Targeting Apolipoprotein C-III for the Management of Severe Hypertriglyceridemia: Current Research and Future Directions.

Hypertriglyceridemia is characterized by elevated triglyceride levels in the blood, which increases the risk of cardiovascular disease and pancreatitis. This condition stems from multiple factors including lifestyle choices, genetics, and conditions such as diabetes and metabolic syndrome. Apolipoprotein C-III (APOC3), a protein for lipid metabolism, hinders enzymes necessary for breaking down triglycerides and thus plays a key role in hypertriglyceridemia. Variations in the APOC3 gene are associated with varying triglyceride levels among individuals. Recent genetic studies and clinical trials have shed light on the potential of targeting APOC3 as a potentially promising therapeutic modality of hypertriglyceridemia. Antisense oligonucleotides like volanesorsen have displayed effectiveness in lowering triglyceride levels in individuals with severe hypertriglyceridemia. This review article delves into how APOC3 influences triglyceride control and its potential use in targeting APOC3 to manage severe hypertriglyceridemia.

An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024.

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin condition which affects all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasised in real-world observations, the unexpected increased frequency of ocular adverse effects became apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if they arise. OBJECTIVES: The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD). METHODS: A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with DROSD expertise, patient representation, and BAD Clinical Standards Unit. A literature search was conducted, and the results reviewed. All recommendations were reviewed, discussed and voted on. RESULTS: The recommendations pertain to dermatology and ophthalmology management, and apply to all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems, e.g. infections, or potentially severe conditions, e.g. a history of corneal transplant (ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged <7 years as ocular complications may affect neuro-ocular development; therefore, irrespective of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or non-responding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications. CONCLUSIONS: Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management; where ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in atopic dermatitis (AD) patients treated with tralokinumab and lebrikizumab.

Disseminated Mucormycosis and T-Cell-Depleted Allogeneic Stem Cell Transplantation: An Unusual Case Study.

INTRODUCTION: Invasive fungal infections are a primary cause of morbidity and mortality in patients with haematological malignancies. CASE PRESENTATION: We describe an unusual clinical and radiological presentation of invasive mucormycosis (IM) in a 69-year-old patient with relapsed acute myeloid leukaemia. The patient was diagnosed with disseminated IM with involvement of the central nervous system in an atypical location, lung, spleen, muscle, bone, and heart, after having completed induction and bridging chemotherapy to allogeneic haematopoietic stem cell transplant (HSCT). Her clinical presentation was atypical with mild neurological symptoms slowly progressing over 2 months and without appropriate signs of systemic inflammation. Mucorales was eventually confirmed from bronchoalveolar lavage and subdural collection. CONCLUSION: This report highlights the difficult challenges of managing disseminated IM in an immunocompromised patient, where close multidisciplinary specialist care enabled successful treatment, followed by T-cell-depleted allogeneic HSCT for a high-risk haematological malignancy.

A Case of Non-cirrhotic Portal Hypertension With Antiphospholipid Syndrome.

Nodular regenerative hyperplasia (NRH) and obliterative portal venopathy (OPV) are two causes of non-cirrhotic portal hypertension (NCPH), which is a vascular liver disease wherein clinical signs of portal hypertension (PHT), such as esophageal varices, ascites, and splenomegaly develop in the absence of cirrhosis and portal vein thrombosis. The etiology often remains unidentified, but herein we present the case of a 56-year-old male with NCPH and refractory ascites who underwent liver biopsy confirming NRH and OPV. Etiological workup revealed beta-2 glycoprotein-1 and anticardiolipin antibodies, concerning antiphospholipid syndrome (APS) despite no prior history of thrombosis. The patient underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure for his refractory ascites and was started on prophylactic anticoagulation owing to a concern for APS with clinical improvement in his ascites and shortness of breath. Pursuing TIPS earlier in the setting of refractory ascites, as well as offering anticoagulation therapy for patients with possible APS to prevent the development of potential thromboses, could be appropriate recommendations to prevent complications in the disease course. This case report highlights the need for further investigations on the etiologies, diagnosis pathways, and treatment options for NCPH.

Personalized Approach to Chronic Antibiotic-Refractory Pouchitis: A Case Report and Review of the Literature.

