Final Outcome Research Articles

Patient characteristics and predictors of mortality among children hospitalised with tuberculosis: A six-year case series study in Uganda.

The high case-fatality rates among children with tuberculosis (TB) are reportedly driven by in-hospital mortality and severe forms of TB. Therefore, there is need to better understand the predictors of mortality among children hospitalised with TB. We examined the patient clinical profiles, length of hospital stay from date of admission to date of final admission outcome, and predictors of mortality among children hospitalised with TB at two tertiary hospitals in Uganda. We conducted a case-series study of children below 15 years of age hospitalised with TB, from January 1st, 2016, to December 31st, 2021. Convenience sampling was done to select TB cases from paper-based medical records at Mulago National Referral Hospital (MNRH) in urban Kampala, and Fort Portal Regional Referral Hospital (FRRH) in rural Fort Portal. We fitted linear and logistic regression models with length of stay and in-hospital mortality as key outcomes. Out of the 201 children hospitalised with TB, 50 were at FRRH, and 151 at MNRH. The male to female ratio was 1.5 with median age of 2.6 years (Interquartile range-IQR 1-6). There was a high prevalence of HIV (67/171, 39%), severe malnutrition reported as weight-for-age Z-score <-3SD (51/168, 30%). Among children with pulmonary TB who initiated anti-tuberculosis therapy (ATT) either during hospitalisation or within seven days prior to hospitalisation; cough (134/143, 94%), fever (111/143, 78%), and dyspnoea (78/143, 55%) were common symptoms. Children with TB meningitis commonly presented with fever (17/24, 71%), convulsions (14/24 58%), and cough (13/24, 54%). The median length of hospital stay was 8 days (IQR 5-15). Of the 199 children with known in-hospital outcomes, 34 (17.1%) died during hospitalisation. TB meningitis was associated with in-hospital mortality (aOR = 3.50, 95% CI = 1.10-11.17, p = 0.035), while male sex was associated with reduced mortality (aOR = 0.33, 95% CI = 0.12-0.95, p = 0.035). Hospitalisation in the urban hospital predicted a 0.48-day increase in natural log-transformed length of hospital stay (ln-length of stay) (95% CI 0.15-0.82, p = 0.005), but not age, sex, HIV, malnutrition, or TB meningitis. In-hospital mortality was high, and significantly driven almost four times higher by TB meningitis, with longer hospital stay among children in urban hospitals. The high in-hospital mortality and long hospital stay may be reduced by timely TB diagnosis and treatment initiation among children.

Clinical predictive factors and imaging biomarkers of treatment response to half dose PDT in patients with chronic central serous chorioretinopathy

PurposeTo determine the clinical and imaging biomarkers of the response to half-dose photodynamic therapy (HD-PDT) in patients with central serous chorioretinopathy (CSC) MethodsClinical records and baseline ophthalmic images of 67 chronic CSC patients who underwent HD-PDT were assessed. In addition to demographic data, optical coherence tomography (OCT), fluorescein angiography (FA) and fundus autofluorescence (FAF) images were analyzed for specific biomarkers. The patients were categorized to early responder and late responder based on the time needed for complete resolution of subretinal fluid after PDT (less than 1 month vs. more than 1 month). The baseline clinical and imaging biomarkers were compared between the two groups. ResultsSeventy-three eyes of 67 patients were included in the study. The mean response time to PDT was 1.63 ± 1.48 months with 82.2% (60/73) of eyes categorized as early responder. The mean response time to PDT in delayed-response group was 4.15±1.51 months. In multivariate analysis, delayed response to PDT was associated with lacking history of systemic corticosteroid consumption, lacking history of pretreatment with eplerenone or acetazolamide before PDT and presence of hyperreflective foci in baseline OCT images (all p values < 0.05). There was no association between final visual outcome and late response to PDT. ConclusionThe presence of inflammatory biomarkers such as hyperreflective foci in baseline OCT images might be indicative of resistance to PDT. Moreover, the effect of pretreatment with mineralocorticoid antagonist on the response to PDT in chronic CSC should be explored in future prospective studies.

