2023

Pre-treatment plasma proteomics-based predictive biomarkers for immune related adverse events in non-small cell lung cancer (2023)

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Type of publication:
Conference abstract

Author(s):
Naidoo J.; Reinmuth N.; Puzanov I.; Bar J.; Kamer I.; Koch I.; Moskovitz M.; Levy-Barda A.; Agbarya A.; Zer A.; Abu-Amna M.; Farrugia D.; Lotem M.; Price G.; Harkovsky T.; Hassani A.; Katzenelson R.; *Chatterjee A.; Yelin B.; Sela I.; Dicker A.; Elon Y.; Harel M.; Leibowitz R.

Citation:
Journal for ImmunoTherapy of Cancer. Conference: 38th Annual Meeting of the Society for Immunotherapy of Cancer's, SITC 2023. San Diego, CA United States. 11(Supplement 1) (pp A1356), 2023. Date of Publication: November 2023.

Abstract:
Background Immune-related adverse events (irAEs) resulting from immune checkpoint inhibitors (ICIs) can substantially affect patient quality of life and treatment trajectory. Currently, there are no reliable pre-treatment biomarkers for predicting the development of irAEs; hence, there is a clinical need for irAE predictive biomarkers. Methods Plasma samples were obtained at baseline from 426 non-small cell lung cancer (NSCLC) patients treated with ICIs as part of an ongoing multi-center clinical trial (NCT04056247; approved by local IRB committees from each site) with irAE-related information. Proteomic profiling of plasma samples was performed using the SomaScan assay (SomaLogic Inc.), enabling deep coverage of approximately 7000 proteins in each sample. A machine learning-based model was developed to predict significant irAEs arising up to 3 months from treatment initiation; significant irAEs were defined as irAEs with CTCAE grade >=3 or irAEs that induced treatment discontinuation. Using the model, we identified a set of plasma proteins, termed Toxicity Associated Proteins (TAPs), that serve as indicators of irAEs depending on their plasma level in the individual patient. Bioinformatic analysis was performed to decipher the biology underlying immunerelated toxicity implied by the TAPs. Results Overall, 60 patients experienced significant irAEs at early onset; 197 patients had low grade irAEs, irAEs at late onset or AEs that are not immune-related; and 169 patients did not display any adverse event. A computational model was generated to predict significant irAEs, showing a strong correlation between the predicted probability of significant irAEs and the observed rate of such events (R2= 0.92; pvalue <0.0001), implying good prediction capabilities. The prediction was based on a set of 449 TAPs. Interestingly, nearly half of these TAPs were previously identified as proteins associated with clinical benefit from ICI therapy, suggesting a close relationship between irAEs and clinical benefit, in accordance with previous reports. A detailed examination of the TAPs revealed some key findings. Patients who experienced irAEs had a larger number of TAPs related to neutrophils, inflammation, and cell death resistance, while the number of lymphocyte-related TAPs was low in these patients. Patients who did not experience irAEs displayed higher levels of extracellular matrix-related proteins. Conclusions We describe a novel computational model for predicting significant irAEs in patients with NSCLC based on proteomic profiling of pre-treatment plasma samples. The TAPs provide insights into the biological processes underlying irAEs. Early prediction of irAEs could enable personalized management plans and mitigation strategies to reduce the risk of irAEs in NSCLC.

A Survey on the Type and Prevalence of Medical Interventions during Labor and Childbirth in Greek Pregnant Women (2023)

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Type of publication:
Journal article

Author(s):
*Papoutsis D.; Chatzipanagiotidou N.

Citation:
Clinical and Experimental Obstetrics and Gynecology. 50(12) (no pagination), 2023. Article Number: 258. Date of Publication: December 2023.