Patients who undergo restorative proctocolectomy and ileoanal anastomosis can develop pouchitis as a common chronic complication. A rare subset of patients fails to respond to multiple antibiotic therapies and develop chronic antibiotic-refractory pouchitis (CARP). We present a case of a 45-year-old male with pouchitis refractory to chronic antibiotic therapy and histology demonstrating chronic inflammatory changes. Management involved mesalamine and probiotics, resulting in a positive clinical response and symptom absence on follow-up. This case highlights the intricacies of treating chronic pouchitis post ileoanal anastomosis, showcasing the efficacy of a personalized approach using mesalamine and probiotics. CARP is emerging as an entity associated with poor quality of life and increased healthcare costs. CARP fails to respond to multiple courses of antibiotic therapy. Therefore, the management of CARP is difficult and limited. Current literature on the management of CARP is scarce and mainly involves immunomodulatory therapy and probiotics. It is essential to keep this differential diagnosis in mind in patients with recurrent pouchitis episodes and start them on immunomodulator treatment and probiotics rather than repeated courses of antibiotics.

The Role of Artificial Intelligence in Improving Patient Outcomes and Future of Healthcare Delivery in Cardiology: A Narrative Review of the Literature.

Cardiovascular diseases exert a significant burden on the healthcare system worldwide. This narrative literature review discusses the role of artificial intelligence (AI) in the field of cardiology. AI has the potential to assist healthcare professionals in several ways, such as diagnosing pathologies, guiding treatments, and monitoring patients, which can lead to improved patient outcomes and a more efficient healthcare system. Moreover, clinical decision support systems in cardiology have improved significantly over the past decade. The addition of AI to these clinical decision support systems can improve patient outcomes by processing large amounts of data, identifying subtle associations, and providing a timely, evidence-based recommendation to healthcare professionals. Lastly, the application of AI allows for personalized care by utilizing predictive models and generating patient-specific treatment plans. However, there are several challenges associated with the use of AI in healthcare. The application of AI in healthcare comes with significant cost and ethical considerations. Despite these challenges, AI will be an integral part of healthcare delivery in the near future, leading to personalized patient care, improved physician efficiency, and anticipated better outcomes.

Haploidentical Transplant with Post-Transplant Cyclophosphamide for Acute Myeloid Leukaemia and Myelodysplastic Syndromes Patients: The Role of Previous Lines of Therapy.

Background: Allogeneic haematopoietic stem-cell transplant is an option, potentially curative, for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Post-transplant cyclophosphamide administration allows for the selection of haploidentical donors in patients who are eligible for the procedure but do not have a fully matched donor since it can overcome the HLA barrier. There is still an active debate on whether intensifying the conditioning regimen is necessary with haploidentical donors when peripheral blood stem cells are used as the graft source. Herein, we report our decennial experience of haploidentical stem-cell transplant using peripheral blood stem cells (haplo-PBSC) at King's College Hospital. Objectives: The primary objective was to evaluate overall survival (OS) following haplo-PBSC. Secondary objectives were total OS for patients with less than two previous lines of therapy, OS according to cytomegalovirus (CMV) reactivation, incidence of transplant-related mortality (TRM), graft-versus-host disease (GVHD) and GVHD-relapse-free survival (GRFS). Results: One-year and three-year total OS were 62% and 43%, respectively, with a median OS of 22 months. One-year and three-year OS for patients with ≤2 and those with >2 previous lines of therapy were 72% and 55%, and 60% and 22%, respectively (p-value=0.04). The median OS in patients with >2 previous and ≤2 lines of therapy was 16 and 49 months, respectively. Cumulative incidence (CI) of relapse was 25% with a median time to relapse of 5 months (range 1 - 38 months). Conclusions: Haploidentical haematopoietic stem-cell transplant is potentially curative in chemosensitive AML and MDS and offers a high rate of prolonged remission. Our cohort further confirms the role of consolidative haploidentical transplant in patients in complete remission and highlights that patients with heavily pre-treated disease may not benefit from this strategy.

The Utility of Artificial Intelligence in the Diagnosis and Management of Pancreatic Cancer.