Converting an interprofessional opioid use disorder simulation from high-fidelity to an online branching pathway scenario

The Covid-19 pandemic caused a disruption in teaching for institutions across the country, particularly for those using simulation-based education. Our team converted a live high-fidelity simulation (HFS) into an online virtual simulation using a storyline and branching pathway approach. The team collaborated with multimedia specialists in video production to create a branching path simulation (BPS), taking interprofessional teams of online students through several decision-making points of a patient's experience in the emergency department (ED). Video vignettes of simulation decision points are incorporated throughout the simulation, with a final outcome eventually emerging. The TeamSTEPPS® Teamwork Attitudes Questionnaire (T-TAQ) was administered before and after the online simulation and descriptive data analysis (paired sample t-test) was conducted using SPSS statistical software. A post simulation satisfaction survey was similarly analyzed.

Quantifying pore structure heterogeneity of shale samples after solvent extraction following anhydrous and hydrous pyrolysis

Heterogeneity is an important pore structure characteristic of shale formations that can impact reservoir transport properties. To better understand the heterogeneity intrinsic to the shale pore structure, gas adsorption and multifractal theory were combined to analyze data from artificially matured shale samples under both anhydrous and hydrous pyrolysis conditions. We compared two sets of samples: one that was kept intact (not treated with organic solvent), and the other set that was treated with an organic solvent to remove any liquid petroleum that was produced during the pyrolysis process. The results revealed differences in the pore structure parameters of the aliquots under these two pyrolysis conditions as well as treated vs. intact. Furthermore, at the same pyrolysis temperature, the disparity in surface area and pore volume before and after extraction of petroleum was found to be greater with anhydrous compared to hydrous pyrolysis conditions. Regardless of the pyrolysis conditions, when the pyrolysis temperature is under 400 °C, pore structural heterogeneity following extraction of petroleum is often small compared to the situation when yield is still present in the pores. As a result, the movable oil under both maturity routes can increase pore structure heterogeneity. Considering the results, when analyzing shale adsorption data for pore structure heterogeneity, experimental design would have an impact on the final outcome and data interpretation. This is the first study that investigates the effect of the movable oil and solvent extraction process on pore structure heterogeneity in relation to the thermal evolution of shale in the presence and absence of water.

Versatility of the medial corticoperiosteal flap: from recalcitrant non-unions up to large bony defects.

Reconstructive microsurgery techniques using vascularized bone grafts have revolutionized the treatment of complex cases associated with recalcitrant non-unions or osteomyelitis. The medial femoral corticoperiosteal flap (MFCP flap) has emerged as a valuable option in bone reconstruction. Its clinical applications have been extended over the years considering this flap from non-unions with minimal bone lost, up to large intercalary defects of the upper and lower extremities. This article aims to present the clinical applications and outcomes of the MFCP flap in various reconstructive scenarios. Seventy-nine patients with persistent non-union and bone defects of the upper and lower limb were evaluated from June 2008 to October 2020. All of them were reconstructed with a corticoperiosteal flap from the medial femoral condyle in our hospital. Previous procedures, bone gap and type of flap used were recorded. Postoperative functional status was assessed with time of bone healing, complications and clinical final outcome. Radiological evidence of bone union was observed at 4.09months (range 2-9). Healing rate was 97% with periosteal corticocancellous flaps (PCC flaps) and 93% with corticoperiosteal flaps (CP flaps). Average follow-up was 14.5months (range 5-28). There were no significant donor site complications. The MFCP flap offers a versatile and reliable option for bone reconstruction. Its ability to provide vascularized bone tissue with low morbidity enhances the healing process and improves outcomes. The MFCP flap has been increasing its applications and it serves as a valuable option in the treatment of recalcitrant non-unions or bony defects irrespective of site and size up to 5cm in the upper and lower extremities.

