Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells.

Thoracic aortic disease (TAD) is often silent until a life-threatening complication occurs. However, genetic information can inform both identification and treatment at an early stage. Indeed, a diagnosis is important for personalised surveillance and intervention plans, as well as cascade screening of family members. Currently, only 20% of heritable TAD patients have a causative mutation identified and, consequently, further advances in genetic coverage are required to define the remaining molecular landscape. The rapid expansion of next generation sequencing technologies is providing a huge resource of genetic data, but a critical issue remains in functionally validating these findings. Induced pluripotent stem cells (iPSCs) are patient-derived, reprogrammed cell lines which allow mechanistic insights, complex modelling of genetic disease and a platform to study aortic genetic variants. This review will address the need for iPSCs as a frontline diagnostic tool to evaluate variants identified by genomic discovery studies and explore their evolving role in biological insight through to drug discovery.

Understanding the current acute aortic syndrome (AAS) pathways-The Collaborative Acute Aortic Syndrome Project (CAASP) protocol.

BACKGROUND: Acute aortic syndrome (AAS) is an emergency associated with high peri-hospital mortality rates. Variable clinical presentation makes timely diagnosis challenging and such delays in diagnosis directly impact patient outcomes. AIMS AND OBJECTIVES: The aims of the Collaborative Acute Aortic Syndrome Project (CAASP) are to characterise and evaluate the current AAS pathways of a cohort of hospitals in the UK, USA and New Zealand to determine if patient outcomes are influenced by the AAS pathway (time to hospital admission, diagnosis and management plan) and demographic, social, geographic and patient-specific factors (clinical presentation and comorbidities). The objectives are to describe different AAS pathways and time duration between hospital admission to diagnosis and management plan instigation, and to compare patient outcomes between pathways. METHODS: The study is a multicentre, retrospective service evaluation project of adult patients diagnosed on imaging with AAS. It will be coordinated by the UK National Interventional Radiology Trainee Research (UNITE) network and Vascular and Endovascular Research Network (VERN) in conjunction with The Aortic Dissection Charitable Trust (TADCT). All AAS cases diagnosed on imaging between 1st January 2018 to 1st June 2021 will be included and followed-up for 6 months. Eligibility criteria include aortic dissection (AD) Type A, Type B, non A/B, penetrating aortic ulcer, and intramural haematoma. Exclusion criteria are non-AAS pathology, acute on chronic AAS, and age<18. This project will evaluate patient demographics, timing of presentation, patient symptoms, risk factors for AD, physical examination findings, timing to imaging and treatment, hospital stay, and mortality. Univariate and multivariate analysis will be used to identify predictors associated with prolonged time to diagnosis or treatment and mortality at 30 days.

A State-of-the-Art Review of Intra-Operative Imaging Modalities Used to Quality Assure Endovascular Aneurysm Repair.

Endovascular aortic aneurysm repair (EVAR) is the preferred method for elective abdominal aortic aneurysm (AAA) repair. However, the success of this technique depends greatly on the technologies available. Intra-operative imaging is essential but can come with limitations. More complex interventions lead to longer operating times, fluoroscopy times, and greater contrast doses. A number of intra-operative imaging modalities to quality assure the success of EVAR have been developed. A systematic literature search was performed with separate searches conducted for each imaging modality in the study: computed tomography (CT), digital subtraction angiography (DSA), fusion, ultrasound, intra-operative positioning system (IOPS), and non-contrast imaging. CT was effective at detecting complications but commonly resulted in increased radiation and contrast dose. The effectiveness of DSA can be increased, and radiation exposure reduced, through the use of adjunctive technologies. We found that 2D-3D fusion was non-inferior to 3D-3D and led to reduced radiation and contrast dose. Non-contrast imaging occasionally led to higher doses of radiation. Ultrasound was particularly effective in the detection of type II endoleaks with reduced radiation and contrast use but was often operator dependent. Unfortunately, no papers made it past full text screening for IOPS. All of the imaging techniques discussed have advantages and disadvantages, and clinical context is relevant to guide imaging choice. Fusion and ultrasound in particular show promise for the future.

Liposarcoma of tongue: A case report.

ABSTRACT: Liposarcoma (LS) is one of the most common malignant tumors. However, oral LS is an extremely rare lesion that is often clinically misdiagnosed as a benign lesion because of its asymptomatic and indolent clinical course. In oral cavity, the tongue is the most frequent site for its occurrence.

Isolated pancreatic myeloid sarcoma: A potential mimicker of pancreatic adenocarcinoma.