Abstract:
Background: The purpose of this study was to identify the type and prevalence of medical interventions during labor and birth in Greek pregnant women. Method(s): We constructed a 49-item web-based questionnaire to capture demographic data, obstetric data and the medical interventions performed during the most recent childbirth of participants. The questionnaire was posted on nationwide electronic media between November 2022 to January 2023. All women who had given birth at least once were eligible for the study, and results were stratified by the timing of their last birth. Result(s): There was a total of 954 women participating in the survey, with 809 women giving birth within the last 10 years and 145 women giving birth between 10 to 20 years ago. In those that gave birth within the past 10 years, the majority had a low-risk pregnancy (78.8%) and the overall cesarean section rate was 42.8%. During labor, women were allowed to change positions and to mobilize in about half of cases, whereas the lithotomy position at birth was reported by 81.4%. Almost 2 in 3 women reported a vaginal examination every hour or even more frequently, with approximately 30% sustaining more than 5 examinations intrapartum. Oxytocin use was reported in 36.9%, epidural use in 69.6%, and episiotomy in 47.3% of women. Women who had their last birth 10-20 years ago when compared to those who gave birth within the last 10 years seem to have experienced higher rates of medical interventions during labor and birth. Conclusion(s): The survey results demonstrate the medicalization of childbirth in Greek pregnant women over the past 20 years. These findings may serve as a benchmark against which to compare and identify possible changes in future birthing practices and to determine which measures to promote normality at birth should be implemented.

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Mastering the Art of Dermatosurgery: Aesthetic Alchemy in Medical Excellence (2023)

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Type of publication:
Journal article

Author(s):
*Ekomwereren, Osatohanmwen; Shehryar, Abdullah; Abdullah Yahya, Noor; Rehman, Abdur; Affaf, Maryam; Chilla, Srikar P; Kumar, Uday; Faran, Nuzhat; I K H Almadhoun, Mohammed Khaleel; Quinn, Maria; Ekhator, Chukwuyem

Citation:
Cureus. 15(11):e49659, 2023 Nov.

Abstract:
Dermatosurgery, a specialized branch within dermatology, has traversed an extraordinary journey through time, shaped by ancient practices, technological leaps, and shifting societal perceptions. This review explores the evolution of dermatosurgery, highlighting its profound transformation from addressing solely medical concerns to seamlessly integrating aesthetics. From its roots in ancient civilizations, where cultural traditions laid the foundation for modern techniques, to the twentieth-century technological renaissance, marked by innovative tools and enhanced understanding of skin anatomy, dermatosurgery has emerged as a dynamic field. Societal notions of beauty and health have significantly influenced dermatosurgery, blurring the lines between medical necessity and elective aesthetic procedures. The delicate balance between satisfying aesthetic desires and upholding medical ethics is a central challenge that
dermatosurgeons face today. Open dialogue between practitioners and patients as well as psychological support plays a pivotal role in navigating this terrain. The training and ethics associated with dermatosurgery have evolved to meet the increasing demand for specialized procedures. Maintaining a focus on patient safety and satisfaction remains paramount as commercial pressures and disparities in access to care loom. Upholding best practices and standards in the field is essential for ensuring consistent, high-quality care for all patients. Looking ahead, dermatosurgery stands on the brink of a transformative era, marked by non-invasive techniques, artificial intelligence (AI) integration, and personalized medicine. The field's ability to harmonize medical science with aesthetic artistry is evident in various case studies, showcasing the intricate balance dermatosurgeons strike between addressing medical concerns and fulfilling aesthetic desires. As dermatosurgery continues to evolve, it promises to provide patients with even more precise, tailored treatments that enhance both their physical well-being and aesthetic satisfaction.

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Vesical Haemangioma in Klippel-Trenaunay-Weber Syndrome: A Clinical Case (2023)

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Type of publication:
Journal article

Author(s):
Mohamed, Ahmed; *Chin, Yew Fung; Farah, Mohamed; Mahmalji, Wasim

Citation:
Cureus. 15(12):e49952, 2023 Dec.

Abstract:
Klippel-Trenaunay-Weber (KTW) syndrome, a rare vascular disorder, often presents with cutaneous capillary malformations and soft tissue hypertrophy. However, urinary tract involvement in the form of vesical haemangiomas is a seldom-encountered clinical condition. We present a case of a 37-year-old male with KTW syndrome who exhibited recurrent gross haematuria, prompting clinical evaluation. Initial diagnostic assessments revealed erythematous changes in the bladder, consistent with haemangiomas. Despite an initial biopsy and diathermy, the patient's symptoms recurred, leading to a subsequent management strategy involving laser fulguration. This case underscores the significance of recognizing cutaneous haemangiomas as potential indicators of urinary tract involvement in KTW syndrome and highlights the challenges in managing vesical haemangiomas, where a multidisciplinary approach is essential for optimal care.