Outcomes of surgical revascularization for pediatric moyamoya disease and syndrome

PurposeMoyamoya disease and syndrome represent rare entities characterized by progressive stenosis and/or occlusion of the intracranial blood vessels. We present our series of patients with moyamoya disease and syndrome stratified by underlying disease and analyze differences in presentation and outcome following surgical revascularization.MethodsThis was an Institutional Review Board (IRB) approved, retrospective review of all patients surgically revascularized by the senior author (SNM) while at Children’s National Hospital in Washington, DC. Demographic data, presenting symptoms and severity, surgical details, and functional and radiographic outcomes were obtained and analyzed for differences among the underlying cohorts of moyamoya disease and syndrome as well as by unilateral or bilateral disease and index or non-index surgeries.ResultsTwenty-two patients were identified with the following underlying diseases: six with idiopathic moyamoya disease, six with sickle cell anemia, five with trisomy 21, and five with neurofibromatosis type 1. Thirty hemispheres were revascularized with a significantly reduced rate of stroke from 3.19 strokes/year (SD = 3.10) to 0.13 strokes/year (SD = 0.25), p = 0.03. When analyzed by underlying cause of moyamoya syndrome, patients with neurofibromatosis type 1 were found to be significantly less likely than the other subtypes of moyamoya syndrome to have had either a clinical stroke (0.0% neurofibromatosis type 1 vs. 100.0% sickle cell, 60.0% trisomy 21, or 83.3% moyamoya disease, p < 0.01) or radiographic stroke (0.0% neurofibromatosis type 1 vs. 100.0% sickle cell, 60.0% trisomy 21, or 83.3% moyamoya disease, p < 0.01) at time of presentation. Patients with moyamoya syndrome associated with sickle cell disease were more likely to present with clinical and radiographic strokes. Additionally, patients with bilateral disease demonstrated no difference in final functional outcome compared to patients with unilateral disease (mRS 0.73 (SD = 1.33) vs. 1.29 (SD = 1.60), p = 0.63).ConclusionIndirect surgical revascularization decreases stroke risk for pediatric patients with different forms of moyamoya disease and moyamoya syndrome. Additionally, these data suggest that sickle cell anemia-associated moyamoya syndrome may represent a more aggressive variant, while neurofibromatosis type 1 may represent a more benign variant.

The predictive value of the Kampala Trauma Score (KTS) in the outcome of multi-traumatic patients compared to the estimated Injury Severity Score (eISS)

PurposeThe classification of trauma patients in emergency settings is a constant challenge for physicians. However, the Injury Severity Score (ISS) is widely used in developed countries, it may be difficult to perform it in low- and middle-income countries (LMIC). As a result, the ISS was calculated using an estimated methodology that has been described and validated in a high-income country previously. In addition, a simple scoring tool called the Kampala Trauma Score (KTS) was developed recently. The aim of this study was to compare the diagnostic accuracy of KTS and estimated ISS (eISS) in order to achieve a valid and efficient scoring system in our resource-limited setting.MethodsWe conducted a cross-sectional study between December 2020 and March 2021 among the multi-trauma patients who presented at the emergency department of Imam Reza hospital, Tabriz, Iran. After obtaining informed consent, all data including age, sex, mechanism of injury, GCS, KTS, eISS, final outcome (including death, morbidity, or discharge), and length of hospital stay were collected and entered into SPSS version 27.0 and analyzed.Results381 multi-trauma patients participated in the study. The area under the curve for prediction of mortality (AUC) for KTS was 0.923 (95%CI: 0.888–0.958) and for eISS was 0.910 (95% CI: 0.877–0.944). For the mortality, comparing the AUCs by the Delong test, the difference between areas was not statistically significant (p value = 0.356). The diagnostic odds ratio (DOR) for the prediction of mortality KTS and eISS were 28.27 and 32.00, respectively.ConclusionIn our study population, the KTS has similar accuracy in predicting the mortality of multi-trauma patients compared to the eISS.