Myeloid sarcoma (MS) is an extramedullary proliferation of immature myeloid cells which may occur as a progression of myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) and as acute myeloid leukemia (AML) relapse. Rarely may it be de novo. Lymph nodes, skin, lungs, intestine are the commonly involved sites. However, an isolated pancreatic MS is seldom reported in the literature. Herein, we report one such case which was misdiagnosed as pancreatic adenocarcinoma on the clinico-radiological examination which misled us away from preoperative diagnostic sampling, and a Whipple pancreaticoduodenectomy was performed. Histopathological examination in conjunction with immunohistochemistry revealed the final diagnosis of isolated MS of the pancreas. We emphasize that although rare, a clinical suspicion along with preoperative histopathological examination may lead to early diagnosis, targeted management, and a better clinical outcome in such cases.

Diagnostic Accuracy of Calculated Tumor Volumes and Apparent Diffusion Coefficient Values in Predicting Endometrial Cancer Grade.

Background: Magnetic resonance imaging (MRI) has been shown to be an accurate imaging technique for the preoperative assessment of local staging of endometrial cancer and for evaluating the depth of myometrial invasion. Materials and Methods: This was a single-center retrospective study performed on patients with histopathologically proven endometrial carcinoma who underwent an MRI examination of the pelvis between October 2017 and May 2020. Results: In the present analysis, mean apparent diffusion coefficient (ADC) values for each histologic grade were 0.72 ± 0.13 × 10-3 mm2/s (G1), 0.76 ± 0.17 × 10-3 mm2/s (G2), and 0.74 ± 0.12 × 10-3 mm2/s (G3), respectively, showing no significant correlation between ADC values and tumor grade (P = 0.73). Overall, ADC minimum was significant in differentiating grades of endometrial carcinoma (P = 0.02) with the ability to differentiate Grade I and II lesions (P = 0.01). A mean tumor volume of 25.2 cc could differentiate low-grade tumors (Grade I and Grade II) from high-grade tumors (Grade III) with a sensitivity and specificity of 88% and specificity of 89%. The tumor volume/uterine volume ratio (TV/UV) differentiates high-grade tumors from low-grade tumors (P < 0.001), however, no significant difference in the ratio was observed among Grade I and II lesions (P = 0.48). The area under the curve of tumor volume was 0.875 (95% confidence interval 0.0-1.00) (P = 0.001), indicating that tumor volume was an effective tool for distinguishing high-grade and low-grade endometrioid adenocarcinomas. The corresponding sensitivity and specificity were 88.0% and 89.0%, respectively. Conclusion: Preoperative noninvasive radiological assessment for tumor volume, TV/ UV or tumor volume/uterine volume is important surrogate markers for preoperative prognostication of endometrial carcinoma.

Pyoderma Gangrenosum with Splenic Abscess- A Rare Association.

Pyoderma gangrenosum is a rare, chronic neutrophilic dermatosis of unknown etiology. The classical clinical feature of pyoderma gangrenosum is a pustule or plaque that rapidly progresses to a painful, necrotic ulcer with undermined violaceous margins. Pyoderma gangrenosum may be associated with underlying inflammatory bowel diseases, hematological malignancies, or rheumatologic disorders in 50-70% of the cases. The visceral involvement by pyoderma gangrenosum is rare. Sterile neutrophilic infiltrates in organs other than the skin are uncommon systemic manifestations of neutrophilic dermatoses, but have occasionally been reported. We report a case of a 38-year-old female with pyoderma gangrenosum and visceral involvement manifesting as splenic abscess.

Proton Pump Inhibitor Induced Subacute Cutaneous Lupus Erythematosus: A Case Series of 7 Patients and Brief Review of Literature.

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) manifests with erythematous, nonscarring, annular, or papulosquamous plaques. Proton pump inhibitors (PPIs) are increasingly being incriminated in its causation, but reports of similar nature from India are lacking. AIMS: To describe the characteristics of seven patients with SCLE induced by PPIs and to review the published cases in order to provide a better perspective of the association. MATERIALS AND METHODS: We describe seven patients of PPI-induced SCLE, seen over a period of 6 years. We also review the literature for additional data on PPI-induced SCLE. The selected publications were reviewed, and relevant clinical and laboratory data were extracted. RESULTS: Of the total seven cases, there were four males and three females with a mean age of 60.2 ± 5.5 years (range 53-70 years). Nine episodes of PPI-induced SCLE were recorded in the seven patients. Of the initial episodes, esomeprazole was implicated in four, pantoprazole in two, and rabeprazole in one patient. Latency period ranged from 2 weeks to 1 year (mean 11.4 ± 16.2 weeks). Morphology was described as annular scaly plaques in six and papulosquamous in one. Antinuclear antibodies and anti-Ro antibodies were positive in all patients. Naranjo probability scale was used in all patients; two were categorized as definite and five as probable. Treatments included drug withdrawal in six patients, topical steroids in one, systemic corticosteroids in all seven, and hydroxychloroquine in one patient, used alone or in combinations. Complete remission was achieved in six cases, while one had partial remission. LIMITATION: Retrospective nature of this study and limited number of patients. CONCLUSION: PPIs can trigger SCLE.

