Practice Changes in Checkpoint Inhibitor-Induced Immune-Related Adverse Event Management at a Tertiary Care Center.

Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions.

Procedural safety of transcatheter aortic valve replacement with Portico valve: a systematic review.

BACKGROUND: The Portico transcatheter aortic heart valve is a self-expandable, fully resheathable bioprosthetic valve with a nitinol frame and porcine pericardial sealing cuff. It has been used among symptomatic severe aortic stenosis (AS) who are at high or extreme surgical risk. However, till date very few studies has been reported with inconclusive evidence for its postprocedure safety outcomes. OBJECTIVE: The authors aim to evaluate the safety of the Portico transcatheter aortic valve replacement system among patients with AS. METHODOLOGY: The authors conducted a systematic literature search on PubMed, Embase, and Scopus from inception till 10th April 2023 by using predefined MESH terms using 'AND' and 'OR'. The following search terms were used: 'Aortic Stenosis' AND 'Transcatheter aortic valve replacement' OR 'Portico valve'. Finally, descriptive statistics were used to summarize the data in this paper. The mean and SD were adopted to describe continuous variables, whereas frequencies and percentages were used for dichotomous data. RESULTS: A total of 7 studies with 2782 patients were included in the analysis. The mean age of patients was 82.3 years, and 54.63% were female. The most common comorbidity was hypertension (65.21%) and diabetes mellitus (26.45%). Among patients of AS with Portico valve implants, postprocedural outcomes including 30-day mortality (2.32%), cardiovascular mortality (2.37%), stroke (2.23%), myocardial infarction (0.94%), major bleeding (3.97%), major vascular complications (4.91%), acute kidney injury (1.37%), and permanent pacemaker implantations in 15.73% patients were reported. Overall, device success was observed in 95.82% of patients. CONCLUSION: Transcatheter aortic valve replacement with the repositionable Portico valve, a new bioprosthesis, appears to have a low postprocedural mortality rate and other clinical outcomes in high-risk patients with severe AS.

Percutaneous coronary intervention versus coronary artery bypass grafting among patients with left ventricular systolic dysfunction: a systematic review and meta-analysis.

Current guidelines have shown the superiority of coronary artery bypass grafting (CABG) over medical therapy. However, there is a paucity of data evaluating the optimal revascularization strategy in patients with ischemic left ventricular systolic dysfunction (LVSD). Objective: The authors aimed to evaluate the clinical outcomes of postpercutaneous coronary intervention (PCI) and CABG among patients with LVSD. Methods: The authors performed a systematic literature search using the PubMed, Embase, Scopus, and the Cochrane Libraries for relevant articles from inception until 30 November 2022. Outcomes were reported as pooled odds ratio (OR), and their corresponding 95% CI using STATA (version 17.0, StataCorp). Results: A total of 10 studies with 13 324 patients were included in the analysis. The mean age of patients in PCI was 65.3 years, and 64.1 years in the CABG group. The most common comorbidities included: HTN (80 vs. 78%) and DM (49.2 vs. 49%). The mean follow-up duration was 3.75 years. Compared with CABG, the PCI group had higher odds of all-cause mortality (OR 1.15, 95% CI 1.01-1.31, P=0.03), repeat revascularization (OR 3.57, 95% CI 2.56-4.97, P<0.001), MI (OR 1.92, 95% CI 1.01-3.86, P=0.048) while the incidence of cardiovascular mortality (OR 1.23, 95% CI 0.98-1.55, P=0.07), stroke (OR 0.73 95% CI: 0.51-1.04, P=0.08), major adverse cardiovascular and cerebrovascular events (OR 1.36, 95% CI 0.99-1.87, P=0.06), and ventricular tachycardia (OR 0.79, 95% CI 0.22-2.86, P=0.72) was comparable between both the procedures. Conclusion: The results of this meta-analysis suggest that CABG is superior to PCI for patients with LVSD. CABG was associated with a lower risk of all-cause mortality, repeat revascularization, and incidence of myocardial infarction compared with PCI in patients with LVSD.

Effects of immunosuppressive treatment on patient outcomes after immune checkpoint inhibitor-related gastrointestinal toxicity.