Community-acquired neonatal SARS-CoV-2 infection: case report

Background and Objectives: Data collection on the incidence of COVID-19 is conducted less frequently in newborns (NB) than in adults. In view of the small number of described neonatal SARS-CoV-2 infections, in this study, we report a clinical case of community-acquired COVID-19 infection in a newborn. Methods: Clinical characteristics were collected from the medical records from April 2021 until the final outcome of the newborn in May 2021. Results: This article discusses the case of a full-term male newborn aged 38 weeks. On the 17th day of life, this newborn was admitted to the pediatric unit with fever and zone 4 jaundice, mild lower chest retraction and tachypnea. The mother was diagnosed with COVID-19. Late neonatal sepsis with pulmonary focus was detected. The newborn was hospitalized and the antigen test for COVID-19 came back positive. The condition of the neonate rapidly deteriorated and he was referred to the neonatal intensive care unit (NICU), where he was intubated and placed on pressure-controlled mechanical ventilation. During his second week in the NICU, he developed severe pulmonary hypertension with decreased peripheral oxygen saturation and tachycardia. The newborn required blood transfusion and was put into prone position during part of the treatment. Reductions in mechanical ventilation parameters were not tolerated by the NB’s organism and he developed progressive hypoxemia. The newborn died 1 month and 3 days after hospitalization. Conclusion: Our study shows a case of community-acquired COVID-19 that progressed to the severe form of the disease.

Near hanging with Multiple Tentative Cuts: A Case Series

Suicide is one of the major global health issues specially in countries having low to medium socioeconomic condition. Hanging is method of choice for adults to commit suicide. Near hanging defined as person who survive a hanging injury for enough time to reach hospital. Tentative cut or self-inflicted injury is an intentional and direct injury to own’s body part. It is also known as self-harm, self-wounding, moderate self-mutilation and parasuicide. Various factors responsible for high mortality in near hanging are low systolic blood pressure (&lt;90), injury severity score (ISS) &gt;15, Glassgow coma scale (GCS) &lt;8, hypoxic brain injury on CT scan. Immediate arrival to hospital and aggressive management of near hanging and its complication can improve the final outcome.

Endogenous Endophthalmitis: A 10-Year Review of Cases on the East Coast of Malaysia.

Purpose Our study aimed to describe the clinical profile of endogenous endophthalmitis, focusing on patient demographics, infection sources, microbial profiles, clinical outcomes, and factors affecting the final visual outcome. Methods A retrospective review was performed on data from 68 eyes of 60 patients diagnosed with endogenous endophthalmitis and hospitalized in two tertiary hospitals on the East Coast of Peninsular Malaysia from January 2011 to December 2020. The analysis encompassed evaluating patient age, gender, laterality, risk factors, infection origins, presenting and final visual acuity, microbial results, treatment responses, and factors affecting final visual outcomes. Results The average age of the patient cohort was 54.9 ± 13.3 years. Females were more likely to have endogenous endophthalmitis than males (33, 55.0% vs. 27, 45.0%). Twenty-seven patients (45.0%) presented with endogenous endophthalmitis in the left eye, while 25 patients (41.7%) had it in the right eye, and eight patients (13.3%) had bilateral involvement. Most patients had underlying predisposing conditions, predominantly diabetes mellitus (53, 88.3%). Infection sources were identified in 42 patients (70.0%), out of which urinary tract infections account for the majority (11, 18.3%). Klebsiella species(14, 22.7%) were the leading pathogens and were significantly associated with liver abscess cases. In this series, the majority of patients had poor presenting and final visual acuity of worse than 3/60 (56, 82.4% and 53, 77.9%, respectively). Thirty-six eyes (52.9%) underwent vitrectomy, resulting in only four eyes (11.11%) achieving final visual acuity better than 6/12. Presenting visual acuity was identified as the factor contributing to the blind final visual outcome (r = 0.707, p < 0.001). Conclusion Females were found to be more commonly affected by endogenous endophthalmitis than males. Klebsiella species were the most commonly isolated microorganisms and were typically associated with liver abscesses. Urinary tract infection was the most common predisposing factor. A majority of the patients had poor presenting and final visual acuity, in which poor visual acuity is a significant indicator of blind visual outcomes.

Artificial intelligence to develop outcomes for critical thinking: A helping start and still up to the educator to develop the final outcome.

Artificial intelligence to develop outcomes for critical thinking: A helping start and still up to the educator to develop the final outcome.

