Author: Jason Curtis

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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Counselling and management of women with genetic predisposition to gynaecological cancers (2024)

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Type of publication:
Journal article

Author(s):
*Malik, Naushabah; *Sahu, Banchhita

Citation:
European Journal of Obstetrics, Gynecology, & Reproductive Biology. 294:44-48, 2024 Mar.

Abstract:
OBJECTIVE: To review the literature with reference to counselling and management of women with genetic predisposition to gynaecological cancers. METHODS: Histochemical analysis, ultrasound, blood investigations, genetic testing, screening and risk-reducing surgery (RRS) are important tools for the management of gynaecological cancers and mortality reduction. Counselling can assist in timely management of gynaecological cancers. Systematic reviews, review articles, observational studies and clinical trials on PubMed, published in the English language, were included in this review. RESULTS: The management of women with genetic predisposition to gynaecological cancers through screening tests and RRS has led to a significant decrease in the risk of malignancy through RRS in cases with BRCA1 and BRCA2 gene mutations. RRS and screening have also been found to reduce the mortality rate and increase the survival rate in women with BRCA1 and BRCA2 gene mutations. The efficacy of endometrial cancer surveillance in women with Lynch syndrome is still unproven. RRS has not been reported to be effective in women with Cowden syndrome. The risk of ovarian malignancies in individuals with germline mutations remains minimal in the general population in comparison with genetic mutations. CONCLUSION: Genetic testing and RRS should be implemented in addition to genetic counselling for proper management and mortality reduction of women predisposed to gynaecological cancers.

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Musculotendinous ruptures of the achilles tendon had greater heel-rise height index compared with mid-substance rupture with non-operative management: A retrospective cohort study (2024)

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Type of publication:
Journal article

Author(s):
*Carmont, Michael R; Gunnarsson, Baldvin; Brorsson, Annelie; Nilsson-Helander, Katarina.

Citation:
Journal of Isakos. 9(2):148-152, 2024 Apr.

Abstract:
INTRODUCTION: Achilles tendon ruptures (ATRs) may occur at varying locations with ruptures at the mid-substance (MS) of the tendon most common, followed tears at the musculotendinous (MT) junction. There is scant literature about the outcome of MT ATR. This study compared the outcome of patients with a MT ATR with patients following a MS ATR. METHODS: The diagnostic features and clinical outcome of 37 patients with a MT ATR were compared with a cohort of 19 patients with a MS ATR. Patients in both groups were managed non-operatively and received the same rehabilitation protocol with weight-bearing rehabilitation in protective functional brace. RESULTS: From February 2009 to August 2023, 556 patients presented with an ATR. Of these, 37 (6.7 %) patients were diagnosed with a MT tear. At final follow-up, at 12 months following injury, the MT group reported an Achilles tendon total rupture score (ATRS) of mean (standard deviation (SD)) of 83.6 (3.5) (95 % confidence interval (CI) 81.8, 85.4) and median (inter-quartile range (IQR)) ATRS of 86 points (78-95.5) and the MS group mean (SD) of 80.3 (8.5) (95%CI) 76.1, 80.5) and median (IQR) of 87 points (59-95) (p = 0.673). Functional evaluation, however, revealed statistically significant differences in mean (SD) heel-rise height index MT group 79 % (25) (95%CI 65.9, 92.1) and MS group 59 % (13) (95%CI 51.9, 67.1) (p = 0.019). In the MT rupture group, there were considerably less complications than the MS rupture group. CONCLUSIONS: When managed non-operatively, with only a 6 weeks period of brace protection, patients have little limitation although have some residual reduction of single heel-rise at the one-year following MT ATR. LEVEL OF EVIDENCE: IV.

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Biomarkers in Prostate Cancer: A Review (2024)

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Type of publication:
Journal article

Author(s):
Ahmadieh, Nizar; Zeidan, Toufic; Chaaya, Celine; *Cain, David; Aoude, Marc; Abouchahla, Anita; Kourie, Hampig Raphael; Nemer, Elie.

Citation:
The Gulf Journal of Oncology. 1(44):81-93, 2024 Jan.

Abstract:
BACKGROUND: Prostate cancer (PC) is the second most common cancer in men worldwide. It's the second leading cause cancer men in death. Prognostic tests based on molecular and biomarker analysis of tumor tissue may improve risk stratification of prostate cancer 2. MATERIALS AND METHODS: After a search on Pubmed for PC biomarkers, 72 papers responded to the objectives and will be included in the review. RESULTS: A plethora of biomarkers are predictive for the prognosis of PC and its response to certain therapies, while others, once thought to be indicative of prognosis in PC, were not. CONCLUSIONS: This study can help in the development of diagnostic and prognostic tests of PC and contribute to the ongoing research into already existing tests.

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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Efficacy of atypical antipsychotics in the treatment of fecal incontinence in children and adolescents: a randomized clinical trial (2024)

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Type of publication:
Randomised controlled trial

Author(s):
Zahed, Ghazal; Fatahi, Somaye; Tabatabaee, Leila; Imanzadeh, Negar; *Seraj, Shaikh Sanjid; Wolters, Benjamin Hernandez; Hosseini, Amirhossein

Citation:
BMC Pediatrics. 24(1):7, 2024 Jan 03.

Abstract:
OBJECTIVES: Functional retentive overflow incontinence (retentive FI) is the most common cause of fecal soiling in children. Based on the clinical experiences, the treatment of retentive FI in patients with comorbid psychiatric disorders was accelerated when Risperidone was used as treatment for their psychiatric comorbidities; therefore, this study was conducted to evaluate the effect of risperidone in the treatment of retentive FI in children and adolescents. METHODS: In this double-blind, randomized, placebo-controlled trial, 140 patients aged 4-16 years eligible for the study were randomized into two groups, receiving either 0.25-0.5 mg of Risperidone syrup (n = 70) or maltodextrin syrup (placebo group, n = 70) every 12 h daily for 12 weeks. Sociodemographic data, including age, sex, weight, height, BMI, BMI z-score, and socioeconomic status, was recorded, and the number of nocturnal FI, diurnal FI, and painful defecations was measured. RESULTS: 136 participants (69 on Risperidone and 67 on placebo) were included in the study. Mean age of participants in the intervention and placebo groups were 7.2 +/- 2.4 years and 8.0 +/- 3.1 years, respectively. The mean number of nocturnal FI (Ptrend=0.39) and diurnal FI (Ptrend=0.48) in patients without psychiatric comorbidities, and the number of painful defecations for participants with and without psychiatric comorbidities (P = 0.49, P = 0.47, respectively) were not significantly different between the groups, but a significant effect was observed in diurnal FI after Risperidone treatment in patients with psychiatric comorbidities (P < 0.001). CONCLUSION: Risperidone, when used along with other non-pharmacological interventions, may be helpful in treating FI in pediatric patients with psychiatric comorbidities.

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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.