PURPOSE: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of certain cancers but cause immune-related adverse events (irAEs). Gastrointestinal irAEs may necessitate extended periods of steroid use and the initiation of selective immunosuppressive therapy (SIT) which could theoretically counteract the effect of ICIs. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS). METHODS: This is a single-center retrospective review exploring cancer outcomes in patients taking ICIs who developed gastrointestinal irAEs within 1 year of ICI initiation. Cancer outcome and progression free survival (PFS) were measured and compared by using IBM SPSS Statistics 26. RESULTS: Of the 116 patients included in this study, 69 received immunosuppression to treat irAEs. The occurrence of colitis and use of immunosuppression for colitis were associated with less cancer progression by later assessment (p < 0.05). Shorter durations of steroids with or without SIT for colitis were associated with less cancer progression within the study window than no immunosuppression (p < 0.05). Immunosuppression has no effect on PFS (p < 0.05). CONCLUSION: Our study reported shorter duration of steroid treatment for colitis may be associated with less cancer progression. Though the use of immunosuppression was not found to impact PFS, this may be confounded by the presence of colitis, which is known to improve cancer outcomes and could mask any negative impact of immunosuppression on survival. It may be preferable to limit long-term immunosuppression in the treatment of immune-mediated colitis to minimize potential complications. Prospective studies are needed to clarify this relationship, and treatments that abrogate the need for immunosuppression in these patients such as fecal microbiota transplantation.

Inflammatory bowel disease and associated cardiovascular disease outcomes: A systematic review.

BACKGROUND: There is limited and conflicting data available regarding the cardiovascular disease outcomes associated with inflammatory bowel disease (IBD). OBJECTIVE: We aim to perform a systematic review to evaluate the cardiovascular outcomes and mortality associated with IBD patients. METHODS: A systematic literature search has been performed on PubMed, Embase, Cochrane, and Scopus from inception till May 2022 without any language restrictions. RESULTS: A total of 2,029,941 patients were included in the analysis from 16 studies. The mean age of the patients was 45.6 years. More females were found compared with males (57% vs 43%). The most common risk factors for cardiovascular disease (CVD) included smoking (24.19%) and alcohol (4.60%). The most common comorbidities includes hypertension (30%), diabetes mellitus (14.41%), dyslipidemia (18.42%), previous CVD (22%), and renal disease (10%). Among outcomes, all-cause mortality among IBD patients was 1.66%; ulcerative colitis (UC): 15.92%; and Crohn disease (CD): 0.30%. Myocardial Infarction (MI) among IBD patients were 1.47%, UC: 30.96%; and CD: 34.14%. CVD events among IBD patients were 1.95%. Heart failure events among IBD patients were 5.49%, stroke events among IBD patients were 0.95%, UC: 2.63%, and CD: 2.41%, respectively. CONCLUSION: IBD patients are at higher risk for adverse cardiovascular outcomes, especially in women. Although there remains a lack of concrete treatment algorithms and assessment parameters that better characterize IBD risk factors, nutritional modifications and physical activity should be at the forefront of CVD prevention in IBD.

Efficacy of lenvatinib versus sorafenib in the primary treatment of advanced hepatocellular carcinoma: A meta-analysis.

Background and Aim: Molecular-targeted agents such as lenvatinib and sorafenib have been approved to treat hepatocellular carcinoma (HCC). However, the choice between these two agents in the primary treatment for advanced HCC is still under debate with conflicting results. We sought to evaluate the efficacy of lenvatinib and sorafenib in patients with HCC. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until February 10, 2023. The primary outcome of this meta-analysis was overall survival (OS). The secondary outcomes were progression-free survival (PFS), time to progression, objective response rate (ORR), and disease control rate (DCR). Results: A total of 13 studies with 3705 patients (1635 on lenvatinib and 2070 on sorafenib) were included in our analysis. The mean age of the patients in both groups was comparable (66.81 vs 65.9 years). Pooled analysis of primary outcomes showed that, compared with sorafenib, lenvatinib was associated with significantly better OS in patients treated with these drugs (HR 0.82, 95% CI: 0.69-0.97, P = 0.02). Pooled analysis also showed that PFS (HR 0.67, 95% CI: 0.57-0.78, P < 0.00001) and time to progression (HR 0.49, 95% CI: 0.31-0.79; P = 0.004) were significantly better in the lenvatinib group compared to the sorafenib group. It also showed that the lenvatinib group had significantly better ORR (odds ratio [OR] 5.43, 95% CI: 3.71-7.97; P < 0.00001) and DCR (OR 2.35, 95% CI: 1.75-3.16; P < 00001) than the sorafenib group. Conclusion: Our study shows that lenvatinib is superior to sorafenib regarding OS and PFS in patients with advanced HCC.