A COMPARATIVE STUDY ON NASAL BONE FRACTURE ASSOCIATED WITH SEPTAL DEVIATION CORRECTED WITH SEPTOPLASTY VERSUS CLOSED REDUCTION

Objective: The dorsum of the nose formed by nasal bones helps to maintain the airway and esthetic appearance of the nose. Faciomaxillary trauma is associated with a nasal bone fracture with or without nasal septal fractures. Nasal bone fractures can lead to deviation of the external nose and nasal obstruction. The management includes correction of nasal bone deformity with either septoplasty or reduction of nasal septal deviation by the non-surgical method. A study was conducted to compare the results of septal deviation corrected by septoplasty and non-surgical reduction of septal deviation combined with nasal bone fracture reduction.The aim of this study was to compare the results of septal deviation corrected by septoplasty and non-surgical reduction of septal deviation combined with nasal bone fracture reduction. Materials: Sixty-two patients with nasal bone fractures with varying degrees of external nose deformity and nasal septal deviation were divided into two groups. Group A consisted of patients treated with septoplasty and nasal bone fracture correction and Group B consisted of patients treated with non-surgical reduction of septal deviation and nasal bone fracture correction. Type I, II, and II nasal bone fractures were included with all types of septal deviations. The subjective improvement in nasal obstruction was assessed using the visual analog scale in both groups. Results: There were 26 males (81.25%) and 06 (18.75%) females in Group A and 25 (83.33%) males and 05 (16.67%) females in Group B. In Group A, 12 (37.5%) patients were aged between 18 and 27 years, 10 (31.25%) patients were aged between 28 and 27 years, 07 (21.87%) patients were aged between 38 and 47 years, and 03 (09.37%) patients were aged between 48 and 57 years. The mean age was 23.54±2.30 years. Conclusion: Nasal bone fractures cause not only esthetic facial deformity but also functional airway obstruction. A thorough clinical examination, computed tomography scan, and patient counseling are necessary. There is no statistically significant difference in the final outcome between the septoplasty and closed reduction of the septal deviation undertaken to relieve nasal obstruction in patients with associated nasal bone fractures.

Urban flood susceptibility mapping using remote sensing, social sensing and an ensemble machine learning model

Flood susceptibility mapping is crucial for urban disaster management. However, the heterogeneity of urban land use and the complexity of terrain pose challenges to the accuracy and generalizability of flood models. In this paper, we propose a framework named the EMF model for urban flood mapping. Specifically, the social sensing and remote sensing were used for flooding information collection. The XGBoost, Support Vector Classifier (SVC), Multilayer Perceptron (MLP), and Multimodal Deep Learning (MDL), were used as the predictive models, and their results were ensembled using a Random Forest model to produce the final outcome. Results show that the EMF model outperforms the standalone models, with an accuracy of 0.942 on the training set and 0.940 on the testing set. The accuracy of the five models is ranked as EMF > MDL > XGBoost > SVC > MLP. The flood map indicates that flooding has a greater impact on the outskirts and suburbs of the city compared to its central urban areas. Farmland is the most affected land type, making up 54.8 % of the flooded area. Overall, the proposed framework enables rapid and accurate identification of flood-prone areas, providing technical support for managers in formulating effective flood prevention strategies.

A Conceptual Review of Allergic Rhinitis According to Ayurveda

The study focuses on the global health concern of allergic rhinitis, a condition that affects approximately 400 million people worldwide. The prevalence of allergic rhinitis characterized by recurrent attacks of sneezing, nasal congestion and rhinorrhoea has increased over the years due to urbanization and environmental pollution. Although modern medicine has developed treatments for allergic rhinitis, it is still incurable. In Ayurveda, there is a concept of Sannipatik disorders, which involves the vitiation of all the three Doshas (Vata, Pitta, and Kapha) in the pathophysiology of the disease. Sannipatik diseases are known to be particularly challenging to treat. The symptoms of allergic rhinitis closely resemble the diseased condition called Sannipatik Pratishayaya in Ayurveda. While modern medicine offers anti-allergic, antihistaminic, corticosteroids, and other treatment options, these are not entirely effective in curing the disease or preventing its recurrence. Additionally, these treatments often come with their own side effects. In contrast, Ayurvedic classical texts provide detailed explanation of the pathophysiology, sign and symptoms and principles of treatment for effective management for Sannipatik Pratishayaya. Thus, the Ayurvedic concept of Sannipatik Pratishyaya and its understanding can be helpful in managing allergic rhinitis. Aim- The aim of the article is to correlate symptomatology of Sannipatik Pratishyaya with allergic rhinitis and discuss the role of various treatment modalities according to Ayurveda. Methods- Literary review of various Ayurvedic texts, electronic databases; online Journals in the field available at various search portals. Result-The final outcome of the study is to find out a permanent treatment measure for this problem that can be further tested by practical application.