Artificial intelligence (AI) has made significant advancements in the medical domain in recent years. AI, an expansive field comprising Machine Learning (ML) and, within it, Deep Learning (DL), seeks to emulate the intricate operations of the human brain. It examines vast amounts of data and plays a crucial role in decision-making, overcoming limitations related to human evaluation. DL utilizes complex algorithms to analyze data. ML and DL are subsets of AI that utilize hard statistical techniques that help machines consistently improve at tasks with experience. Pancreatic cancer is more common in developed countries and is one of the leading causes of cancer-related mortality worldwide. Managing pancreatic cancer remains a challenge despite significant advancements in diagnosis and treatment. AI has secured an almost ubiquitous presence in the field of oncological workup and management, especially in gastroenterology malignancies. AI is particularly useful for various investigations of pancreatic carcinoma because it has specific radiological features that enable diagnostic procedures without the requirement of a histological study. However, interpreting and evaluating resulting images is not always simple since images vary as the disease progresses. Secondly, a number of factors may impact prognosis and response to the treatment process. Currently, AI models have been created for diagnosing, grading, staging, and predicting prognosis and treatment response. This review presents the most up-to-date knowledge on the use of AI in the diagnosis and treatment of pancreatic carcinoma.

Autoimmune Hypoglycemia With Anti-Insulin Autoantibodies in an Eighty-One-Year-Old Woman Without Apparent Risk Factors.

Background/Objective: Insulin autoimmune syndrome (IAS) is a very rare cause of hypoglycemia presenting with recurrent fasting or postprandial hypoglycemia episodes with elevated serum insulin levels and insulin autoantibodies. The objective of this case is to highlight the importance of considering IAS in patients with hypoglycemia. Case Report: We present a case of an 81-year-old female who presented with symptoms of hypoglycemia. She was found to have hyperinsulinemic hypoglycemic episodes without any apparent risk factors for IAS. She had positive-insulin autoantibodies in her serum leading to the diagnosis of IAS. Acutely, hypoglycemia was managed with D50 pushes, oral glucose, and glucagon injection. Discussion: Patients who present with hypoglycemia due to endogenous hyperinsulinemia should have IAS considered as a possible differential diagnosis. Insulin autoantibodies are measured as the gold standard diagnostic test for IAS. Foods with a low glycemic index are the primary treatment for IAS. Conclusion: This case presentation highlights the importance of considering IAS as a differential diagnosis in patients presenting with hypoglycemia secondary to hyperinsulinemia, even in the absence of apparent risk factors.

Myeloablative Dose of Busulfan and Fludarabine Combined with In Vivo T Cell Depletion Is Safe and Effective Conditioning for Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative strategy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The prediction of transplantation-related mortality (TRM) using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and an arbitrary upper age limit of 55 years for administering myeloablative conditioning (MAC) are common strategies to ensure a safe procedure. The use of reduced-toxicity conditioning regimens is an additional approach to providing safe and effective myeloablation. Herein we report the outcome of AML and MDS patients conditioned with fludarabine and a myeloablative dose of busulfan (FB4) stratified by age and HCT-CI score. The primary objective was overall survival (OS) for patients age ≥55 years. Secondary objectives were total OS, TRM, graft-versus-host disease (GVHD), and GVHD, relapse-free survival (GRFS). The 2 year OS was 72% in patients age <55 and 51% in patients age ≥55. In patients age ≥55 with an HCT-CI <2, the estimated 2 year OS was 64%, with median OS not reached. In those with HCT-CI ≥2, the 2-year OS was 43%, with a median OS of 14 months. The total cumulative incidence of relapse was 30% regardless of age or HCT-CI score. FB4 conditioning regimen offers a high rate of prolonged remission with a relapse rate similar to that reported in previous studies. These positive outcomes suggest that this conditioning platform can be offered to patients age ≥55 years in the absence of comorbidities, and that age should not be the sole determinant of conditioning intensity.

Fludarabine-Melphalan-Campath, Followed by Unmanipulated Peripheral-Blood Haematopoietic Stem Cells, Can Still Cure Lymphoma.