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Direct to test: the trend to chest CT scanning requests through primary care. (2023)

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Type of publication:
Conference abstract

Author(s):
Nahar R.; *Bosher O.; *Makan A.; Crawford E.; Srinivasan K.; Moudgil H.;

Citation:
Thorax. Conference: British Thoracic Society Winter Meeting 2023. London United Kingdom. 78(Supplement 4) (pp A258), 2023. Date of Publication: November 2023.

Abstract:
Background/Objectives Although the concept of 'direct to test' managing patients from primary care is not new, emphasis has been on improving cancer outcomes through earlier radiological detection; evidence on how General Practitioners (GPs) currently request chest CT (computer tomography) scans dealing with a broader range of diagnoses amid the backlog of referrals into secondary care in the post COVID-19 era, is anecdotal. This work (1) documents the uptake and nature of chest CT scans requested, (2) reports on appropriateness and standard of referrals, and (3) outlines subsequent findings. Methods 12 month computer data collected retrospectively on all patients undergoing chest CT scans at this secondary care hospital; GP referrals were identified through practice codes. Results 279/1230 (23%) of chest CT scans undertaken were requested through primary care; mean age of patients was 67.6 (SD 12.2, range 20-91) years with 48% males. Uptake/ trend over the preceding 12 months are shown in figure 1, GP requests remaining low. All were HRCT (High Resolution CT) rather than staging CT used to stage lung cancer or CTPA (CT Pulmonary Angiograms) investigating pulmonary thrombo-embolic disease (PTE). 263 (94%) of requests were to establish a new finding and 16 (6%) as follow up assessing earlier detected pulmonary nodules; 178 (64%) of referrals were based on symptoms with a provisional diagnosis only proposed in 140 (50%). Referral standards adequately outlining clinical context was only found in 142 (51%) but referral pathway considered appropriate in 268 (96%) with the remainder probably best referred directly to cancer pathways. Findings included bronchiectasis (23%), emphysema (15%), interstitial (including occupational) lung disease (15%) and lung cancer (2%) but with inconclusive or no new radiological finding in 117 (42%). Conclusions Approximately 23% of chest CT scans are currently being requested through primary care; although the type of CT and most referrals are appropriate, with most lung cancer and PTEs on alternate referral pathways, there remains concern where pulmonary nodules are being followed outside of a more dedicated protocol and clinic. Benefits to the patient, how GPs manage the high number of inconclusive results, and patterns of referrals to secondary care require further assessment.

Assessing continued benefits of 4C scores for mortality among patients with COVID-19 pneumonitis admitted to a teaching district general hospital (2023)

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Type of publication:
Conference abstract

Author(s):
Cox D.; Koshy K.; *Moudgil N.; *Makan A.; *Crawford E.; *Moudgil H.; *Srinivasan K.;

Citation:
Thorax. Conference: British Thoracic Society Winter Meeting 2023. London United Kingdom. 78(Supplement 4) (pp A201), 2023. Date of Publication: November 2023.