Comorbidities and final outcome of post COVID-19 associated oral mucormycosis patients: a cross-sectional study

BackgroundMucormycosis is an invasive and possibly fatal fungal infection that frequently affects the mouth. Co-infection in post COVID-19 patients is an emerging concern, owing to their complex nature and higher mortality. Therefore, this study aimed to report the underlying risk factors, clinical characteristics, presentation, and final outcome of COVID-19 associated oral mucormycosis cases.ResultsThis study included 51 patients with oral mucormycosis 28 (55%) males and 23 (45%) females. Twenty-three patients (45%) presented with deep necrotic ulcer, 16 patients (31%) presented with superficial ulcer, and 12 patients (23%) of them presented with fistula. The overall survival rate was 51% (26 patients recovered). On the other hand, mortality rate was 49% (25 patients), of which 68% suffered from uncontrolled diabetes mellitus.ConclusionsThe mortality rate of COVID-19 associated mucormycosis cases with oral manifestations was found to be quite high mostly due to delayed diagnosis and lack of timely treatment. Thus, increasing the awareness of dentists and maxillofacial surgeons is crucial for the early diagnosis of oral mucormycosis which is vital to improve prognosis of this serious infection. This is of high importance in view of the escalating numbers of mucormycosis cases being recorded worldwide.

Abstract PO2-17-01: Impact of the introduction of CDK4/6 inhibitors on treatment duration in patients with HR+, HER2– advanced breast cancer: Final analysis of TreatER+ight, a Canadian prospective, real-world, observational study

Abstract Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are the established first-line targeted therapy (TT) for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2–) advanced breast cancer (ABC). TreatER+ight, the first prospective, real-world study evaluating the treatment patterns, safety and effectiveness of ET alone or ET + TT in Canadian patients with HR+, HER2– ABC (2016 to 2020) recorded ET as the standard of care (SOC) in the first interim analysis report. However, treatment with CDK4/6i combined with ET have rapidly evolved as the SOC in the metastatic setting. Methods: This prospective, multicenter, observational study (NCT02753686) enrolled patients with HR+, HER2‒ ABC with or without prior exposure to ET and up to one line of prior CT in the advanced setting. The patients were enrolled by the line of their therapy (first-line, second-line or third-line) and grouped into 2 cohorts (ET and ET + TT). Duration of therapy, and overall survival (OS) are estimated using Kaplan–Meier method. Here, we report the final outcome with CDK4/6i treatment evolution with sequencing strategy and duration in routine clinical practice. Results: At data cutoff (December 1, 2022), a total of 439 enrolled patients (ET, n=104; ET + TT, n=335) from 25 centers in Canada, constituted the full analysis set. The median age (range) was 71.5 (37.0–96.0) years in ET cohort and 65.0 (23.0-87.0) years in ET + TT cohort. About 84.6% and 66.4% were postmenopausal patients in the ET and ET + TT cohorts, respectively. Patients with ECOG PS scores 0 to 1 composed of 82.0% and 93.5% in the ET and ET + TT cohorts, respectively. In the overall population, ET alone and ET + CDK4/6i were the most common treatment received by patients in first-line (43.5% and 43.3%) and second-line (36.3% and 24.6%) treatment settings. In third-line treatment setting, CT was the most common treatment received by patients (38.4%). Conclusions: Data from final analysis of TreatER+ight have further confirmed the evolution to primary use of CDK4/6i-based combination therapy in the first-line setting for Canadian patients with HR+, HER2– ABC. Additional details on duration of therapy by CDK4/6i agents, overall survival data and age subgroup analysis will be presented at SABCS 2023 Table 1_Baseline characteristics, treatment patterns, and duration of treatment Citation Format: Catherine Doyle, Ana Elisa Lohmann, Nayyer Iqbal, Jan-Willem Henning, Swati Kulkarni, Nadia Califaretti, John Hilton, Cristiano Ferrario, Nathaniel Bouganim, Mihaela Mates, Stephanie Guillemette, Ricardo Leite, Stephen Chia. Impact of the introduction of CDK4/6 inhibitors on treatment duration in patients with HR+, HER2– advanced breast cancer: Final analysis of TreatER+ight, a Canadian prospective, real-world, observational study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-01.