Background: The second decade of this millennium was characterized by a widespread availability of chimeric antigen receptor T-cell (CAR-T) therapies to treat relapsed and refractory lymphomas. As expected, the role and indication of allogeneic haematopoietic stem cell transplant (allo-HSCT) in the management of lymphoma changed. Currently, a non-neglectable proportion of patients will be considered candidate for an allo-HSCT, and the debate of which transplant platform should be offered is still active. Objectives: to report the outcome of patients affected with relapsed/refractory lymphoma and transplanted following reduced intensity conditioning at King's College Hospital, London, between January 2009 and April 2021. Methods: Conditioning was with 150mg/m2 of fludarabine and melphalan of 140mg/m2. The graft was unmanipulated G-CSF mobilized peripheral blood haematopoietic stem cells (PBSC). Graft-versus-host disease (GVHD) prophylaxis consisted of pre-transplant Campath at the total dose of 60 mg in unrelated donors and 30 mg in fully matched sibling donors and ciclosporin. Results: One-year and five years OS were 87% and 79.9%, respectively, and median OS was not reached. The cumulative incidence of relapse was 16%. The incidence of acute GVHD was 48% (only grade I/II); no cases of grade III/IV were diagnosed. Chronic GVHD occurred in 39% of patients. TRM was 12%, with no cases developed within day 100 and 18 months after the procedure. Conclusions: The outcomes of heavily pretreated lymphoma patients are favorable, with median OS and survival not reached after a median of 49 months. In conclusion, even if some lymphoma subgroups cannot be treated (yet) with advanced cellular therapies, this study confirms the role of allo-HSCT as a safe and curative strategy.

Evaluation Methods and Measurement Challenges for Industrial Exoskeletons.

In recent years, exoskeleton test methods for industrial exoskeletons have evolved to include simulated laboratory and field environments. Physiological, kinematic, and kinetic metrics, as well as subjective surveys, are used to evaluate exoskeleton usability. In particular, exoskeleton fit and usability can also impact the safety of exoskeletons and their effectiveness at reducing musculoskeletal injuries. This paper surveys the state of the art in measurement methods applied to exoskeleton evaluation. A notional classification of the metrics based on exoskeleton fit, task efficiency, comfort, mobility, and balance is proposed. In addition, the paper describes the test and measurement methods used in supporting the development of exoskeleton and exosuit evaluation methods to assess their fit, usability, and effectiveness in industrial tasks such as peg in hole, load align, and applied force. Finally, the paper includes a discussion of how the metrics can be applied towards a systematic evaluation of industrial exoskeletons, current measurement challenges, and future research directions.

Outcomes of Acute Mesenteric Ischemia in End-Stage Renal Disease and Predictors of Mortality: A Nationwide Assessment.

Background Acute mesenteric ischemia (AMI) is an uncommon disease caused by obstruction of blood flow to the bowel, which can lead to high mortality rates. End-stage renal disease (ESRD) is another disease commonly seen in the elderly. There are limited data evaluating the relationship between AMI and ESRD, but it has been shown that ESRD patients have a higher risk of mesenteric ischemia than the general population. Methods This retrospective analysis utilized the National Inpatient Sample database for 2016, 2017, and 2018 to identify patients with AMI. Patients were then divided into two groups, AMI with ESRD and AMI only. All-cause in-patient mortality, hospital length of stay (LOS), and total costs were identified. The Student's t-test was used to analyze continuous variables, while Pearson's Chi-square test was used to analyze categorical variables. Results A total of 169,245 patients were identified, with 10,493 (6.2%) having ESRD. The AMI with ESRD group had a significantly higher mortality rate than the AMI-only group (8.5% vs 4.5%). Patients with ESRD had a longer LOS (7.4 days vs 5.3 days; P = 0.00), and higher total hospital cost ($91,520 vs $58,175; P = 0.00) compared to patients without ESRD. Conclusion The study found that patients with ESRD who were diagnosed with AMI had a significantly higher mortality rate, longer hospital stays, and higher hospital costs than patients without ESRD.

Outcomes of Portal Vein Thrombosis in Smokers With and Without Cirrhosis and Predictors of Mortality: A Nationwide Assessment.

Portal vein thrombosis (PVT) is a rare condition that can lead to numerous complications, like variceal bleeding, hepatic encephalopathy, and chronic liver disease. PVT has various etiologies, including liver disease, infections, and hyper-coagulable disorders. Cirrhosis, a chronic progressive liver condition characterized by liver fibrosis, is one of the risk factors for the development of PVT. Secondly, smoking also increases the risk of PVT. The aim of this study is to identify outcomes in patients with PVT who smoked with and without cirrhosis. This study was performed using the National Inpatient Sample (NIS) database for the years 2016, 2017, and 2018. The study identified 33,314 patients diagnosed with PVT who smoked, of which 14,991 had cirrhosis, and 18,323 did not have cirrhosis. Patients with PVT and cirrhosis had significantly higher in-hospital mortality, upper gastrointestinal bleeds, acute kidney injury, and peritonitis compared to patients without cirrhosis. The results of the study show that patients with PVT and cirrhosis who smoke have a higher risk of unfavorable outcomes.