Reducing ileus after colorectal surgery: A network meta-analysis of therapeutic interventions.

BACKGROUND: Several treatment strategies for avoiding post-operative ileus have been evaluated in randomised controlled trials. This network meta-analysis aimed to explore the relative effectiveness of these different therapeutic interventions on ileus outcome measures. METHODS: A systematic literature review was performed to identify randomized controlled trials (RCTs) comparing treatments for post-operative ileus following colorectal surgery. A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method. Direct and indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analysis. RESULTS: A total of 48 randomised controlled trials were included in this network meta-analysis reporting on 3614 participants. Early feeding was found to be the best treatment for time to solid diet tolerance and length of hospital stay with a probability of P = 0.96 and P = 0.47, respectively. Early feeding resulted in significantly shorter time to solid diet tolerance (Mean Difference (MD) 58.85 h; 95% Credible Interval (CrI) -73.41, -43.15) and shorter length of hospital stay (MD 2.33 days; CrI -3.51, -1.18) compared to no treatment. Epidural analgesia was ranked best treatment for time to flatus (P = 0.29) and time to stool (P = 0.268). Epidural analgesia resulted in significantly shorter time to flatus (MD -18.88 h; CrI -33.67, -3.44) and shorter time to stool (MD -26.05 h; 95% CrI -66.42, 15.65) compared to no intervention. Gastrograffin was ranked best treatment to avoid the requirement for post-operative nasogastric tube insertion (P = 0.61) however demonstrated limited efficacy (OR 0.50; CrI 0.143, 1.621) compared to no intervention. Nasogastric and nasointestinal tube insertion, probiotics, and acupuncture were found to be least efficacious as interventions to reduce ileus. CONCLUSION: This network meta-analysis identified early feeding as the most efficacious therapeutic intervention to reduce post-operative ileus in patients undergoing colorectal surgery, in addition to highlighting other therapies that require further investigation by high quality study. In patients undergoing colorectal surgery, emphasis should be placed on early feeding as soon as can be appropriately initiated to support the return of gastrointestinal motility.

Diagnostic utility of multiple site duodenal biopsies in celiac disease.

BACKGROUND: Celiac Disease involves the small intestine patchily affecting more frequently the proximal small bowel but the histological changes have been observed till terminal ileum. Of late in addition to D2, the duodenal bulb (D1 region) biopsies have been found helpful in identifying a small group of patients with CD. Therefore, multiple site biopsies are recommended as histological changes are not uniform throughout small intestine. METHODS: During this present 1.5 years prospective study, we evaluated 84 cases of suspected celiac disease with respect to the light microscopy (D1, D2, and D3 biopsy) and serology (anti tTg and or EMA). Histological examination was done according to Modified Marsh grading system. RESULTS: Out of 84 cases with raised anti tTg, the segmental biopsies significantly increased the diagnostic accuracy from 39/44 cases (88.6%) to 43/44 cases (97.7%) and 44/44 cases (100%) when D2 alone, D1 + D2 and D1 + D2 + D3 biopsies were evaluated, respectively. Of the suspected cases of celiac disease patients (tTg > 10 ULN and associated weight loss, diarrhea), additional D3 biopsy increased the diagnostic yield by 2.1%, compared to D1, D2 region biopsy and 6.38% compared to standard D2 biopsy alone. Of the 28 cases (tTg > 10 times ULN + EMA positive and associated weight loss, diarrhea), the potential celiac disease (histologically Type 1/Normal) cases reduced from 28.5% (standard D2 region alone) to 21.4% and 17.8% when additional biopsies were taken from D1 region and D3 region, respectively, and additional D3 biopsy increased the diagnostic yield by 10.8% (compared to standard D2 biopsy alone) and 3.7% (compared to D1 and D2 biopsy). CONCLUSION: We believe multiple sites duodenal biopsies including D3 region biopsies might increase the diagnostic accuracy of adult celiac disease in addition to sensitive and specific serologic tests.