Abstract PO2-04-05: FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES

Abstract Background Brain metastases (BM) are a severe complication of HER2-positive metastatic breast cancer. In the absence of any immediate indication for local therapy, the tyrosine-kinase inhibitor tucatinib combined with trastuzumab and capecitabine (TTC) is regarded as the preferred systemic treatment option for active BM, while data on the activity of antibody-drug conjugates (ADC) is limited. In the primary outcome analysis of TUXEDO-1, an intracranial response rate (RR) of 73.3% was reported with the ADC trastuzumab-deruxtecan (T-DXd). Here, we report final progression-free survival (PFS) and overall survival (OS) results of this study. Patients and Methods: TUXEDO-1 is a prospective, single-centre, single-arm phase 2 trial. Adult patients with HER2-positive BC and active BM (newly diagnosed untreated or progressing after prior local therapy), prior treatment with trastuzumab and pertuzumab, ECOG performance status 0 or 1 without indication for immediate local therapy were accrued and received T-DXd until progression, inacceptable toxicity, or withdrawal for any other reason. The primary endpoint was intracranial RR centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria in the intention-to-treat population; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population (PPP). Results A total number of 15 patients were accrued; one patient was found to have dural metastases only upon restaging, resulting in a PPP of 14 patients. Patients had received a median number of two prior treatment lines (range, 1-5), 60% had progressive brain metastases and 60% had received prior T-DM1. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). A total of 238 cycles of T-DXd were administered (median 11.5 cycles; range 4-42). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event (AE) was fatigue (n=3; 20%). A total of 8 serious AEs were reported in 8 patients. Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL and neurocognitive functioning were maintained over the entire treatment duration and a significant deterioration of global QoL was observed upon progression (p=0.036). Most patients received TTC (n=5) or local therapy (n=4) as next subsequent treatment line. Ancillary biomarker studies are ongoing, and results will be presented at the meeting. Discussion In TUXEDO-1, T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive breast cancer BM. The safety profile was consistent with previous reports. T-DXd did not impair QoL and neurocognitive functioning was maintained. Results therefore support the concept of ADCs as systemic therapy for active BM. Citation Format: Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Angelika Maria Starzer, Maximilian Mair, Heidrun Forstner, Beate Rottenmanner, Marie-Bernadette Aretin, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegül Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Georg Pfeiler, Christian F. Singer, Ansgar Weltermann, Luzia Berchtold, Matthias Preusser. FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-05.

Association of socio-demographic factors with clinical outcome among hospitalized patients in first and second waves of COVID-19 pandemic: Study from the developing world.

