine with and without aura have increased prevalence in IBD patients. Further study of this topic will be helpful to clarify the prevalence of migraine, establish this population's response to treatment, and better understand the reason(s) for a low rate of treatment.

Patient Radiation Doses Assessment at Diagnostic X-rays Department of King Khalid hospital (KKH)-Majmaah.

BACKGROUND: The study was conducted on patients who received diagnostic X-rays in King Khalid Hospital (KKH), Majmaah. INTRODUCTION: The study included the seven most frequently performed investigations, which were carried out on over 1504 patients using digital radiography equipment. METHODS: The X-ray tube's output and exposure parameters were used to calculate the effective dose (ED) and patient entry surface air kerma (ESAK). Additionally, based on these results, conversion coefficients were determined. This study also examined the 75th percentile distributions of ESAK and KAP. The findings of this research were compared with the findings of other researchers throughout the country and the world. The study presents the uncertainty U values, as well as the mean ESAK, KAP, and ED values. RESULTS: The results of the ESAK, KAP, and ED values were 0.12-5.74 mGy, 0.9-1.84 Gy cm2, and 0.01-0.23 mSv, respectively. As a result, the dosages were much lower than those previously published for the European DRL, national standards, and other studies. CONCLUSION: The study concludes that during dose surveys, the importance of detecting and comprehending radiation doses, as well as the proper technique for taking the finest photos possible, can be emphasized to patients in order to assist them in avoiding radioactive particles and radiation exposure.

Coronary artery bypass grafting after acute ST-elevation myocardial infarction.

OBJECTIVES: The study objectives were to describe the trends and outcomes of isolated coronary artery bypass grafting after ST-elevation myocardial infarction using a nationwide database. METHODS: We queried the 2002-2016 National Inpatient Sample database for hospitalized patients with ST-elevation myocardial infarction who underwent isolated coronary artery bypass grafting. We report temporal trends, predictors, and outcomes of coronary artery bypass grafting in the early (2002-2010) and recent (2011-2016) cohorts. RESULTS: Of 3,347,470 patients hospitalized for ST-elevation myocardial infarction, 7.7% underwent isolated coronary artery bypass grafting. The incidence of isolated coronary artery bypass grafting after ST-elevation myocardial infarction decreased over time (9.2% in 2002 vs 5.5% in 2016, Ptrend < .001), whereas perioperative crude in-hospital mortality did not change (5.1% in 2002 vs 4.2% in 2016, Ptrend = .66), coinciding with an increase in the burden of comorbidities. There was an increase in performing isolated coronary artery bypass grafting on hospitalization day 3 or more, as well as an increase in the use of mechanical support devices and precoronary artery bypass grafting percutaneous coronary intervention. In the early cohort, isolated coronary artery bypass grafting on days 1 and 2 was associated with higher in-hospital mortality. In the recent cohort, coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more and lower rates of acute kidney injury, ischemic stroke, ventricular arrhythmia, and length of hospital stay. CONCLUSIONS: In this nationwide analysis, there has been a decline in the use of isolated coronary artery bypass grafting after ST-elevation myocardial infarction. Isolated coronary artery bypass grafting on day 1 was performed in sicker patients and was associated with higher in-hospital mortality than coronary artery bypass grafting performed on day 3 or more. In the recent cohort, isolated coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more.

Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature.

Brugada syndrome is an inherited cardiac channelopathy arising from mutations in voltage-gated cardiac sodium channels. Idiopathic epilepsy portrays a coalescent underlying pathophysiological mechanism pertaining to the premature excitation of neuronal voltage-gated ion channels resulting in the disruption of presynaptic neurons and the unregulated release of excitatory neurotransmitters. The coexistence of epilepsy and Brugada syndrome may be explained by mutations in voltage-gated ion channels, which are coexpressed in cardiac and neural tissue. Moreover, the incidence of sudden unexpected death in epilepsy has been associated with malignant cardiac arrhythmias in the presence of mutations in voltage-gated ion channels. Lamotrigine is an antiepileptic drug that inhibits neuronal voltage-gated sodium channels, thus stabilizing neural impulse propagation and controlling seizure activity in the brain. However, lamotrigine has been shown to inhibit cardiac voltage-gated sodium channels resulting in a potential arrhythmogenic effect and the ability to unmask Brugada syndrome in genetically susceptible individuals. We are reporting a case of a 27-year-old male patient with a background of presumed idiopathic epilepsy who was initiated on lamotrigine therapy resulting in the unmasking of Brugada syndrome and the onset of syncopal episodes. This case provides further evidence for the arrhythmogenic capacity of lamotrigine and highlights the relationship between epilepsy and Brugada syndrome. In this report, we aim to review the current literature regarding the associations between epilepsy and Brugada syndrome and the impact of lamotrigine therapy on such patients.

The Potential Role of CD44 and CD133 in Colorectal Stem Cell Cancer.

Colorectal cancer (CRC) is the most preventable malignancy globally, with a high mortality rate. Cancer stem cells (CSCs) are found previously in multiple types of cancer; CRC is one of them, and it has been correlated with several biomarkers. The two most essential markers related to colorectal CSCs are CD44 and CD133, which play a significant role in diagnosis, treatment, and prognosis. Unfortunately, the CSCs with positive CD44 and CD133 biomarkers illustrated an alarming prognosis. Several trials were trying to target those markers to improve the prognosis and cure. We aimed to review the papers that relate to the two markers in terms of diagnosis, treatment, and prognosis.

Lupus Anticoagulant-Hypoprothrombinemia Syndrome and Pseudotumor Cerebri as an Initial Presentation of Systemic Lupus Erythematosus in a 16-Year-Old Male Patient: A Case Report and Literature Review.

BACKGROUND Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is an exceptionally rare disease caused by prothrombin antibodies, resulting in reduced factor II levels. This disease can present with significant bleeding and is usually associated with autoimmune disorders, particularly systemic lupus erythematosus (SLE). There are currently no guidelines for the treatment of LAHPS, and corticosteroids remain the criterion standard therapy. Pseudotumor cerebri is a disease that involves an idiopathic rise in intracranial pressure in association with papilledema. The coexistence of pseudotumor cerebri with SLE is rare, with an overall incidence of 0.7%. CASE REPORT A 16-year-old male initially presented to our hospital with nausea, headaches, and decreased visual acuity. He was diagnosed with pseudotumor cerebri based on the findings of papilledema and a raised opening pressure on lumbar puncture. Three months later, he presented with macroscopic hematuria and persistent epistaxis. Further investigation revealed a prolonged activated partial thromboplastin time and prothrombin time, along with positive LA and reduced Factor II levels, resulting in a diagnosis of LAHPS. The patient received a dose of 1 mg/kg/day of prednisolone along with hydroxychloroquine, and he had a complete recovery with cessation of bleeding and normalization of laboratory parameters. CONCLUSIONS We are reporting a case of pseudotumor cerebri with a further presentation of LAHPS in a patient found to have SLE. As both associations are rare in the presence of SLE, it is vital to recognize them early to initiate adequate management and intervention to avoid life-threatening complications.