Pancreatic Heterotopia at the Gastroesophageal Junction: A Case Report and Review of the Literature.

Pancreatic heterotopia is characterized by the presence of pancreatic tissue in a location outside of its typical anatomical position. Symptoms of pancreatic heterotopia vary based on the location of the ectopic tissue. It is commonly asymptomatic and often diagnosed incidentally during routine endoscopy. Clinically significant pancreatic heterotopia is often secondary to inflammation, bleeding, obstruction, and malignant transformation. The most common location of heterotopic pancreas is within 5 cm of the pylorus usually on the greater curvature. Involvement of the gastroesophageal junction is extremely rare. In this report, we describe the case of a 57-year-old woman who was diagnosed with ectopic pancreatic tissue at the gastroesophageal junction by esophagogastroduodenoscopy after presenting with symptoms of dyspepsia.

Hepatic Dystrophic Calcification Secondary to Transarterial Chemoembolization: Case Report and Review of Literature.

Hepatocellular carcinoma (HCC) is a common malignancy usually treated with surgery. Patients who are not suitable for surgery undergo transarterial chemoembolization (TACE) which involves injecting anti-cancer drugs and embolizing agents into the hepatic artery. Although it is a relatively safe procedure with minor side effects, TACE can rarely cause dystrophic calcification in the liver. We report a case of a 58-year-old female who presented with right-sided chest pain. The patient had been previously treated for HCC with a TACE procedure. A chest x-ray revealed hepatic calcification which was likely secondary to the prior TACE. This case study emphasizes the significance of considering TACE as a potential cause of hepatic dystrophic calcification.

A Comprehensive Review of the Neurological Manifestations of Celiac Disease and Its Treatment.

Celiac disease (CD) is a common chronic inflammatory disorder occurring in genetically predisposed individuals secondary to gluten ingestion. CD usually presents with gastrointestinal symptoms such as pain, bloating, flatulence, and constipation or diarrhea. However, individuals can present in a nonclassical manner with only extraintestinal symptoms. The neurological manifestations of CD include ataxia, cognitive impairment, epilepsy, headache, and neuropathy. A lifelong gluten-free diet is the current recommended treatment for CD. This review discusses the relevant neurological manifestations associated with CD and the novel therapeutics. Further research is required to get a better understanding of the underlying pathophysiology of the neurological manifestations associated with CD. Clinicians should keep CD in the differential diagnosis in individuals presenting with neurological dysfunction of unknown cause.

Thromboembolic Events in Patients with Inflammatory Bowel Disease: A Comprehensive Overview.

Inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the intestines. The underlying inflammation activates the coagulation cascade leading to an increased risk of developing arterial and venous thromboembolic events such as deep vein thrombosis and pulmonary embolism. Patients with IBD are at a 2-3-fold increased risk of developing thromboembolism. This risk increases in patients with active IBD disease, flare-ups, surgery, steroid treatment, and hospitalization. These complications are associated with significant morbidity and mortality making them important in clinical practice. Clinicians should consider the increased risk of thromboembolic events in patients with IBD and manage them with appropriate prophylaxis based on the risk. In this review, we discuss the literature associated with the pathophysiology of thromboembolism in patients with IBD, summarize the studies describing the various thromboembolic events, and the management of thromboembolism in patients with IBD.

An Unusual Case of Drug-Induced Liver Injury Secondary to Nitrofurantoin Use.

Nitrofurantoin is a commonly prescribed antibiotic for uncomplicated urinary tract infections. Despite a number of side effects, it is increasingly prescribed due to its low cost, high efficacy, and minimal antimicrobial resistance. One of the rare, however significant side effects of nitrofurantoin is idiosyncratic drug-induced liver toxicity. It commonly presents with abdominal pain and elevated liver enzymes. Interestingly, it can cause either an acute or a chronic hepatitis-like syndrome that can be severe and lead to liver failure or cirrhosis. We present a case of a healthy 24-year-old female who presented with epigastric abdominal pain, which was found to be drug-induced liver injury (DILI) secondary to her recent nitrofurantoin use.