Abstract:
Background and Objectives The 4C (Coronavirus Clinical Characterisation Consortium) score incorporating patient comorbidities with measures of acute physiology and inflammation is an internationally validated prognostic tool for in-hospital mortality introduced early during the COVID-19 pandemic. With the subsequent strong uptake of SARS-CoV-2- RNA vaccines, more targeted therapies, changing virulence of the coronavirus (now predominantly omicron), and fewer reported deaths, the goal/objectives of this work were to determine continuing relevance of 4C scores by (1) reporting their distribution categorised with risk profile and (2) further analysing mortality in the immediate in-hospital setting and at 12 months. Methods Retrospective computer-based data including SARSCoV- 2-RNA vaccination status/boosters collected for patients with confirmed infection and COVID-19 pneumonitis admitted during 2 months to July 2022; subsequent analysis for mortality was by regression analysis accepting statistically significant findings for standardised beta coefficients at p<.05 adjusting for demographics, vaccination status and targeted COVID-19 directed (Remdesivir/Tocilizumab) therapeutic variables as well as oxygen (O2) and use of medical devices. Results 62 patients (47% males), with mean (SD, range) age 75.8 (15.4, 32-101) years were identified; 19 (30.6%), with mean survival 70 (67, 6-237) days (median 40 days), had died (9 in the initial admission and 10 during follow up). 55 (88.7%) had been vaccinated at least once. Distribution of 4C scores with mortality in-hospital and during follow up are shown in table 1; 8/9 (88.9%) in-hospital and 17/19 (89.5%) overall deaths were from patients with high or very high 4C scores. Independent variables statistically significant on regression analysis for in-hospital mortality included positively with 4C score (p= .018) and high O2/medical ventilatory devices (p= .000), and negatively with age (p= .048), dexamethasone (p= .046), and targeted COVID treatments (p= .036) but not gender, status/number of vaccines, or low dose O2 use. None of the variables were significant at 12 months. Conclusions Analysis of this real-life data has shown continued role for 4C scores outside of their original validation; despite no statistical significance among independent variables at 12 months, the continued mortality (30.6% in the cohort) likely reflects on the significant burden of co-morbidity.

Evidence-based frozen elephant trunk practice: a narrative review (2023)

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Type of publication:
Journal article

Author(s):
Kayali F.; Chikhal R.; Agbobu T.; Jubouri M.; *Patel R.; Chen E.P.; Mohammed I.; Bashir M.

Citation:
Cardiovascular Diagnosis and Therapy. 13(6) (pp 1104-1117), 2023. Date of Publication: 2023.

Abstract:
Background and Objective: The frozen elephant trunk (FET) allows a single-stage repair of complex arch pathologies due to its stented and non-stented hybrid prosthesis (HP) features. FET inherently has its own related complications including distal stent graft-induced new entry (dSINE), failure of aortic remodelling, endoleak, reintervention, and kinking of the stent. The aim of this narrative review is to discuss the latest evidence regarding the postoperative clinical outcomes of the FET procedure. Another aim is to provide an overview of results achieved using different FET devices on the global arch prostheses market. <Method(s): A comprehensive literature search was conducted using multiple electronic databases to identify and extract the relevant data and information. Key Content and Findings: This review found that the literature reported a 5-12% mortality rate post- FET, with varying figures depending on the prosthesis type. Between 0-18.2% of patients developed dSINE, while 0.1-28% developed endoleak. Reintervention occurred in 0-28% of patients and the incidence of kinking has been quoted between 0-8% in the literature. Reporting aortic remodelling rates was challenging due to the lack of standardisation and various measurements reported; however, all studies included in this review reported relative increase in true lumen diameter, reduction in the false lumen diameter, and/or false lumen thrombosis. Conclusion(s): In conclusion, FET can achieve a favourable postoperative profile in terms of survival, complications and aortic remodelling, and remains the gold-standard treatment for thoracic aortic pathologies implicating the arch and descending thoracic aorta.

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Transregional Study Highlighting the Increasing Burden of Urology Cancer Multidisciplinary Team Meetings Around the UK (2023)

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Type of publication:
Journal article

Author(s):
Kasmani, Zain; Mohamed, Wail; Siddiqui, Zain; Boksh, Saddek; Ganapathi, Shaswath; Saidani, Zakaria; Wijayasuriya, Don S; Donati-Bourne, Jack.

Citation:
Cureus. 15(11):e48501, 2023 Nov.