Malignant fibroma presenting as a hypoglycemia and coma in a 45-year-old male patient: A case report.

Solitary fibrous tumors (SFTs) are a rare group of spindle cell neoplasm of submesothelial origin with malignant potential and can present as hypoglycemia secondary to excess secretion of insulin-like growth factor II (IGF-II) from the tumor. Early diagnosis and treatment are very important in such cases to prevent hypoxic injury to the brain secondary to hypoglycemia. Here, we are presenting a case of a 45-year-old male patient, who presented with recurrent episodes of hypoglycemia spells, and later on, it was diagnosed that hypoglycemic spells were secondary to fibroma.

Klippel Feil Syndrome presenting with tricuspid regurgitation and cardiopulmonary distress secondary to dysplastic thoracic cage and spine: A case report.

Background: Klippel Feil syndrome is a rare multifactorial disease that occurs due to a combination of genetic and environmental factors. It is a complex disease that requires lifelong treatment by multidisciplinary teams. Case report: We present a case of a 15-year-old girl who presented with fever and shortness of breath and was found to have Klippel Feil Syndrome with a unique presentation of tricuspid regurgitation with cardiopulmonary distress secondary to dysplastic thoracic cage and spine. Discussion: Patients with Klippel feil syndrome are at increased risk for infection and cardiovascular problems. Proper surgical and medical management are required for patient wellbeing. Delay in diagnosis and management can be fatal with worse outcome.

A rare case of pediatric pancreatic pseudocyst.

We present a case report of a 2-year-old boy who presented to a local hospital to evaluate vague abdominal symptoms of one-month duration. The patient, therefore, had an open cystogastrostomy and drainage of the free abdominal fluid with minimal complications. He was monitored for several days after his surgery.

Symptomatology, prognosis and clinical findings of STEMI as a ramification of COVID-19: A systematic review and proportion meta-analysis.

Background: There is an increasing COVID-19 population with concurrent STEMI. SARS-CoV-2 poses a significant risk of hypercoagulable and/or prothrombotic events due to the disturbance in hemostasis by affecting all three components of the Virchow's triad. These abnormalities in hemostasis are an increased risk factor for cardiovascular events, including acute thrombotic occlusion of coronary arteries leading to myocardial infarction. Objective: The objective of this study is to collate the prognosis, symptomatology and clinical findings of COVID-19 adverse events causing STEMI. Methods: Databases were queried with various keyword combinations to find applicable articles. Cardiovascular risk factors, symptomatology, mortality and rates of PCI were analyzed using random-effect model. Results: 15 studies with a total of 379 patients were included in the final analysis. Mean age of patients was 62.82 ± 36.01, with a male predominance (72%, n = 274). Hypertension, dyslipidemia and diabetes mellitus were the most common cardiovascular risk factors among these patients, with a pooled proportion of 72%, 59% and 40% respectively. Dyspnea (61%, n = 131) was the most frequent presenting symptom, followed by chest pain (60%, n = 101) and fever (56%, n = 104). 62% of the patients had obstructive CAD during coronary angiography. The primary reperfusion method used in the majority of cases was percutaneous coronary intervention (64%, n = 124). Mortality, which is the primary outcome in our study, was relatively high, with a rate of 34% across studies. Conclusion: Our findings show that most cases have been found in males, while the most common risk factors were Hypertension and Diabetes Mellitus. In most COVID-19 cases with ST-segment myocardial infarction, most hospitalized patients underwent primary percutaneous coronary intervention instead of fibrinolysis. The in-hospital mortality was significantly higher, making this report significant. As the sample size and reported study are considerably less, it warrants a further large-scale investigation to generalize it.

Bevacizumab and Sinus Venous Thrombosis: A Literature Review.