Recent disease resurgence in China indicates that corona virus infectious disease is still a pertinent public health problem. We stand at a juncture where we are still unsure about the initial dilemmas regarding its birth, therapies, and the emerging novel strains. Medical literature has focused on the clinical, laboratory, radiological, and therapeutic aspects of disease management. There is paucity of literature on the association between socio-demographic variables on disease severity and clinical outcome. This retrospective observational study analyzing the socio-demographic variables was performed at a dedicated COVID care center in western Maharashtra, India. Electronic records of all individuals who were admitted to this hospital from July 29 2020, to June 14, 2021, and diagnosed COVID-19 positive by reverse transcriptase polymerase chain reaction (RT-PCR) were identified after due institutional ethical clearance. Patients admitted from July 29, 2020, to February 27, 2021, were categorized as patients presenting during the 'first wave of viral pandemic'. Those admitted from March 01, 2021, to June 14, 2021, have been included as patients admitted during 'second wave of viral pandemic'. The following outcome parameters were collected (presenting symptoms, duration of symptoms before the individual presented for diagnostic RT-PCR, total duration of symptoms, severity of disease at onset, duration of hospital stay, the final outcome (discharge/death) and Charlson's comorbidity index). The linear regression model was used to establish association between socio-demographic factors and disease severity at onset (mild/moderate/severe/critical). A total of 37033 patients were screened, and the positivity rate with RT-PCR was 16.99% (n = 6275) during the study period. Out of which 45% (n = 2824) of the patients had mild disease requiring home isolation and the remaining 55% of patients required admission. 1590 patients from the first wave and 910 from the second wave of COVID-19 were hospitalized and included in the study after exclusion. The mean age of patients in first wave was 49 years and that in second wave was 54 years with 77.6% and 70.6% males in two waves, respectively. The burden of critical cases was higher in second wave as computed to first wave (10% vs 8%). The second wave had more outreach in the rural population as compared to second one (17.8% vs 12.2%). The mean duration from the onset of symptoms to hospitalization was 03 and 04 days, respectively, in two waves. Mortality associated in two waves was 11.9% and 24%, respectively (P < 0.05). Higher Charlson's comorbidity index was associated with higher mortality, and the cumulative survival from urban area was more as compared to the rural population (log rank - 9.148, P = 0.0002). The second COVID-19 wave had significantly higher case mortality. It affected elderly patients and those with rural background. The factors associated with higher mortality during COVID-19 pandemic were rural background, higher Charlson's comorbidity index and late presentation to the hospital. Ongoing vaccine campaigns, thus, should focus on rural areas and individuals with comorbidities especially in developing and least developed countries.

Customized m-RCNN and hybrid deep classifier for liver cancer segmentation and classification

Diagnosing liver disease presents a significant medical challenge in impoverished countries, with over 30 billion individuals succumbing to it each year. Existing models for detecting liver abnormalities suffer from lower accuracy and higher constraint metrics. As a result, there is a pressing need for improved, efficient, and effective liver disease detection methods. To address the limitations of current models, this method introduces a deep liver segmentation and classification system based on a Customized Mask-Region Convolutional Neural Network (cm-RCNN). The process begins with preprocessing the input liver image, which includes Adaptive Histogram Equalization (AHE). AHE helps dehaze the input image, remove color distortion, and apply linear transformations to obtain the preprocessed image. Next, a precise region of interest is segmented from the preprocessed image using a novel deep strategy called cm-RCNN. To enhance segmentation accuracy, the architecture incorporates the ReLU activation function and the modified sigmoid activation function. Subsequently, a variety of features are extracted from the segmented image, including ResNet features, shape features (area, perimeter, approximation, and convex hull), and enhanced median binary pattern. These extracted features are then used to train a hybrid classification model, which incorporates classifiers like SqueezeNet and DeepMaxout models. The final classification outcome is determined by averaging the scores obtained from both classifiers.

Covid-19 Outcome Prediction Model by Using Radio-Diagnostic Methods

Research goal: The goal of this research is to create a prediction model for a possible outcome (death or survival) of COVID-19, which model incorporates the easily available radio diagnostic methods such as classical radiology and the disease scoring system. Part of the goal of this study is to define the chances and probabilities of occurrence of death as a result of the primary disease and to identify the risk factors that have the highest influence on the final outcome of COVID-19. Methodology: The methodological approach used in this study is the binary logistic regression which is part of the group of generalized linear statistical methods. Results: Results show that patients with complications and comorbidities have the highest chances of death from COVID-19 (OR 16,53 with CI 8,21 - 33,25 and 4,08 with CI 1,34 - 12,38). Men are also exposed to higher but insignificant mortality risk with OR 1,55 with CI 0,86 - 2,80. Every additional year of age increases the mortality risks by 1,06 times (CI 1,03 - 1,09), while every additional score of the primary disease leads to increased chances of unwanted outcome by 1,24 (CI 1,04 - 1,47). Conclusion: The mortality outcome of COVID-19 is not an exclusive consequence of the primary disease but it is usually determined in correlation with different comorbidities and existing complications as well as other standard influencing factors such as age and gender. Contribution and significance of the research: The primary importance of this research is the fact that it allows for an improved precision and upgrade to the basic model of standard factors by using new predictors, specifically secondary complications from the radio-graphic picture and scoring of the primary disease, which leads to higher utilization of cheap and easily available radio-diagnostic methods.