Abstract:
Introduction: The urology multidisciplinary team meeting (MDT) is the key weekly meeting that allows the opportunity to review results and discuss management plans for all urological cancers within a department. As populations age and cancer detection and management improve, the demand for the MDT will increase. We conducted a collaborative transregional study within the UK to evaluate the current workload on the urology MDT. Methods: The study was divided into two parts: a multicenter retrospective audit and a snapshot survey. Three UK hospitals in Birmingham, Liverpool, and Cardiff were recruited into the multicenter study. Each hospital provided full MDT lists for all weekly meetings between August 2017 and 2022. Retrospective data gathered included the number of patients discussed per week, the average age of patients per week, the time allocated to their weekly MDT, and the total number of consultants in the department. The second part of the study involved the distribution of an online questionnaire to urologists across the UK to obtain a snapshot picture with the above parameters. Results Snapshot data from 34 different UK hospitals showed MDT length ranged from 1-6 hours, patients discussed ranged from 10-90 per week, and the maximum average discussion time was 3.8 minutes per case. Furthermore, 76% (N = 28/37) of respondents said unnecessary cases were discussed. Varied suggestions were provided on how the MDT could be improved. Multicenter five-year data showed a rise in mean total numbers of patients discussed per week in all centers: a 34.8% increase in Birmingham (from 34.5 patients to 46.5 patients), a 23.5% increase in Liverpool (27.2 patients to 33.6 patients), and a 38.8% increase in Cardiff (22.7 patients to 31.5 patients). Hours per meeting were Birmingham (2), Liverpool (3), and Cardiff (4), which meant the average minutes per patient discussion were Birmingham (2.6), Liverpool (5.4), and Cardiff (7.6). Conclusion There is a rapidly rising trend across UK regions for the number of patients being discussed in the urology MDT meeting. The MDT structure and function across the country are highly variable. There is consensus that the MDT discusses cases that are unnecessary, and this has been recognized for many years. Widespread implementation of the latest MDT management guidelines is urgently required to ensure MDT meetings are able to function effectively and efficiently into the future.

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Radiological and Imaging Evidence in the Diagnosis and Management of Microbial Infections: An Update (2023)

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Type of publication:
Journal article

Author(s):
Vaishnav, Aditya; *Gurukiran, Gurukiran; Ighodaro, Osazuwa; Kandi, Venkataramana

Citation:
Cureus. 15(11):e48756, 2023 Nov.

Abstract:
Microbial infections are extremely prevalent throughout the world. Bacteria, fungi, parasites, and viruses generally cause them. Most microbial infections spread from humans to humans and from animals to humans. A vast majority of microbial infections are self-limiting. However, some microbial infections result in severe morbidity and mortality. The diagnosis of microbial infections generally depends on the direct demonstration of microbes in human clinical specimens through microscopy followed by culture. Some microbes are uncultivable, and among those that are cultivable, some take a very long time to grow in the laboratory. This causes delays in the diagnosis that may result in poor patient outcomes. Serological and molecular methods like enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), respectively, have been extensively used to diagnose infectious diseases. However, these require costly infrastructure and adequate personnel training. In this context, alternative, more efficient, and rapid detection methods for the diagnosis of microbial infections are warranted. In this review, we comprehensively discuss the role played by radiological investigations in the diagnosis and management of infectious diseases.

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Orbital Onset: The Intricate Journey From Ear Abscess to Cavernous Sinus Thrombosis in a Diabetic Male (2023)

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Type of publication:Journal article

Author(s):*Ekomwereren, Osatohanmwen; Sunkara, Vyshnavidevi; Grezenko, Han; Hamid, Yusra H; Faran, Nuzhat; Abubakar, Muhammad.

Citation:Cureus. 15(11):e48922, 2023 Nov.

Abstract:Cavernous sinus thrombosis (CST) is a rare, yet severe condition often linked to infections in the nasal and facial areas. We present a case of a 43-year-old male farmer with diabetes who initially showed ear abscess symptoms that progressed to vision loss and CST-like symptoms. Self-treatment and an unidentified medication regimen may have worsened his condition. Advanced diagnostic evaluations, particularly magnetic resonance imaging with magnetic resonance venography, confirmed CST, likely originating from the ear infection spreading to the eyes, causing bilateral orbital cellulitis. Treatment with antibiotics, anticoagulants, and supportive therapy stabilized the patient's condition. This case emphasizes the importance of early detection and intervention in CST, especially in atypical presentations, and the need for comprehensive diagnostic and therapeutic approaches.

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