Pediatric glioma treatment can be confounded by eloquent anatomical location and pathologic and genetic characteristics. Current literature suggests that the vascular endothelial growth factor (VEGF) inhibitor bevacizumab has been linked to enhancing disease control; however, its safety and effectiveness are unknown. Bevacizumab has been linked with an increased incidence of intratumoral hemorrhage as well as arterial and venous thromboembolism. A rare adverse effect of chemotherapeutic treatment with bevacizumab is sinus venous thrombosis (SVT), with only a few cases reported to date. This review highlights the pathophysiology of bevacizumab, its rare and life-threatening side effect of SVT, and future recommendations.

Association Between Helicobacter pylori Infection and Serum Iron Profile.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is reported to be the most frequent cause of morbidity and mortality in cases of upper gastrointestinal (GI) diseases. There is paucity of research between the possible association of H. pylori and iron stores and iron deficiency anemia (IDA). In this study, we will determine if there is an association between serum total iron-binding capacity (TIBC), serum iron and ferritin levels, and H. pylori infection. METHODS: This case-control study was conducted in the gastroenterology ward of a major hospital in Pakistan from December 2020 to April 2021. Three hundred patients diagnosed with H. pylori were enrolled along with 300 participants in the control group. H. pylori was confirmed or excluded with the help of Giemsa stained gastric biopsy specimens. Blood was sent to the laboratory to test for ferritin, serum iron, and TIBC. Each sample was drawn in the morning to avoid any fluctuations. RESULTS: The mean serum iron level was significantly lower in participants with H. pylori infection compared to those who did not have H. pylori infection (110.72 ± 28.38 ug/dL vs. 162.5 ± 21.18 ug/dL; p-value: <0.0001). Serum ferritin level was significantly higher in participants with H. pylori infection (536.82 ± 117.0 ng/dL vs. 391.31 ± 101.54 ng/dL; p-value: <0.0001). CONCLUSION:  In comparison with the control group, TIBC and serum iron levels were found to be lower in the case group.

Arteriovenous Malformations in Proximal Part of Ileum: A Case Report.

Arteriovenous malformations in the ileum are a rare cause of gastrointestinal bleeding in young adults with few reported cases and pose difficulty in diagnosing. They usually present with chronic gastrointestinal bleed. A 30-year-old woman presented with an acute episode of hematochezia with a history of intermittent melena for 1.5 years. Complete blood count revealed a low hemoglobin level of 3.5g/dl and hypochromic microcytic anemia. Oesophago-gastro-duodenoscopy was normal; however, a colonoscopy revealed the terminal ileum and colon filled with blood. Computed tomography-Angiogram showed local intraluminal contrast extravasation in the ileum. Explorative laparotomy and on-table enteroscopy were performed identifying a small elevated, pigmented, and eroded mucosa (5 to 6 mm) in proximal ileum; resection and primary anastomosis were performed. The patient was followed after surgical resection and her symptoms improved dramatically with no additional episodes of melena and with the normalization of hemoglobin.

Role of Cod Liver Oil in Preventing Myocardial Infarction.

INTRODUCTION: Omega-3 fatty acids have for long been shown to reduce the incidence of cardiovascular (CV) diseases. Omega-3 fatty acids mainly exist in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid in fish oils. Cod liver oil is found to have a high concentration of these omega-3 fatty acids. This study aims to explore the benefits of using cod liver oil in reducing the incidence of myocardial infarction (MI) among at-risk patients.  Method: This open-label placebo-controlled two-arm interventional study was conducted in the internal medicine and cardiology unit of tertiary care hospital between January 2018 to January 2021. During this period, 870 patients at risk of CV events were enrolled in the study after obtaining informed consent. The study group received 415 mg cod liver oil daily, in addition to their current treatment, in a bottle without label and the control group received no additional treatment to their standard treatment. Patients were followed up for 12 months or till the development of MI. RESULT: Patients treated with cod liver oil had comparatively fewer incidences of MI; however, the difference was not significant (p-value: 0.09). Furthermore, the difference was non-significant for both fatal and non-fatal MI. The relative risk for total MI incidence was 0.70 (0.44-1.10). CONCLUSION: According to our study, adding cod liver oil to the diet does not play a major role in reducing the risk of MI. Further large-scale studies are needed to understand the role of cod liver oil in reducing the risk of CV events, including MI.

Deleterious Variants in WNT10A, EDAR, and EDA Causing Isolated and Syndromic Tooth Agenesis: A Structural Perspective from Molecular Dynamics Simulations.

The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.